Tetrahydroisoquinolines as factor Xa inhibitors

A compound having the formula:

• wherein:
• Y is O or S;
• B is a 5-7 membered aryl or heteroaryl comprising 1 to 3 heteroatoms selected from the group consisting of N, O, and S, each aryl or heteroaryl optionally substituted with 1 to 3 R4d substiuents;
• R1 is a member selected from the group consisting of:
• hydrogen, —C1-6alkyl, —C0-6alkyl-aryl, heteroaryl and —C2-6alkenyl;
• R2 is a member selected from the group consisting of:
• —C0-6alkyl-aryl, —C3-8cycloalkylaryl, heteroaryl, —C3-8cycloalkylheteroaryl, —C3-8cycloalkyl, —C3-8cycloalkenyl, heteromonocyclyl, fused heterobicyclyl and unfused heterobicyclyl, optionally substituted with from 1 to 3 R2a substituents, wherein each heterocyclyl comprises 5 to 12 ring atoms, 1 to 4 of which are members independently selected from the group consisting of N, O and S;
• A-Q-D-(CR7R8)n2—NR6n1 is selected from the group consisting of:
• wherein W is O, S or NH;
• each dashed line independently indicates a single or double bond;
• and the wavy line indicates the point of attachment to the rest of the molecule;
• each R2a, R3d, R4d and R11g member independently selected from the group consisting of:
• H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, —O—C0-2alkyl-CF3, —C0-2alkyl-CF3, —C0-2alkyl-CN, —C0-2alkyl-NO2, —C0-2alkyl-NR12aR12b, —C0-2alkyl-SO2NR12aR12b, —C0-2alkyl-SO2R12a, —C0-2alkyl-SOR12a, —C0-2alkyl-CF3, —C0-2alkyl-OR12a, —C0-2alkyl-SR12a, —O—CH2—CH2-OR12a, —O—CH2—CO2R12a, —N(R12a)—CH2—CH2—OR12b, —C0-2alkyl-C(O)NR12aR12b, —C0-2alkyl-CO2R12a, —(CH2)mN(R12a)—C(O)R12b, —C0-2alkyl-N(R12c)—C(O)NR12aR12b, —C0-2alkyl-C(═NR12c)NR12aR12b, —C0-2alkyl-C(═NR12a)R12b, —C0-2alkyl-N(R12d)C(═NR12c)NR12aR12b, —C0-2alkyl-N(R12a)—SO2—R12b, ═O, ═S, ═NR12a, 5- or 6-membered aryl, 5- or 6-membered heteroaryl and 5- to 7-membered heterocyclyl, each of which is optionally substituted with a member independently selected from the group consisting of halo, CF3, OCF3, SCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —C0-2H, —CO2C1-4alkyl, —CONR12aR12b, ═O, ═S, —OH, —CN and —NO2,;
• wherein each heteroaryl or heterocyclyl comprises 1 to 4 heteroatoms, independently selected from the group consisting of N, O and S,
• each R11a, R11b, R12a, R12b, R12c and R12d are members independently selected from the group consisting of:
• H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C0-4alkylaryl, C0-4alkyl-heteroaryl, —C0-6alkyl-COC1-4alkyl, —C0-6alkyl-SO2-C1-4alkyl, —C0-6alkyl-SO2—N(C1-4alkyl, C1-4alkyl), —C0-6alkyl-N(C1-4alkyl, C1-4alkyl) and —C1-6alkyl-O—C0-6alkyl, wherein 1-3 hydrogen atoms on the aryl or heteroaryl ring may be independently replaced with a member selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CON(C1-4alkyl, C1-4alkyl), —OH, —CN and NO2;
• or can be taken together with the nitrogen atom to which they are attached to form a 3-8 membered heterocyclyl group, comprising 1 to 4 heteroatoms selected from the group consisting of N, O and S, optionally substituted with 1 to 4 R13 substituents selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, ═S, —OH, —CN and NO2;
• the subscript n2 is an integer of 0 to 1;
• each subscript n3 and n4 is an integer of 0 to 2;
• the subscript m is an integer of 0 to 3;
• and
• pharmaceutically acceptable salts thereof.

A compound having the formula:

• wherein:
• Y is O or S;
• B is a 5-7 membered aryl or heteroaryl comprising 1 to 3 heteroatoms selected from the group consisting of N, O, and S, each aryl or heteroaryl optionally substituted with 1 to 3 R4d substiuents;
• R1 is a member selected from the group consisting of:
• hydrogen, —C1-6alkyl, —C0-6alkyl-aryl, heteroaryl and —C2-6alkenyl;
• R2 is a member selected from the group consisting of:
• —C0-6alkyl-aryl, —C3-8cycloalkylaryl, heteroaryl, —C3-8cycloalkylheteroaryl, —C3-8cycloalkyl, —C3-8cycloalkenyl, heteromonocyclyl, fused heterobicyclyl and unfused heterobicyclyl, optionally substituted with from 1 to 3 R2a substituents, wherein each heterocyclyl comprises 5 to 12 ring atoms, 1 to 4 of which are members independently selected from the group consisting of N, O and S;
• A-Q-D-(CR7R8)n2—NR6n1 is selected from the group consisting of:
• wherein W is O, S or NH;
• each dashed line independently indicates a sinizle or double bond;
• and the wavy line indicates the point of attachment to the rest of the molecule;
• each R2a, R3d, R4d and R11g member independently selected from the group consisting of:
• H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, —O—C0-2alkyl-CF3, —C0-2alkyl-CF3, —C0-2alkyl-CN, —C0-2alkyl-NR12aR12b, —C0-2alkly-SO2NR12aR12b, —C0-2alkyl-SO2R12a, —C0-2alkyl-SOR12a, —C0-2alkyl-CF3, —C0-2alkyl-OR12a, —C0-2alkyl-SR12a, —O—CH2—CH2-OR12a, —O—CH2—CO2R12a, —N(R12a)—CH2—CH2—OR12b, —C0-2alkyl-C(O)NR12aR12b, —C0-2alkyl-CO2R12a, —(CH2)mN(R12a)—C(O)R12b, —C0-2alkyl-N(R12c)—C(O)NR12aR12b, —C0-2alkyl-C(═NR12c)NR12aR12b, —C0-2alkyl-C(═NR12a)R12b, —C0-2alkyl-N(R12d)C(═NR12c)NR12aR12b, —C0-2alkyl-N(R12a)—SO2—R12b, ═O, ═S, ═NR12a, 5- or 6-membered aryl, 5- or 6-membered heteroaryl and 5- to 7-membered heterocyclyl, each of which is optionally substituted with a member independently selected from the group consisting of halo, CF3, OCF3, SCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —C0-2H, —CO2C1-4alkyl, —CONR12aR12b, ═O, ═S, —OH, —CN and —NO2,;
• wherein each heteroaryl or heterocyclyl comprises 1 to 4 heteroatoms, independently selected from the group consisting of N, O and S,
• each R11a, R11b, R12a, R12b, R12c and R12d are members independently selected from the group consisting of:
• H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C0-4alkylaryl, C0-4alkyl-heteroaryl, —C0-6alkyl-COC1-4alkyl, —C0-6alkyl-SO—C1-4alkyl, —C0-6alkyl-SO2—N(C1-4alkyl, C1-4alkyl), —C0-6alkyl-N(C1-4alkvl, C1-4alkyl) and —C1-6alkyl-O—C0-6alkyl, wherein 1-3 hydrogen atoms on the aryl or heteroaryl ring may be independently replaced with a member selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CON(C1-4alkyl, C1-alkyl), —OH, —CN and NO2,;
• or can be taken together with the nitrogen atom to which they are attached to form a 3-8 membered heterocyclyl group, comprising 1 to 4 heteroatoms selected from the group consisting of N, O and 5, optionally substituted with 1 to 4 R13 substituents selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CON(C1-4alkyl, C1-4alkyl), ═O, ═S, —OH, —CN and NO2;
• R6 is selected from the group consisting of:
• hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C0-4alkylC3-8cycloalkyl, —C0-6alkyl-aryl and —C0-6alkyl-heteraryl;
• the subscript ni is an integer of 0 to 1;
• each subscript n3 and n4 is an integer of 0 to 2;
• the subscript m is an integer of 0 to 3;
• and
• pharmaceutically acceptable salts thereof.

A compound having the formula:

• wherein:
• Y is O or S;
• B is a 5-7 membered aryl or heteroaryl comprising 1 to 3 heteroatoms selected from the group consisting of N, O, and S, each aryl or heteroaryl optionally substituted with 1 to 3 R4dsubstiuents;
• R1 is a member selected from the group consisting of:
• hydrogen, —C1-6alkyl, —C0-6alkyl-aryl, heteroaryl and —C2-6alkenyl;
• R2 is a member selected from the group consisting of:
• —C0-6alkyl-aryl, —C3-8cycloalkylaryl, heteroaryl, —C3-8cycloalkylheteroaryl, —C3-8cycloalkyl, —C3-8cycloalkenyl, heteromonocyclyl, fused heterobicyclyl and unfused heterobicyclyl, optionally substituted with from 1 to 3 R2a substituents, wherein each heterocyclyl comprises 5 to 12 ring atoms, 1 to 4 of which are members independently selected from the group consisting of N, O and S;
• A-Q-D-(CR7R8)n2—NR6n1 is selected from the group consisting of:
• wherein W is O, S or NH;
• each dashed line independently indicates a single or double bond;
• and the wavy line indicates the point of attachment to the rest of the molecule;
• each R2a, R3d and R4d is a member independently selected from the group consisting of:
• H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, —O—C0-2alkyl-CF3, —C0-2alkyl-CF3, —C0-2alkyl-CN, —C0-2alkyl-NO2, —C0-2alkyl-NR12aR12b, —C0-2alkyl-SO2NR12aR12b, —C0-2alkyl-SO2R12a, —C0-2alkyl-SOR12a, —C0-2alkyl-CF3, —C0-2alkyl-SR12a,—O—CH2—CH2—OR12a, —O—CH2—CO2R12a, —N(R12a)—CH2—CH2—OR12b, —C0-2alkyl-C(O)NR12aR12b, —C0-2alkyl-CO2R12a, —(CH2)mN(R12a)—C(O)R12b, —C0-2alkyl-N(R12c)—C(O)NR12aR12b, —C0-2alkyl-C(═NR12c)NR12aR12b, —C0-2alkyl-C(═NR12a)R12b, —C0-2alkyl-N(R12d)C(═NR12c)NR12aR12b, —C0-2alkyl-N(R12a)—SO2—R12b, ═O, ═S, ═NR12a, 5- or 6-membered aryl, 5- or 6-membered heteroaryl and 5- to 7-membered heterocyclyl, each of which is optionally substituted with a member independently selected from the group consisting of halo, CF3, OCF3, SCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, CONR12aR12b, ═O, ═S, —OH, —CN and —NO2;
• wherein each heteroaryl or heterocyclyl comprises 1 to 4 heteroatoms, independently selected from the group consisting of N, O and S,
• each R11g is independently selected from the group consisting of C1-6alkyl, —C0-2alkyl-NR12aR12b and ═O;
• each R11a, R11b, R12a, R12b, R12c, and R12d are members independently selected from the group consisting of:
• H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C0-4alkylaryl, C0-4alkyl-heteroaryl, —C0-6alkyl-COC1-4alkyl, —C0-6alkyl-SO2—C1-4alkyl, —C0-6alkyl-SO2—N(C1-4alkyl, C1-4alkyl), —C0-6alkyl-N(C1-4alkyl, C1-4alkyl) and —C1-6alkyl-O—C0-6alkyl, wherein 1-3 hydrogen atoms on the aryl or heteroaryl ring may be independently replaced with a member selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CON(C1-4alkyl, C1-4alkyl), —OH, —CN and NO2;
• or can be taken together with the nitrogen atom to which they are attached to form a 3-8 membered heterocyclyl group, comprising 1 to 4 heteroatoms selected from the group consisting of N, O and S, optionally substituted with 1 to 4 R13 substituents selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CON(C1-4alkyl, C1-4alkyl), ═O, ═S, —OH, —CN and NO2;
• R6 is selected from the group consisting of:
• hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C0-4alkylC3-8cycloalkyl, —C0-6alkyl-aryl and —C0-6alkyl-heteraryl;
• each subscript n1 and n2 is an integer of 0 to 1;
• each subscript n3 and n4 is an integer of 0 to 2;
• the subscript m is an integer of 0 to 3;
• and
• pharmaceutically acceptable salts thereof.

A compound of having the formula:

• wherein:
• Y is O or S;
• B is a 5-7 membered aryl or heteroaryl comprising 1 to 3 heteroatoms selected from the group consisting of N, O, and S, each aryl or heteroaryl optionally substituted with 1 to 3 R4dsubstiuents;
• R1 is a member selected from the group consisting of:
• hydrogen, —C1-6alkyl, —C0-6alkyl-aryl, heteroaryl and —C2-6alkenyl;
• R2 is a member selected from the group consisting of:
• —C0-6alkyl-aryl, —C3-8cycloalkylaryl, heteroaryl, —C3-8cycloalkylheteroaryl, —C3-8cycloalkyl, —C3-8cycloalkenyl, heteromonocyclyl, fused heterobicyclyl and unfused heterobicyclyl, optionally substituted with from 1 to 3 R2a substituents, wherein each heterocyclyl comprises 5 to 12 ring atoms, 1 to 4 of which are members independently selected from the group consisting of N, O and S;
• A-Q-D-(CR7R8)n2—NR6n1 is selected from the group consisting of:
• wherein W is O, S or NH;
• and
• the wavy line indicates the point of attachment to the rest of the molecule;
• and each dashed line independently indicates a single or double bond;
• each R2a, R3d, R4d and R11g member independently selected from the group consisting of:
• H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, —O—C0-2alkyl-CF3, —C0-2alkyl-CF3, —C0-2alkyl-CN, —C0-2alkyl-NO2, —C0-2alkyl-NR12aR12b, —C0-2alkly-SO2NR12aR12b, —C0-2alkyl-SO2R12a, —C0-2alkyl-SOR12a, —C0-2alkyl-CF3, —C0-2alkyl-OR12a, —C0-2alkyl-SR12a, —O—CH2—CH2-OR12a, —O—CH2—CO2R12a, —N(R12a)—CH2—CH2—OR12b, —C0-2alkyl-C(O)NR12aR12b, —C0-2alkyl-CO2R12a, —(CH2)mN(R12a)—C(O)R12b, —C0-2alkyl-N(R12c)—C(O)NR12aR12b, —C0-2alkyl-C(═NR12c)NR12aR12b, —C0-2alkyl-C(═NR12a)R12b, —C0-2alkyl-N(R12d)C(═NR12c)NR12aR12b, —C0-2alkyl-N(R12a)—SO2—R12b, ═O, ═S, ═NR12a, 5- or 6-membered aryl, 5- or 6-membered heteroaryl and 5- to 7-membered heterocyclyl, each of which is optionally substituted with a member independently selected from the group consisting of halo, CF3, OCF3, SCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CONR12aR12b, ═O, ═S, —OH, —CN and —NO2;
• wherein each heteroaryl or heterocyclyl comprises 1 to 4 heteroatoms, independently selected from the group consisting of N, O and S,
• each R11a, R11b, R12a, R12b, R12c and R12d are members independently selected from the group consisting of:
• H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C0-4alkylaryl, C0-4alkyl-heteroaryl, —C0-6alkyl-COC1-4alkyl, —C0-6alkyl-SO2-C1-4alkyl, —C0-6alkyl-SO2—N(C1-4alkyl, C1-4alkyl), —C0-6alkyl-N(C1-4alkyl, C1-4alkyl) and —C1-6alkyl-O—C0-6alkyl, wherein 1-3 hydrogen atoms on the aryl or heteroaryl ring may be independently replaced with a member selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CON(C1-4alkyl, C1-4alkyl), —OH, —CN and NO2;
• or can be taken together with the nitrogen atom to which they are attached to form a 3-8 membered heterocyclyl group, comprising 1 to 4 heteroatoms selected from the group consisting of N, O and S, optionally substituted with 1 to 4 R13 substituents selected from the group consisting of halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-4alkylC3-8cycloalkyl, C1-4alkoxy, —CO2H, —CO2C1-4alkyl, —CON(C1-4alkyl, C1-4alkyl), ═O, ═S, —OH, —CN and NO2;
• R6 is selected from the group consisting of:
• hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C0-4alkylC3-8cycloalkyl, —C0-6alkyl-aryl and —C0-6alkyl-heteraryl;
• each subscript n1 and n2 is an integer of 0 to 1;
• each subscript n3 and n4 is an integer of 0 to 2;
• the subscript m is an integer of 0 to 3;
• and
• pharmaceutically acceptable salts thereof.

A compound selected from the group consisting of:

• N-[4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(1N-oxo-pyridin-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3S)-N-[4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(pyrrolidinylimino)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(dimethylaminoimino)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[3-(dimethylaminoimino)benzyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, and N-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)benzyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(pyrrolidinylcarbonyl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[1-(pyridin-4-yl)piperidin-4-yl]methyl-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4(4methyl-homopiperazinyl)]phenyl-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• 4-(1-methylpiperidin-4-yl)piperazinyl 2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-(1isopropylpiperidin 4-yl) 2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(2-dimethylaminomethyl-imidazol-1-yl)-2-fluorophenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(3-oxo-morpholin-4-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(3thiazolidinylcarbonyl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(3-oxazolidinylcarbonyl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(N-methyl-N-pyridin-4-yl-amino)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-5-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(pyrrolidinylimino)phenyl]-2N-(4-chlorophenylaminocarbonyl)-5-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(dimethylaminoimino)phenyl]-2N-(4-chlorophenylaminocarbonyl)-5-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3S)-N-[4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3S)-N-[4-(pyrrolidinylimino)phenyl]-2N-(4-chlorophenylaminocarbonyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3S)-N-[4-(dimethylaminoimino)phenyl]-2N-(4-chlorophenylaminocarbonyl)-6,7-diemthoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-5N-(4-chlorophenylaminocarbonyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridine-6-carboxamide;
• N-[4-(dimethylaminoimino)phenyl]-5N-(4-chlorophenylaminocarbonyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridine-6-carboxamide;
• N-[4-(4-methyl-homopiperazinyl)]phenyl-5N-(4-chlorophenylaminocarbony)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine-6-carboxamide;
• N-[4-(4-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;
• N-[4-(1 N-oxo-pyridin-2-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;
• N-[4-(4-methyl-homopiperazinyl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;
• N-[4-(3-oxo-morpholin-4yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-2,3-dihydro-1H-isoindole-1-carboxamide;
• N-[4-(1N-oxo-pyridin-2-yl)phenyl]-1N-(4-chlorophenylaminocarbonyl)-indoline-2-carboxamide;
• (3S) N-[4-(4-methyl-homopiperazinyl)]phenyl-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) N-[4-(4-methyl-homopiperazinyl)-2-fluorophenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) N-[4-(2-pyridon-1-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3S) N-[4-(2-pyridon-1-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) N-[4-(2-pyridon-1-yl)-2-fluorophenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(2-pyridon-1-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(4-methyl-homopiperazinyl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• N-[4-(2-thiopyridon-1-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R)4-(2-piperidinon-1-yl)piperidin-1-yl 2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) 4-(2-pyridon-1-yl)piperidin-1-yl 2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) 4-(3-morpholinon-4-yl)piperidin-1-yl 2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) N-[4-(4-methyl-2-piperazinon-1-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) N-[4-(4-methyl-2-homopiperazinon-1-yl)phenyl]-2N-(4-chlorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) N-[4-(2-pyridon-1-yl)phenyl]-2N-(4-fluorophenylaminocarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• (3R) N-[4-(2-pyridon-1-yl)phenyl]-2N-[5-(2-chlorothiophene)aminocarbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
• and (3R) N-[4-(4-methyl-homopiperazin-1-yl)phenyl]-2N-[5-(2-chlorothiophene)aminocarbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide.