1, 8-Naphthyridine derivatives and their use to treat diabetes and related disorders

Abstract

The invention relates generally to naphthyridine derivatives of the formula wherein one of U, X, Y and Z is nitrogen and the others are C—R, where R is hydrogen or a substituent. More specifically, the invention relates to 1,8-naphthyridine derivatives and pharmaceutical compositions containing such derivatives. Methods of the invention comprise administration of a naphthyridine derivative of the invention for the treatment of diabetes and related disorders.

1 . A compound of the formula I  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, and A-R 9 , or  
 R 1  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloalkenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ; 
 R 10  is selected from nitro, nitrile, hydroxy, halogen, acyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, NR 11 R 12 , C(═O)OR 11 , C(═O)NHR 11 , NHC(═O)R 13 , NHS(═O) 2 R 13 , S(═O) 0-2 R 13 , S(═O) 2 NHR 11 , cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 0.1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O);  
 R 13  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, and cycloalkenyl of 4-6 carbon atoms;  
 R 11  and R 12  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, and cycloalkenyl of 4-6 carbon atoms;  
 A is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, and haloalkyl of 1-8 carbon atoms;  
 R 9  is selected from hydroxy, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, O-A-R 14 , NR 11 R 12 ; or  
 R 9  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 5-8 carbon atoms, all of which may be substituted with 1-3 of R 10 , or  
 R 9  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 14  is selected from cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 5-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 ;  
 
 R 2  is selected from NR 15 R 16 , S(O) 0-2 R 17 , and OR 17 ; 
 R 15  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, A-R 9 , C(═O)R 18 , C(═O)NHR 18 , S(═O) 2 NHR 18 ;  
 R 18  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or  
 R 18  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, and alkynyl of 2-6 carbon atoms, all of which may be substituted with 1-3 of halogen or alkoxy of 1-6 carbon atoms, or  
 R 18  is A-R 9 ;  
 R 16  is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, and A-R 9 , or  
 R 16  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or  
 R 15  and R 16  combine, together with the nitrogen atom to which they are attached, to form a heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, or a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 17  is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, and alkynyl of 2-8 carbon atoms, haloalkyl of 1-8 carbon atoms, A-R 9 , or  
 R 17  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 ;  
 
 R 3  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O)O-2, and O, cycloalkenyl of 4-8 carbon atoms, and heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or  
 R 3  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, hydrogen, nitro, halogen, NR 19 R 20 , A-OR 19 , A-NR 19 R 20 , and A-R 20 ; 
 R 19  and R 20  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 9 , or  
 R 19  and R 20  are independently selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 5-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 
 R 4  is selected from ═O, ═S, and OR 21 ; 
 R 21  is hydrogen, or  
 R 21  is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 ;  
 
 R 5  and R 6  are independently selected from cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, aryl of 6-10 carbon atoms, and heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms, all of which may be substituted with 1-3 of R 10 , or  
 R 5  and R 6  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or  
 R 5  and R 6  are independently selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, haloalkyl of 1-8 carbon atoms, alkoxy of 1-8 carbon atoms, haloalkoxy of 1-8 carbon atoms, cycloalkoxy of 3-8 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ; 
 Q is selected from O and S(═O) 0-2 ;  
 R 22  is selected from hydrogen, alkyl of 1-8 carbon atoms, haloalkyl of 1-8 carbon atoms, and cycloalkyl of 3-8 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-8 carbon atoms, haloalkoxy of 1-8 carbon atoms, and cycloalkoxy of 3-8 carbon atoms, or R 23  is selected from cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, aryl of 6-10 carbon atoms, and heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-8 carbon atoms, haloalkoxy of 1-8 carbon atoms, and cycloalkoxy of 3-8 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, aryl of 6-10 carbon atoms, and heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or 
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a heteroaryl of 2-9 carbon atoms and 14 heteroatoms, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, aryl of 6-10 carbon atoms, and heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, aryl of 6-10 carbon atoms, and heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, aryl of 6-10 carbon atoms, and heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms, all of which may be substituted with 1-3 of R 10 ;  
 R 29  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 
 R 7  is selected from cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, aryl of 6-10 carbon atoms, and heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms, all of which may be substituted with 1-3 of R 10 , or  
 R 7  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , A(OR 22 )—R 23 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or  
 R 7  is selected from hydrogen, nitrile, nitro, hydroxy, alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, haloalkyl of 1-8 carbon atoms, alkoxy of 1-8 carbon atoms, haloalkoxy of 1-8 carbon atoms, cycloalkoxy of 3-8 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ;  
 and pharmaceutically acceptable salts thereof,  
 with the provisio that the compound is not:  
 1,5-dimethyl-2-(methylamino)-7-(4-morpholinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(4-methyl-1-piperazinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(1-pyrrolidinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(1-piperidinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(4-methyl-1-piperazinyl)-3-nitro-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-3-nitro-7-(1-pyrrolidinyl)-1,8-naphthyridin-4(1H)-one, or  
 1-(3-chlorophenyl)-2-(4-morpholinyl)-1,8-naphthyridin-4(1H)-one.  
 
   
   
       2 . The compound of  claim 1 , wherein R 4  is ═O.  
   
   
       3 . The compound of  claim 1 , wherein R 3  is selected from cycloalkyl of 3-6 carbon atoms, heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, both of which may be substituted with 1-3 of R 10 , or 
 R 3  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, hydrogen, nitro, halogen, NR 19 R 20 , A-OR 19 , A-NR 19 R 20  and A-R 20 .    
   
   
       4 . The compound of  claim 3 , wherein R 19  and R 20  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms and A-R 9 , or wherein R 19  and R 20  are independently selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(O) 0-2  and O, cycloalkyl of 3-6 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, wherein one or more of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 .  
   
   
       5 . The compound of  claim 1 , wherein R 3  is selected from cycloalkyl of 3-6 carbon atoms, heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, both of which may be substituted with 1-3 of R 10 , or 
 R 3  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, hydrogen, nitro, halogen, NR 19 R 20 , A-OR 19 , A-NR 19 R 20 , and A-R 20 ; and    R 4  is ═O.    
   
   
       6 . The compound of  claim 5 , wherein R 19  and R 20  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms and A-R 9 , or wherein R 19  and R 20  are independently selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(O) 0-2  and O, cycloalkyl of 3-6 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, wherein one or more of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 .  
   
   
       7 . The compound of  claim 1 , wherein R 2  is NR 15 R 16 .  
   
   
       8 . The compound of  claim 7 , wherein 
 R 15  is selected from hydrogen, alkyl of 1-6 carbon atoms, cylcoalkyl of 3-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, A-R 9 , C(═O)R 18 , C(═O)NHR 18 , and S(═O) 2 NHR 18 ;    R 18  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-6 carbon atoms, and 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or    R 18  is alkyl of 1-6 carbon atoms, which may be substituted with 1-3 of halogen or alkoxy of 1-6 carbon atoms, or    R 18  is A-R 9 ; and    R 16  is selected from alkyl of 1-6 carbon atoms and A-R 9 , or    R 16  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-8 carbon atoms, and 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or    R 15  and R 16  combine, together with the nitrogen atom to which they are attached, to form a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, or a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 .    
   
   
       9 . The compound of  claim 1 , wherein R 2  is NR 15 R 16 ; 
 R 3  is selected from cycloalkyl of 3-6 carbon atoms, heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, both of which may be substituted with 1-3 of R 10 , or    R 3  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, hydrogen, nitro, halogen, NR 19 R 20 , A-OR 19 , A-NR 19 R 20 , and A-R 20 ; and    R 4  is ═O.    
   
   
       10 . The compound of  claim 9 , wherein 
 R 15  is selected from hydrogen, alkyl of 1-6 carbon atoms, cylcoalkyl of 3-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, A-R 9 , C(═O)R 18 , C(═O)NHR 18 , and S(═O) 2 NHR 18 ;    R 18  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-6 carbon atoms, and 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or    R 18  is alkyl of 1-6 carbon atoms, which may be substituted with 1-3 of halogen or alkoxy of 1-6 carbon atoms, or    R 18  is A-R 9 ; and    R 16  is selected from alkyl of 1-6 carbon atoms and A-R 9 , or    R 16  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-8 carbon atoms, and 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or    R 15  and R 16  combine, together with the nitrogen atom to which they are attached, to form a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, or a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 .    
   
   
       11 . The compound of  claim 10 , selected from the group consisting of:  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       12 . The compound of  claim 9 , wherein R 19  and R 20  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms and A-R 9 , or wherein R 19  and R 20  are independently selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(O) 0-2  and O, cycloalkyl of 3-6 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, wherein one or more of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 .  
   
   
       13 . The compound of  claim 1  or  9 , wherein R 5  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or 
 R 5  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 5  is selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ; 
 R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or  
 R 23  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ; and  
 R 29  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 .  
   
   
   
       14 . The compound of  claim 13 , wherein R 5  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or 
 R 5  is 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR, C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 5  is selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , and A-C(═O)R 24 ; 
 R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or  
 R 23  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, wherein one or more of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ; and  
 R 29  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 .  
   
   
   
       15 . The compound of  claim 14  selected from the group consisting of:  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       16 . The compound of  claim 1  or  9 , wherein R 6  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or 
 R 6  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 6  is selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ; 
 R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or  
 R 23  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with I-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ; and  
 R 29  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 .  
   
   
   
       17 . The compound of  claim 16 , wherein R 6  is selected from cycloalkyl of 3-6 carbon atoms, all of which may be substituted with 1-3 of R 10 , or 
 R 6  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 6  is selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , S(═O) 0-2 —R 29 , S(═O) 0-2 -A-NR 24 R 25 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ;    R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;    R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or    R 23  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or    R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;    with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;    R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or    R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or    R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or    R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, monocyclic heteroaryl and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;    R 26  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or    R 26  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or    R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;    R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or    R 27  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or    R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;    R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 26 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or    R 28  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or    R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;    R 30  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or    R 30  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or    R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or    R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ;    R 29  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or    R 29  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or    R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 .    
   
   
       18 . The compound of  claim 17  selected from the group consisting of:  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       19 . The compound of  claim 1  or  9 , wherein R 7  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or 
 R 7  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 7  is selected from hydrogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ; 
 R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or  
 R 23  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ;  
 R 29  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 .  
   
   
   
       20 . The compound of  claim 19 , wherein R 7  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or 
 R 7  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 7  is selected from hydrogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ; 
 R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or  
 R 23  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ;  
 R 29  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 2 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 .  
   
   
   
       21 . The compound of  claim 20  selected from the group consisting of:  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       22 . A compound of the formula I  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, and A-R 9 , or  
 R 1  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloalkenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ; 
 R 10  is selected from nitro, nitrile, hydroxy, halogen, acyl of 1-6 carbon atoms, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, NR 11 R 12 , C(═O)OR 11 , C(═O)NHR 11 , NHC(═O)R 13 , NHS(═O) 2 R 13 , S(═O) 0-2 R 13 , S(═O) 2 NHR 11 , cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O);  
 R 13  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, and cycloalkenyl of 4-6 carbon atoms;  
 R 11  and R 12  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, and cycloalkenyl of 4-6 carbon atoms;  
 A is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, and haloalkyl of 1-8 carbon atoms;  
 R 9  is selected from hydroxy, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, O-A-R 14 , NR 11 R 12 ; or  
 R 9  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 5-8 carbon atoms, all of which may be substituted with 1-3 of R 10 , or  
 R 9  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 14  is selected from cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 5-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 ;  
 
 R 2  is NR 15 R 16 ; 
 R 15  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, A-R 9 , C(═O)R 18 , C(═O)NHR 18 , S(═O) 2 NHR 18 ;  
 R 18  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or  
 R 18  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, and alkynyl of 2-6 carbon atoms, all of which may be substituted with 1-3 of halogen or alkoxy of 1-6 carbon atoms, or  
 R 18  is A-R 9 ;  
 
 R 6  is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, and A-R 9 , or 
 R 16  is selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or  
 R 15  and R 16  combine, together with the nitrogen atom to which they are attached, to form a heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(═O) 0-2  and O, or a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 
 R 3  is selected from cycloalkyl of 3-6 carbon atoms, heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, both of which may be substituted with 1-3 of R 10 , or  
 R 3  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, hydrogen, nitro, halogen, NR 19 R 20 , A-OR 19 , A-NR 19 R 20 , and A-R 20 ; 
 R 19  and R 20  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 9 , or  
 R 19  and R 20  are independently selected from aryl of 6-10 carbon atoms, heteroaryl of 2-9 carbon atoms and 1-4 heteroatoms selected from N, S(O) 0-2  and O, cylcoalkyl of 3-8 carbon atoms, cycloalkenyl of 5-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, wherein said heterocycloalkyl and said heterocycloakenyl may further be fused with phenyl or a 5-6 membered heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 
 R 4  is selected from ═O, ═S, and OR 21 ; 
 R 21  is hydrogen, or  
 R 21  is selected from alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 ;  
 
 R 5  and R 6  are independently selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or  
 R 5  and R 6  are independently selected from is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or  
 R 5  and R 6  are independently selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ; 
 Q is selected from O and S(═O) 0-2 ;  
 R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or  
 R 23  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 2 R 26 , A-C(═O)R 24 , A C(═O)OR 24 , and A-C(═O)NR 24 R 25 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, a 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ; and  
 R 29  is selected from alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 ;  
 
 R 7  is selected from cycloalkyl of 3-6 carbon atoms, cycloalkenyl of 4-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or  
 R 7  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O and 5-7 membered heterocycloalkenyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one or more of the carbon atoms in said heterocycloalkyl or heterocycloalkenyl may be oxidized to C(═O), wherein said heterocycloalkyl or said heterocycloalkenyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or  
 R 7  is selected from hydrogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A_NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ;  
 and pharmaceutically acceptable salts thereof  
 with the provisio that the compound is not:  
 1,5-dimethyl-2-(methylamino)-7-(4-morpholinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(4-methyl-1-piperazinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(1-pyrrolidinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(1-piperidinyl)-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-7-(4-methyl-1-piperazinyl)-3-nitro-1,8-naphthyridin-4(1H)-one,  
 1,5-dimethyl-2-(methylamino)-3-nitro-7-(1-pyrrolidinyl)-1,8-naphthyridin-4(1H)-one, or  
 1-(3-chlorophenyl)-2-(4-morpholinyl)-1,8-naphthyridin-4(1H)-one.  
 
   
   
       23 . The compound of  claim 22 , wherein 
 R 4  is ═O; 
 R 15  is selected from hydrogen, alkyl of 1-6 carbon atoms, cylcoalkyl of 3-8 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, A-R 9 , C(═O)R 18 , C(═O)NHR 18 , and S(═O) 2 NHR 18 ;  
 R 18  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-6 carbon atoms, and 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or  
 R 18  is alkyl of 1-6 carbon atoms, which may be substituted with 1-3 of halogen or alkoxy of 1-6 carbon atoms, or  
 R 18  is A-R 9 ; and  
 R 16  is selected from alkyl of 1-6 carbon atoms and A-R 9 , or  
 R 16  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-8 carbon atoms, and 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, all of which may be substituted with 1-3 of R 10 , or  
 R 15  and R 16  combine, together with the nitrogen atom to which they are attached, to form a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, or a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 19  and R 20  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms and A-R 9 , or wherein R 19  and R 20  are independently selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(O) 0-2  and O, cycloalkyl of 3-6 carbon atoms, 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(O) 0-2  and O, wherein one or more of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ; and  
   R 5  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or    R 5  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 5  is selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A_NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , and A-C(═O)R 24 ; 
 R 22  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and cycloalkyl of 3-6 carbon atoms;  
 R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, or  
 R 23  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 23  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 with the proviso for A(OR 22 )—R 23  that when R 23  is selected from hydroxy, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, and cycloalkoxy of 3-6 carbon atoms, A is not CH;  
 R 24  and R 25  are independently selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 24  and R 25  are independently selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  are independently selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or  
 R 24  and R 25  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and O, or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), all of which may be substituted with 1-3 of R 10 ;  
 R 26  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 26  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 26  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 27  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, and A-R 23 , or  
 R 27  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 27  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 28  is selected from hydrogen, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , C(═O)R 24 , C(═O)OR 26 , C(═O)NR 25 R 30 , S(═O) 26 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 2 R 2 , or  
 R 28  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 28  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
 R 30  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A(OR 22 )—R 23 , and A-R 23 , or  
 R 30  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 30  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , or  
 R 25  and R 30  combine, together with the nitrogen atom to which they are attached, to form a 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , or a monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 ;  
 R 29  is selected from alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A-C(═O)R 24 , A-C(═O)OR 24 , A-C(═O)NR 24 R 25 , A-NR 27 R 28 , or  
 R 29  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2 , and O, all of which may be substituted with 1-3 of R 10 , or  
 R 29  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, O, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 ;  
   R 6  is selected from cycloalkyl of 3-6 carbon atoms, all of which may be substituted with 1-3 of R 10 , or    R 6  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2  and O, and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 6  is selected from hydrogen, halogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , S(═O) 0-2 —R 29 , S(═O) 0-2 -A-NR 24 R 25 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 ;    R 7  is selected from cycloalkyl of 3-6 carbon atoms, phenyl, and monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms, all of which may be substituted with 1-3 of R 10 , or    R 7  is selected from 5-7 membered heterocycloalkyl of 3-6 carbon atoms and 1-2 heteroatoms selected from N, S(═O) 0-2 , and/or wherein one of the carbon atoms in said heterocycloalkyl may be oxidized to C(═O), wherein said heterocycloalkyl may be substituted with 1-3 of R 10 , A-R 23 , A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , S(═O) 2 R 26 , A-C(═O)R 24 , A-C(═O)OR 24 , or A-C(═O)NR 24 R 25 , or    R 7  is selected from hydrogen, nitrile, nitro, hydroxy, alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, A-R 23 , A(OR 22 )—R 23 , NR 27 R 28 , A-NR 27 R 28 , A-Q-R 29 , Q-R 29 , Q-A-NR 24 R 25 , C(═O)R 24 , C(═O)OR 24 , C(═O)NR 24 R 25 , A-C(═O)R 24 , A-C(═O)OR 24 , and A-C(═O)NR 24 R 25 .    
   
   
       24 . The compound of  claim 23 , wherein R 1  is selected from alkyl of 1-8 carbon atoms, and A-R 9 , or 
 R 1  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cycloalkyl of 3-6 carbon atoms, all of which may be substituted with 1-3 of R 10 ; 
 A is selected from alkyl of 1-6 carbon atoms, and haloalkyl of 1-8 carbon atoms;  
 R 9  is selected from hydroxy, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-6 carbon atoms, O-A-R 14 , NR 11 R 12 ; or  
 R 9  is selected from phenyl, monocyclic heteroaryl of 2-5 carbon atoms and 1-3 heteroatoms selected from N, S(═O) 0-2  and O, cylcoalkyl of 3-6 carbon atoms, all of which may be substituted with 1-3 of R 10 .  
   
   
   
       25 . The compound of  claim 24 , wherein R 1  is phenyl, which may be substituted with 1-3 of R 10 .  
   
   
       26 . A method of treating or preventing a disease or condition selected from the group consisting of diabetes (Type 1 or Type 2), maturity-onset diabetes of the young (MODY), latent autoimmune diabetes adult (LADA), impaired glucose tolerance (IGT), impaired fasting glucose (EFG), gestational diabetes, and metabolic syndrome X, comprising administering to a mammal an effective amount of a compound of  claim 1  or  22 .  
   
   
       27 . The method of  claim 26 , wherein said disease or condition is diabetes (Type 1 or Type 2).  
   
   
       28 . The method of  claim 27 , wherein said disease or condition is Type 2 diabetes.  
   
   
       29 . The method of  claim 26 , further comprising administering a PPAR-agonist, an insulin sensitizer, a sulfonylurea, an insulin secretagogue, a hepatic glucose output lowering compound, an x-glucosidase inhibitor or insulin in combination with said compound of  claim 1  or  22 .  
   
   
       30 . The method of  claim 29 , wherein said PPAR-agonist is selected from rosiglitazone and pioglitazone.  
   
   
       31 . The method of  claim 29 , wherein said sulfonylurea is selected from glibenclamide, glimepiride, chlorpropamide, and glipizide.  
   
   
       32 . The method of  claim 29 , wherein said insulin secretagogue is selected from GLP-1, GIP, PAC/VPAC receptor agonists, secretin, nateglinide, meglitinide, repaglinide, glibenclamide, glimepiride, chlorpropamide, and glipizide.  
   
   
       33 . The method of  claim 29 , wherein said α-glucosidase inhibitor is selected from acarbose, miglitol and voglibose.  
   
   
       34 . The method of  claim 29 , wherein said hepatic glucose output lowering compound is metformin.  
   
   
       35 . The method of  claim 26 , further comprising administering an HMG-CoA reductase inhibitor, nicotinic acid, a bile acid sequestrant, a fibric acid derivative, antihypertensive drug, or an anti-obesity drug in combination with said compound of  claim 1  or  22 .  
   
   
       36 . The method of  claim 35 , wherein said anti-obesity drug is selected from a −3 agonist, a CB-1 antagonist, and a lipase inhibitor.  
   
   
       37 . A method of treating or preventing secondary causes of diabetes selected from glucocorticoid excess, growth hormone excess, pheochromocytoma, and drug-induced diabetes, comprising administering to a mammal an effective amount of a compound of  claim 1  or  22 .  
   
   
       38 . A method of increasing the sensitivity of pancreatic beta cells to an insulin secretagogue, comprising administering to a mammal an effective amount of a compound of  claim 1  or  22 .  
   
   
       39 . The method of  claim 38 , wherein said insulin secretagogue is selected from GLP-1, GIP, PAC/VPAC receptor agonists, secretin, nateglinide, meglitinide, repaglinide, glibenclamide, glimepiride, chlorpropamide, and glipizide.  
   
   
       40 . A pharmaceutical composition, comprising a compound according to  claim 1  or  22  and a pharmaceutically acceptable carrier.