Certain alkylene diamine-substituted heterocycles

A compound selected from Formula I-XV,

• 102 103 104
• or a pharmaceutically acceptable salt thereof, wherein
• X is N or CR14;
• W is S, O, or NR15;
• Y is N or CR3;
• E, F, and G are each, independently, CR3 or N;
• 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
• 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 may contain from 1 to 3 double bonds, from 0 to 2 heteroatoms, 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;
• Q is O or NR15;
• 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, C, —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;
• C—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;
• C—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 position 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, C—C6 alkyl-NR8R9, CONR8R9, C1-C6 alkyl-CONR8R9, COOR7, C1-C6 alkyl-COOR7, CN, C—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), 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-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-C10cycloalkyl) 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-NR1R9, 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-C10cycloalkyl, 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 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), 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;
• 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, C—C6 alkyl-OR13, C—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, COOR3, CN, SO2NR8R9, SO2R13, with the proviso that when R7 is SO2R3, 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 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-C]o 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;
• 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.