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US 2023/0054084 A1Published application
Compounds and methods of use
AssigneeTango Therapeutics, Inc.
InventorsKevin M. Cottrell, John P. Maxwell, Douglas A. Whittington
Life of this patent
Estimating the term…
Abstract
Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof: wherein X1, X2, X3, X4, X5, A, L, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
Claims106
A compound of Formula (I)
- or a pharmaceutically acceptable salt thereof;
- wherein:
- X1, X2, X3, X4 and X5 are each independently N or CRx;
- L is a bond, —C(═O)—, —NH— or —O—;
- Ring A is a carbocycle, heterocycle or a 5-6 membered monocyclic heteroaryl;
- R1 is a 5-6 membered heteroaryl substituted with 0-3 instances of R4;
- each R2 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each R3 is independently selected from H, C1-C6 alkyl, —C1-C6 heteroalkyl, C3-C9 carbocyclyl, 3-7 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, 5-6 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, carbocyclyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted;
- each R4 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each Rx is independently selected from hydrogen, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2 wherein each alkyl, carbocyclyl, heterocyclyl, heterocyclylalkyl, cycloalkylalkyl is optionally substituted;
- each R5 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, C6-C10 aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3, —S(═O)2N(R3)2, or two R5 can be taken together with the atoms to which they are attached to form a —C3-C9 carbocyclyl or a 3-10 membered heterocyclyl;
- m is 0, 1, 2 or 3;
- and
- n is 0, 1, 2 or 3.
11 more elements
A compound of Formula (VI)
- or a pharmaceutically acceptable salt thereof,
- wherein:
- X1, X2, X3, X4 and X5 are each independently N or CRx;
- L is a bond, —C(═O)—, —NH— or —O—;
- Ring A is a carbocycle, heterocycle or a 5-6 membered monocyclic heteroaryl;
- R1 is a 5-6 membered heteroaryl substituted with 0-3 instances of R4;
- each R2 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each R3 is independently selected from H, C1-C6 alkyl, —C1-C6 heteroalkyl, C3-C9 carbocyclyl, 3-7 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, 5-6 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, carbocyclyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted;
- each R4 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each Rx is independently selected from hydrogen, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2 wherein each alkyl, carbocyclyl, heterocyclyl, heterocyclylalkyl, cycloalkylalkyl is optionally substituted;
- each R5 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, C6-C10 aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3, —S(═O)2N(R3)2, or two R5 can be taken together with the atoms to which they are attached to form a —C3-C9 carbocyclyl or a 3-10 membered heterocyclyl;
- m is 0, 1, 2 or 3;
- and
- n is 0, 1, 2 or 3.
11 more elements
A compound of Formula (IV) or a pharmaceutically acceptable salt thereof, wherein:
- R1 is a 5-6 membered heteroaryl substituted with 0-3 instances of R4;
- each R2 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each R3 is independently selected from H, C1-C6 alkyl, C3-C9 carbocyclyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, 5-6 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, carbocyclyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted;
- each R4 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each R5 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, C6-C10 aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3, —S(═O)2N(R3)2, or two R5 can be taken together with the atoms to which they are attached to form a —C3-C9 carbocyclyl or a 3-10 membered heterocyclyl;
- each R8 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, C6-C10 aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3, —S(═O)2N(R3)2, or two R8 can be taken together with the atoms to which they are attached to form a —C3-C9 carbocyclyl or a 3-10 membered heterocyclyl;
- m is 0, 1, 2 or 3;
- and
- p is 0, 1, 2 or 3.
6 more elements
A compound of Formula (V) or a pharmaceutically acceptable salt thereof, wherein
- X6 is N, NH, CHRx or CRx;
- R1 is a 5-6 membered heteroaryl substituted with 0-3 instances of R4;
- each R2 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroaryl alkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each R3 is independently selected from H, C1-C6 alkyl, —C1-C6 heteroalkyl, C3-C9 carbocyclyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, 5-6 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, carbocyclyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted;
- each R4 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2;
- each Rx is independently selected from hydrogen, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3 and —S(═O)2N(R3)2 wherein each alkyl, carbocyclyl, heterocyclyl, heterocyclylalkyl, cycloalkylalkyl is optionally substituted;
- each R5 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, C6-C10 aryl, 5-10 membered, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3, —S(═O)2N(R3)2, or two R5 can be taken together with the atoms to which they are attached to form a —C3-C9 carbocyclyl or a 3-10 membered heterocyclyl;
- each R8 is independently selected from ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 carbocyclyl, 3-10 membered heterocyclyl, C6-C10 aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, —OR3, —N(R3)2, —C(═O)R3, —C(═O)OR3, —NR3C(═O)R3, —NR3C(═O)OR3, —C(═O)N(R3)2, —OC(═O)N(R3)2, —S(═O)R3, —S(═O)2R3, —SR3, —S(═O)(═NR3)R3, —NR3S(═O)2R3, —S(═O)2N(R3)2, or two R8 can be taken together with the atoms to which they are attached to form a —C3-C9 carbocyclyl or a 3-10 membered heterocyclyl;
- m is 0, 1, 2 or 3;
- and
- p is 0, 1, 2 or 3.
8 more elements
Dependencies are inferred from the claim text.