Certain alkylene diamine-substituted heterocycles

A compound selected from Formulae II, IV, V, VII–IX and XI

• or a pharmaceutically acceptable salt thereof, wherein
• X is C (carbon);
• 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;
• R2 is H,
• C1–C6 alkyl which optionally forms a C3–C6 aminocarbocycle or a C2–C5 aminoheterocycle with A or B, each optionally substituted at each occurrence with R7, C3–C10 cycloalkyl, or
• (C3–C10 cycloalkyl) C1–C6 alkyl;
• or R2 and R6 jointly form with the 2 nitrogen atoms to which they are bound a C2–C5 aminoheterocycle optionally substituted at each position 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 position with R7 or,
• A and R2 jointly form a C3–C6 aminocarbocycle or a C2–C5 aminoheterocycle optionally substituted at each position 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 C3–C6 aminocarbocycle or a C2–C5 aminoheterocycle optionally substituted at each carbon occurrence 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, heterocycloalkyl, 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, isoquinolyl, 2-, 4-, or 5-thiazolyl, benzothiadiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-triazinyl, 2-pyrazinyl, 2-, or 3-furanyl, 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 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), wherein 2 adjacent alkyl substituents can optionally form together a C3–C10 cycloalkyl ring, a C3–C10 cycloalkenyl ring or a heterocycloalkyl ring;
• C3–C10 cycloalkyl, (C3–C10 cycloalkyl) C1–C6 alkyl, C3–C10 cycloalkenyl, C2–C6 alkenyl, C2–C6 alkynyl, each of which is optionally with 1 to 6 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, 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 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), wherein 2 adjacent alkyl substituents can optionally form together a C3–C10 cycloalkyl ring, C3–C10 cycloalkenyl ring or a heterocycloalkyl 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), wherein 2 adjacent alkyl substituents can optionally form together a C3–C10 cycloalkyl ring, a C3–C10 cycloalkenyl ring or a heterocycloalkyl 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)tetrahydrothiopyranyl, 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 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 2 nitrogen atoms to which they are bound, a C2–C5 aminoheterocycle optionally substituted at each position 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, COOR13, 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 C3–C6 aminocarbocycle or a C2–C5 aminoheterocycle each optionally substituted at each occurrence with 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;
• 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, C3–C6 aminocarbocycle, or C2–C5 aminoheterocycle;
• 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;
• 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.