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US 2026/0308156 A1Published application
Pyrazolotriazinecarbonitriles useful as kinase inhibitors
AssigneeBristol-Myers Squibb Company
InventorsLI-QIANG SUN, ZHIZHEN BARBARA ZHENG, MURALI T.G. DHAR, ASHVINIKUMAR V. GAVAI, JENNIFER X. QIAO, DAVID K. WILLIAMS, PATRICE GILL, JOHN S. TOKARSKI, SREEKANTHA RATNA KUMAR, HIMA KIRAN POTTURI, SOUMEN CHAKROBORTY, PITANI VEERA VENKATA SRINIVAS
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Abstract
The invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof. The Formula I imidazotriazines inhibit protein Formula (I) kinase activity thereby making them useful as anticancer agents.
Claims15
A compound of Formula (I):
- or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
- R1 is independently C1-4 alkyl, C3-4 cycloalkyl substituted with 0-1 R1a;
- R1a is independently F or C1-4 alkyl;
- R2 and R3 are independently Cl, cyano, C1-4 alkoxy, C1-4 fluoroalkoxy, or C3-4 cycloalkyl;
- R4 is independently
- R5 is independently H, C1-4 fluoroalkyl, —C(═O)(C1-4 alkyl), —C(O)(C1-4 fluoroalkyl), —C(═O)C(C1-2 alkyl)(C1-2 fluoroalkyl)(OH), —C(═O)O(C1-4 alkyl), —C(═O)CH2O(C1-2 alkyl), —C(═O)CH2OC(═O)(C1-2 alkyl), —C(═O)NHR10, —C(═O)C(═O)NHR11, —SO2(C1-4 alkyl), C1-4 alkyl substituted with 0-2 Ra, —(CH2)0-1—C3-6 cycloalkyl substituted with 0-2 Rd, —X-(4- to 7-membered heterocyclic ring including 1 to 2 ring heteroatoms which are independently N, N(Rb), O, or S(O)p, and wherein the heterocyclic ring is partially saturated or fully saturated, and is substituted with 0 to 2 Re), or —X-(5-membered heteroaryl wherein from 1 to 4 ring atoms are each independently N, or N(Rb), wherein the heteroaryl is substituted with 0 to 1 Rd);
- X is independently a bond, —CH2—, —C(═O)—, —C(═O)CH2—, —CH2C(═O)—, or —C(═O)O—;
- R6 is independently C1-4 alkyl substituted with 0-1 OH, C1-4 fluoroalkyl, or C3-4 cycloalkyl;
- R7 and R8 are independently H, C1-4 alkyl substituted with 0-2 Re, —C(═O)(C1-4 alkyl), —C(═O)O(C1-4 alkyl), —CH2C(═O)NH2, —SO2(C1-2 alkyl),
- R9 is independently H, C1-4 alkyl substituted with 0-2 Re, —C(═O)(C1-4 alkyl), —C(═O)O(C1-4 alkyl), or;
- R10 is independently C1-4 alkyl substituted with 0-2 Rc, C1-4 fluoroalkyl, or C3-4 cycloalkyl;
- R11 is independently H, C1-4 alkyl, or C3-4 cycloalkyl;
- Ra is independently halogen, OH, C1-4alkoxy, —C(═O)NH2, —C(═O)O(C1-4 alkyl), C3-4 cycloalkyl substituted with 0-1 Rd, or
- Rb is independently H, C1-4 alkyl substituted with 0-2 Re, —C(═O)(C1-4 alkyl), —C(═O)C(C1-2 alkyl)(C1-2 fluoroalkyl)(OH), —C(═O)O(C1-4 alkyl), —C(═O)C(═O)NH2, —SO2(C1-4 alkyl substituted with 0-1 Re), C3-4 cycloalkyl substituted with 0-1 Rd,
- Rc is independently C1-2 alkoxy;
- Rd is independently D, halogen, OH, NH2, C1-4alkyl, or —SO2(C1-4alkyl);
- Re is independently oxo or Rd;
- Rf is independently F, OH, C1-4 alkoxy, or —C(═O)NH2.
- n is independently 0, 1 or 2;
- and
- p is independently 0, 1 or 2.
18 more elements
A compound of Formula (III):
- or a stereoisomer, a tautomer, or pharmaceutically acceptable salt thereof, wherein:
- R5 is independently H, C1-4 fluoroalkyl, —C(═O)(C1-2 alkyl), —C(═O)(C1-2 fluoroalkyl), —C(═O)C(CH3)(CF3)(OH), —C(═O)O(C1-4 alkyl), —C(═O)CH2O(C1-2 alkyl), —C(═O)CH2OC(═O)(C1-2 alkyl), —C(═O)NHR10, —C(═O)C(═O)NHR11, —SO2(C1-2 alkyl), C1-4 alkyl substituted with 0-2 Ra, —(CH2)0-1—C3-4 cycloalkyl substituted with 0-1 Rd,
- R6 is independently C1-2 alkyl substituted with 0-1 OH, CF3, or cyclopropyl;
- R10 is independently C1-4 alkyl substituted with 0-2 Rc, C1-4 fluoroalkyl, or C3-4 cycloalkyl;
- R11 is independently H, C1-4 alkyl, or C3-4 cycloalkyl;
- Ra is independently F, OH, C1-2alkoxy, —C(═O)NH2, —C(═O)O(C1-2 alkyl), or C3-4 cycloalkyl substituted with 0-1 Rd;
- Rb is independently H, C1-4 alkyl substituted with 0-2 Rf, —C(═O)(C1-2 alkyl), —C(═O)C(CH3)(CF3)(OH), —C(═O)O(C1-2 alkyl), —C(═O)C(═O)NH2, —SO2(C1-2 alkyl substituted with 0-1 Re), C3-4 cycloalkyl substituted with 0-1 Rd,
- Rc is independently C1-2 alkoxy;
- Rd is independently F, OH, or —SO2(C1-2 alkyl);
- Rf is independently F, OH, C1-2 alkoxy, or —C(═O)NH2;
- and
- n is independently 0, 1 or 2.
9 more elements
Dependencies are inferred from the claim text.