US2012232048A1PendingUtilityA1

Method for modulating gpr119 g protein-coupled receptor and selected compounds

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Assignee: WACKER DEAN APriority: Jul 17, 2007Filed: Apr 24, 2012Published: Sep 13, 2012
Est. expiryJul 17, 2027(~1 yrs left)· nominal 20-yr term from priority
Inventors:Dean A. WackerKaren A. RossiYing Wang
A61P 5/50A61P 9/00A61P 3/08A61P 3/04A61P 43/00A61P 5/48A61P 3/06A61P 9/12A61P 9/10A61P 3/10A61P 31/00A61P 31/18A61P 27/06A61P 33/00A61P 3/00A61P 25/18A61P 35/00A61P 27/04A61P 27/02A61P 25/00A61P 31/04A61P 25/28A61P 19/08A61P 17/02A61P 19/00A61P 1/18A61P 13/12A61P 13/00C07D 401/12C07D 401/14
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Claims

Abstract

A method of modulating the activity of the GPR119 G protein-coupled receptor comprising administering to a mammalian patient in need thereof a therapeutically effective amount of at least one compound of Formula I or Formula IA and, optionally, an additional therapeutic agent.

Claims

exact text as granted — not AI-modified
1 . A method of modulating activity of the GPR119 G protein-coupled receptor comprising administering to a mammalian patient in need thereof a therapeutically effective amount of at least one compound of Formula I and, optionally, an additional therapeutic agent wherein the compound of Formula I is 
       
         
           
           
               
               
           
         
       
       and enantiomers, diastereomers and pharmaceutically acceptable salts thereof having ring A and ring B, wherein:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ; 
 G is CH or N; 
 Q is C or N; 
 X is CH or N, provided that Q and X are not both N; 
 Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ; 
 n 1  is 0-2; 
 n 2  is 0-2; 
 n 3  is 1-2; 
 R 1  is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ; 
 R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl; 
 R 2  is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O) 2 R 5 , —C(═O)NR 3 R 5 , —C(═O)R 5  or —C(═O)OR 5 , wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; 
 R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each contain 1-4 heteroatoms selected from N, O and S; 
 R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's; 
 R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , 
 
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a , and the heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl each contain 1-4 heteroatoms selected from N, O and S; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a , and the heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl each contain 1-4 heteroatoms selected from N, O and S; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; and 
 R 20  and R 21  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         2 . A method according to  claim 1  wherein:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ; 
 G is CH or N; 
 Q is C or N; 
 X is CH or N, provided that Q and X are not both N; 
 Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ; 
 n 1  is 0-2; 
 n 2  is 0-2; 
 n 3  is 1-2; 
 R 1  is phenyl, pyridinyl, pyrazinyl or pyrimindinyl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ; 
 R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl; 
 R 2  is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O) 2 R 5 , —C(═O)NR 3 R 5 , —C(═O)R 5  or —C(═O)OR 5 , wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; 
 R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; 
 R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's; 
 R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , 
 
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; and 
 R 20  and R 21  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)Rio and —OC(═O)R 10 . 
 
     
     
         3 . A method according to  claim 1  wherein:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ; 
 G is CH or N; 
 Q is C or N; 
 X is CH or N, provided that Q and X are not both N; 
 Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ; 
 n 1  is 0-2; 
 n 2  is 0-2; 
 n 3  is 1-2; 
 R 1  is each of which 
 
       
         
           
           
               
               
           
         
       
       may be optionally substituted with one or more members selected from the group consisting of R 1a , R 1b , R 1c , R 1d  and R 1e ;
 R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl; 
 R 2  is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O) 2 R 5 , —C(═O)NR 3 R 5 , —C(═O)R 5  or —C(═O)OR 5 , wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; 
 R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the heteroaryl; 
 R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's; 
 R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , 
 
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 ; —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 ; —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; 
 R 20  and R 21  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         4 . A method according to  claim 1  wherein:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ; 
 G is CH or N; 
 Q is C or N; 
 X is CH or N, provided that Q and X are not both N; 
 Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ; 
 n 1  is 0-2; 
 n 2  is 0-2; 
 n 3  is 1-2; 
 R 1  is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ; 
 R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl; 
 R 2  is aryl, heteroaryl, heterocyclyl, —C(═O)NR 3 R 5 , —C(═O)R 5  or —C(═O)OR 5 , wherein the aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; 
 R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; 
 R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's; 
 R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , 
 
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 ; —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; and 
 R 20  and R 21  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         5 . A method according to  claim 1  wherein:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ; 
 G is CH or N; 
 Q is C or N; 
 X is CH or N, provided that Q and X are not both N; 
 Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ; 
 n 1  is 0-2; 
 n 2  is 0-2; 
 n 3  is 1-2; 
 R 1  is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ; 
 R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl; 
 R 2  is heteroaryl or —C(═O)OR 5 , wherein the heteroaryl may be optionally substituted with one or more R 6 's; 
 R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; 
 R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's; 
 R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , 
 
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; and 
 R 20  and R 21  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)Rio and —OC(═O)Rio. 
 
     
     
         6 . A method according to  claim 1  wherein:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ; 
 G is CH or N; 
 Q is C or N; 
 X is CH or N, provided that Q and X are not both N; 
 Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ; 
 n 1  is 0-2; 
 n 2  is 0-2; 
 n 3  is 1-2; 
 R 1  is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ; 
 R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl; 
 R 2  is heteroaryl which may be optionally substituted with one or more R 6 's; 
 R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; 
 R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , 
 
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )OR 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; and 
 R 20  and R 21  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         7 . A method according to  claim 1  wherein:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ; 
 G is CH or N; 
 Q is C or N; 
 X is CH; 
 Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ; 
 n 1  is 0-2; 
 n 2  is 0-2; 
 n 3  is 1-2; 
 R 1  is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ; 
 R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl; 
 R 2  is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O) 2 R 5 , —C(═O)NR 3 R 5 , —C(═O)R 5  or —C(═O)OR 5 , wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; 
 R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; 
 R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's; 
 R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , 
 
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 ; —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 ; —OCF 3 , —OR 14 ; 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; 
 R 20  is hydrogen; and 
 R 21  is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         8 . A method according to  claim 1 , wherein the compound is selected from compounds of Formula I in which:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ;   G is CH or N;   Q is C;   X is CH;   Y is CH 2 , N(R 3 ), C(═O), O, OCR 9 R 9 , S, S(═O) or S(O) 2 ;   n 1  is 0-2;   n 2  is 0-2;   n 3  is 2;   R 1  is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ;   R 1a , R 1b , R 1c , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's; provided that at least one of R 1a , R 1b , R 1c , R 1d  and R 1e  is heteroaryl;   R 2  is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O) 2 R 5 , —C(═O)NR 3 R 5 , —C(═O)R 5  or —C(═O)OR 5 , wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R 6 's;   R 3  is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl;   R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's;   R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 ,   
       —OH, —SH, —SR 10 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)NR 9 S(O) 2 R 9 , —S(O) 2 NR 9 C(═O)OR 9 , —S(O) 2 NR 9 C(═O)NR 9 R 9 , —C(═O)NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —C(═NR 14 )NR 9 R 9 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 14 , —S(O) 2 NR 14 C(═O)OR 14 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ;
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 10 , —S(O) 2 NR 14 C(═O)OR 10 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8 , ═O and arylalkyl;
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH 2 , —CN, —NO 2 , —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , 
 
       —OH, —SH, —SR 14 , —S(O) 3 H, —P(O) 3 H 2 , —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)NR 14 S(O) 2 R 9 , —S(O) 2 NR 14 C(═O)OR 9 , —S(O) 2 NR 14 C(═O)NR 14 R 14 , —C(═O)NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —C(═NR 14 )NR 14 R 14 , —NHC(═NR 14 )NR 14 R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and arylalkyl;
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; 
 R 20  is hydrogen; and 
 R 21  is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         9 . A method according to  claim 1 , wherein the compound is selected from compounds of Formula I in which:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ;   G is CH or N;   Q is C;   X is CH;   Y is O, OCR 9 R 9 , or S;   n 1  is 1;   n 2  is 1;   n 3  is 2;   R 1  is phenyl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ;   R 1a , R 1b , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, halo, —CN, —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl and cycloalkyl may each be optionally substituted with one or more R 6 's;   R 1c  is a 5-6 membered monocyclic heteroaryl which may be optionally substituted with one or more R 6 's;   R 2  is heteroaryl or —C(═O)OR 5 , wherein the heteroaryl may be optionally substituted with one or more R 6 's;   R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's;   R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 ,   
       —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH 2 , —CN, —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ; 
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH 2 , —CN, —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and ═O; 
 R 10 , at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, halo, —NH 2 , —CN, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8  and —NR 14 S(O 2 )R 8 ; 
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; 
 R 20  is hydrogen; and 
 R 21  is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         10 . A method according to  claim 1 , wherein the compound is selected from compounds of Formula I in which:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ;   G is N;   Q is C;   X is CH;   Y is O;   n 1  is 1;   n 2  is 1;   n 3  is 2;   R 1  is phenyl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R 1a , R 1b , R 1c , R 1d  and R 1e ;   R 1a , R 1b , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, halo, —CN, —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl and cycloalkyl may each be optionally substituted with one or more R 6 's;   R 1c  is a 5-6 membered monocyclic heteroaryl which may be optionally substituted with one or more R 6 's;   R 2  is heteroaryl or —C(═O)OR 5 , wherein the heteroaryl may be optionally substituted with one or more R 6 's;   R 5  is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R 6 's;   R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 ,   
       —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl and cycloalkyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH 2 , —CN, —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ; 
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl, which may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH 2 , —CN, —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and ═O; 
 R 10 , at each occurrence, is independently selected from alkyl, cycloalkyl and aryl, which may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, halo, —NH 2 , —CN, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8  and —NR 14 S(O 2 )R 8 ; 
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; 
 R 20  is hydrogen; and 
 R 21  is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —C(═O)R 10  and —OC(═O)R 10 . 
 
     
     
         11 . A method according to  claim 1 , wherein the compound is selected from compounds of Formula I in which:
 ring A is optionally substituted with one or more R's shown as R 20  and R 21 ;   G is N;   Q is C;   X is CH;   Y is O;   n 1  is 1;   n 2  is 1;   n 3  is 2;   R 1  is   
       
         
           
           
               
               
           
         
         R 1a , R 1b , R 1d  and R 1e  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, halo, —CN, —OCF 3 , —OR 10 , —OH, —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —OC(═O)NR 9 R 9 , —S(═O)R 10 , —S(O) 2 R 10 , —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl and cycloalkyl may each be optionally substituted with one or more R 6 's; 
         R 1c  is a 5-6 membered monocyclic heteroaryl which may be optionally substituted with one or more R 6 's; 
         R 2  is pyridinyl, pyrimidinyl or —C(═O)OR 5 , wherein the pyridinyl and pyrimidinyl may each be optionally substituted with one or more R 6 's; 
         R 5  is alkyl, aryl or cycloalkyl, each of which may be optionally substituted with one or more R 6 's; 
         R 6 , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR 10 , —OCF 3 , —OR 10 , —OH, —SH, —SR 10 , 
       
       —C(═O)NR 9 R 9 , —NR 9 R 9 , —S(O) 2 NR 9 R 9 , —NR 9 S(O) 2 CF 3 , —C(═O)R 10 , —NR 9 C(═O)H, —NR 9 C(═O)R 10 , —OC(═O)R 10 , —S(═O)R 10 , —S(O) 2 R 10 , ═O, —NR 9 C(═O)OR 8  and —NR 9 S(O 2 )R 8 , wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R 9a ;
 R 8 , at each occurrence, is independently selected from the group consisting of alkyl and cycloalkyl, each of which may be optionally substituted with one or more R 8a 's; 
 R 8a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH 2 , —CN, —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , ═O, —NR 14 C(═O)OR 14  and —NR 14 S(O 2 )R 14 ; 
 R 9 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each be optionally substituted with 0-5 R 9a ; 
 R 9a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH 2 , —CN, —C(═O)OH, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8 , —NR 14 S(O 2 )R 8  and ═O; 
 R 10 , at each occurrence, is independently selected from alkyl, cycloalkyl and aryl, which may each be optionally substituted with 0-3 R 10a ; 
 R 10a , at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, halo, —NH 2 , —CN, —C(═O)OR 14 , —OCF 3 , —OR 14 , —OH, —C(═O)NR 14 R 14 , —NR 14 R 14 , —S(O) 2 NR 14 R 14 , —NR 14 S(O) 2 CF 3 , —C(═O)R 14 , —NR 14 C(═O)H, —NR 14 C(═O)R 14 , —OC(═O)R 14 , —S(═O)R 14 , —S(O) 2 R 14 , —NR 14 C(═O)OR 8  and —NR 14 S(O 2 )R 8 ; 
 R 14 , at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl; 
 R 20  is hydrogen; and 
 R 21  is selected from the group consisting of hydrogen, alkyl, haloalkyl, halo and —CN. 
 
     
     
         12 . The method of  claim 1  comprising the use of an additional therapeutic agent. 
     
     
         13 . The method of  claim 12  wherein the additional therapeutic agent is a dipeptidyl peptidase-IV (DPP4) inhibitor.

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