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US 2026/0028358 A1Published application
Substituted heteroaromatic amines and uses thereof
AssigneeKumquat Biosciences Inc.
InventorsBaogen Wu, Pingda Ren, Liansheng Li
Life of this patent
Estimating the term…
Abstract
The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of oncogenic protein.
Claims20
A compound of Formula (II-a):
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R2 is —OR12;
- R3 is independently selected at each occurrence from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 carbocycle, and 3- to 8-membered heterocycle, each of which is optionally substituted with one, two, or three R20;
- R6 is selected from hydrogen, halogen, and C1-3 haloalkyl;
- m is 0, 1, 2, or 3;
- n is 1 or 2;
- R12 is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle), wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle) are optionally substituted with one, two, or three R20;
- R20 is independently selected at each occurrence from halogen, oxo, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C0-6 alkyl-(C3-12 carbocycle), -(2- to 6-membered heteroalkyl)-(C3-12 carbocycle), —C0-6 alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), —OR22, —SR22, —N(R22)(R23), ═NR22 ═C(R21)2, —C(O)OR22, —OC(O)N(R22)(R23), —N(R22)C(O)N(R22)(R23), —N(R22)C(O)OR22, —N(R22)S(O)2R22, —C(O)R22, —S(O)R22, —OC(O)R22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —N(R22)C(O)R22, —OS(O)2R22, —S(O)2R22, —S(O)(NR22)R22, —S(O)2N(R22)(R23), —S(O)(NR22)N(R22)(R23), and —OCH2C(O)OR22;
- wherein two R20 attached to the same or adjacent atoms optionally join to form C3-12 carbocycle or 3- to 12-membered heterocycle;
- wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C0-6 alkyl-(C3-12 carbocycle), -(2- to 6-membered heteroalkyl)-(C3-12 carbocycle), —C0-6 alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C3-12 carbocycle, and 3- to 12-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, oxo, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —OR22, —SR22, —N(R22)(R23) —NR22 ═C(R21)2, —C(O)OR22, —OC(O)N(R22)(R23), —N(R22)C(O)N(R22)(R23), —N(R22)C(O)OR22, —N(R22)S(O)2R22, —C(O)R22, —S(O)R22, —OC(O)R22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —N(R22)C(O)R22, —OS(O)2R22, —S(O)2R22, —S(O)(NR22)R22, —S(O)2N(R22)(R23), and —S(O)(NR22)N(R22)(R23);
- R21 is independently selected at each occurrence from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle), or two R21 are taken together with the carbon atom to which they are attached to form C3-12 carbocycle or 3- to 12-membered heterocycle, each of which is optionally substituted with one, two, or three substituents independently selected from halogen, C1-3 alkyl, C1-3 haloalkyl, and —OH;
- R22 is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle);
- and
- R23 is independently selected at each occurrence from hydrogen and C1-6 alkyl;
- or R22 and R23 attached to the same nitrogen atom form 3- to 10 membered heterocycle.
12 more elements
(canceled)
A method of treating cancer in a subject comprising a Ras mutant protein, the method comprising:
- inhibiting the Ras mutant protein of said subject by administering to said subject a compound of Formula (II-a), or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is characterized in that upon contacting the Ras mutant protein, said Ras mutant protein exhibits reduced Ras signaling output:
- wherein:
- R2 is —OR12;
- R3 is independently selected at each occurrence from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-s carbocycle, and 3- to 8-membered heterocycle, each of which is optionally substituted with one, two, or three R20;
- R6 is selected from hydrogen, halogen, and C1-3 haloalkyl;
- m is 0, 1, 2, or 3;
- n is 1 or 2;
- R12 is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle), wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle) are optionally substituted with one, two, or three R20;
- R20 is independently selected at each occurrence from halogen, oxo, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C0-6 alkyl-(C3-12 carbocycle), -(2- to 6-membered heteroalkyl)-(C3-12 carbocycle), —C0-6 alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), —OR22, —SR22, —N(R22)(R23), ═NR22, ═C(R21)2, —C(O)OR22, —OC(O)N(R22)(R23), —N(R22)C(O)N(R22)(R23), —N(R22)C(O)OR22, —N(R22)S(O)2R22, —C(O)R22, —S(O)R22, —OC(O)R22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —N(R22)C(O)R22, —OS(O)2R22, —S(O)2R22, —S(O)(NR22)R22, —S(O)2N(R22)(R23), —S(O)(NR22)N(R22)(R23), and —OCH2C(O)OR22;
- wherein two R20 attached to the same or adjacent atoms optionally join to form C3-12 carbocycle or 3- to 12-membered heterocycle;
- wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C0-6 alkyl-(C3-12 carbocycle), -(2- to 6-membered heteroalkyl)-(C3-12 carbocycle), —C0-6 alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C3-12 carbocycle, and 3- to 12-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, oxo, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —OR22, —SR22, —N(R22)(R23)═NR22, ═C(R21)2, —C(O)OR22, —OC(O)N(R22)(R23), —N(R22)C(O)N(R22)(R23), —N(R22)C(O)OR22, —N(R22)S(O)2R22, —C(O)R22, —S(O)R22, —OC(O)R22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —N(R22)C(O)R22, —OS(O)2R22, —S(O)2R22, —S(O)(NR22)R22, —S(O)2N(R22)(R23), and —S(O)(NR22)N(R22)(R23);
- R21 is independently selected at each occurrence from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle), or two R21 are taken together with the carbon atom to which they are attached to form C3-12 carbocycle or 3- to 12-membered heterocycle, each of which is optionally substituted with one, two, or three substituents independently selected from halogen, C1-3 alkyl, C1-3 haloalkyl, and —OH;
- R22 is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle);
- and
- R23 is independently selected at each occurrence from hydrogen and C1-6 alkyl;
- or R22 and R23 attached to the same nitrogen atom form 3- to 10 membered heterocycle.
13 more elements
Dependencies are inferred from the claim text.