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US 12,319,703 B2Granted
Macrocyclic fused pyrazoles as Mcl-1 inhibitors
AssigneesAscentage Pharma (Suzhou) Co., Ltd., The Regents of the University of Michigan, Ascentage Pharma Group Corp Limited
InventorsGuozhi Tang, Dongbo Li, Liugen Li, Xianchan Zha, Wenming Chen, Shaomeng Wang, Chao-Yie Yang
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Abstract
Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R1a, R1b, L1, L2, L3, X, A, B and C are as defined as set forth in the specification. Also provided compounds of Formula IA for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.
Claims20
A compound of Formula III:
- wherein:
- R is selected from the group consisting of hydrogen and C1-C6 alkyl;
- X is selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O)2—, and —N(R3)—;
- R3 is selected from the group consisting of hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, hydroxyalkyl, —C(═O)R4, and —S(═O)2R5;
- R4 is selected from the group consisting of C1-C4 alkyl, C1-C4 haloalkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted 4- to 8-membered heterocyclo, optionally substituted C6-C10 aryl, optionally substituted 5- to 10-membered heteroaryl, and (C6-C10 aryl)C1-C4 alkyl;
- R5 is selected from the group consisting of C1-C4 alkyl, C1-C4 haloalkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted 4- to 8-membered heterocyclo, optionally substituted C6-C10 aryl, optionally substituted 5- to 10-membered heteroaryl, and (C6-C10 aryl)C1-C4 alkyl;
- {circle around (A)} is selected from the group consisting of:
- R2a, R2b, R2c, and R2d are each independently selected from the group consisting of hydrogen, halo, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
- R6a, R6b, R6c, R6d, R6e, and R6f are each independently selected from the group consisting of hydrogen, halo, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
- {circle around (B)} is selected from the group consisting of arylenyl and heteroarylenyl;
- wherein:
- m is 0, 1, or 2;
- n is or 1;
- with the proviso that when m is 0, Z is —CR13aR13b—;
- Z is selected from the group consisting of —CR13aR13b—, —O—, —S—, S(═O)—, S(═O)2—, and —N(R10)—;
- R10 is selected from the group consisting of hydrogen, C1-C4 alkyl, —C(═O)2R11, and —S(═O)2R12;
- R11 is selected from the group consisting of C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl;
- R12 is selected from the group consisting of C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl;
- and
- R13a and R13b are independently selected from the group consisting of hydrogen and C1-C4 alkyl,
- or a pharmaceutically acceptable salt thereof.
18 more elements
A compound selected from the group consisting of
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.