Granted Patent B2

US 12,234,244 · App. 17/716,707 · Granted Feb 25, 2025

Inventors: Liansheng Li (San Diego, CA); Jun Feng (San Diego, CA); Tao Wu (Carlsbad, CA); Pingda Ren (San Diego, CA); Yi Liu (San Diego, CA); Yuan Liu (San Diego, CA); Yun Oliver Long (San Diego, CA)

Assignee: Araxes Pharma LLC

C07D495/04C07D215/46C07D215/54C07D217/22C07D239/84C07D239/94C07D239/95C07D241/44C07D401/04C07D401/12C07D403/04C07D409/04C07D487/04

Abstract

Claims (33)

1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the following structure:

or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,

wherein:

R 1 is aryl;

wherein the aryl is monocyclic or bicyclic; and

wherein the aryl is optionally substituted with one or more substituents independently selected from the group consisting of halo, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, cyano-C 1 -C 6 alkyl, aminylcarbonyl-C 1 -C 6 alkyl, hydroxy-C 1 -C 6 alkyl, alkoxy-C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl-alkyl, C 2 -C 6 alkynyl, aminylcarbonyl, C 1 -C 6 alkyl-aminylcarbonyl, C 3 -C 8 cycloalkyl-aminylcarbonyl, C 1 -C 6 alkylaminyl, C 1 -C 6 alkyl-carbonylaminyl, hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, aminylsulfone, C 3 -C 8 cycloalkyl, cyano-C 3 -C 8 cycloalkyl, C 1 -C 6 alkyl-cycloalkyl, aminylcarbonyl-C 3 -C 8 cycloalkyl, fused C 3 -C 8 cycloalkyl, and heteroaryl;

R 2a is halo;

A is CR 2b , or N;

R 2b is H, F, Cl, methyl, CH 2 N(CH 3 ) 2 , OH, C 1 -C 6 alkoxy, or monocyclic heteroaryl, wherein the monocyclic heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, cyano, methyl, CH 2 N(CH 3 ) 2 , trifluoromethyl, ethyl, ethynyl C(═O)NH 2 , NH 2 , alkylaminyl, heterocyclylaminyl, pyrazolylaminyl, OH, alkoxy, heterocyclyloxy, aryloxy, cyclopropyl, piperidinyl, morpholinyl, aryl, and heteroaryl;

Y is CR 6 , —C(O)—, N, or —NR 5 —;

Z is CR 6 , N, or —NH—;

R 5 is H or C 1 -C 6 alkyl;

each R 6 is independently H, F, Cl, cyano, methyl, CH 2 N(CH 3 ) 2 , NH 2 , C 1 -C 6 alkylaminyl, monocyclic heterocyclylalkylaminyl, monocyclic heterocyclylaminyl, monocyclic heteroarylalkylaminyl, monocyclic heteroarylaminyl, OH, C 1 -C 6 alkoxy, oxo, monocyclic heterocyclylalkyloxy, monocyclic heteroarylalkyloxy, monocyclic heterocyclyloxy, monocyclic heteroaryloxy, unsubstituted pyrazolyl, or unsubstituted thiazolyl, wherein each monocyclic heterocyclylalkylaminyl, monocyclic heterocyclylaminyl, monocyclic heteroarylalkylaminyl, monocyclic heteroarylaminyl, monocyclic heterocyclylalkyloxy, monocyclic heteroarylalkyloxy, monocyclic heterocyclyloxy, and monocyclic heteroaryloxy is optionally and independently substituted with at least one substituent independently selected from the group consisting of methyl and CH 2 CF 3 ;

L 1 is a bond;

each R 3a is independently H, halo, cyano, C 1 -C 6 alkyl, cyanoalkyl, aminylcarbonylalkyl, carboxyalkyl, aminylalkyl, alkylaminylalkyl, hydroxyalkyl, C 2 -C 6 alkynyl, aminylcarbonyl, CO 2 H, NH 2 , or OH;

each R 3b is independently H, halo, cyano, C 1 -C 6 alkyl, cyanoalkyl, aminylcarbonylalkyl, carboxyalkyl, aminylalkyl, alkylaminylalkyl, hydroxyalkyl, C 2 -C 6 alkynyl, aminylcarbonyl, CO 2 H, NH 2 , or OH;

each R 4a is independently H, halo, cyano, C 1 -C 6 alkyl, cyanoalkyl, aminylcarbonylalkyl, carboxyalkyl, aminylalkyl, alkylaminylalkyl, hydroxyalkyl, C 2 -C 6 alkynyl, aminylcarbonyl, CO 2 H, NH 2 , or OH;

each R 4b is independently H, halo, cyano, C 1 -C 6 alkyl, cyanoalkyl, aminylcarbonylalkyl, carboxyalkyl, aminylalkyl, alkylaminylalkyl, hydroxyalkyl, C 2 -C 6 alkynyl, aminylcarbonyl, CO 2 H, NH 2 , or OH;

L 2 is a bond;

and

is a single bond or double bond;

with the proviso that if Z is —NH—, then Y is —C(O)—.

2. The pharmaceutical composition of claim 1 , wherein R 2a is F or Cl.

3. The pharmaceutical composition of claim 2 , wherein R 2b is H, F, Cl, methyl, OH, or C 1 -C 6 alkoxy.

4. The pharmaceutical composition of claim 3 , wherein R 1 is phenyl, wherein the phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halo, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, cyano-C 1 -C 6 alkyl, aminylcarbonyl-C 1 -C 6 alkyl, hydroxy-C 1 -C 6 alkyl, alkoxy-C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl-alkyl, C 2 -C 6 alkynyl, aminylcarbonyl, C 1 -C 6 alkyl-aminylcarbonyl, C 3 -C 8 cycloalkyl-aminylcarbonyl, C 1 -C 6 alkylaminyl, C 1 -C 6 alkyl-carbonylaminyl, hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, aminylsulfone, C 3 -C 8 cycloalkyl, cyano-C 3 -C 8 cycloalkyl, C 1 -C 6 alkyl-cycloalkyl, aminylcarbonyl-C 3 -C 8 cycloalkyl, fused C 3 -C 8 cycloalkyl, and heteroaryl.

5. The pharmaceutical composition of claim 4 , wherein R 1 is:

6. The pharmaceutical composition of claim 4 , wherein R 1 is:

7. The pharmaceutical composition of claim 2 , wherein Y is CR 6 or —C(O)—.

8. The pharmaceutical composition of claim 7 , wherein Z is N or —NH—.

9. The pharmaceutical composition of claim 8 , wherein Z is N.

10. The pharmaceutical composition of claim 8 , wherein Z is —NH—.

11. The pharmaceutical composition of claim 8 , wherein A is CR 2b .

12. The pharmaceutical composition of claim 8 , wherein A is N.

Continuity (9)

References Cited (400)