FIELD: pharmaceutical chemistry.
SUBSTANCE: group of inventions includes a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, (1R,3S)-3-[3-({[3-(methoxymethyl)-1-methyl-1 H-pyrazol-5-yl]carbonyl}amino)-1 H-pyrazol-5-yl]cyclopentyl propan-2-ylcarbamate, (1R,3S)-3-(3-{[(3-methyl-1,2-oxazol-5-yl)acetyl]amino}-1H-pyrazol-5-yl)cyclopentyl(1-methylcyclopropyl)carbamate or a pharmaceutically acceptable solvate thereof, a pharmaceutical composition and use based on these compounds, as well as a method for the treatment of cancer associated with inhibition of CDK2 activity. In formula (I), R1 is -L1-(5–10 membered heteroaryl containing 1–4 heteroatoms, each selected from N, O and S) or -L1-(C6-C12 aryl), where the specified 5–10-membered heteroaryl or C6-C12 aryl is optionally substituted with one or two R4; R2 and R3 are independently H, C1-C6 alkyl, C1-C6 fluoroalkyl, -L2-(C3-C7 cycloalkyl), or -L2-(4-7 membered heterocyclyl containing 1–2 heteroatoms, each selected from N or O), where each specified C1-C6 alkyl and C1-C6 fluoroalkyl is optionally substituted with one R5 and each specified C3-C7 cycloalkyl and 4–7-membered heterocyclyl optionally substituted with one or two R6; or R2 and R3 are taken together with the N-atom to which they are attached to form a 4–6 membered heterocyclyl optionally containing an additional heteroatom that is O as a ring member, wherein the said 4–6 membered heterocyclyl optionally substituted with one to three R8; each L1 and L2 is independently a bond or C1-C2 alkylene; each R4 is independently F, Cl, OH, CN, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, C1-C4 fluoroalkoxy, C3-C8 cycloalkyl, SO2R12, or SO2NR10R11, where each C1-C4 alkyl and C1-C4 fluoroalkyl is optionally substituted with one R13; each R5 is independently OH, C1-C4 alkoxy or NR10R11; each R6 is independently F, OH, C1-C4 alkyl or C1-C4 fluoroalkyl, where each C1-C4 alkyl and C1-C4 fluoroalkyl is optionally substituted with one R13; each R8 is independently F, OH, C1-C4 alkyl, C1-C4 alkoxy, or CN; each R10 and R11 independently represents H or C1-C4 alkyl; each R12 is C1-C4 alkyl or C3-C6 cycloalkyl; each R13 is independently OH, C1-C4 alkoxy or NR14R15; and each R14 and R15 independently represents H or C1-C4 alkyl.
EFFECT: compounds of formula (I) with inhibitory activity against CDK2.
20 cl, 2 dwg, 5 tbl, 18 ex
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