US 2026/0200897 A1Published application

4-((5-(3-(4-(pyridin-2-yl)cyclopentyl)-1h-pyrazol-3-yl)amino)-benzenesulfonamide derivatives and similar compounds as cdk inhibitors for the treatment of cancer

AssigneeBeOne Medicines I GmbH

InventorsChangxin Huo, Yu Zhao, Yucheng Wang, Huaqing Liu, Zhiwei Wang

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Abstract

Disclosed herein are compounds used as inhibitors of cyclin-dependent kinases. Disclosed herein is the use of these inhibitors for inhibiting cyclin-dependent kinases, and the use of such compounds for treating cancer.

Claims18

Dependent claims

A compound of Formula (I)

or a N-oxide thereof, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a tautomer, or a deuterated analog thereof, or a prodrug thereof, wherein:
m is 0, 1, 2, 3, or 4, provided that the valency theory has been met;
n is 0, 1, 2, 3, 4, or 5, provided that the valency theory has been met;
is independently a single bond or double bond;
ring A is selected from a heteroaryl ring and an aryl ring;
X1 is a single bond or 0;
X2, X3, X4, and X5 are each independently selected from N and C;
R1 is each independently selected from halogen, —C1-C8alkyl, —C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, —CN, and —OH, wherein each of said —C1-C5alkyl, C3-C5cycloalkyl, or 3- to 8-membered heterocyclyl is optionally substituted with at least one substituent independently selected from halogen, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, —OH, —C6-C12aryl, 5- to 12-membered heteroaryl, and oxo (═O);
R5 is selected from —SO2R5a and —SO2NR5aR5b, wherein R5a and R5b are each independently selected from hydrogen and —C1-C3alkyl;
R6 is selected from hydrogen, —C1-C3alkyl, and —C3-C5cycloalkyl;
or
R5 and R6, together with the atoms to which they are attached, form a 5- to 12-membered ring, said ring comprising S(═O)2 or S(═O), and additional 0-2 heteroatom(s) independently selected from nitrogen and oxygen as ring member(s);
said ring is optionally substituted with at least one substituent R5c;
R5c is each independently selected from halogen, —C1-C5alkyl, —C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, —C6-C12aryl, 5- to 12-membered heteroaryl, and oxo (═O);
ring B is selected from 5- to 7-membered heterocyclyl, phenyl, and 5- to 7-membered heteroaryl;
R2 is each independently selected from halogen, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C3-C8cycloalkyl, 3- to 8-membered heterocyclyl, —C6-C12aryl, 5- to 12-membered heteroaryl, oxo (═O), —OR2a, —CN, —C(O)R2a, —CO2R2a, —NR2aR2b, —NR2aCOR2b, and —NR2aCO2R2b, wherein each of said —C1-C8alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, —C6-C12aryl or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent independently selected from halogen, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, C6-C12aryl, 5- to 12-membered heteroaryl, oxo (═O), —CN, —OR2c, —C1-C5alkyl-OR2c, —C(O)R2c, —CO2R2c, —NR2cR2d, —NR2cCOR2d, and —NR2cCO2R2d;
R2a, R2b, R2c and R2d are each independently selected from hydrogen, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, C6-C12aryl, and 5- to 12-membered heteroaryl, wherein each of said —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, C6-C12aryl, or 5- to 12-membered heteroaryl is optionally substituted with at least one substituent selected from halogen, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, C6-C12aryl, 5- to 12-membered heteroaryl, oxo (═O), —CN, —OH, and —C1-C8alkoxyl;
R7 is selected from hydrogen, —C1-C3alkyl, and —C3-C5cycloalkyl;
or
adjacent R2 and R7, together with the atoms to which they are attached, form a 3- to 12-membered ring, said ring comprising 0-3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur as ring member(s);
said ring is optionally substituted with at least one substituent R7a;
R7a is each independently selected from halogen, —C1-C8alkyl, —C3-C5cycloalkyl, 3- to 8-membered heterocyclyl, —C6-C12aryl, 5- to 12-membered heteroaryl, and oxo (═O);
R3 and R4 are each independently selected from hydrogen, —C1-C8alkyl, C3-C5cycloalkyl, and —C(O)R3a;
wherein each of said —C1-C8alkyl and C3-C5cycloalkyl is optionally substituted with at least one substituent independently selected from halogen, oxo (═O), —CN, —OR3b and —NR3bR3c;
and
R3a, R3b and R3c are each independently selected from hydrogen, —C1-C5alkyl, and C3-C5cycloalkyl;
wherein each of said —C1-C5alkyl and C3-C5cycloalkyl is optionally substituted with at least one substituent independently selected from halogen, —C1-C8alkyl, C3-C5cycloalkyl, oxo (═O), —CN, —OH, and —C1-C5alkoxyl.

24 more elements