US2011177011A1PendingUtilityA1
Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of bruton's tyrosine kinase by such compounds

Individually held — no corporate assignee on recordPriority: Jun 4, 2003Filed: Jan 23, 2008Published: Jul 21, 2011
Est. expiryJun 4, 2023(expired)· nominal 20-yr term from priority
Inventors:Kevin S. Currie Robert W. Desimone Scott A. Mitchell Douglas A. Pippin James Darrow Xiaobing Qian Mark Velleca Dapeng Qian
A61P 37/02A61P 35/00A61P 29/00C07D 487/04
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References
Claims
Abstract

Compounds of Formula I-a and all pharmaceutically-acceptable forms thereof, are described herein. The variables R 1 , R 2 , R 3 , Z 1 , Q, and A shown in Formula I-a are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I-a, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I-a effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases. Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity. Methods of treatment include administering a compound of Formula I-a as a single active agent or administering a compound of Formula I-a in combination with one or more other therapeutic agent. A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I-a under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.
Claims

exact text as granted — not AI-modified
1 - 86 . (canceled) 
     
     
         87 . A pharmaceutical composition, comprising at least one pharmaceutically acceptable carrier or excipient and a compound of Formula 1 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, hydrate or diastereomer thereof, wherein 
       A is 0 or 1; 
       R 1  is
 substituted phenyl wherein the substituent is
 hydroxy, 
 CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 mono-, di- or tri-substituted C 2 -C 6  alkenyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 2 -C 6  alkynyl, 
 mono-, di- or tri-substituted C 2 -C 6  alkynyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 mono-, di- or tri-substituted C 1 -C 6 hydroxyalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 mono-, di- or tri-substituted C 1 -C 6 hydroxyalkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 mono-, di- or tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 mono-, di- or tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 mono-, di- or tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 mono-, di- or tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 heterocycloalkyl, 
 mono-, di- or tri-substituted heterocycloalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 aryl, 
 mono-, di- or tri-substituted aryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 heteroaryl, 
 mono-, di- or tri-substituted heteroaryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 mono-, di- or tri-substituted-C 1 -C 6 alkyl(C═O)OR 10 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkyl(C═O)NR 10 R 11 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 mono-, di- or tri-substituted-C 1 -C 6 alkylNR 10 (SO 2 )R 11 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkyl(SO 2 )R 10 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 -L-G, where
 L is 
 C 1 -C 2 alkylene, 
 mono-, di- or tri-substituted C 1 -C 2 alkylene, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 0 -C 2 alkylene-O—, 
 mono-, di- or tri-substituted C 0 -C 2 alkylene-O—, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, 
 mono-, di- or tri-substituted —(C 1 -C 2 alkylene)(C═O)—, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 G is 
 heterocycloalkyl, 
 mono-, di- or tri-substituted heterocycloalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 3 -C 7 cycloalkyl, 
 mono-, di- or tri-substituted C 3 -C 7 cycloalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 aryl, 
 mono-, di- or tri-substituted aryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 heteroaryl, 
 mono-, di- or tri-substituted heteroaryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 
 
 or 
 substituted heteroaryl wherein the substituent is
 oxo, 
 —CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 mono-, di- or tri-substituted C 2 -C 6  alkenyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 2 -C 6  alkynyl, 
 mono-, di- or tri-substituted C 2 -C 6  alkynyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 mono-, di- or tri-substituted C 1 -C 6 hydroxyalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 mono-, di- or tri-substituted C 1 -C 6 hydroxyalkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 mono-, di- or tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 mono-, di- or tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 mono-, di- or tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 mono-, di- or tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 heterocycloalkyl, 
 mono-, di- or tri-substituted heterocycloalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 aryl, 
 mono-, di- or tri-substituted aryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 heteroaryl, 
 mono-, di- or tri-substituted heteroaryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 mono-, di- or tri-substituted-C 1 -C 6 alkyl(C═O)OR 10 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkyl(C═O)NR 10 R 11 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 mono-, di- or tri-substituted-C 1 -C 6 alkylNR 10 (SO 2 )R 11 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkyl(SO 2 )R 10 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , 
 mono-, di- or tri-substituted-C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 -L-G, where
 L is 
 C 1 -C 2 alkylene, 
 mono-, di- or tri-substituted C 1 -C 2 alkylene, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 0 -C 2 alkylene-O—, 
 mono-, di- or tri-substituted C 0 -C 2 alkylene-O—, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, 
 mono-, di- or tri-substituted —(C 1 -C 2 alkylene)(C═O)—, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 G is 
 heterocycloalkyl, 
 mono-, di- or tri-substituted heterocycloalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 C 3 -C 7 cycloalkyl, 
 mono-, di- or tri-substituted C 3 -C 7 cycloalkyl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 aryl, 
 mono-, di- or tri-substituted aryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 heteroaryl, 
 mono-, di- or tri-substituted heteroaryl, wherein the substituents are independently halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, or phenyl, 
 
 
 R 10 , R 11 , and R 12  are independently hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 10 cycloalkyl, or heterocycloalkyl, 
 R 1  is optionally further substituted with 1 or more substituents which are independently hydroxy, nitro, cyano, amino, —SO 2 NH 2 , halogen, C 1 -C 6  alkyl, C 2 -C 6 alkanoyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 6  alkylthio, C 3 -C 7 cycloalkyl, (C 1 -C 6  alkoxy)C 0 -C 6 alkyl, (mono-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, (di-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, or
 C 1 -C 6 alkoxycarbonyl; 
 
 R 2  is
 C 1 -C 7  alkyl, 
 (C 1 -C 6 alkoxy)C 0 -C 6 alkoxy, 
 (heterocycloalkyl) C 0 -C 2 alkyl, 
 (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, 
 (phenyl)C 0 -C 2 alkyl, 
 mono-, di-, or tri-substituted (phenyl)C 0 -C 2 alkyl, wherein the substituents are independently hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, or —(C═O)R 13  wherein R 13  is C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, or heteroaryl; 
 (phenoxy)C 0 -C 2 alkyl, 
 mono-, di-, or tri-substituted (phenoxy)C 0 -C 2 alkyl, wherein the substituents are independently hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, or —(C═O)R 13  wherein R 13  is C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, or heteroaryl; 
 (heteroaryl)C 0 -C 2 alkyl, 
 mono-, di-, or tri-substituted (heteroaryl)C 0 -C 2 alkyl, wherein the substituents are independently hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, or —(C═O)R 13  wherein R 13  is C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, or heteroaryl; 
 
 Z 1  is 
 
       
         
           
           
               
               
           
         
         R 4  is
 Hydrogen, 
 C 1 -C 6 alkyl, 
 substituted C 1 -C 6 alkyl wherein the substituent is hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, or —C(O)R 14  wherein R 14  is C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, or phenyl; 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl, wherein the substituent is hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, or —C(O)R 14  wherein R 14  is C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, or phenyl; 
 heterocycloalkyl, 
 substituted heterocycloalkyl, wherein the substituent is hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, or —C(O)R 14  wherein R 14  is C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, or phenyl; 
 phenyl, 
 substituted phenyl, wherein the substituent is hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, or —C(O)R 14  wherein R 14  is C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, or phenyl; 
 heteroaryl, 
 substituted heteroaryl, wherein the substituent is hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, or —C(O)R 14  wherein R 14  is C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, or phenyl; 
 
         Q is phenyl or pyridyl; 
         R 3  is
 hydrogen, 
 halogen, 
 C 1 -C 7  alkyl, 
 heterocycloalkyl, 
 mono-, di-, or tri-substituted heterocycloalkyl, wherein the substituents are independently hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, or —C(O)R 14 , 
 C 3 -C 7 cycloalkyl, 
 mono-, di-, or tri-substituted C 3 -C 7 cycloalkyl, wherein the substituents are independently hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, or —C(O)R 14 , 
 heteroaryl, 
 mono-, di-, or tri-substituted heteroaryl, wherein the substituents are independently hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, or —C(O)R 14 . 
 
       
     
     
         88 . A pharmaceutical composition of  claim 87 , wherein the composition is formulated as an injectable fluid, an aerosol, a cream, a gel, a tablet, a pill, a capsule, a syrup, ophthalmic solution, or a transdermal patch. 
     
     
         89 . A packaged pharmaceutical composition, comprising
 a pharmaceutical composition in a container; and instructions for using the composition to treat a patient suffering from an disease responsive to Btk inhibition, wherein the pharmaceutical composition comprises   (a) at least one pharmaceutically acceptable carrier or excipient and   (b) the compound of Formula I-a   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, hydrate or diastereomer thereof, wherein 
         A is chosen from 0 and 1; 
         R 1  is chosen from 
         phenyl substituted with a group chosen from
 hydroxy, 
 —CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 substituted C 2 -C 6  alkenyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkenyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 2 -C 6  alkynyl, 
 substituted C 2 -C 6  alkynyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkynyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 substituted C 1 -C 6 hydroxyalkyl chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 substituted C 1 -C 6 hydroxyalkoxy chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 substituted —C 1 -C 6 alkyl(C═O)OR 10  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkyl(C═O)OR 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 substituted —C 0 -C 6 alkyl(SO 2 )R 10  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(SO 2 )R 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 -L-G, where
 L is chosen from
 C 1 -C 2 alkylene, 
 substituted C 1 -C 2 alkylene chosen from mono-, di-, and tri-substituted C 1 -C 2 alkylene wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 0 -C 2 alkylene-O—, 
 substituted C 0 -C 2 alkylene-O— chosen from mono-, di-, and tri-substituted C 0 -C 2 alkylene-O— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, and 
 substituted —(C 1 -C 2 alkylene)(C═O)— chosen from mono-, di-, and tri-substituted —(C 1 -C 2 alkylene)(C═O)— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 G is chosen from
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, and 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 
 
         heteroaryl substituted with a group chosen from
 hydroxy, 
 —CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 substituted C 2 -C 6  alkenyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkenyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 2 -C 6  alkynyl, 
 substituted C 2 -C 6  alkynyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkynyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 substituted C 1 -C 6 hydroxyalkyl chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 substituted C 1 -C 6 hydroxyalkoxy chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 substituted —C 1 -C 6 alkyl(C═O)OR 10  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkyl(C═O)OR 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 substituted —C 0 -C 6 alkyl(SO 2 )R 10  chosen from mono-, di-, and tri-substituted-C 0 -C 6 alkyl(SO 2 )R 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 -L-G, where
 L is chosen from
 C 1 -C 2 alkylene, 
 substituted C 1 -C 2 alkylene chosen from mono-, di-, and tri-substituted C 1 -C 2 alkylene wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 0 -C 2 alkylene-O—, 
 substituted C 0 -C 2 alkylene-O— chosen from mono-, di-, and tri-substituted C 0 -C 2 alkylene-O— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, and 
 substituted —(C 1 -C 2 alkylene)(C═O)— chosen from mono-, di-, and tri-substituted —(C 1 -C 2 alkylene)(C═O)— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 G is chosen from
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, and 
 
 
 
         substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
         R 1  is optionally further substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, —SO 2 NH 2 , halogen, C 1 -C 6  alkyl, C 2 -C 6 alkanoyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 6  alkylthio, C 3 -C 7 cycloalkyl, (C 1 -C 6  alkoxy)C 0 -C 6 alkyl, (mono-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, (di-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, and C 1 -C 6 alkoxycarbonyl; 
         R 2  is chosen from
 C 1 -C 7  alkyl, 
 (C 1 -C 6 alkoxy)C 0 -C 6 alkoxy, 
 (heterocycloalkyl)C 0 -C 2 alkyl, 
 (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, 
 (phenyl)C 0 -C 2 alkyl, 
 substituted (phenyl)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (phenyl)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl, 
 (phenoxy)C 0 -C 2 alkyl, 
 substituted (phenoxy)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (phenoxy)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl, 
 (heteroaryl)C 0 -C 2 alkyl, and 
 substituted (heteroaryl)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (heteroaryl)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl; 
 
         Z 1  is chosen from 
       
       
         
           
           
               
               
           
         
         
           wherein 
         
         R 4  is chosen from
 hydrogen, 
 C 1 -C 6 alkyl, 
 C 1 -C 6 alkyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 C 3 -C 7 cycloalkyl, 
 C 3 -C 7 cycloalkyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 heterocycloalkyl, 
 heterocycloalkyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 phenyl, 
 phenyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 heteroaryl, 
 heteroaryl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 
         Q is chosen from phenyl and pyridyl; and 
         R 3  is chosen from
 hydrogen, 
 halogen, 
 C 1 -C 7  alkyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono —C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, and —C(O)R 14 , 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono —C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, and —C(O)R 14 , 
 heteroaryl, and 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono —C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, and −C(O)R 14 . 
 
       
     
     
         90 . A packaged pharmaceutical composition, comprising a pharmaceutical composition of  claim 87  in a container; and instructions for using the composition to treat a patient suffering from an disease responsive to Btk inhibition. 
     
     
         91 . The packaged pharmaceutical composition of  claim 89  wherein the disease responsive to Btk inhibition is cancer. 
     
     
         92 . The packaged pharmaceutical composition of  claim 89  wherein the disease responsive to Btk inhibition is an autoimmune disease, an inflammatory disease, or an acute inflammatory reaction. 
     
     
         93 . A method for treating a patient having a disease responsive to inhibition of Btk activity, comprising administering to the patient an effective amount of the compound of Formula I-a 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, hydrate or diastereomer thereof, wherein
 A is chosen from 0 and 1; 
 R 1  is chosen from 
 phenyl substituted with a group chosen from
 hydroxy, 
 —CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 substituted C 2 -C 6  alkenyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkenyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 2 -C 6  alkynyl, 
 substituted C 2 -C 6  alkynyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkynyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 substituted C 1 -C 6 hydroxyalkyl chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 substituted C 1 -C 6 hydroxyalkoxy chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 substituted —C 1 -C 6 alkyl(C═O)OR 10  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkyl(C═O)OR 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 substituted —C 0 -C 6 alkyl(SO 2 )R 10  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(SO 2 )R 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 -L-G, where
 L is chosen from
 C 1 -C 2 alkylene, 
 substituted C 1 -C 2 alkylene chosen from mono-, di-, and tri-substituted C 1 -C 2 alkylene wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 0 -C 2 alkylene-O—, 
 substituted C 0 -C 2 alkylene-O— chosen from mono-, di-, and tri-substituted C 0 -C 2 alkylene-O— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, and 
 substituted —(C 1 -C 2 alkylene)(C═O)— chosen from mono-, di-, and tri-substituted —(C 1 -C 2 alkylene)(C═O)— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 G is chosen from
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, and 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 
 
 heteroaryl substituted with a group chosen from hydroxy,
 —CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 substituted C 2 -C 6  alkenyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkenyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 2 -C 6  alkynyl, 
 substituted C 2 -C 6  alkynyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkynyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 substituted C 1 -C 6 hydroxyalkyl chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 substituted C 1 -C 6 hydroxyalkoxy chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 substituted —C 1 -C 6 alkyl(C═O)OR 10  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkyl(C═O)OR 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 substituted —C 0 -C 6 alkyl(SO 2 )R 10  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(SO 2 )R 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 -L-G, where
 L is chosen from
 C 1 -C 2 alkylene, 
 substituted C 1 -C 2 alkylene chosen from mono-, di-, and tri-substituted C 1 -C 2 alkylene wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 0 -C 2 alkylene-O—, 
 substituted C 0 -C 2 alkylene-O— chosen from mono-, di-, and tri-substituted C 0 -C 2 alkylene-O— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, and 
 substituted —(C 1 -C 2 alkylene)(C═O)— chosen from mono-, di-, and tri-substituted —(C 1 -C 2 alkylene)(C═O)— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 G is chosen from
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, and 
 
 
 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 R 1  is optionally further substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, —SO 2 NH 2 , halogen, C 1 -C 6  alkyl, C 2 -C 6 alkanoyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 6  alkylthio, C 3 -C 7 cycloalkyl, (C 1 -C 6  alkoxy)C 0 -C 6 alkyl, (mono-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, (di-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, and C 1 -C 6 alkoxycarbonyl; 
 R 2  is chosen from
 C 1 -C 7  alkyl, 
 (C 1 -C 6 alkoxy)C 0 -C 6 alkoxy, 
 (heterocycloalkyl)C 0 -C 2 alkyl, 
 (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, 
 (phenyl)C 0 -C 2 alkyl, 
 substituted (phenyl)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (phenyl)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl, 
 (phenoxy)C 0 -C 2 alkyl, 
 substituted (phenoxy)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (phenoxy)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl, 
 (heteroaryl)C 0 -C 2 alkyl, and 
 substituted (heteroaryl)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (heteroaryl)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl 
 
 Z 1  is chosen from 
 
       
         
           
           
               
               
           
         
         
           wherein 
         
         R 4  is chosen from
 hydrogen, 
 C 1 -C 6 alkyl, 
 C 1 -C 6 alkyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 C 3 -C 7 cycloalkyl, 
 C 3 -C 7 cycloalkyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 heterocycloalkyl, 
 heterocycloalkyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 phenyl, 
 phenyl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 heteroaryl, 
 heteroaryl substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, halogen, oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6  alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, and —C(O)R 14  wherein R 14  is chosen from C 1 -C 6  alkyl, C 1 -C 3 haloalkyl, and phenyl; 
 
         Q is chosen from phenyl and pyridyl; and 
         R 3  is chosen from
 hydrogen, 
 halogen, 
 C 1 -C 7  alkyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono —C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, and —C(O)R 14 , 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono —C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, and —C(O)R 14 , 
 heteroaryl, and 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6 -alkoxy)C 1 -C 6  alkoxy, mono —C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6  alkyl, and —C(O)R 14    
 
       
     
     
         94 . A method for treating a patient having a disease responsive to inhibition of Btk activity, comprising administering an effective amount of the pharmaceutical composition according to  claim 87  to the patient. 
     
     
         95 . A method for increasing sensitivity of cancer cells to chemotherapy, comprising administering to a patient undergoing chemotherapy with a chemotherapeutic agent an amount of the pharmaceutical composition of  claim 87 , sufficient to increase the sensitivity of cancer cells to the chemotherapeutic agent. 
     
     
         96 . A pharmaceutical composition of  claim 87 , wherein in the compound of formula I, A is 0. 
     
     
         97 . A pharmaceutical composition of  claim 87 , wherein in the compound of formula I, A is 1. 
     
     
         98 . A pharmaceutical composition of  claim 87 , wherein in the compound of formula I,
 R 1  is chosen from   phenyl substituted with
 hydroxy, 
 —CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 substituted C 2 -C 6  alkenyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkenyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 2 -C 6  alkynyl, 
 substituted C 2 -C 6  alkynyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkynyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 substituted C 1 -C 6 hydroxyalkyl chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 substituted C 1 -C 6 hydroxyalkoxy chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 substituted —C 1 -C 6 alkyl(C═O)OR 10  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkyl(C═O)OR 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 substituted —C 0 -C 6 alkyl(SO 2 )R 10  chosen from mono-, di-, and tri-substituted-C 0 -C 6 alkyl(SO 2 )R 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 -L-G, where
 L is chosen from
 C 1 -C 2 alkylene, 
 substituted C 1 -C 2 alkylene chosen from mono-, di-, and tri-substituted C 1 -C 2 alkylene wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 0 -C 2 alkylene-O—, 
 substituted C 0 -C 2 alkylene-O— chosen from mono-, di-, and tri-substituted C 0 -C 2 alkylene-O— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, and 
 substituted —(C 1 -C 2 alkylene)(C═O)— chosen from mono-, di-, and tri-substituted —(C 1 -C 2 alkylene)(C═O)— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 G is chosen from
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 
   pyridyl substituted with
 hydroxy, 
 —CHO, 
 —COOH, 
 —CONH 2 , 
 —CONHOH, 
 C 2 -C 6  alkenyl, 
 substituted C 2 -C 6  alkenyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkenyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 2 -C 6  alkynyl, 
 substituted C 2 -C 6  alkynyl chosen from mono-, di-, and tri-substituted C 2 -C 6  alkynyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkyl, 
 substituted C 1 -C 6 hydroxyalkyl chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 1 -C 6 hydroxyalkoxy, 
 substituted C 1 -C 6 hydroxyalkoxy chosen from mono-, di-, and tri-substituted C 1 -C 6 hydroxyalkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (mono-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy, 
 substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (di-C 1 -C 6 alkylamino)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkylamino)C 0 -C 6 alkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, 
 substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy chosen from mono-, di-, and tri-substituted (C 1 -C 6 alkoxy)(C 1 -C 6 alkoxy)C 1 -C 6 alkoxy wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkyl(C═O)OR 10 , 
 substituted —C 1 -C 6 alkyl(C═O)OR 10  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkyl(C═O)OR 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(C═O)NR 10 R 11 , 
 substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(C═O)NR 10 R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 1 -C 6 alkylNR 10 (SO 2 )R 11 , 
 substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  chosen from mono-, di-, and tri-substituted —C 1 -C 6 alkylNR 10 (SO 2 )R 11  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)R 11 , 
 substituted —C 0 -C 6 alkylNR 10 (C═O)R 11  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)R 11 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkyl(SO 2 )R 10 , 
 substituted —C 0 -C 6 alkyl(SO 2 )R 10  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkyl(SO 2 )R 10  wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 ) 
 substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12  chosen from mono-, di-, and tri-substituted —C 0 -C 6 alkylNR 10 (C═O)NR 11 R 12 , wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 -L-G, where
 L is chosen from
 C 1 -C 2 alkylene, 
 substituted C 1 -C 2 alkylene chosen from mono-, di-, and tri-substituted C 1 -C 2 alkylene wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 0 -C 2 alkylene-O—, 
 substituted C 0 -C 2 alkylene-O— chosen from mono-, di-, and tri-substituted C 0 -C 2 alkylene-O— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 —(C═O)—, 
 —(C 1 -C 2 alkylene)(C═O)—, and 
 substituted —(C 1 -C 2 alkylene)(C═O)— chosen from mono-, di-, and tri-substituted —(C 1 -C 2 alkylene)(C═O)— wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 G is chosen from
 heterocycloalkyl, 
 substituted heterocycloalkyl chosen from mono-, di-, and tri-substituted heterocycloalkyl, wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 C 3 -C 7 cycloalkyl, 
 substituted C 3 -C 7 cycloalkyl chosen from mono-, di-, and tri-substituted C 3 -C 7 cycloalkyl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 aryl, 
 substituted aryl chosen from mono-, di-, and tri-substituted aryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, 
 heteroaryl, 
 substituted heteroaryl chosen from mono-, di-, and tri-substituted heteroaryl wherein the substituents are independently selected from halogen, hydroxy, amino, oxo, —COOH, —CONH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, C 1 -C 4 alkylthio, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 4 alkoxycarbonyl, mono-C 1 -C 4 alkylamino, di-C 1 -C 4 alkylamino, mono-C 1 -C 4 alkylcarboxamide, di-C 1 -C 4 alkylcarboxamide, and phenyl, and 
 
 
   wherein R 1  is optionally further substituted with 1 or more substituents independently chosen from hydroxy, nitro, cyano, amino, —SO 2 NH 2 , halogen, C 1 -C 6  alkyl, C 2 -C 6 alkanoyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 6  alkylthio, C 3 -C 7 cycloalkyl, (C 1 -C 6  alkoxy)C 0 -C 6 alkyl, (mono-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, (di-C 1 -C 6  alkylamino)C 0 -C 6  alkyl, and C 1 -C 6 alkoxycarbonyl.   
     
     
         99 . A pharmaceutical composition of  claim 87 , wherein in the compound of formula I,
 R 2  is chosen from
 (phenyl)C 0 -C 2 alkyl, 
 substituted (phenyl)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (phenyl)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl, 
 (phenoxy)C 0 -C 2 alkyl, 
 substituted (phenoxy)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (phenoxy)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl, 
 (pyridyl)C 0 -C 2 alkyl, and 
 substituted (pyridyl)C 0 -C 2 alkyl chosen from mono-, di-, and tri-substituted (pyridyl)C 0 -C 2 alkyl wherein the substituents are independently chosen from hydroxy, nitro, cyano, amino, halogen, —SO 2 NH 2 , oxo, —COOH, C 1 -C 6  alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 6  alkylthio, (C 1 -C 6  alkoxy)C 1 -C 6  alkoxy, aminoC 1 -C 6 alkyl, mono-C 1 -C 6  alkylamino, di-C 1 -C 6  alkylamino, mono-C 1 -C 6 alkylcarboxamide, di-C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkoxycarbonyl, phenyl, heteroaryl, and —(C═O)R 13  wherein R 13  is chosen from C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 2 alkyl, C 1 -C 3 haloalkyl, heterocycloalkyl, phenyl, and heteroaryl. 
   
     
     
         100 . A pharmaceutical composition of  claim 87 , wherein in the compound of formula I,
 Z 1  is chosen from   
       
         
           
           
               
               
           
         
         and 
         R 4  is chosen from hydrogen, C 1 -C 6 alkyl, and C 3 -C 7 cycloalkyl. 
       
     
     
         101 . A pharmaceutical composition of  claim 87 , wherein in the compound of formula I, R 3  is chosen from hydrogen and methyl.
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Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of bruton&#39;s tyrosine kinase by such compounds

Abstract

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Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of bruton's tyrosine kinase by such compounds
