FIELD: chemistry.
SUBSTANCE: present invention relates to a PD-L1 antagonist compound, specifically to a compound of formula (I) or a pharmaceutically acceptable salt or isomer thereof. In Formula (I): L1 is selected from: -CRARB- and -C(O)-; L2, L3, are selected from: -(CRCRD)p, -(CRCRD)p-NRz-(CRCRD)q-, -(CRCRD)p-O-(CRCRD)q- and -C(O)-; W1, W2 each independently represents CRL or N; R1 each independently represents hydrogen or -NRaRb, or -O(C1-C6 alkyl), -O(C0-C6 alkylene)(C3-C6 cycloalkyl) or -O(C0-C6 alkylene)(3–6-membered heterocycloalkyl containing one nitrogen atom) substituted with 0, 1, 2 or 3 substitutes; R2 represents hydrogen, halogen, nitro, cyano, -NRaRb, -SO2Ra, -S(O)Ra, C1-C6 alkyl, -O(C1-C6 alkyl), -O(C3-C6 cycloalkyl), halogen(C1-C6 alkyl) or C3-C6 cycloalkyl; R3 and R4 each independently represents hydrogen or halogen; R5 is independently hydrogen, halogen, cyano, C1-C6 alkyl, halogen(C1-C6 alkyl) or C3-C6 cycloalkyl; Cy is a benzene ring or six-membered heteroaryl substituted with 0, 1, 2 or 3 R6, wherein the six-membered heteroaryl can optionally contain 1 or 2 nitrogen atoms; R6 is hydrogen, halogen, C1-C6 alkyl, C3-C6 cycloalkyl or -O(C1-C6 alkyl), substituted with 0, 1, 2 or 3 halogens, -O(C0-C6 alkylene)(C3-C6 cycloalkyl) or -O(C0-C6 alkylene)(3–6 membered heterocycloalkyl); RL is hydrogen, -O(C1-C6 alkyl), -O(C3-C6 cycloalkyl), halogen or cyano; T is -(C1-C6 alkyl), -(C0-C6 alkylene)-(C3-C12 cycloalkyl) or -(C0-C6 alkylene)-(3–12-membered heterocycle containing at least one heteroatom selected from the group consisting of a nitrogen atom and an oxygen atom) substituted with 0, 1, 2 or 3 substituents; A is -(C1-C6 alkyl), -(C0-C6 alkylene)-(C3-C12 cycloalkyl), -(C0-C6 alkylene)-(3–12-membered heterocycle containing at least one nitrogen atom), -(C0-C6 alkylene)-(C6-C10 aryl) or -(C0-C6 alkylene)-(5–10 membered heteroaryl containing at least one nitrogen atom), substituted with 0, 1, 2 or 3 substitutes; m, o each independently represents 0, 1 or 2; and p, q each independently represents 0, 1, 2 or 3; values RA, RB, RC, RD, Ra and Rb are defined in the claims. Also disclosed is a compound selected from a group of individual compounds, a pharmaceutical composition, use of said compounds or a pharmaceutical composition, a method of treating and a method of inhibiting binding of PD-L1 with PD-1.
EFFECT: disclosed compounds have inhibitory activity on PD-L1/PD-1 and can be used to treat/prevent disorders responsive to inhibition of PD-L1 binding with PD-1.
29 cl, 1 tbl, 173 ex
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