FIELD: chemistry.
SUBSTANCE: invention relates to a compound with formula (I) or its tautomer or pharmaceutically acceptable salt, where R1 is independently chosen from halogen, nitrile, C1-4 alkyl, hydroxyC1-4 alkyl, C1-4 alkoxy, C2-4 alkynyl, -O0.1 -(CR x Ry )v -CO2 H, -S(O) d -C1-6 alkyl and -S(O)d -heterocyclic group containing 6 ring members containing two heteroatoms, chosen from N and O; R 2 is chosen from hydrogen, C1-4 alkyl, hydroxyC1-4 alkyl, and -(CR x Ry)u -CO2 H; s is chosen from 0 and 1; R3 is hydrogen or -(A)t -(CR x Ry)q -X; t is chosen from 0 and 1; q is chosen from 0, 1 and 2; where when R3 is -(A)t -(CR x Ry)q -X then (i) at least one of s, t and q is not 0 and (ii) when t is 0 then s is equal to 1 and q is not equal to 0; A represents a C3-6 cycloalkyl group or a heterocyclic group containing 4-5 ring members, wherein said heterocyclic group contains one or two heteroatoms chosen from N and O; X is chosen from hydrogen, halogen, -CN, -OR9, -(CH2 ) v -CO2 H, -NHSO2 R x, and -C(=O)NR x R y ; R4 and R5 are halogen; R6 and R are independently chosen from hydrogen, C1-6 alkyl, hydroxyC1-6alkyl, -(CH2)j-O-C1-6 alkyl, -C1-6 alkyl-NR x Ry, - (CR x Ry)p -CONR x Ry, a heterocyclic group containing 5 or 6 ring members containing one or two heteroatoms chosen from O and N, -CH2 -heterocyclic group containing 6 ring members containing two heteroatoms , which are N, and C3-8 cycloalkyl, where said cycloalkyl or heterocyclic groups may be optionally substituted with one or more Rz groups; R9 is chosen from hydrogen and C-1-6 alkyl; Rx and Ry are independently chosen from hydrogen, halogen, C 1-6 alkyl, and hydroxyC1-6 alkyl; or groups Rx and Ry together with the nitrogen atom to which they are attached, can combine to form a saturated heterocyclyl group containing 5 ring members; Rz is independently chosen from halogen, C1-6 alkyl, hydroxy, -(CH2)r -CO2 C1-6 alkyl, and -(CH2)r -CO 2 H; a, j, d, n, r and p are independently chosen from 0, 1 and 2; m is independently chosen from 1 and 2; u is chosen from 0, 1, 2 and 3; and v is chosen from 0 and 1. The invention also relates to compounds represented by formulas (VIIf), (Iw), and specific compounds represented in the claims. The invention relates to a process for the preparation of compounds with formula (I). The compounds of the invention are intended for use in therapy to inhibit the MDM2-p53 interaction.
EFFECT: derivatives of isoindolin-1-one for use in therapy for inhibition of MDM2-p53 interaction. 45 cl, 1 tbl, 137 ex
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