US2023082167A1PendingUtilityA1
Novel tricyclic compounds

Assignee: ABBVIE INCPriority: Jun 10, 2008Filed: Jan 14, 2022Published: Mar 16, 2023
Est. expiryJun 10, 2028(~1.9 yrs left)· nominal 20-yr term from priority
Inventors:Neil Wishart Maria A. Argiriadi David J. Calderwood Anna Ericsson Bryan A. Fiamengo Kristine E. Frank Michael Friedman Dawn M. George Eric R. Goedken Nathan S. Josephsohn Biqin C. Li Michael Morytko Kent D. Stewart Jeffrey W. Voss Grier A. Wallace Lu Wang Kevin R. Woller
A61P 31/04C07D 498/14A61P 9/12A61P 33/08A61P 13/12A61P 35/02A61P 37/06A61P 9/00A61P 7/02A61P 17/00A61P 35/00A61P 31/22A61P 25/14C07D 513/14A61P 17/06C07D 471/14A61P 37/00A61P 21/00C07D 487/14A61P 31/12A61P 25/00A61P 7/06A61P 27/02A61P 31/00A61P 29/00A61P 11/00A61P 9/10A61P 1/00A61P 15/00A61P 9/04A61P 37/02A61K 31/4985A61P 43/00A61P 25/16A61P 37/08A61P 19/02A61P 25/28A61P 27/10A61P 3/10
PatentIndex Score
Cited by
References
Claims
Abstract

The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.
Claims

exact text as granted — not AI-modified
What is claimed: 
     
         1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
 T is N, U is N, X is CR 3  and Y is N; or 
 T is CR 6 , U is N, X is CR 3  and Y is N; or 
 T is N, U is CR 4 , X is CR 3  and Y is N; or 
 T is CR 6 , U is CR 4 , X is CR 3  and Y is N; or 
 T is CR 6 , U is N, X is NR 3  and Y is C; or 
 T is O, U is N, X is CR 3  and Y is C; or 
 T is NR 6 , U is N, X is CR 3  and Y is C; or 
 T is CR 6 , U is CR 4 , X is NR 3  and Y is C; or 
 T is S, U is N, X is CR 3  and Y is C; 
 R 1 , R 2  and R 5  are each independently hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)(R b ), —C(O)R a , —C(OH)R a R b , —N(R a )S(O) 2 —R b , —S(O) 2 N(R a )(R b ), —CF 3 , —OCF 3 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 1 -C 10 ) heterocyclyl, or optionally substituted (C 6 -C 10 )aryl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or optionally substituted (C 1 -C 10 )heteroaryl linked through a nitrogen; 
 
 R 3  is hydrogen, an optionally substituted bridged (C 5 -C 12 )cycloalkyl, optionally substituted bridged (C 2 -C 10 )heterocyclyl, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl; or 
 R 3  is -A-D-E-G, wherein: 
 A is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
 D is an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
 E is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —OC(O)—R e , —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
 E is 
 
       
         
           
           
               
               
           
         
         where in all cases, E is linked to either a carbon or a nitrogen atom in D; 
         G is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —OC(O)N(R a ), —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted —(C 1 -C 6 )alkyl, an optionally substituted —(C 2 -C 6 )alkenyl, an optionally substituted —(C 2 -C 6 )alkynyl, an optionally substituted —(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 10 )heteroaryl, an optionally substituted —(C 1 -C 10 ) heterocyclyl, an optionally substituted —(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
         R 4  and R 6  are each independently a hydrogen, halogen, deuterium, an optionally substituted bridged (C 5 -C 12 )cycloalkyl group, optionally substituted bridged (C 2 -C 10 )heterocyclyl group, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl or -J-L-M-Q; 
         wherein: 
         J is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
         L is a bond, an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
         M is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —OC(O)—R e , C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e —C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
         M is 
       
       
         
           
           
               
               
           
         
       
       where in all cases, M is linked to either a carbon or a nitrogen atom in L;
 Q is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted (C 1 -C 6 )alkyl, an optionally substituted (C 2 -C 6 )alkenyl, an optionally substituted (C 2 -C 6 )alkynyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 ) heterocyclyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
 R a  and R b  are each independently hydrogen, deuterium, an optionally substituted (C 1 -C 10 )alkyl, an optionally substituted (C 2 -C 10 )alkenyl, an optionally substituted (C 2 -C 10 )alkynyl, an optionally substituted (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 )heterocyclyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heterocyclyl; and 
 R e  for each occurrence is independently a bond, an optionally substituted (C 1 -C 10 )alkylene, an optionally substituted (C 2 -C 10 )alkenylene, an optionally substituted (C 2 -C 10 )alkynylene, an optionally substituted —(C 1 -C 10 )alkylene-O—(C 1 -C 10 )alkylene group, an optionally substituted (C 3 -C 10 )cycloalkylene, an optionally substituted (C 6 -C 10 )arylene, an optionally substituted (C 1 -C 10 )heteroarylene, or an optionally substituted (C 1 -C 10 )heterocyclylene; 
 provided that when the compound is 
 
       
         
           
           
               
               
           
         
         R 3  is defined as above and R 6  is not linked to the pyrazole ring by a nitrogen or oxygen atom; and 
         provided that when the compound is 
       
       
         
           
           
               
               
           
         
         when R 3  is H, CH 3  or —C(O)OH then R 4  is not H, —C(O)OCH 2 CH 3 , —C(O)NH-optionally substituted phenyl, —NHC(O)-optionally substituted phenyl or —S(O) 2 —phenyl. 
       
     
     
         2 . The compound of  claim 1  wherein T is N, U is N, X is CR 3  and Y is N and forms a compound of Formula (Ia) 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 1  wherein T is CR 6 , U is N, X is CR 3  and Y is N and forms a compound of Formula (Ib) 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1  wherein T is N, U is CR 4 , X is CR 3  and Y is N and forms a compound of Formula (Ic) 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 1  wherein T is CR 6 , U is CR 4 , X is CR 3  and Y is N and forms a compound of Formula (Id) 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1  wherein T is CR 6 , U is N, X is NR 3  and Y is C and forms a compound of Formula (Ie) 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1  wherein T is O, U is N, X is CR 3  and Y is C and forms a compound of Formula (If) 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 1  wherein T is NR 6 , U is N, X is CR 3  and Y is C and forms a compound of Formula (Ig) 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 1  wherein T is CR 6 , U is CR 4 , X is NR 3  and Y is C and forms a compound of Formula (Ih) 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 1  wherein T is S, U is N, X is CR 3  and Y is C and forms a compound of Formula (Ii) 
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 1  wherein R 3  is hydrogen, an optionally substituted bridged (C 5 -C 12 )cycloalkyl group, optionally substituted bridged (C 2 -C 10 )heterocyclyl group, optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl or optionally substituted (C 2 -C 10 )heterocyclyl. 
     
     
         12 . The compound of  claim 11  wherein R 3  is optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, optionally substituted cyclohexyl, optionally substituted phenyl, optionally substituted adamantanyl, optionally substituted azetidinyl, optionally substituted bicyclo[2.1.1]hexyl, optionally substituted bicyclo[2.2.1]heptyl, optionally substituted bicyclo[2.2.2]octyl, optionally substituted bicyclo[3.2.1]octyl, optionally substituted bicyclo[3.1.1]heptyl, optionally substituted azabicyclo[3.2.1]octanyl, optionally substituted azabicyclo[2.2.1]heptanyl, optionally substituted 2-azabicyclo[3.2.1]octanyl, optionally substituted azabicyclo[3.2.2]nonanyl, optionally substituted bicyclo[2.2.1]hept-2-enyl, optionally substituted piperidinyl, optionally substituted pyrrolidinyl or optionally substituted tetrahydrofuranyl. 
     
     
         13 . The compound of  claim 1  wherein R 3  is A-D-E-G and A is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—, —N(R a )—, —S—, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—, —N(R a )S(O) 2 — or —N(R a )C(O)N(R b )—. 
     
     
         14 . The compound of  claim 13  wherein D is an optionally substituted azetidinyl, optionally substituted bicyclo[2.2.2]octanylene, optionally substituted bicyclo[2.2.1]heptylene, optionally substituted bicyclo[2.1.1]hexylene, optionally substituted cyclobutylene, optionally substituted cyclopentylene, optionally substituted cyclohexylene, optionally substituted bicyclo[2.2.1]hept-2-enylene, optionally substituted piperidinyl, or optionally substituted pyrrolidinyl. 
     
     
         15 . The compound of  claim 14  wherein E is —R e —C(O)—R e —, R e —O—R e , —R e —S(O) 2 —R e —, —R e —N(R a )—R e , —R e —N(R a )C(O)—R e —, —R e —C(O)N(R a )R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )R e —. 
     
     
         16 . The compound of  claim 15  wherein G is —OR a , —CN, —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), optionally substituted (C 1 -C 6 )alkyl, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, optionally substituted phenyl, optionally substituted pyridazine, optionally substituted pyrazine, optionally substituted pyrimidine, optionally substituted pyrazole, optionally substituted pyrrolidine, optionally substituted quinazoline, optionally substituted pyridine, optionally substituted thiazolidine or optionally substituted triazole. 
     
     
         17 . The compound of  claim 16  wherein
 A is a bond; 
 D is optionally substituted cyclopentylene, optionally substituted bicyclo[2.2.2]octanylene, optionally substituted azetidinyl, or optionally substituted piperidinyl; 
 E is —R e —C(O)—R e —, —R e —N(R a )—R e —, —R e —S(O) 2 N(R a )—R e , —R e —S(O) 2 —R e —, or —R e —N(R a )S(O) 2 —R e —;
 wherein R e  for each occurrence is independently a bond or an optionally substituted (C 1 -C 6 )alkylene; and 
 
 G is —CN, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, optionally substituted phenyl, optionally substituted pyrazine, optionally substituted pyridazine, optionally substituted pyrazole, or optionally substituted pyridine. 
 
     
     
         18 . The compound of  claim 17  wherein R 1 , R 2 , R 4 , R 5  and R 6  where present are each independently hydrogen or an optionally substituted —(C 1 -C 4 )alkyl. 
     
     
         19 . The compound of  claim 18  wherein the compound is a compound of Formula (Ia) 
       
         
           
           
               
               
           
         
       
     
     
         20 . The compound of  claim 18  wherein the compound is a compound of Formula (Ib) 
       
         
           
           
               
               
           
         
       
     
     
         21 . The compound of  claim 18  wherein the compound is a compound of Formula (Ic) 
       
         
           
           
               
               
           
         
       
     
     
         22 . The compound of  claim 19  wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         23 . The compound of  claim 19  wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         24 . The compound of  claim 19  wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         25 . The compound of  claim 21  wherein
 A is a bond; 
 D is optionally substituted cyclopentylene or optionally substituted piperidine; 
 E is —R e —N(R a )—R e —, —R e —S(O) 2 N(R a )—R e , —R e —C(O)—R e , —R e —S(O) 2 —R e , or —R e —N(R a )S(O) 2 —R e —; and 
 G is —CN, optionally substituted phenyl, optionally substituted pyrazine, optionally substituted pyridazine, optionally substituted pyrazole, or optionally substituted pyridine. 
 
     
     
         26 . The compound of  claim 20  wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         27 . The compound of  claim 18  wherein G is optionally substituted phenyl, optionally substituted pyrazine, optionally substituted pyrazole, optionally substituted pyridazine or optionally substituted pyridine. 
     
     
         28 . The compound of  claim 11  wherein R 2  and R 5  are each independently hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)(R b ), —C(O)R a , —C(OH)R a R b , —N(R a )S(O) 2 —R b , —S(O) 2 N(R a )(R b ), —CF 3 , —OCF 3 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 12 )cycloalkyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl or optionally substituted (C 1 -C 10 )heterocyclyl. 
     
     
         29 . The compound of  claim 28  wherein R 1  is optionally substituted (C 6 -C 10 )aryl or optionally substituted (C 1 -C 10 )heteroaryl. 
     
     
         30 . The compound of  claim 29  wherein R 2  is hydrogen, halogen, —CN, —C(O)NR a R b , —CF 3 , optionally substituted —(C 1 -C 6 )alkyl, optionally substituted —(C 3 -C 6 )cycloalkyl, optionally substituted benzo(b)thienyl, optionally substituted benzimidazolyl, optionally substituted benzofuranyl, optionally substituted benzoxazolyl, optionally substituted benzothiazolyl, optionally substituted benzothiadiazolyl, optionally substituted furanyl, optionally substituted imidazolyl, optionally substituted indolinyl, optionally substituted indolyl, optionally substituted indazolyl, optionally substituted isoxazolyl, optionally substituted isoindolinyl, optionally substituted morpholinyl, optionally substituted oxadiazolyl, optionally substituted phenyl, optionally substituted piperazinyl, optionally substituted piperidinyl, optionally substituted pyranyl, optionally substituted pyrazolyl, optionally substituted pyrazolo[3,4-d]pyrimidinyl, optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyrrolidinyl, optionally substituted pyrrolyl, optionally substituted optionally pyrrolo[2,3-d]pyrimidinyl, substituted quinolinyl, optionally substituted thiomorpholinyl, optionally substituted tetrahydropyranyl, optionally substituted tetrahydrofuranyl, optionally substituted tetrahydroindolyl, optionally substituted thiazolyl, or optionally substituted thienyl. 
     
     
         31 . The compound of  claim 30  wherein R 1  is optionally substituted azaindole, optionally substituted benzofuran, optionally substituted benzothiazole, optionally substituted benzoxazole, optionally substituted dihydropyrroloimidazole, optionally substituted furan, optionally substituted imidazole, optionally substituted imidazoxazole, optionally substituted imidazopyrazine, optionally substituted imidazopyridine, optionally substituted indazole, optionally substituted indole, optionally substituted isoquinoline, optionally substituted isothiazole, optionally substituted isoxazole, optionally substituted oxadiazole, optionally substituted oxazole, optionally substituted pyrazole, optionally substituted pyridine, optionally substituted pyrimidine, optionally substituted pyrazolopyridine, optionally substituted pyrrole, optionally substituted quinoline, optionally substituted quinazoline, optionally substituted thiazole, or optionally substituted thiophene. 
     
     
         32 . The compound of  claim 31  wherein R 5  is hydrogen, halogen, —NH 2  or —N(R a )(R b ). 
     
     
         33 . The compound of  claim 32  wherein T is CH, U is N, Y is N, and X is CR 3  wherein R 3  is optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 12 )cycloalkyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl or optionally substituted (C 2 -C 10 )heterocyclyl. 
     
     
         34 . The compound of  claim 32  wherein T is CH, U is N, Y is C and X is NR 3  wherein R 3  is optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, or optionally substituted (C 2 -C 10 )heterocyclyl. 
     
     
         35 . The compound of  claim 32  wherein T is N, U is N, Y is N and X is CR 3  wherein R 3  is optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl or optionally substituted (C 2 -C 10 )heterocyclyl. 
     
     
         36 . The use of a compound of Formula 2: 
       
         
           
           
               
               
           
         
         to form a compound of Formula (Ia) 
       
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
 R p  is a hydrogen, —SO 2 N(CH 3 ) 2 , —SO 2 (2,4,6-trimethylphenyl), —SO 2 phenyl, —SO 2 (4-butylphenyl), —SO 2 (4-methylphenyl), —SO 2 (4-methoxyphenyl), —C(O)OCH 2 CCl 3 , —C(O)OCH 2 CH 2 Si(CH 3 ) 3 , —C(O)OC(CH 3 ) 3 , —C(O)OC(CH 3 ) 2 (CCl 3 ), —C(O)O-1-adamantyl, —CH═CH 2 , —CH 2 CH 2 Cl, —CH(OCH 2 CH 3 )CH 3 , —CH 2 CH 2 -2-pyridyl, —CH 2 CH 2 -4-pyridyl, —Si(C(CH 3 ) 3 )(CH 3 ) 2 , —Si(CH(CH 3 ) 2 ) 3 , —CH 2 phenyl, —CH 2 (4-CH 3 O-phenyl), —CH 2 (3,4-di-methoxyphenyl), —CH 2 (2-nitrophenyl), -(2,4-dinitrophenyl), —CH 2 C(O)phenyl, —C(phenyl) 3 , —CH(phenyl) 2 , —C(phenyl) 2 (4-pyridyl), —N(CH 3 ) 2 , —CH 2 OH, —CH 2 OCH 3 , —CH(OCH 2 CH 3 ) 2 , —CH 2 OCH 2 CH 2 Cl, —CH 2 OCH 2 CH 2 Si(CH 3 ) 3 , —CH 2 OC(CH 3 ) 3 , —CH 2 OC(O)C(CH 3 ) 3 , —CH 2 OCH 2 phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl) 2 ; 
 R 1 , R 2  and R 5  are each independently hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)(R b ), —C(O)R a , —C(OH)R a R b , —N(R a )S(O) 2 —R b , —S(O) 2 N(R a )(R b ), —CF 3 , —OCF 3 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 1 -C 10 ) heterocyclyl, or optionally substituted (C 6 -C 10 )aryl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or optionally substituted (C 1 -C 10 )heteroaryl linked through a nitrogen; 
 
 R 3  is hydrogen, an optionally substituted bridged (C 5 -C 12 )cycloalkyl, optionally substituted bridged (C 2 -C 10 )heterocyclyl, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl; or 
 R 3  is -A-D-E-G, wherein: 
 A is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
 D is an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
 E is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —OC(O)—R e , —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
 E is 
 
       
         
           
           
               
               
           
         
         where in all cases, E is linked to either a carbon or a nitrogen atom in D; 
         G is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —OC(O)N(R a ), —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted —(C 1 -C 6 )alkyl, an optionally substituted —(C 2 -C 6 )alkenyl, an optionally substituted —(C 2 -C 6 )alkynyl, an optionally substituted —(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 10 )heteroaryl, an optionally substituted —(C 1 -C 10 ) heterocyclyl, an optionally substituted —(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
         R a  and R b  are each independently hydrogen, deuterium, an optionally substituted (C 1 -C 10 )alkyl, an optionally substituted (C 2 -C 10 )alkenyl, an optionally substituted (C 2 -C 10 )alkynyl, an optionally substituted (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 )heterocyclyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heterocyclyl; and 
         R e  for each occurrence is independently a bond, an optionally substituted (C 1 -C 10 )alkylene, an optionally substituted (C 2 -C 10 )alkenylene, an optionally substituted (C 2 -C 10 )alkynylene, an optionally substituted —(C 1 -C 10 )alkylene-O—(C 1 -C 10 )alkylene group, an optionally substituted (C 3 -C 10 )cycloalkylene, an optionally substituted (C 6 -C 10 )arylene, an optionally substituted (C 1 -C 10 )heteroarylene, or an optionally substituted (C 1 -C 10 )heterocyclylene. 
       
     
     
         37 . The use of a compound of Formula 3: 
       
         
           
           
               
               
           
         
       
       to form a compound of Formula (Ib) 
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
 R p  is a hydrogen, —SO 2 N(CH 3 ) 2 , —SO 2 (2,4,6-trimethylphenyl), —SO 2 phenyl, —SO 2 (4-butylphenyl), —SO 2 (4-methylphenyl), —SO 2 (4-methoxyphenyl), —C(O)OCH 2 CCl 3 , —C(O)OCH 2 CH 2 Si(CH 3 ) 3 , —C(O)OC(CH 3 ) 3 , —C(O)OC(CH 3 ) 2 (CCl 3 ), —C(O)O-1-adamantyl, —CH═CH 2 , —CH 2 CH 2 Cl, —CH(OCH 2 CH 3 )CH 3 , —CH 2 CH 2 -2-pyridyl, —CH 2 CH 2 -4-pyridyl, —Si(C(CH 3 ) 3 )(CH 3 ) 2 , —Si(CH(CH 3 ) 2 ) 3 , —CH 2 phenyl, —CH 2 (4-CH 3 O-phenyl), —CH 2 (3,4-di-methoxyphenyl), —CH 2 (2-nitrophenyl), -(2,4-dinitrophenyl), —CH 2 C(O)phenyl, —C(phenyl) 3 , —CH(phenyl) 2 , —C(phenyl) 2 (4-pyridyl), —N(CH 3 ) 2 , —CH 2 OH, —CH 2 OCH 3 , —CH(OCH 2 CH 3 ) 2 , —CH 2 OCH 2 CH 2 Cl, —CH 2 OCH 2 CH 2 Si(CH 3 ) 3 , —CH 2 OC(CH 3 ) 3 , —CH 2 OC(O)C(CH 3 ) 3 , —CH 2 OCH 2 phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl) 2 ; 
 R 1 , R 2  and R 5  are each independently hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)(R b ), —C(O)R a , —C(OH)R a R b , —N(R a )S(O) 2 —R b , —S(O) 2 N(R a )(R b ), —CF 3 , —OCF 3 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 1 -C 10 ) heterocyclyl, or optionally substituted (C 6 -C 10 )aryl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or optionally substituted (C 1 -C 10 )heteroaryl linked through a nitrogen; 
 
 R 3  is hydrogen, an optionally substituted bridged (C 5 -C 12 )cycloalkyl, optionally substituted bridged (C 2 -C 10 )heterocyclyl, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl; or 
 R 3  is -A-D-E-G, wherein: 
 A is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
 D is an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
 E is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —OC(O)—R e , —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
 E is 
 
       
         
           
           
               
               
           
         
         where in all cases, E is linked to either a carbon or a nitrogen atom in D; 
         G is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —OC(O)N(R a ), —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted —(C 1 -C 6 )alkyl, an optionally substituted —(C 2 -C 6 )alkenyl, an optionally substituted —(C 2 -C 6 )alkynyl, an optionally substituted —(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 10 )heteroaryl, an optionally substituted —(C 1 -C 10 ) heterocyclyl, an optionally substituted —(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
         R 6  is a hydrogen, halogen, deuterium, an optionally substituted bridged (C 5 -C 12 )cycloalkyl group, optionally substituted bridged (C 2 -C 10 )heterocyclyl group, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl or -J-L-M-Q; 
         wherein: 
         J is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
         L is a bond, an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
         M is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —OC(O)—R e , —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e —C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
         M is 
       
       
         
           
           
               
               
           
         
       
       where in all cases, M is linked to either a carbon or a nitrogen atom in L;
 Q is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted (C 1 -C 6 )alkyl, an optionally substituted (C 2 -C 6 )alkenyl, an optionally substituted (C 2 -C 6 )alkynyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 ) heterocyclyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
 R a  and R b  are each independently hydrogen, deuterium, an optionally substituted (C 1 -C 10 )alkyl, an optionally substituted (C 2 -C 10 )alkenyl, an optionally substituted (C 2 -C 10 )alkynyl, an optionally substituted (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 )heterocyclyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heterocyclyl; and 
 R e  for each occurrence is independently a bond, an optionally substituted (C 1 -C 10 )alkylene, an optionally substituted (C 2 -C 10 )alkenylene, an optionally substituted (C 2 -C 10 )alkynylene, an optionally substituted —(C 1 -C 10 )alkylene-O—(C 1 -C 10 )alkylene group, an optionally substituted (C 3 -C 10 )cycloalkylene, an optionally substituted (C 6 -C 10 )arylene, an optionally substituted (C 1 -C 10 )heteroarylene, or an optionally substituted (C 1 -C 10 )heterocyclylene. 
 
     
     
         38 . The use of a compound of Formula 4: 
       
         
           
           
               
               
           
         
         to form a compound of Formula (Ic) 
       
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
 R p1  is hydrogen, —SO 2 N(CH 3 ) 2 , —SO 2 (2,4,6-trimethylphenyl), —SO 2 phenyl, —SO 2 (4-butylphenyl), —SO 2 (4-methylphenyl), —SO 2 (4-methoxyphenyl), —C(O)OCH 2 CCl 3 , —C(O)OCH 2 CH 2 Si(CH 3 ) 3 , —C(O)OC(CH 3 ) 3 , —C(O)OC(CH 3 ) 2 (CCl 3 ), —C(O)O-1-adamantyl, —CH═CH 2 , —CH 2 CH 2 Cl, —CH(OCH 2 CH 3 )CH 3 , —CH 2 CH 2 -2-pyridyl, —CH 2 CH 2 -4-pyridyl, —Si(C(CH 3 ) 3 )(CH 3 ) 2 , —Si(CH(CH 3 ) 2 ) 3 , —CH 2 phenyl, —CH 2 (4-CH 3 O-phenyl), —CH 2 (3,4-di-methoxyphenyl), —CH 2 (2-nitrophenyl), -(2,4-dinitrophenyl), —CH 2 C(O)phenyl, —C(phenyl) 3 , —CH(phenyl) 2 , —C(phenyl) 2 (4-pyridyl), —N(CH 3 ) 2 , —CH 2 OH, —CH 2 OCH 3 , —CH(OCH 2 CH 3 ) 2 , —CH 2 OCH 2 CH 2 Cl, —CH 2 OCH 2 CH 2 Si(CH 3 ) 3 , —CH 2 OC(CH 3 ) 3 , —CH 2 OC(O)C(CH 3 ) 3 , —CH 2 OCH 2 phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl) 2 ; 
 R p2  is hydrogen, —C(O)O—C(CH 3 ) 3 , —C(O)OCH 2 -phenyl, —C(O)O-fluoren-9-yl, —C(O)CH 3 , —C(O)CF 3 , —C(O)—CH(CH 3 ) 2 , —CH 2 -phenyl, —CH 2 -(4-methoxyphenyl), —S(O) 2 -phenyl or —S(O) 2 -(4-methylphenyl); 
 R 1 , R 2  and R 5  are each independently hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)(R b ), —C(O)R a , —C(OH)R a R b , —N(R a )S(O) 2 —R b , —S(O) 2 N(R a )(R b ), —CF 3 , —OCF 3 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 1 -C 10 ) heterocyclyl, or optionally substituted (C 6 -C 10 )aryl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or optionally substituted (C 1 -C 10 )heteroaryl linked through a nitrogen; 
 
 R 3  is hydrogen, an optionally substituted bridged (C 5 -C 12 )cycloalkyl, optionally substituted bridged (C 2 -C 10 )heterocyclyl, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl; or 
 R 3  is -A-D-E-G, wherein: 
 A is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
 D is an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
 E is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —OC(O)—R e , —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
 E is 
 
       
         
           
           
               
               
           
         
         where in all cases, E is linked to either a carbon or a nitrogen atom in D; 
         G is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —OC(O)N(R a ), —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted —(C 1 -C 6 )alkyl, an optionally substituted —(C 2 -C 6 )alkenyl, an optionally substituted —(C 2 -C 6 )alkynyl, an optionally substituted —(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 10 )heteroaryl, an optionally substituted —(C 1 -C 10 ) heterocyclyl, an optionally substituted —(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
         R 4  is a hydrogen, halogen, deuterium, an optionally substituted bridged (C 5 -C 12 )cycloalkyl group, optionally substituted bridged (C 2 -C 10 )heterocyclyl group, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl or -J-L-M-Q; 
         wherein: 
         J is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
         L is a bond, an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
         M is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —OC(O)—R e , —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e —C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
         M is 
       
       
         
           
           
               
               
           
         
       
       where in all cases, M is linked to either a carbon or a nitrogen atom in L;
 Q is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted (C 1 -C 6 )alkyl, an optionally substituted (C 2 -C 6 )alkenyl, an optionally substituted (C 2 -C 6 )alkynyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 ) heterocyclyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
 R a  and R b  are each independently hydrogen, deuterium, an optionally substituted (C 1 -C 10 )alkyl, an optionally substituted (C 2 -C 10 )alkenyl, an optionally substituted (C 2 -C 10 )alkynyl, an optionally substituted (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 )heterocyclyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heterocyclyl; and 
 R e  for each occurrence is independently a bond, an optionally substituted (C 1 -C 10 )alkylene, an optionally substituted (C 2 -C 10 )alkenylene, an optionally substituted (C 2 -C 10 )alkynylene, an optionally substituted —(C 1 -C 10 )alkylene-O—(C 1 -C 10 )alkylene group, an optionally substituted (C 3 -C 10 )cycloalkylene, an optionally substituted (C 6 -C 10 )arylene, an optionally substituted (C 1 -C 10 )heteroarylene, or an optionally substituted (C 1 -C 10 )heterocyclylene. 
 
     
     
         39 . The use of a compound of Formula 5 
       
         
           
           
               
               
           
         
       
       to form a compound of Formula (Id) 
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
 R p  is hydrogen, —SO 2 N(CH 3 ) 2 , —SO 2 (2,4,6-trimethylphenyl), —SO 2 phenyl, —SO 2 (4-butylphenyl), —SO 2 (4-methylphenyl), —SO 2 (4-methoxyphenyl), —C(O)OCH 2 CCl 3 , —C(O)OCH 2 CH 2 Si(CH 3 ) 3 , —C(O)OC(CH 3 ) 3 , —C(O)OC(CH 3 ) 2 (CCl 3 ), —C(O)O-1-adamantyl, —CH═CH 2 , —CH 2 CH 2 Cl, —CH(OCH 2 CH 3 )CH 3 , —CH 2 CH 2 -2-pyridyl, —CH 2 CH 2 -4-pyridyl, —Si(C(CH 3 ) 3 )(CH 3 ) 2 , —Si(CH(CH 3 ) 2 ) 3 , —CH 2 -phenyl, —CH 2 (4-CH 3 O-phenyl), —CH 2 (3,4-di-methoxyphenyl), —CH 2 (2-nitrophenyl), -(2,4-dinitrophenyl), —CH 2 C(O)phenyl, —C(phenyl) 3 , —CH(phenyl) 2 , —C(phenyl) 2 (4-pyridyl), —N(CH 3 ) 2 , —CH 2 OH, —CH 2 OCH 3 , —CH(OCH 2 CH 3 ) 2 , —CH 2 OCH 2 CH 2 Cl, —CH 2 OCH 2 CH 2 Si(CH 3 ) 3 , —CH 2 OC(CH 3 ) 3 , —CH 2 OC(O)C(CH 3 ) 3 , —CH 2 OCH 2 phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl) 2 ; 
 R 1 , R 2  and R 5  are each independently hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)(R b ), —C(O)R a , —C(OH)R a R b , —N(R a )S(O) 2 —R b , —S(O) 2 N(R a )(R b ), —CF 3 , —OCF 3 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 1 -C 10 ) heterocyclyl, or optionally substituted (C 6 -C 10 )aryl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or optionally substituted (C 1 -C 10 )heteroaryl linked through a nitrogen; 
 
 R 3  is hydrogen, an optionally substituted bridged (C 5 -C 12 )cycloalkyl, optionally substituted bridged (C 2 -C 10 )heterocyclyl, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl; or 
 R 3  is -A-D-E-G, wherein: 
 A is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
 D is an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
 E is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —OC(O)—R e , —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
 E is 
 
       
         
           
           
               
               
           
         
         where in all cases, E is linked to either a carbon or a nitrogen atom in D; 
         G is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —OC(O)N(R a ), —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted —(C 1 -C 6 )alkyl, an optionally substituted —(C 2 -C 6 )alkenyl, an optionally substituted —(C 2 -C 6 )alkynyl, an optionally substituted —(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 10 )heteroaryl, an optionally substituted —(C 1 -C 10 ) heterocyclyl, an optionally substituted —(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
         R 4  and R 6  are each independently a hydrogen, halogen, deuterium, an optionally substituted bridged (C 5 -C 12 )cycloalkyl group, optionally substituted bridged (C 2 -C 10 )heterocyclyl group, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl or -J-L-M-Q; 
         wherein: 
         J is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
         L is a bond, an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 6 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
         M is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —OC(O)—R e , —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e —C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
         M is 
       
       
         
           
           
               
               
           
         
       
       where in all cases, M is linked to either a carbon or a nitrogen atom in L;
 Q is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted (C 1 -C 6 )alkyl, an optionally substituted (C 2 -C 6 )alkenyl, an optionally substituted (C 2 -C 6 )alkynyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 ) heterocyclyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
 R a  and R b  are each independently hydrogen, deuterium, an optionally substituted (C 1 -C 10 )alkyl, an optionally substituted (C 2 -C 10 )alkenyl, an optionally substituted (C 2 -C 10 )alkynyl, an optionally substituted (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 )heterocyclyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heterocyclyl; and 
 R e  for each occurrence is independently a bond, an optionally substituted (C 1 -C 10 )alkylene, an optionally substituted (C 2 -C 10 )alkenylene, an optionally substituted (C 2 -C 10 )alkynylene, an optionally substituted —(C 1 -C 10 )alkylene-O—(C 1 -C 10 )alkylene group, an optionally substituted (C 3 -C 10 )cycloalkylene, an optionally substituted (C 6 -C 10 )arylene, an optionally substituted (C 1 -C 10 )heteroarylene, or an optionally substituted (C 1 -C 10 )heterocyclylene. 
 
     
     
         40 . The use of a compound of Formula 6 
       
         
           
           
               
               
           
         
       
       to prepare a compound of Formula (Ig) or Formula (If) or Formula (Ii) 
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
 R p  is a hydrogen, —SO 2 N(CH 3 ) 2 , —SO 2 (2,4,6-trimethylphenyl), —SO 2 phenyl, —SO 2 (4-butylphenyl), —SO 2 (4-methylphenyl), —SO 2 (4-methoxyphenyl), —C(O)OCH 2 CCl 3 , —C(O)OCH 2 CH 2 Si(CH 3 ) 3 , —C(O)OC(CH 3 ) 3 , —C(O)OC(CH 3 ) 2 (CCl 3 ), —C(O)O-1-adamantyl, —CH═CH 2 , —CH 2 CH 2 Cl, —CH(OCH 2 CH 3 )CH 3 , —CH 2 CH 2 -2-pyridyl, —CH 2 CH 2 -4-pyridyl, —Si(C(CH 3 ) 3 )(CH 3 ) 2 , —Si(CH(CH 3 ) 2 ) 3 , —CH 2 phenyl, —CH 2 (4-CH 3 O-phenyl), —CH 2 (3,4-di-methoxyphenyl), —CH 2 (2-nitrophenyl), -(2,4-dinitrophenyl), —CH 2 C(O)phenyl, —C(phenyl) 3 , —CH(phenyl) 2 , —C(phenyl) 2 (4-pyridyl), —N(CH 3 ) 2 , —CH 2 OH, —CH 2 OCH 3 , —CH(OCH 2 CH 3 ) 2 , —CH 2 OCH 2 CH 2 Cl, —CH 2 OCH 2 CH 2 Si(CH 3 ) 3 , —CH 2 OC(CH 3 ) 3 , —CH 2 OC(O)C(CH 3 ) 3 , —CH 2 OCH 2 phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl) 2 ; 
 R x  is a hydrogen, fluorine, chlorine, bromine, iodine, —OS(O) 2 CH 3 , —OS(O) 2 CF 3 , —OS(O) 2 phenyl, or —OS(O) 2 (4-methylphenyl); 
 R 1 , R 2  and R 5  are each independently hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)(R b ), —C(O)R a , —C(OH)R a R b , —N(R a )S(O) 2 —R b , —S(O) 2 N(R a )(R b ), —CF 3 , —OCF 3 , optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 1 -C 10 ) heterocyclyl, or optionally substituted (C 6 -C 10 )aryl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or optionally substituted (C 1 -C 10 )heteroaryl linked through a nitrogen; 
 
 R 3  is hydrogen, an optionally substituted bridged (C 5 -C 12 )cycloalkyl, optionally substituted bridged (C 2 -C 10 )heterocyclyl, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl; or 
 R 3  is -A-D-E-G, wherein: 
 A is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
 D is an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
 E is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —OC(O)—R e , —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
 E is 
 
       
         
           
           
               
               
           
         
         where in all cases, E is linked to either a carbon or a nitrogen atom in D; 
         G is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —OC(O)N(R a ), —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted —(C 1 -C 6 )alkyl, an optionally substituted —(C 2 -C 6 )alkenyl, an optionally substituted —(C 2 -C 6 )alkynyl, an optionally substituted —(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 10 )heteroaryl, an optionally substituted —(C 1 -C 10 ) heterocyclyl, an optionally substituted —(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
         R 6  is a hydrogen, halogen, deuterium, an optionally substituted bridged (C 5 -C 12 )cycloalkyl group, optionally substituted bridged (C 2 -C 10 )heterocyclyl group, optionally substituted (C 1 -C 8 )alkyl, optionally substituted (C 3 -C 10 )cycloalkyl, optionally substituted (C 3 -C 8 )cycloalkenyl, optionally substituted (C 6 -C 10 )aryl, optionally substituted (C 1 -C 10 )heteroaryl, optionally substituted (C 2 -C 10 )heterocyclyl or -J-L-M-Q; 
         wherein: 
         J is a bond, —C(O)—, optionally substituted (C 1 -C 6 )alkylene, optionally substituted (C 2 -C 6 )alkenylene, optionally substituted (C 2 -C 6 )alkynylene, optionally substituted (C 3 -C 12 )cycloalkylene, optionally substituted (C 2 -C 6 )heterocyclylene, —C(O)N(R a )—R e —, —N(R a )C(O)—R e —, —O—R e —, —N(R a )—R e —, —S—R e —, —S(O) 2 —R e —, —S(O)R e —, —C(O—R a )(R b )—R e —, —S(O) 2 N(R a )—R e —, —N(R a )S(O) 2 —R e — or —N(R a )C(O)N(R b )—R e —; 
         L is a bond, an optionally substituted (C 1 -C 8 )alkylene, optionally substituted bridged (C 5 -C 12 )cycloalkylene, optionally substituted (C 3 -C 10 )cycloalkylene, optionally substituted bridged (C 5 -C 10 )cycloalkenylene, optionally substituted (C 3 -C 10 )cycloalkenylene, optionally substituted (C 6 -C 10 )arylene, optionally substituted (C 1 -C 10 )heteroarylene, optionally substituted bridged (C 2 -C 10 )heterocyclylene or an optionally substituted (C 2 -C 10 )heterocyclylene; 
         M is a bond, —R e —, —R e —C(O)—R e —, —R e —C(O)C(O)—R e —, —R e —C(O)O—R e —, —R e —OC(O)—R e , —R e —C(O)C(O)N(R a )—R e —, —R e —N(R a )—C(O)C(O)—R e —, —R e —O—R e —, —R e —S(O) 2 —R e —, —R e —S(O)—R e —, —R e —S—R e —, —R e —N(R a )—R e —, —R e —N(R a )C(O)—R e —, —R e —C(O)N(R a )R e —, —R e —OC(O)N(R a )—R e —, —R e —N(R a )C(O)OR e —, —R e —N(R a )C(O)N(R b )—R e —, —R e —N(R a )S(O) 2 —R e —, or —R e —S(O) 2 N(R a )—R e —; or 
         M is 
       
       
         
           
           
               
               
           
         
       
       where in all cases, M is linked to either a carbon or a nitrogen atom in L;
 Q is hydrogen, deuterium, —N(R a )(R b ), halogen, —OR a , —SR a , —S(O)R a , —S(O) 2 R a , —NO 2 , —C(O)OR a , —CN, —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)N(R b ) 2 , —C(O—R a )(R b ) 2 , —C(O)R a , —CF 3 , —OCF 3 , —N(R a )S(O) 2 R b , —S(O) 2 N(R a )(R b ), —S(O) 2 N(R a )C(O)R b , an optionally substituted (C 1 -C 6 )alkyl, an optionally substituted (C 2 -C 6 )alkenyl, an optionally substituted (C 2 -C 6 )alkynyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 ) heterocyclyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkyl-(C 1 -C 10 )heterocyclyl;
 wherein in a moiety containing —N(R a )(R b ), the nitrogen, R a  and R b  may form a ring such that —N(R a )(R b ) represents an optionally substituted (C 2 -C 10 )heterocyclyl or an optionally substituted (C 1 -C 10 ) heteroaryl linked through a nitrogen; 
 
 R a  and R b  are each independently hydrogen, deuterium, an optionally substituted (C 1 -C 10 )alkyl, an optionally substituted (C 2 -C 10 )alkenyl, an optionally substituted (C 2 -C 10 )alkynyl, an optionally substituted (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl, an optionally substituted (C 3 -C 10 )cycloalkyl, an optionally substituted (C 6 -C 10 )aryl, an optionally substituted (C 1 -C 10 )heteroaryl, an optionally substituted (C 1 -C 10 )heterocyclyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 3 -C 10 )cycloalkyl, an optionally substituted —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heteroaryl, or an optionally substituted —(C 1 -C 6 )alkylene-(C 1 -C 10 )heterocyclyl; and 
 R e  for each occurrence is independently a bond, an optionally substituted (C 1 -C 10 )alkylene, an optionally substituted (C 2 -C 10 )alkenylene, an optionally substituted (C 2 -C 10 )alkynylene, an optionally substituted —(C 1 -C 10 )alkylene-O—(C 1 -C 10 )alkylene group, an optionally substituted (C 3 -C 10 )cycloalkylene, an optionally substituted (C 6 -C 10 )arylene, an optionally substituted (C 1 -C 10 )heteroarylene, or an optionally substituted (C 1 -C 10 )heterocyclylene. 
 
     
     
         41 . A pharmaceutical composition comprising a compound of Formula (I) as defined in  claim 1   
       
         
           
           
               
               
           
         
       
       a pharmaceutically acceptable carrier and excipient and a second therapeutic agent selected from the group consisting of cytokine suppressive anti-inflammatory drugs, antibodies to or antagonists of other human cytokines or growth factors, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-12, IL-15, IL-16, IL-21, IL-23, interferons, EMAP-II, GM-CSF, FGF, PDGF, CTLA or their ligands including CD154, HUMIRA™, REMICADE™, SIMPONI™ (golimumab), CIMZIA™, ACTEMRA™, CDP 571, soluble p55 or p75 TNF receptors, ENBREL™, Lenercept, TNFα converting enzyme inhibitors, IL-1 inhibitors, Interleukin 11, IL-18 antagonists, IL-12 antagonists, IL-12 antibodies, soluble IL-12 receptors, IL-12 binding proteins, non-depleting anti-CD4 inhibitors FK506, rapamycin, mycophenolate mofetil, leflunomide, NSAIDs, ibuprofen, corticosteroids, phosphodiesterase inhibitors, adensosine agonists, antithrombotic agents, complement inhibitors, adrenergic agents, IL-1β converting enzyme inhibitors, T-cell signalling kinase inhibitors, metalloproteinase inhibitors, sulfasalazine, 6-mercaptopurines, derivatives p75TNFRIgG, sIL-1RI, sIL-1RII, sIL-6R, celecoxib, hydroxychloroquine sulfate, rofecoxib, infliximab, naproxen, valdecoxib, sulfasalazine, meloxicam, acetate, gold sodium thiomalate, aspirin, triamcinolone acetonide, propoxyphene napsylate/apap, folate, nabumetone, diclofenac, piroxicam, etodolac, diclofenac sodium, oxaprozin, oxycodone HCl, hydrocodone bitartrate/apap, diclofenac sodium/misoprostol, fentanyl, anakinra, tramadol HCl, salsalate, sulindac, cyanocobalamin/fa/pyridoxine, acetaminophen, alendronate sodium, morphine sulfate, lidocaine hydrochloride, indomethacin, glucosamine sulf/chondroitin, amitriptyline HCl, sulfadiazine, oxycodone HCl/acetaminophen, olopatadine HCl misoprostol, naproxen sodium, omeprazole, cyclophosphamide, rituximab, IL-1 TRAP, MRA, CTLA4-IG, IL-18 BP, anti-IL-12, anti-IL15, VX-740, Roflumilast, IC-485, CDC-801, S1P1 agonists, FTY720, PKC family inhibitors, Ruboxistaurin, AEB-071, Mesopram, methotrexate, leflunomide, corticosteroids, budenoside, dexamethasone, sulfasalazine, 5-aminosalicylic acid, olsalazine, IL-1β converting enzyme inhibitors, IL-1ra, T cell signaling inhibitors, tyrosine kinase inhibitors, 6-mercaptopurines, IL-11, mesalamine, prednisone, azathioprine, mercaptopurine, infliximab, methylprednisolone sodium succinate, diphenoxylate/atrop sulfate, loperamide hydrochloride, omeprazole, folate, ciprofloxacin/dextrose-water, hydrocodone, bitartrate/apap, tetracycline hydrochloride, fluocinonide, metronidazole, thimerosal/boric acid, cholestyramine/sucrose, ciprofloxacin hydrochloride, hyoscyamine sulfate, meperidine hydrochloride, midazolam hydrochloride, oxycodone HCl/acetaminophen, promethazine hydrochloride, sodium phosphate, sulfamethoxazole/trimethoprim, polycarbophil, propoxyphene napsylate, hydrocortisone, multivitamins, balsalazide disodium, codeine phosphate/apap, colesevelam HCl, cyanocobalamin, folic acid, levofloxacin, natalizumab, interferon-gamma, methylprednisolone, azathioprine, cyclophosphamide, cyclosporine, methotrexate, 4-aminopyridine, tizanidine, interferon-β1a, AVONEX®, interferon-β1b, BETASERON®, interferon α-n3, interferon-α, interferon β1A-IF, Peginterferon α 2b, Copolymer 1, COPAXONE®, hyperbaric oxygen, intravenous immunoglobulin, cladribine, cyclosporine, FK506, mycophenolate mofetil, leflunomide, NSAIDs, corticosteroids, prednisolone, phosphodiesterase inhibitors, adensosine agonists, antithrombotic agents, complement inhibitors, adrenergic agents, antiinflammatory cytokines, interferon-β, IFNβ1a, IFNβ1b, copaxone, corticosteroids, caspase inhibitors, inhibitors of caspase-1, antibodies to CD40 ligand and CD80, alemtuzumab, dronabinol, daclizumab, mitoxantrone, xaliproden hydrochloride, fampridine, glatiramer acetate, natalizumab, sinnabidol, α-immunokine NNSO3, ABR-215062, AnergiX.MS, chemokine receptor antagonists, BBR-2778, calagualine, CPI-1189, liposome encapsulated mitoxantrone, THC.CBD, cannabinoid agonists, MBP-8298, mesopram, MNA-715, anti-IL-6 receptor antibody, neurovax, pirfenidone allotrap 1258 (RDP-1258), sTNF-R1, talampanel, teriflunomide, TGF-beta2, tiplimotide, VLA-4 antagonists, interferon gamma antagonists, IL-4 agonists, diclofenac, misoprostol, naproxen, meloxicam, indomethacin, diclofenac, methotrexate, azathioprine, minocyclin, prednisone, etanercept, rofecoxib, sulfasalazine, naproxen, leflunomide, methylprednisolone acetate, indomethacin, hydroxychloroquine sulfate, prednisone, sulindac, betamethasone diprop augmented, infliximab, methotrexate, folate, triamcinolone acetonide, diclofenac, dimethylsulfoxide, piroxicam, diclofenac sodium, ketoprofen, meloxicam, methylprednisolone, nabumetone, tolmetin sodium, calcipotriene, cyclosporine, diclofenac sodium/misoprostol, fluocinonide, glucosamine sulfate, gold sodium thiomalate, hydrocodone bitartrate/apap, risedronate sodium, sulfadiazine, thioguanine, valdecoxib, alefacept, and efalizumab, diclofenac, naproxen, ibuprofen, piroxicam, indomethacin, COX2 inhibitors, rofecoxib, valdecoxib, hydroxychloroquine, steroids, prednisolone, budenoside, dexamethasone, cytotoxics, azathioprine, cyclophosphamide, mycophenolate mofetil, inhibitors of PDE4, purine synthesis inhibitor, sulfasalazine, 5-aminosalicylic acid, olsalazine, Imuran®, CTLA-4-IgG, anti-B7 family antibodies, anti-PD-1 family antibodies, anti-cytokine antibodies, fonotolizumab, anti-IFNg antibody, anti-receptor receptor antibodies, anti-IL-6 receptor antibody, antibodies to B-cell surface molecules, LJP 394, Rituximab, anti-CD20 antibody and lymphostat-B.
Cited by (0)

No later patents cite this yet.
References (0)

No backward citations on record.