US 2013/0096136 A1Published application

Inhibitors of Protein Tyrosine Kinase Activity

AssigneeMethylGene Inc.

InventorsSeiji Hata, Yohei Yuki, Stephen William Claridge, Stéphane Raeppel, Arkadii Vaisburg

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Abstract

The present invention provides new compounds and methods for treating a disease responsive to inhibition of kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity of growth factor receptors, for example a disease responsive to inhibition of receptor type tyrosine kinase signaling, or for example, a disease responsive to inhibition of VEGF receptor signaling.

Claims14

Dependent claims

A compound comprising Formula (I):

including N-oxides, hydrates, solvates, tautomers, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein,
D is selected from the group consisting of an aromatic, heteroaromatic, cycloalkyl or heterocyclic ring system, C1-C6alkyl-heterocyclyl-C(O)—, C1-C6alkyl-heterocyclyl-C1-C6alkyl-N(R6)—C(O)—, (R6)(R6)N—C(O)—O-heterocyclyl-C(O)—, heterocyclyl-C(O)—, PivO-heterocyclyl-C(O)—, C1-C6alkyl-O—C(O)-heterocyclyl-C(O)—, C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C(O)—, (C1-C6alkyl)(Box)N-heterocyclyl-C(O)—, HO-heterocyclyl-C(O)—, HO—C(O)-heterocyclyl-C(O)—, C1-C6alkyl-C(O)—O-heterocyclyl-C(O)—, (R6)(R6)N—C1-C6alky-N(R6)—C(O)-heterocyclyl-C(O)—, C1-C6alkyl-heterocyclyl-C(O)-heterocyclyl-C(O)— and (R6)(R6)N-heterocyclyl-C(O)—, wherein each of the aromatic, heteroaromatic, cycloalkyl and heterocyclic groups is optionally substituted with 1 or more independently selected R38;
M is an optionally substituted fused heterocyclic moiety;
Z is selected from the group consisting of —O—, —S(O)0-2— and —NR5—, wherein R5 is selected from the group consisting of H, optionally substituted C1-C5alkyl, an optionally substituted (C1-C5)acyl and C1-C6 alkyl-O—C(O), wherein C1-C6 alkyl is optionally substituted;
Ar is a group of the formulas C-1 or C-2,
wherein A4, A5, A6 and A7 are independently selected from the group consisted of —CH— or N, and A8 is O, S(O)0-2, CH2, NH, NC1-4-alkyl or NC1-4-cycloalkyl;
G is a group B-L, wherein
B is selected from the group consisting of O, S(O)0-2, CH2, NH, NC1-4-alkyl or NC1-4-cycloalkyl;
L is independently selected from the group consisted of cycloalkyl, heterocyclyl, aryl or heteroaryl wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally substituted by 1-3 R20;
wherein
R38 is selected from the group consisting of C2-C6alkynyl-heterocyclyl, H(O)C— and C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)—, R37O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—(CH2)1-6—N(A)-(CH2)1-4—, C1-C6alkyl-S(O)2—(CH2)2—N(A)-CH2—, R37O—(CH2)j—[(CH2)iO]x—(CH2)i1—N(A)-(CH2)j1—, R37O—C(O)—C0-C6alkyl-heterocyclyl-CH2—, R37O—(CH2)j—[(CH2)iO]x—(CH2)i1—N(R39)—C(O)—, R37—O—C(O)—C1-C6alkyl-heterocyclyl-C(O)—, HOOC—C1-C6alkyl-N(A)-CH2—, (HOOC)(NR9R10)—C1-C6alkyl-N(A)-CH2—, R37O—C(O)—C1-C6alkyl-C(O)—, (R9)(R10)N—C1-C6alkyl-C(O)-heterocyclyl-CH2—, cycloalkyl-N(R39)—C(O)—O—C1-C6alkyl-, R37—O—C1-C6alkyl-O—C1-C6alkyl-C(O)—, (R9)(R10)N—C(O)—C1-C6alkyl-heterocyclyl-CH2—, (R9)(R10)N—C1-C6alkyl-C(O)—O—C1-C6alkyl-heterocyclyl-CH2—, NC—C1-C6alkyl-heterocyclyl-CH2—, F3C—C1-C6alkyl-heterocyclyl-CH2—, C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)-(5 to 10-membered heterocyclyl)-C1-C6alkyl-, (optionally substituted 8- to 10-membered fused heterocyclyl)-C1-C6alkyl-, F-heterocyclyl-C1-C6alkyl-, heteroaryl-C1-C6alkyl-heterocyclyl-C1-C6alkyl-, R37—C1-C6alkyl-O—C1-C6alkyl-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-O-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-heterocyclyl-C1-C6alkyl-, heterocyclyl-C1-C6alkyl-O-aryl-N(R6)—C1-C6alkyl-, (heteroaryl substituted with one or more C1-C6alkyl)-N(R6)—C1-C6alkyl-, (C1-C6alkyl)2N—C1-C6alkyl-aryl-N(R6)—C1-C6alkyl-, (C1-C6alkyl)2N—C1-C6alkyl-C(O)-aryl-N(R6)—C1-C6alkyl-, heterocyclyl-C1-C6alkyl-O-aryl-N(R6)—C1-C6alkyl-, (R6)2N-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkylC(O)—O—C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, heteroaryl-C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-S(O)2—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-O—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, (heterocyclyl optionally substituted with one or more C1-C6alkyl)-C1-C6alkyl-, (C1-C6alkyl)2N—C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C(O)—C1-C6alkyl-, heterocyclyl-C(O)—C1-C6alkyl-, C1-C6alkyl-O—C(O)—C1-C6alkyl-, C1-C6alkyl-O—C(O)—C1-C6alkyl-heteroaryl-N(R6)—C(O)—C1-C6alkyl-, (C1-C6alkyl)2N-heterocyclyl-C(O)—C1-C6alkyl-, heteroaryl-C1-C6alkyl-N(R6)—C(O)—C1-C6alkyl-, (Boc)(H)N-heterocyclyl-C(O)—C1-C6alkyl-, C1-C6alkyl-O—C(O)-heterocyclyl-C(O)—C1-C6alkyl-, Boc-heterocyclyl-C(O)—C1-C6alkyl-, Ac—O—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, (Boc)(H)N—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, NH2—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, (C1-C6alkyl)(H)N—C(O)-heterocyclyl-C(O)—C1-C6alkyl-, NH2-heterocyclyl-C(O)—C1-C6alkyl-, R37O—C1-C6alkyl-O—C1-C6alkyl-heterocyclyl-C(O)—, C1-C6alkyl-O—C(O)—N(R6)-heterocyclyl-C(O)—, (R6)(R6)N-heterocyclyl-C(O)—, (R6)(R6)N-heterocyclyl-C1-C6alkyl-, heterocyclyl-O—C1-C6alkyl-, C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C(O)—, (R6)(R6)N—C(O)-heterocyclyl-O—C1-C6alkyl-, C2-C6alkenyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-heterocyclyl-O—C1-C6alkyl-, R37a—C1-C6alkyl-N(R6)-heterocylcyl-C1-C6alkyl-, R37O—(CH2)j—[(CH2)1O]x—C1-C6alkyl-N(R6)-heterocyclyl-C1-C6alkyl-, halogen-C1-C6alkyl-heterocyclyl-C1-C6alkyl-, halogen-C1-C6alkyl-N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-N(R6)-heterocyclyl-C1-C6alkyl-, R37—O—C(O)—C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, (C1-C6alkyl)(H)N—C(O)-heterocyclyl-N[C1-C6alkyl-C(O)—OH]—C1-C6alkyl-, C1-C6alkyl-O—C(O)-heterocylcyl-C1-C6alkyl-, HO—C(O)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, (C1-C6alkyl)(C1-C6alkyl)N-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-[(C1-C6alkyl)(C1-C6alkyl)heterocyclyl]-C1-C6alkyl-, C2-C6alkenyl-C(O)-[(C1-C6alkyl)(C1-C6alkyl)heterocyclyl]-C1-C6alkyl-, R37—O—C1-C6alkyl-[(C1-C6alkyl)(C1-C6alkyl)heterocyclyl]-C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-NR(6)—C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-N[C(O)—NH—C1-C6alkyl]-C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-N[C(O)—C1-C6alkyl]-C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-[C(O)—C1-C6alkyl-OH]-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-heterocyclyl-C1-C6alkyl-, spiro-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-spiro-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C2-C6alkenyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C2-C8alkenyl-C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C1-C6alkyl-N(R6)—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C(O)—, (R6)(R6)N—C(O)-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, C2-C6alkenyl-C(O)—O—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C(O)-heterocyclyl-C(O)—, R37O—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-heterocyclyl-C1-C6alkyl-(heterocyclyl)-, R37O—C(O)—C1-C6alkyl-heterocyclyl-C(O)—, R37O—C1-C6alkyl-heterocyclyl-C(O)—, R37O—C1-C6alkyl-C(O)-heterocyclyl-C(O)—, C1-C6alkyl-O—C(O)—N(R6)—C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—(CH2)n[(CH2)iO]x—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, HO-heterocyclyl-C1-C6alkyl-, R37O-cycloalkyl-C(O)-heterocyclyl-C1-C6alkyl- and R37O—(CH2)n[(CH2)iO]x—C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl;
A is selected from the group consisting of —C(O)—C1-C6alkyl-N(R39)—C(O)—C1-C6alkyl-N(R9)(R10), —C(O)—N(R39)—C1-C6alkyl, —C(═NR37)—C1-C6alkyl, —C(O)—(CH2)n—S(O)2—C1-C6alkyl, —C(O)—N(R39)-cycloalkyl, —C(O)—N(R9)(R10), (R37O)(R37a0)P(O)O—C1-C6alkyl-C(O)—, —C(═NR37)—H and —C1-C6alkyl-CF3;
each R6 is independently H or C1-C6alkyl;
R37 is selected from the group consisting of H, C1-C6alkyl and C3-C10cycloalkyl;
R37a is selected from the group consisting of H, C1-C6alkyl and C3-C10cycloalkyl;
j is an integer ranging from 0 to 4, alternatively 0 to 2;
i is 2 or 3;
x is an integer ranging from 0 to 6, alternatively 2 or 3;
i1 is 2 or 3;
j1 is an integer ranging from 0 to 4, alternatively 1 or 2;
n is an integer ranging from 0 to 4;
R39 is selected from the group consisting of H, —OH, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)n2(C6-C10 aryl), —(CH2)n2(C5-C10 heteroaryl), —(CH2)n2(5-10 membered heterocyclyl), —(CH2)n2—O—(CH2)i2OR37 and —(CH2)n2OR37, wherein the alkyl, aryl, heteroaryl and heterocyclyl moieties of the foregoing R39 groups are optionally substituted;
R9 is selected from the group consisting of H, —OH, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)n3(C6-C10 aryl), —(CH2)n3(C5-C10 heteroaryl), —(CH2)n3(5-10 membered heterocyclyl), —(CH2)n3O(CH2)i3OR37 and —(CH2)n3OR37, wherein the alkyl, aryl, heteroaryl and heterocyclyl moieties of the foregoing R9 groups are optionally substituted;
R10 is selected from the group consisting of H, —OH, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)n4(C6-C10 aryl), —(CH2)n4(C5-C10 heteroaryl), —(CH2)n4(5-10 membered heterocyclyl), —(CH2)n4O(CH2)i4OR37 and —(CH2)n4OR37, wherein the alkyl, aryl, heteroaryl and heterocyclyl moieties of the foregoing R10 groups are optionally substituted;
R20 is selected from the group consisting of —H, halogen, trihalomethyl, —CN, —NO2, —NH2, —OR3, C3-6-cycloalkyl, C1-6-alkoxy, C3-6-cycloalkoxy, CF3, CCl3, —OCF3, —NR3R4, —S(O)0-2R3, —S(O)2NR3R3, —C(O)OR3, —C(O)NR3R3, —N(R3)SO2R3, —N(R3)C(O)R3, —N(R3)C(O)OR3, —C(O)R3, —C(O)SR3, C1-C4 alkoxy, C1-C4 alkylthio, —O(CH2)n6aryl, —O(CH2)n6heteroaryl, —(CH2)n6(aryl), —(CH2)n6(heteroaryl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CH2(CH2)0-4-T2, an optionally substituted C1-4 alkylcarbonyl, C1-4 alkoxy, an amino optionally substituted by C1-4 alkyl optionally substituted by C1-4 alkoxy, —(CH2)n6P(═O)(C1-C6alkyl)2, a saturated or unsaturated three- to seven-membered cycloalkyl or heterocyclic group, —SiMe3 and —SbF5;
n2 is an integer ranging from 0 to 6;
i2 is an integer ranging from 2 to 6;
n3 is an integer ranging from 0 to 6;
i3 is an integer ranging from 2 to 6;
n4 is an integer ranging from 0 to 6;
and
i4 is an integer ranging from 2 to 6
each R3 is independently selected from the group consisting of —H and R4;
R4 is selected from the group consisting of a (C1-C6)alkyl, an aryl, a lower arylalkyl, a heterocyclyl and a lower heterocyclyl-alkyl, each of which is optionally substituted, or
R3 and R4, taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, the optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional annular heteroatom selected from the group consisting of N, O, S and P;
T2 is selected from the group consisting of —OH, —OMe, —OEt, —NH2, —NHMe, —NMe2, —NHEt and —NEt2, and wherein the aryl, heteroaryl, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl are optionally substituted;
and
n6 is an integer ranging from 0 to 6.

35 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound comprising Formula (I):

including N-oxides, hydrates, solvates, tautomers, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein,
D is selected from the group consisting of an aromatic, heteroaromatic, cycloalkyl or heterocyclic ring system, C1-C6alkyl-heterocyclyl-C(O)—, C1-C6alkyl-heterocyclyl-C1-C6alkyl-N(R6)—C(O)—, (R6)(R6)N—C(O)—O-heterocyclyl-C(O)—, heterocyclyl-C(O)—, PivO-heterocyclyl-C(O)—, C1-C6alkyl-O—C(O)-heterocyclyl-C(O)—, C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C(O)—, (C1-C6alkyl)(Box)N-heterocyclyl-C(O)—, HO-heterocyclyl-C(O)—, HO—C(O)-heterocyclyl-C(O)—, C1-C6alkyl-C(O)—O-heterocyclyl-C(O)—, (R6)(R6)N—C1-C6alky-N(R6)—C(O)-heterocyclyl-C(O)—, C1-C6alkyl-heterocyclyl-C(O)-heterocyclyl-C(O)— and (R6)(R6)N-heterocyclyl-C(O)—, wherein each of the aromatic, heteroaromatic, cycloalkyl and heterocyclic groups is optionally substituted with 1 or more independently selected R38;
M is an optionally substituted fused heterocyclic moiety;
Z is selected from the group consisting of —O—, —S(O)0-2— and —NR5—, wherein R5 is selected from the group consisting of H, optionally substituted C1-C5alkyl, an optionally substituted (C1-C5)acyl and C1-C6 alkyl-O—C(O), wherein C1-C6 alkyl is optionally substituted;
Ar is a group of the formulas C-1 or C-2,
wherein A4, A5, A6 and A7 are independently selected from the group consisted of —CH— or N, and A8 is O, S(O)0-2, CH2, NH, NC1-4-alkyl or NC1-4-cycloalkyl;
G is a group B-L, wherein
B is selected from the group consisting of O, S(O)0-2, CH2, NH, NC1-4-alkyl or NC1-4-cycloalkyl;
L is independently selected from the group consisted of cycloalkyl, heterocyclyl, aryl or heteroaryl wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally substituted by 1-3 R20;
wherein
R38 is selected from the group consisting of C2-C6alkynyl-heterocyclyl, H(O)C— and C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)—, R37O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—(CH2)1-6—N(A)-(CH2)1-4—, C1-C6alkyl-S(O)2—(CH2)2—N(A)-CH2—, R37O—(CH2)j—[(CH2)iO]x—(CH2)i1—N(A)-(CH2)j1—, R37O—C(O)—C0-C6alkyl-heterocyclyl-CH2—, R37O—(CH2)j—[(CH2)iO]x—(CH2)i1—N(R39)—C(O)—, R37—O—C(O)—C1-C6alkyl-heterocyclyl-C(O)—, HOOC—C1-C6alkyl-N(A)-CH2—, (HOOC)(NR9R10)—C1-C6alkyl-N(A)-CH2—, R37O—C(O)—C1-C6alkyl-C(O)—, (R9)(R10)N—C1-C6alkyl-C(O)-heterocyclyl-CH2—, cycloalkyl-N(R39)—C(O)—O—C1-C6alkyl-, R37—O—C1-C6alkyl-O—C1-C6alkyl-C(O)—, (R9)(R10)N—C(O)—C1-C6alkyl-heterocyclyl-CH2—, (R9)(R10)N—C1-C6alkyl-C(O)—O—C1-C6alkyl-heterocyclyl-CH2—, NC—C1-C6alkyl-heterocyclyl-CH2—, F3C—C1-C6alkyl-heterocyclyl-CH2—, C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)-(5 to 10-membered heterocyclyl)-C1-C6alkyl-, (optionally substituted 8- to 10-membered fused heterocyclyl)-C1-C6alkyl-, F-heterocyclyl-C1-C6alkyl-, heteroaryl-C1-C6alkyl-heterocyclyl-C1-C6alkyl-, R37—C1-C6alkyl-O—C1-C6alkyl-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-O-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-heterocyclyl-C1-C6alkyl-, heterocyclyl-C1-C6alkyl-O-aryl-N(R6)—C1-C6alkyl-, (heteroaryl substituted with one or more C1-C6alkyl)-N(R6)—C1-C6alkyl-, (C1-C6alkyl)2N—C1-C6alkyl-aryl-N(R6)—C1-C6alkyl-, (C1-C6alkyl)2N—C1-C6alkyl-C(O)-aryl-N(R6)—C1-C6alkyl-, heterocyclyl-C1-C6alkyl-O-aryl-N(R6)—C1-C6alkyl-, (R6)2N-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkylC(O)—O—C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, heteroaryl-C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-S(O)2—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-O—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, (heterocyclyl optionally substituted with one or more C1-C6alkyl)-C1-C6alkyl-, (C1-C6alkyl)2N—C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C(O)—C1-C6alkyl-, heterocyclyl-C(O)—C1-C6alkyl-, C1-C6alkyl-O—C(O)—C1-C6alkyl-, C1-C6alkyl-O—C(O)—C1-C6alkyl-heteroaryl-N(R6)—C(O)—C1-C6alkyl-, (C1-C6alkyl)2N-heterocyclyl-C(O)—C1-C6alkyl-, heteroaryl-C1-C6alkyl-N(R6)—C(O)—C1-C6alkyl-, (Boc)(H)N-heterocyclyl-C(O)—C1-C6alkyl-, C1-C6alkyl-O—C(O)-heterocyclyl-C(O)—C1-C6alkyl-, Boc-heterocyclyl-C(O)—C1-C6alkyl-, Ac—O—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, (Boc)(H)N—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, NH2—C1-C6alkyl-C(O)-heterocyclyl-C(O)—C1-C6alkyl-, (C1-C6alkyl)(H)N—C(O)-heterocyclyl-C(O)—C1-C6alkyl-, NH2-heterocyclyl-C(O)—C1-C6alkyl-, R37O—C1-C6alkyl-O—C1-C6alkyl-heterocyclyl-C(O)—, C1-C6alkyl-O—C(O)—N(R6)-heterocyclyl-C(O)—, (R6)(R6)N-heterocyclyl-C(O)—, (R6)(R6)N-heterocyclyl-C1-C6alkyl-, heterocyclyl-O—C1-C6alkyl-, C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C(O)—, (R6)(R6)N—C(O)-heterocyclyl-O—C1-C6alkyl-, C2-C6alkenyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-heterocyclyl-O—C1-C6alkyl-, R37a—C1-C6alkyl-N(R6)-heterocylcyl-C1-C6alkyl-, R37O—(CH2)j—[(CH2)1O]x—C1-C6alkyl-N(R6)-heterocyclyl-C1-C6alkyl-, halogen-C1-C6alkyl-heterocyclyl-C1-C6alkyl-, halogen-C1-C6alkyl-N(R6)-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-N(R6)-heterocyclyl-C1-C6alkyl-, R37—O—C(O)—C1-C6alkyl-N(R6)—C(O)—N(R6)-heterocyclyl-C1-C6alkyl-, (C1-C6alkyl)(H)N—C(O)-heterocyclyl-N[C1-C6alkyl-C(O)—OH]—C1-C6alkyl-, C1-C6alkyl-O—C(O)-heterocylcyl-C1-C6alkyl-, HO—C(O)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, (C1-C6alkyl)(C1-C6alkyl)N-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-[(C1-C6alkyl)(C1-C6alkyl)heterocyclyl]-C1-C6alkyl-, C2-C6alkenyl-C(O)-[(C1-C6alkyl)(C1-C6alkyl)heterocyclyl]-C1-C6alkyl-, R37—O—C1-C6alkyl-[(C1-C6alkyl)(C1-C6alkyl)heterocyclyl]-C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-NR(6)—C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-N[C(O)—NH—C1-C6alkyl]-C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-N[C(O)—C1-C6alkyl]-C1-C6alkyl-, C1-C6alkyl-O—C1-C6alkyl-[C(O)—C1-C6alkyl-OH]-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-heterocyclyl-C1-C6alkyl-, spiro-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-spiro-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-heterocyclyl-C1-C6alkyl-, C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C2-C6alkenyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C2-C8alkenyl-C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C1-C6alkyl-N(R6)—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, heterocyclyl-C(O)—, (R6)(R6)N—C(O)-heterocyclyl-C1-C6alkyl-, R37O—C(O)—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, C2-C6alkenyl-C(O)—O—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, (R6)(R6)N—C(O)-heterocyclyl-C(O)—, R37O—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, R37O—C1-C6alkyl-heterocyclyl-C1-C6alkyl-(heterocyclyl)-, R37O—C(O)—C1-C6alkyl-heterocyclyl-C(O)—, R37O—C1-C6alkyl-heterocyclyl-C(O)—, R37O—C1-C6alkyl-C(O)-heterocyclyl-C(O)—, C1-C6alkyl-O—C(O)—N(R6)—C1-C6alkyl-C(O)—O—C1-C6alkyl-C(O)-heterocyclyl-C1-C6alkyl-, R37O—(CH2)n[(CH2)iO]x—C1-C6alkyl-N(R6)—C(O)-heterocyclyl-C1-C6alkyl-, HO-heterocyclyl-C1-C6alkyl-, R37O-cycloalkyl-C(O)-heterocyclyl-C1-C6alkyl- and R37O—(CH2)n[(CH2)iO]x—C1-C6alkyl-C(O)—N(R6)-heterocyclyl-C1-C6alkyl;
A is selected from the group consisting of —C(O)—C1-C6alkyl-N(R39)—C(O)—C1-C6alkyl-N(R9)(R10), —C(O)—N(R39)—C1-C6alkyl, —C(═NR37)—C1-C6alkyl, —C(O)—(CH2)n—S(O)2—C1-C6alkyl, —C(O)—N(R39)-cycloalkyl, —C(O)—N(R9)(R10), (R37O)(R37a0)P(O)O—C1-C6alkyl-C(O)—, —C(═NR37)—H and —C1-C6alkyl-CF3;
each R6 is independently H or C1-C6alkyl;
R37 is selected from the group consisting of H, C1-C6alkyl and C3-C10cycloalkyl;
R37a is selected from the group consisting of H, C1-C6alkyl and C3-C10cycloalkyl;
j is an integer ranging from 0 to 4, alternatively 0 to 2;
i is 2 or 3;
x is an integer ranging from 0 to 6, alternatively 2 or 3;
i1 is 2 or 3;
j1 is an integer ranging from 0 to 4, alternatively 1 or 2;
n is an integer ranging from 0 to 4;
R39 is selected from the group consisting of H, —OH, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)n2(C6-C10 aryl), —(CH2)n2(C5-C10 heteroaryl), —(CH2)n2(5-10 membered heterocyclyl), —(CH2)n2—O—(CH2)i2OR37 and —(CH2)n2OR37, wherein the alkyl, aryl, heteroaryl and heterocyclyl moieties of the foregoing R39 groups are optionally substituted;
R9 is selected from the group consisting of H, —OH, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)n3(C6-C10 aryl), —(CH2)n3(C5-C10 heteroaryl), —(CH2)n3(5-10 membered heterocyclyl), —(CH2)n3O(CH2)i3OR37 and —(CH2)n3OR37, wherein the alkyl, aryl, heteroaryl and heterocyclyl moieties of the foregoing R9 groups are optionally substituted;
R10 is selected from the group consisting of H, —OH, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)n4(C6-C10 aryl), —(CH2)n4(C5-C10 heteroaryl), —(CH2)n4(5-10 membered heterocyclyl), —(CH2)n4O(CH2)i4OR37 and —(CH2)n4OR37, wherein the alkyl, aryl, heteroaryl and heterocyclyl moieties of the foregoing R10 groups are optionally substituted;
R20 is selected from the group consisting of —H, halogen, trihalomethyl, —CN, —NO2, —NH2, —OR3, C3-6-cycloalkyl, C1-6-alkoxy, C3-6-cycloalkoxy, CF3, CCl3, —OCF3, —NR3R4, —S(O)0-2R3, —S(O)2NR3R3, —C(O)OR3, —C(O)NR3R3, —N(R3)SO2R3, —N(R3)C(O)R3, —N(R3)C(O)OR3, —C(O)R3, —C(O)SR3, C1-C4 alkoxy, C1-C4 alkylthio, —O(CH2)n6aryl, —O(CH2)n6heteroaryl, —(CH2)n6(aryl), —(CH2)n6(heteroaryl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CH2(CH2)0-4-T2, an optionally substituted C1-4 alkylcarbonyl, C1-4 alkoxy, an amino optionally substituted by C1-4 alkyl optionally substituted by C1-4 alkoxy, —(CH2)n6P(═O)(C1-C6alkyl)2, a saturated or unsaturated three- to seven-membered cycloalkyl or heterocyclic group, —SiMe3 and —SbF5;
n2 is an integer ranging from 0 to 6;
i2 is an integer ranging from 2 to 6;
n3 is an integer ranging from 0 to 6;
i3 is an integer ranging from 2 to 6;
n4 is an integer ranging from 0 to 6;
and
i4 is an integer ranging from 2 to 6
each R3 is independently selected from the group consisting of —H and R4;
R4 is selected from the group consisting of a (C1-C6)alkyl, an aryl, a lower arylalkyl, a heterocyclyl and a lower heterocyclyl-alkyl, each of which is optionally substituted, or
R3 and R4, taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, the optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional annular heteroatom selected from the group consisting of N, O, S and P;
T2 is selected from the group consisting of —OH, —OMe, —OEt, —NH2, —NHMe, —NMe2, —NHEt and —NEt2, and wherein the aryl, heteroaryl, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl are optionally substituted;
and
n6 is an integer ranging from 0 to 6.

35 more elements