Heterocyclic CETP inhibitors

A compound of formula Ia or Ib

• or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein:
• A is heteroaryl, which is substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 3) —OR6, 4) (C1-C6)-alkylthio, 5) cyano, 6) nitro, 7) —NR9R10, 8) aryl, which may be optionally substituted with one or more R20's, 9) arylalkyl, which may be optionally substituted with one or more R20's, 10) heteroaryl, which may be optionally substituted with one or more R20's, 11) heteroarylalkyl, which may be optionally substituted with one or more R20's, 12) heterocyclyl, which may be optionally substituted with one or more R20's, 13) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 14) halo(C1-C6)alkyl, 15) —COR6, 16) ═O, 17) —S(O)pR6, 18) —SO2NHR6, 19) —COOR6, 20) —NHC(CN)NHR6, 21) —CONR6R6;
• and 27) cycloalkyl, which may be optionally substituted with one or more R20'S;
• B is
• phenyl, which is substituted with more than one substituent selected from the group consisting of:
• 1) halo, 2) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 3) —OR6, 4) (C1-C6)-alkylthio, 5) cyano, 6) nitro, 7) aryl, which may be optionally substituted with one or more R20's, 8) arylalkyl, which may be optionally substituted with one or more R20's, 9) heteroaryl, which may be optionally substituted with one or more R20's, 10) heteroarylalkyl, which may be optionally substituted with one or more R20's, 11) heterocyclyl, which may be optionally substituted with one or more R20's, 12) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 13) halo(C1-C6)alkyl, 14) —COR6, 15) —S(O)pR6, 16) —SO2NHR6, 17) —COOR6, 18) —NHC(CN)NHR6, 19) —CONR6R6;
• and 20) cycloalkyl, which may be optionally substituted with one or more R20's;
• C is alkyl, which is substituted with aryl, which may be optionally substituted with one or more R20's;
• R1 is —C(O)R3;
• R3 is
• (a) aryl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 3) —OR6, 4) (C1-C6)-alkylthio, 5) cyano, 6) nitro, 7) —NR9R10, 8) aryl, which may be optionally substituted with one or more R20's, 9) arylalkyl, which may be optionally substituted with one or more R20's, 10) heteroaryl, which may be optionally substituted with one or more R20's, 11) heteroarylalkyl, which may be optionally substituted with one or more R20's, 12) heterocyclyl, which may be optionally substituted with one or more R20's, 13) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 14) halo(C1-C6)alkyl, 15) —CONR6R6, 16) (C2-C6)-alkenyl, 17) ═O, 18) (C2-C6)-alkynyl, 19) —COR6, 20) —S(O)pR6, 21) —SO2NHR6, 22) —COOR6, 23) —NHC(CN)NHR6;
• and 24) cycloalkyl, which may be optionally substituted with one or more R20's;
• or
• (b) alkenyl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 3) —OR6, 4) (C1-C6)-alkylthio, 5) cyano, 6) nitro, 7) —NR9R10, 8) aryl, which may be optionally substituted with one or more R20's, 9) arylalkyl, which may be optionally substituted with one or more R20's, 10) heteroaryl, which may be optionally substituted with one or more R20's, 11) heteroarylalkyl, which may be optionally substituted with one or more R20's, 12) heterocyclyl, which may be optionally substituted with one or more R20's, 13) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 14) halo(C1-C6)alkyl, 15) —CONR6R6, 16) (C2-C6)-alkenyl, 17) (C2-C6)-alkynyl, 18) —COR6, 19) —S(O)pR6, 20) —SO2NHR6, 21) —COOR6, 22) —NHC(CN)NHR6;
• and 23) cycloalkyl, which may be optionally substituted with one or more R20'S;
• R6, at each occurrence, is independently:
• (a) alkyl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR9R10, 9) aryl, which may be optionally substituted with one or more R20's, 10) heteroaryl, which may be optionally substituted with one or more R20's, 11) heterocyclyl, which may be optionally substituted with one or more R20's, 12) halo(C1-C6) alkyl, 13) (C2-C6)-alkenyl, 14) —COOH, 15) —CONR36R36, 16) ═O, 17) (C2-C6)-alkynyl, 18) —COR36, 19) —S(O)pR36, 20) —SO2NHR36, 21) —COOR36, 22) —NHC(CN)NHR36;
• and 23) cycloalkyl, which may be optionally substituted with one or more R20's;
• (b) aryl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR9R10, 9) aryl, which may be optionally substituted with one or more R20's, 10) arylalkyl, which may be optionally substituted with one or more R20's, 11) heteroaryl, which may be optionally substituted with one or more R20's, 12) heteroarylalkyl, which may be optionally substituted with one or more R20's, 13) heterocyclyl, which may be optionally substituted with one or more R20's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 15) halo(C1-C6)alkyl, 16) —COOH, 17) —CONR36R36, 18) ═O, 19) (C2-C6)-alkynyl, 20) —COR36, 21) —S(O)pR36, 22) —SO2NHR36, 23) —COOR36, 24) —NHC(CN)NHR36;
• and 25) cycloalkyl, which may be optionally substituted with one or more R20's;
• (c) cycloalkyl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR9R10, 9) aryl, which may be optionally substituted with one or more R20's, 10) arylalkyl, which may be optionally substituted with one or more R20's, 11) heteroaryl, which may be optionally substituted with one or more R20's, 12) heteroarylalkyl, which may be optionally substituted with one or more R20's, 13) heterocyclyl, which may be optionally substituted with one or more R20's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 15) halo(C1-C6)alkyl, 16) (C2-C6)-alkenyl, 17) —COOH, 18) —CONR36R36, 19) ═O, 20) (C2-C6)-alkynyl, 21) —COR36, 22) —S(O)pR36, 23) —SO2NHR36, 24) —COOR36, 25) —NHC(CN)NHR36;
• and 26) cycloalkyl, which may be optionally substituted with one or more R20's;
• (d) heteroaryl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR9R10, 9) aryl, which may be optionally substituted with one or more R20's, 10) arylalkyl, which may be optionally substituted with one or more R20's, 11) heteroaryl, which may be optionally substituted with one or more R20's, 12) heteroarylalkyl, which may be optionally substituted with one or more R20's, 13) heterocyclyl, which may be optionally substituted with one or more R20's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 15) halo(C1-C6)alkyl, 16) (C2-C6)-alkenyl, 17) —COOH, 18) —CONR36R36, 19) ═O, 20) (C2-C6)-alkynyl, 21) —COR36, 22) —S(O)pR36, 23) —SO2NHR36, 24) —COOR36, 25) —NHC(CN)NHR36;
• and 26) cycloalkyl, which may be optionally substituted with one or more R20's;
• (e) heterocyclyl, other than heteroaryl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R20's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR9R10, 9) aryl, which may be optionally substituted with one or more R20's, 10) arylalkyl, which may be optionally substituted with one or more R20's, 11) heteroaryl, which may be optionally substituted with one or more R20's, 12) heteroarylalkyl, which may be optionally substituted with one or more R20's, 13) heterocyclyl, which may be optionally substituted with one or more R20's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R20's, 15) halo(C1-C6)alkyl, 16) (C2-C6)-alkenyl, 17) —COOH, 18) —CONR36R36, 19) ═O, 20) (C2-C6)-alkynyl, 21) —COR36, 22) —S(O)pR36, 23) —SO2NHR36, 24) —COOR36, 25) —NHC(CN)NHR36;
• and 26) cycloalkyl, which may be optionally substituted with one or more R20's;
• or
• (f) hydrogen;
• or two R6's are taken together to form a 3- to 9-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R20's;
• R9 and R10 are independently:
• (a) hydrogen;
• (b) —[(C═O)Or]saryl, wherein the aryl may be optionally substituted with one or more R20's;
• (c) —[(C═O)Or]s(C2-C8)-alkenyl, wherein the alkenyl may be optionally substituted with one or more R20's;
• (d) —[(C═O)Or]s(C1-C8)alkyl, wherein the alkyl may be optionally substituted with one or more R20's;
• (e) heterocyclyl optionally substituted with one or more R20's;
• (f) —CONR26R26;
• (g) —(C2-C6)-alkynyl;
• (h) —COR26;
• (i) —S(O)pR26;
• (j) —SO2NHR26;
• (k) —COOR26;
• (l) —NHC(CN)NHR26;
• or m) —[(C═O)Or]scycloalkyl, wherein the cycloalkyl may be optionally substituted with one or more R20's;
• or R9 and R10 are taken together with the nitrogen to which both are attached to form a 3- to 8-membered ring, which may optionally contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R20's;
• R20 is:
• (a) halo;
• (b) (C1-C6)-alkyl, which may be optionally substituted with one or more R21's;
• (c) —OR26;
• (d) (C1-C6)-alkylthio;
• (e) cyano;
• (f) nitro;
• (g) —NR29R30;
• (h) aryl, which may be optionally substituted with one or more R21's;
• (i) arylalkyl, which may be optionally substituted with one or more R21's;
• (j) heteroaryl, which may be optionally substituted with one or more R21's;
• (k) heteroarylalkyl, which may be optionally substituted with one or more R21's;
• (l) heterocyclyl, which may be optionally substituted with one or more R21's;
• (m) heterocyclylalkyl, which may be optionally substituted with one or more R21's;
• (n) halo(C1-C6)alkyl;
• (o) (C2-C6)-alkenyl;
• (p) ═O;
• (q) —(C2-C6)-alkynyl;
• (r) —COR26;
• (s) —S(O)pR26;
• (t) —SO2NHR26;
• (u) —COOR26;
• (v) —NHC(CN)NHR26;
• (w) cycloalkyl, which may be optionally substituted with one or more R21's;
• (x) cycloalkylalkyl, which may be optionally substituted with one or more R21's;
• or (y) —CONR26R26;
• R21 is:
• (a) halo;
• (b) (C1-C6)-alkyl;
• (c) —OR26;
• (d) (C1-C6)-alkylthio;
• (e) cyano;
• (f) nitro;
• (g) —NR29R30;
• (h) aryl;
• (i) arylalkyl;
• (j) heteroaryl;
• (k) heteroarylalkyl;
• (l) heterocyclyl;
• (m) heterocyclylalkyl;
• (n) halo(C1-C6)alkyl;
• (o) —CONR26R26;
• (p) (C2-C6)-alkenyl;
• (q) ═O;
• (r) (C2-C6)-alkynyl;
• (s) cycloalkyl;
• (t) cycloalkylalkyl;
• (u) —COR26;
• (v) —S(O)pR26;
• (w) —SO2NHR26;
• (x) —COOR26;
• or (y) —NHC(CN)NHR26;
• R26, at each occurrence, is independently:
• (a) alkyl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R40's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR29R30, 9) aryl, which may be optionally substituted with one or more R40's, 10) heteroaryl, which may be optionally substituted with one or more R40's, 11) heterocyclyl, which may be optionally substituted with one or more R40's, 12) halo(C1-C6) alkyl, 13) (C2-C6)-alkenyl, 14) —COOH, 15) —CONR36R36, 16) ═O, 17) (C2-C6)-alkynyl, 18) —COR36, 19) —S(O)pR36, 20) —SO2NHR36, 21) —COOR36, 22) —NHC(CN)NHR36;
• and 23) cycloalkyl, which may be optionally substituted with one or more R40's;
• (b) aryl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R40's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR29R30, 9) aryl, which may be optionally substituted with one or more R40's, 10) arylalkyl, which may be optionally substituted with one or more R40's, 11) heteroaryl, which may be optionally substituted with one or more R40's, 12) heteroarylalkyl, which may be optionally substituted with one or more R40's, 13) heterocyclyl, which may be optionally substituted with one or more R40's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R40's, 15) halo(C1-C6)alkyl, 16) —COOH, 17) —CONR36R36, 18) ═O, 19) (C2-C6)-alkynyl, 20) —COR36, 21) —S(O)pR36, 22) —SO2NHR36, 23) —COOR36, 24) —NHC(CN)NHR36;
• and 25) cycloalkyl, which may be optionally substituted with one or more R40's;
• (c) cycloalkyl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R40's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR29R30, 9) aryl, which may be optionally substituted with one or more R40's, 10) arylalkyl, which may be optionally substituted with one or more R40's, 11) heteroaryl, which may be optionally substituted with one or more R40's, 12) heteroarylalkyl, which may be optionally substituted with one or more R40's, 13) heterocyclyl, which may be optionally substituted with one or more R40's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R40's, 15) halo(C1-C6)alkyl, 16) (C2-C6)-alkenyl, 17) —COOH, 18) —CONR36R36, 19) ═O, 20) (C2-C6)-alkynyl, 21) —COR36, 22) —S(O)pR36, 23) —SO2NHR36, 24) —COOR36, 25) —NHC(CN)NHR36;
• and 26) cycloalkyl, which may be optionally substituted with one or more R40's;
• (d) heteroaryl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R40's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR29R30, 9) aryl, which may be optionally substituted with one or more R40's, 10) arylalkyl, which may be optionally substituted with one or more R40's, 11) heteroaryl, which may be optionally substituted with one or more R40's, 12) heteroarylalkyl, which may be optionally substituted with one or more R40's, 13) heterocyclyl, which may be optionally substituted with one or more R40's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R40's, 15) halo(C1-C6)alkyl, 16) (C2-C6)-alkenyl, 17) —COOH, 18) —CONR36R36, 19) ═O, 20) (C2-C6)-alkynyl, 21) —COR36, 22) —S(O)pR36, 23) —SO2NHR36, 24) —COOR36, 25) —NHC(CN)NHR36;
• and 26) cycloalkyl, which may be optionally substituted with one or more R40's;
• (e) heterocyclyl, other than heteroaryl, which may be optionally substituted with one or more substituents selected from the group consisting of:
• 1) halo, 2) —OH, 3) (C1-C6)-alkyl, which may be optionally substituted with one or more R40's, 4) —OR36, 5) (C1-C6)-alkylthio, 6) cyano, 7) nitro, 8) —NR29R30, 9) aryl, which may be optionally substituted with one or more R40's, 10) arylalkyl, which may be optionally substituted with one or more R40's, 11) heteroaryl, which may be optionally substituted with one or more R40's, 12) heteroarylalkyl, which may be optionally substituted with one or more R40's, 13) heterocyclyl, which may be optionally substituted with one or more R40's, 14) heterocyclylalkyl, which may be optionally substituted with one or more R40's, 15) halo(C1-C6)alkyl, 16) (C2-C6)-alkenyl, 17) —COOH, 18) —CONR36R36, 19) ═O, 20) (C2-C6)-alkynyl, 21) —COR36, 22) —S(O)pR36, 23) —SO2NHR36, 24) —COOR36, 25) —NHC(CN)NHR36;
• and 26) cycloalkyl, which may be optionally substituted with one or more R40's;
• or
• (f) hydrogen;
• or two R26's are taken together to form a 3- to 9-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R40's;
• R29 and R30 are independently hydrogen, —[(C═O)Or]saryl, —[(C═O)Or]salkenyl, —[(C═O)Or]salkyl, heterocyclyl, —CONR46R46, alkynyl, —COR36, —S(O)pR36, —SO2NHR36, —COOR36, —C(CN)NHR36, or cycloalkyl, wherein the aryl, alkyl, alkenyl, cycloalkyl or heterocyclyl may be optionally substituted with one or more R40's;
• or R29 and R30 are taken together with the nitrogen to which both are attached to form a 3- to 8-membered ring, which may optionally contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R40's;
• R36, at each occurrence, is independently alkyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, other than heteroaryl, wherein the alkyl, aryl, cycloalkyl, heteroaryl or heterocyclyl may be optionally substituted with one or more R40's;
• R40 is halo, —OH, alkyl, alkyloxy, alkylthio, cyano, nitro, —NR49R50, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, haloalkyl, haloalkyloxy, —CONR49R50, alkenyl, arylalkyloxy, ═O, alkynyl, cycloalkyl, cycloalkylalkyl, —COR49, —S(O)pR49, —SO2NHR49, —COOR49, or —NHC(CN)NHR49;
• R49 and R50, at each occurrence, are independently hydrogen, alkyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, other than heteroaryl;
• r is 0 to 5;
• s is 0 to 4;
• and
• p is 1 or 2;
• excluding compounds having the following formula: