CPC C07D 401/04 (2013.01) [A61K 31/437 (2013.01); A61K 31/454 (2013.01); A61K 31/501 (2013.01); A61K 31/506 (2013.01); A61K 31/5355 (2013.01); A61K 31/5383 (2013.01); A61K 45/06 (2013.01); C07D 401/14 (2013.01); C07D 519/00 (2013.01)] | 20 Claims |
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
X5 is N or C-R5;
X7 is N or C-R7;
R1 is hydrogen, halo, —CN, —OR12, —N(R12)2, —SR12, —C1-8 alkyl optionally substituted with 1 to 3 Z1,
C3-6 cycloalkyl optionally substituted with 1 to 3 Z1, or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z1;
R2 is hydrogen, halo, —CN, —OR12, —N(R12)2, —SR12, —C1-8 alkyl optionally substituted with 1 to 3 Z1,
C3-6 cycloalkyl optionally substituted with 1 to 3 Z1, or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z1;
R3 is hydrogen, C1-8 alkyl optionally substituted with 1 to 3 Z1, C3-10 alkenyl optionally substituted with 1 to 3 Z1, C3-10 alkynyl optionally substituted with 1 to 3 Z1, C3-10 cycloalkyl optionally substituted with 1 to 3 Z1, or 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z1; or
R2 and R3 are taken together with the atoms to which they are attached to form an optionally substituted 6 to 8 membered heterocyclyl ring;
R4 is hydrogen, C1-8 alkyl optionally substituted with 1 to 3 Z1, C3-10 alkenyl optionally substituted with 1 to 3 Z1, C3-10 alkynyl optionally substituted with 1 to 3 Z1, C3-10 cycloalkyl optionally substituted with 1 to 3 Z′, or 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z1;
R5 is hydrogen, halo, —CN, or —OR12;
R6 is
where q is 0, 1 or 2, and
n is 0, 1, 2, 3, 4, 5, or 6;
R7 is hydrogen, halo, —CN, or —OR12;
R9 is C1-8 alkyl optionally substituted with 1 to 3 Z1, C2-8 alkenyl optionally substituted with 1 to 3 Z1, C2-8 alkynyl optionally substituted with 1 to 3 Z1, C3-10 cycloalkyl optionally substituted with 1 to 3 Z1, 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z1, C6-10 aryl optionally substituted with 1 to 3 Z1, or 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1;
R10 is hydrogen, C1-8 alkyl optionally substituted with 1 to 3 Z10, or C3-6 cycloalkyl optionally substituted with 1 to 3 Z10;
R11 is hydrogen, C1-8 alkyl optionally substituted with 1 to 4 Z10, C3-8 cycloalkyl optionally substituted with 1 to 4 Z10, or 4-12-membered heterocyclyl optionally substituted with 1 to 4 Z10; or
R10 and R11 are taken together with the nitrogen to which they are attached to form a 4-12-membered heterocyclyl optionally substituted with 1 to 4 Z10;
each R12 is independently hydrogen, C1-8 alkyl optionally substituted with 1 to 3 Z1b, C3-8 alkenyl optionally substituted with 1 to 3 Z1b, C3-8 alkynyl optionally substituted with 1 to 3 Z1b, C3-10 cycloalkyl optionally substituted with 1 to 3 Z1b, 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z1b, C6-10 aryl optionally substituted with 1 to 3 Z1b, or 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1b;
R13 is C1-8 alkyl optionally substituted with 1 to 3 Z1b, C3-8 alkenyl optionally substituted with 1 to 3 Z1b, C3-8 alkynyl optionally substituted with 1 to 3 Z1b, C3-10 cycloalkyl optionally substituted with 1 to 3 Z1b, 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z1b, C6-10 aryl optionally substituted with 1 to 3 Z1b, or 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1b;
R15 is C6-10 aryl optionally substituted with 1 to 3 Z1 or 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1;
each R17 is independently hydrogen, halo, —NO2, —N3, —CN, C1-8 alkyl optionally substituted by 1 to 3 Z1a, C2-8 alkenyl optionally substituted by 1 to 3 Z1a, C2-8 alkynyl optionally substituted by 1 to 3 Z1a, C3-8 cycloalkyl optionally substituted by 1 to 3 Z1a, 6-10 membered aryl optionally substituted by 1 to 3 Z1a, 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z1a, 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1a, —OR20, —C(O)R20, —C(O)OR20, —C(O)N(R20)2, —N(R20)2, —N(R20)3+, —N(R20)C(O)R20, —N(R20)C(O)OR20, —N(R20)C(O)N(R20)2, —N(R20)S(O)2(R20), —NR20S(O)2N(R20)2, —NR20S(O)2O(R20), —NS(O)(R20)2, —OC(O)R20, —OC(O)OR20, —OC(O)N(R20)2, —Si(R20)3, —SR20, —S(O)R20, —SF5, —S(O)(NR20)R20, —S(NR20)(NR20)R20, —S(O)(NR20)N(R20)2, —S(O)(NCN)R20, —S(O)2R20, —S(O)2N(R20)2, —C(O)N(R20)S(O)2R20, or —S(O)2N(R20)C(O)R20; or two R17 on the same or different carbon atoms are taken together to form a 3-8-membered ring optionally substituted with 1 to 4 Z1;
each R18 independently hydrogen, halo, —NO2, —N3, —CN, C1-8 alkyl optionally substituted by 1 to 3 Z1a, C2-8 alkenyl optionally substituted by 1 to 3 Z1a, C2-8 alkynyl optionally substituted by 1 to 3 Z1a, C3-8 cycloalkyl optionally substituted by 1 to 3 Z1a, 6-10 membered aryl optionally substituted by 1 to 3 Z1a, 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z1a, 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1a, —OR20, —C(O)R20, —C(O)OR20, —C(O)N(R20)2, —N(R20)2, —N(R20)3+, —N(R20)C(O)R20, —N(R20)C(O)OR20, —N(R20)C(O)N(R20)2, —N(R20)S(O)2(R20), —NR20S(O)2N(R20)2, —NR20S(O)2O(R20), —NS(O)(R20)2, —OC(O)R20, —OC(O)OR20, —OC(O)N(R20)2, —Si(R20)3, —SR20, —S(O)R20, —SF5, —S(O)(NR20)R20, —S(NR20)(NR20)R20, —S(O)(NR20)N(R20)2, —S(O)(NCN)R20, —S(O)2R20, —S(O)2N(R20)2, —C(O)N(R20)S(O)2R20, or —S(O)2N(R20)C(O)R20;
each Z1 is independently halo, —NO2, —N3, —CN, C1-8 alkyl optionally substituted by 1 to 3 Z1a, C2-8 alkenyl optionally substituted by 1 to 3 Z1a, C2-8 alkynyl optionally substituted by 1 to 3 Z1a, C3-8 cycloalkyl optionally substituted by 1 to 3 Z1a, 6-10 membered aryl optionally substituted by 1 to 3 Z1a, 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z1a, 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1a, —OR20, —C(O)R20, —C(O)OR20, —C(O)N(R20)2, —N(R20)2, —N(R20)3+, —N(R20)C(O)R20, —N(R20)C(O)OR20, —N(R20)C(O)N(R20)2, —N(R20)S(O)2(R20), —NR20S(O)2N(R20)2, —NR20S(O)2O(R20), —NS(O)(R20)2, —OC(O)R20, —OC(O)OR20, —OC(O)N(R20)2, —Si(R20)3, —S(O)R20, —SF5, —S(O)(NR20)R20, —S(NR20)(NR20)R20, —S(O)(NR20)N(R20)2, —S(O)(NCN)R20, —S(O)2R20, —S(O)2N(R20)2, —C(O)N(R20)S(O)2R20, or —S(O)2N(R20)C(O)R20;
each Z1a is independently oxo, halo, —NO2, —N3, —CN, C1-8 alkyl optionally substituted by 1 to 3 Z1b, C2-8 alkenyl optionally substituted by 1 to 3 Z1b, C2-8 alkynyl optionally substituted by 1 to 3 Z1b, C3-8 cycloalkyl optionally substituted by 1 to 3 Z1b, 6-10 membered aryl optionally substituted by 1 to 3 Z1b, 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z1b, 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1b, —OR21, —C(O)R21, —C(O)OR21, —C(O)N(R21)2, —N(R21)2, —N(R21)3+, —N(R21)C(O)R21, —N(R21)C(O)OR21, —N(R21)C(O)N(R21)2, —N(R21)S(O)2(R21), —NR21S(O)2N(R21)2, —NR21S(O)2O(R21), —NS(O)(R21)2, —OC(O)R21, —OC(O)OR21, —OC(O)N(R21)2, —Si(R21)3, —SR21, —S(O)R21, —SF5, —S(O)(NR21)R21, —S(NR21)(NR21)R21, —S(O)(NR21)N(R21)2, —S(O)(NCN)R21, —S(O)2R21, —S(O)2N(R21)2, —C(O)N(R21)S(O)2R21, or —S(O)2N(R21)C(O)R21;
each Z10 is independently selected from oxo, halo, —CN, C1-8 alkyl optionally substituted by 1 to 3 Z1b, C3-8 cycloalkyl optionally substituted by 1 to 3 Z1b, aryl optionally substituted by 1 to 3 Z1b, 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z1b, 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1b, —OR22, —C(O)R22, —C(O)OR22, —C(O)N(R22)2, —N(R22)2, —N(R22)3+, —N(R22)C(O)R22, —N(R22)C(O)OR22, —N(R22)C(O)N(R22)2, —N(R22)S(O)2R22, —OC(O)R22, —OC(O)OR22, —OC(O)—N(R22)2, and —S—R22; and
each R20, R21 and R22 is independently hydrogen, C1-8 alkyl optionally substituted with 1 to 3 Z1b, C2-8 alkenyl optionally substituted with 1 to 3 Z1b, C2-8 alkynyl optionally substituted with 1 to 3 Z1b, C3-10 cycloalkyl optionally substituted with 1 to 3 Z1b, 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z1b, C6-10 aryl optionally substituted with 1 to 3 Z1b, or 5-10 membered heteroaryl optionally substituted with 1 to 3 Z1b;
each Z1b is independently oxo, hydroxy, halo, —NO2, —N3, —CN, C1-9 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-15 cycloalkyl, C1-8 haloalkyl, C6-10 aryl, 5-10 membered heteroaryl heteroaryl, 4-10 membered heterocyclyl, —O(C1-9 alkyl), —O(C2-6 alkenyl), —O(C2-6 alkynyl), —O(C3-15 cycloalkyl), —O(C1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), —OC(O) (C1-9 alkyl), —OC(O)(C2-6 alkenyl), —OC(O)(C2-6 alkenyl), —OC(O)(C2-6 alkynyl), —OC(O)(C3-15 cycloalkyl), —OC(O)(C1-8 haloalkyl), —OC(O)(aryl), —OC(O)(heteroaryl), —OC(O)(heterocyclyl), —NH2, —NH(C1-9 alkyl), —NH(C2-6 alkenyl), —NH(C2-6 alkynyl), —NH(C3-15 cycloalkyl), —NH(C1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C1-9 alkyl)2, —N(C3-15 cycloalkyl)2, —N(C2-6 alkenyl)2, —N(C2-6 alkynyl)2, —N(C3-15 cycloalkyl)2, —N(C1-8 haloalkyl)2, —N(aryl)2, —N(heteroaryl)2, —N(heterocyclyl)2, —N(C1-9 alkyl)(C3-15 cycloalkyl), —N(C1-9 alkyl)(C2-6 alkenyl), —N(C1-9 alkyl)(C2-6 alkynyl), —N(C1-9 alkyl)(C3-15 cycloalkyl), —N(C1-9 alkyl)(C1-8 haloalkyl), —N(C1-9 alkyl)(aryl), —N(C1-9 alkyl)(heteroaryl), —N(C1-9 alkyl)(heterocyclyl), —C(O)(C1-9 alkyl), —C(O)(C2-6 alkenyl), —C(O)(C2-6 alkynyl), —C(O)(C3-15 cycloalkyl), —C(O)(C1-8 haloalkyl), —C(O)(aryl), —C(O)(heteroaryl), —C(O)(heterocyclyl), —C(O)O(C1-9 alkyl), —C(O)O(C2-6 alkenyl), —C(O)O(C2-6 alkynyl), —C(O)O(C3-15 cycloalkyl), —C(O)O(C1-8 haloalkyl), —C(O)O(aryl), —C(O)O(heteroaryl), —C(O)O(heterocyclyl), —C(O)NH2, —C(O)NH(C1-9 alkyl), —C(O)NH(C2-6 alkenyl), —C(O)NH(C2-6 alkynyl), —C(O)NH(C3-15 cycloalkyl), —C(O)NH(C1-8 haloalkyl), —C(O)NH(aryl), —C(O)NH(heteroaryl), —C(O)NH(heterocyclyl), —C(O)N(C1-9 alkyl)2, —C(O)N(C3-15 cycloalkyl)2, —C(O)N(C2-6 alkenyl)2, —C(O)N(C2-6 alkynyl)2, —C(O)N(C1-8 haloalkyl)2, —C(O)N(aryl)2, —C(O)N(heteroaryl)2, —C(O)N(heterocyclyl)2, —NHC(O)(C1-9 alkyl), —NHC(O)(C2-6 alkenyl), —NHC(O)(C2-6 alkynyl), —NHC(O)(C3-15 cycloalkyl), —NHC(O)(C1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C1-9 alkyl), —NHC(O)O(C2-6 alkenyl), —NHC(O)O(C2-6 alkynyl), —NHC(O)O(C3-15 cycloalkyl), —NHC(O)O(C1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C1-9 alkyl), —NHC(O)NH(C2.6 alkenyl), —NHC(O)NH(C2-6 alkynyl), —NHC(O)NH(C3-15 cycloalkyl), —NHC(O)NH(C1-8 haloalkyl), —NHC(O)NH(aryl), —NHC(O)NH(heteroaryl), —NHC(O)NH(heterocyclyl), —SH, —S(C1-9 alkyl), —S(C2-6 alkenyl), —S(C2-6 alkynyl), —S(C3-15 cycloalkyl), —S(C1-8 haloalkyl), —S(aryl), —S(heteroaryl), —S(heterocyclyl), —NHS(O)(C1-9 alkyl), —N(C1-9 alkyl)(S(O)(C1-9 alkyl), —S(O)N(C1-9 alkyl)2, —S(O)(C1-9 alkyl), —S(O)(NH)(C1-9 alkyl), —S(O)(C2-6 alkenyl), —S(O)(C2-6 alkynyl), —S(O)(C3-15 cycloalkyl), —S(O)(C1-8 haloalkyl), —S(O)(aryl), —S(O)(heteroaryl), —S(O)(heterocyclyl), —S(O)2(C1-9 alkyl), —S(O)2(C2-6 alkenyl), —S(O)2(C2-6 alkynyl), —S(O)2(C3-15 cycloalkyl), —S(O)2(C1-8 haloalkyl), —S(O)2(aryl), —S(O)2(heteroaryl), —S(O)2(heterocyclyl), —S(O)2NH(C1-9 alkyl), or —S(O)2N(C1-9 alkyl)2;
wherein any alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl of Z1b is optionally substituted with one or more halo, C1-9 alkyl, C1-8 haloalkyl, —OH, —NH2, —NH(C1-9 alkyl), —NH(C3-15 cycloalkyl), —NH(C1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C1-9 alkyl)2, —N(C3-15 cycloalkyl)2, —NHC(O)(C3-15 cycloalkyl), —NHC(O)(C1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C1-9 alkyl), —NHC(O)O(C2-6 alkynyl), —NHC(O)O(C3-15 cycloalkyl), —NHC(O)O(C1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C1-9 alkyl), —S(O)(NH)(C1-9 alkyl), —S(O)2(C1-9 alkyl), —S(O)2(C3-15 cycloalkyl), —S(O)2(C1-8 haloalkyl), —S(O)2(aryl), —S(O)2(heteroaryl), —S(O)2(heterocyclyl), —S(O)2NH(C1-9 alkyl), —S(O)2N(C1-9 alkyl)2, —O(C3-15 cycloalkyl), —O(C1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), or —O(C1-9 alkyl).
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