A compound selected from the Formulae II, III, IV, VII, VIII, IX, X, XI, XII, XIII and XIV
- or a pharmaceutically acceptable salt thereof wherein
- X is N or CR14, provided that in Formulae II, III, IV, VII, IX, XI, XIII and XIV, X is nitrogen and that in Formulae X and XII, X is CR14.
- W is NR15
- I and J are each, independently,
- C═O, S, O CR3R16 or NR15 when single bonded to both adjacent ring atoms, or N or CR3 when double bonded to an adjacent ring atom;
- K is
- N or CR3 when double bonded to L or J, or
- O, S, C═O, CR3R16, or NR15 when single bonded to both adjacent ring atoms, or
- O, S, C═O, CR3R16, or NR15 when single bonded to both adjacent ring atoms, or N or CR3 when double bonded to an adjacent ring atom;
- L is
- N or CR16 when single bonded to all atoms to which it is attached, or
- C (carbon) when double bonded to K;
- the 6- or 7-membered ring that contains I, J, K and L contains from 1 to 3 double bonds, one or two nitrogen atom and from 0 to 2 C═O groups, wherein the carbon atom of such groups are part of the ring and the oxygen atom is a substituent on the ring;
- R1 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, halo, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7;
- C1-C6 cyanoalkyl, NR8R9, C1-C6 alkyl-NR8R9;
- R2is
- H,
- C1-C6 alkyl which optionally forms, with A or B, a C2-C6 ring comprising a nitrogen atom and 0 or 1 additional heteroatom selected from nitrogen, oxygen and sulfur, wherein each ring is optionally substituted at each carbon atom with R7,
- C3-C10 cycloalkyl, or
- (C3-C10 cycloalkyl) C1-C6 alkyl;
- or R2 and R6 jointly form with the two nitrogen atoms to which they are bound, a C4-C5 ring, wherein the ring is optionally substituted at each carbon atom with R7;
- A is (CH2)m where m is 1, 2 or 3 and is optionally mono- or di-substituted on each occurrence with C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, cyano, halo, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7;
- C1-C6 cyanoalkyl, NR8R9, C1-C6 alkyl-NR8R9, or
- A and B jointly form a C3-C6 carbocycle, optionally substituted at each carbon with R7 or,
- A and R2 jointly form a C2-C6 ring comprising a nitrogen atom and 0 or 1 additional heteroatom selected from nitrogen, oxygen and sulfur, wherein each ring is optionally substituted at each carbon atom with R7;
- B is (CH2)n where n is 1, 2 or 3 and is optionally mono- or di-substituted on each carbon atom with C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, halo, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7;
- C1-C6 cyanoalkyl, NR8R9, C1-C6 alkyl-NR8R9, or
- B and R2 jointly form a C2-C6 ring comprising a nitrogen atom and 0 or 1 additional heteroatom selected from nitrogen, oxygen and sulfur, wherein each ring is optionally substituted at each carbon atom with R7;
- R3 and R16 are independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl,(C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, halogen, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7, C1-C6 cyanoalkyl, NR8R9, C1-C6 alkyl-NR8R9;
- R4 is selected from aryl or heteroaryl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, trifluromethylsulfonyl, OR7, C1-C6 alkyl-OR7, NR8R9, C1-C6 alkyl-NR8R9, CONR8R9, C1-C6 alkyl-CONR8R9, COOR7, C1-C6 alkyl-COOR7, CN, C1-C6 alkyl-CN, SO2NR8R9, SO2R7, aryl, heteroaryl, heterocyclcalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl) with the proviso that at least one of the positions ortho or para to the point of attachment of the aryl or heteroaryl ring to the heterocyclic core is substituted;
- R5 is selected from:
- C1-C6 alkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, each of which is substituted with 1 to 5 groups independently selected at each occurrence from halo, C1-C2 haloalkyl, OR7, cyano, NR8R9, CONR8R9, COOR7, SO2NR8R9, SO2R7, NR11COR12, NR11SO2R7;
- C1-C6 arylalkyl, C1-C6 heteroarylalkyl, C5-C8 arylcycloalkyl, or C5-C8 heteroarylcycloalkyl, where aryl is phenyl or naphthyl, and heteroaryl is 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, triazinyl, 1-, 2- or 4-imidazolyl, 2-,4-, or 5-oxazolyl, isoxazolyl, indolyl, pyrazolyl, quinolyl, iosquinolyl, 2-, 4-, or 5-thiazolyl, benzothiadiazolyl, 1-, 3- or 4-pyrazolyl, 1-,3- or 4-triazolyl, 2-triazinyl, 2-pyrazinyl, 2-, or 3-fulranyl, 2-, or 3-thienyl, 2-, or 3-benzothienyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloakyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, trifluromethylsulfonyl, OR7, NR8R9, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9, COOR7, CN, SO2NR8R9, SO2R7aryl, heteroaryl, heterocycloalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl), with the proviso that 2 adjacent substituents can optionally form together a C3-C10 cycloalkyl ring, a C3-C10 cycloalkenyl ring or a heterocycloalkyl ring;
- C3-C10cycloalkyl, (C3-C10 cycloakyl) C1-C6 alkyl, C1-C6 alkenyl, C2-C6 alkenyl, C2-C6 alkynyl, each of which is optionally substituted with 1 to substituents independently selected at each occurrence from C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloakyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, OR7, NR8R9, with the proviso that when two OR7 or NR8R9 substituents are geminally located on the same carbon R7 is not H and they can form together a C2-C4 ketal, oxazoline,oxazolidine, imidazoline, or imidazolidine heterocycle, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9, COOR7, CN, oxo, hydroximino, C1-C6 alkoximino, SO2NR8R9, SO2R7, heterocycloalkyl, aryl, heteroaryl, where aryl or heteroaryl is optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloakyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, trifluromethylsulfonyl, OR7, NR8R9, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9, COOR7, CN, oxo, hydroximino, C1-C6 alkoximino, SO2NR8R9, SO2R7, aryl, heteroaryl, heterocycloalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl), with the proviso that 2 adjacent substituents can optionally form together a C3-C10 cycloalkyl ring, a C3-C10 cycloakenyl ring or a heterocyclalkyl ring;
- aryl or heteroaryl, optionally substituted with 1 to 5 substituents independently selected at each occurrence from halogen C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, trifluromethylsulfonyl, OR7, NR8R9, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9, COOR7, CN, SO2NR8R9, SO2R7, aryl, heteroaryl, heterocycloalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl), with the proviso that 2 adjacent substituents can optionally form together a C3-C10 cycloalkyl ring, a C3-C10 cycloakenyl ring or a heterocyclalkyl ring;
- or
- 3- or 4-piperidinyl, 3-pyrrolidinyl, 3- or 4-tetrahydropyranyl, 3-tetrahydrofuranyl, 3- or 4-tetrahydropyranyl, 3-tetrahydrofuranyl, 3- or 4-tetrahydrothiopyranyl, 3- or 4-(1,1-dioxo) tetrahydrothipyranyl, 1-azabicyclo[4.4.0]decyl, 8-azabicyclo[3.2.1]octanyl, norbornyl, quinuclidinyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from R7, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9,COOR7;
- R6 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C4 alkenyl, C1-C6 arylalkyl, C1-C6 heteroarylalkyl where aryl or heteroaryl are optionally substituted with 1 to 5 substituents independently selected at each occurrence from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, OR13, NR8R9, C1-C6 alkyl-OR13, C1-C6 alkyl-NR8R9,CONR8R9,COOR7, CN, SO2NR8R9, SO2R7,
- or R6 and R2, as mentioned above, jointly form, with the two nitrogen atoms to which they are bound, a C4-C5 ring, wherein the ring is optionally substituted at each carbon with R7;
- R7 is H, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C3 haloalkyl, or heterocycloalkyl, C1-C8 alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C1-C8 alkanoyl, aroyl, heteroaroyl, aryl, heteroaryl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl each optionally substituted with 1 to 5 substituents independently selected at each occurrence from halogen, C1-C6 haloalkyl, OR13, NR8R9, C1-C6 alkyl-OR13, C1-C6 alkyl-NR8R9,CONR8R9,COOR7, CN, SO2NR8R9, SO2R13, with the proviso that when R7 is SO2R13, R13 cannot be H;
- R8 and R9 are independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C3-C10 cycloalkenyl, C2-C6 alkynyl, heterocycloalkyl, C1-C8 alkanoyl, aroyl, heteroaroyl, aryl, heteroaryl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl, or R8 and R9, taken together, can form a C2-C6 ring comprising a nitrogen atom and 0 or 1 additional heteroatom selected from nitrogen, oxygen and sulfur, wherein each ring is optionally substituted at each carbon atom with C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C3 haloalkyl, heterocycloalkyl, C1-C8 alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C1-C8 alkanoyl, aroyl, heteroaroyl, aryl, heteroaryl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl
- R11 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl;
- R12 is selected from H, aryl, heteroaryl, C1-C6 alkyl, (C3-C10 cycloalkyl, C3-C10 cycloalkyl) C1-C6 alkyl, optionally substituted with OR7, NR8R9 or a C2-C6 ring comprising a nitrogen atom and 0 or 1 additional heteroatom selected from nitrogen, oxygen and sulfur;
- R13 is independently selected at each occurrence from H, C1-C6 alkyl, (C3-C10 cycloalkyl, C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, with the proviso that for SO2NR8R9, SO2R13, R13 cannot be H;
- R14 is H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halo, or CN;
- and
- R15 is selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 alkyl-OR7, C2-C6 cyanoalkyl, C2-C6 alkyl-NR8R9.