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US 12,565,502 B2Granted
Substituted 1′,2′-dihydro-3′h-spiro[cyclohexane-1,4′-pyrimido[5′,4′:4,5]pyrrolo[2,1-c] [1,2,4]triazin]-3′-ones as cyclin-dependent kinase inhibitors
AssigneePharmacosmos Holding A/S
InventorJay Copeland Strum
Life of this patent
Estimating the term…
Abstract
This invention is in the area of cell cycle inhibiting compounds for the treatment of disorders involving abnormal cellular proliferation, and include selective CDK2 inhibitors for medical therapy and their pharmaceutically acceptable salts and compositions. The inhibitors are pyrimidine-based N-heterocyclic compounds of formula:
Claims27
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (III):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- X1 is CH, CR2, CR4, or N;
- X2 is CH, CR2, CR4, or N;
- X3 is CH, CR2, CR4, or N;
- X4 is CH, CR2, CR4, or N;
- X5 is CH, CR2, CR4, or N;
- each R2 is independently C(O)R6, C(S)R6, NR14C(O)R6, NR14C(S)R6, NR14S(O)R6, NR14S(O)2R6, OC(O)R6, OC(S)R6, OS(O)R6, OS(O)2R6, S(O)R6, or S(O)2R6,
- each R4 is independently hydrogen, halogen, cyano, alkyl, haloalkyl, C(O)R6, C(S)R6, NR14R15, NR14C(S)R6, NR14S(O)R6, NR14S(O)2R6, OR14, OC(S)R6, OS(O)R6, OS(O)2R6, S(O)R6, S(O)2R6, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- each R6 is independently hydrogen, alkyl, alkenyl, alkynyl, NR7R7, OR7, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R8 substituents;
- each R7 is independently hydrogen, alkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each alkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R8 substituents;
- each R8 is independently halogen, alkyl, haloalkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, NR12R13, S(O)2alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- each R12 is independently hydrogen, alkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, C(O)alkyl, C(S)alkyl, S(O)alkyl, S(O)2alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- each R13 is independently hydrogen, alkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, C(O)alkyl, C(S)alkyl, S(O)alkyl, S(O)2alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- R1 and R1, together with the ring carbon atom to which they are attached, form a cyclohexylene, wherein the cyclohexylene is optionally substituted with 1 or 2 independently selected R50 substituents;
- each R50 is independently halogen, cyano, alkyl, haloalkyl, C(O)R6, C(S)R6, NR14R15, NR14C(S)R6, NR14S(O)R6, NR14S(O)2R6, OR14, OC(S)R6, OS(O)R6, OS(O)2R6, S(O)R6, S(O)2R6, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- R3 is hydrogen, alkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, C(O)R6, C(S)alkyl, NR14R15, OR14, S(O)2alkyl, heterocyclyl, aryl, or heteroaryl;
- each R14 is independently hydrogen, alkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, C(O)R6, C(S)alkyl, S(O)2alkyl, heterocyclyl, or heteroaryl;
- and
- each R15 is independently hydrogen, alkyl, alkylene-aryl, alkylene-heteroaryl, alkenyl, alkynyl, C(O)R6, C(S)alkyl, S(O)2alkyl, heterocyclyl, or heteroaryl;
- with the provisos that:
- (1) at least one of X1, X2, X3, X4, and X5 is CR2;
- and
- (2) no more than two of X1, X2, X3, X4, and X5 are N.
21 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the following structure:
- .
Dependencies are inferred from the claim text.