Importance

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Abstract

Compounds of formula (1a) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, —C₁-Cealkyl, —C₁-Ceaminoalkyl, —C₁-C₆hydroxyalkyl, -haloC₁-C₆alkyl, —C₁-C₆alkoxyl, -haloC₁—C6alkyl, —CH₂OC(O)CrC₆alkyl, —C(O)OC₁, —C₆alkyI, —NHC(O)C₁, —C6alkyl, —NHS(O)₂C₁-C₆alkyl, —S(O)₂C₁-C₆alkyl, —S(O)₂NH₂, and —C(O)NJJ; Ring B is a 6-10 membered arylene or a 5-6 membered heteroarylene comprising at least one heteroatom selected from N, 0 or S; and wherein the aryl or heteroaryl is optionally, substituted with one or more substituents selected from —NJJ, —OJ, halo, C₁-C₆alkyl, -haloC₁-C6alkyl, —C₁-C₆alkoxy, -haloC₁-C₆alkoxyl, and —C(0)NJJ; Ring C is selected from a 5-10 membered heteroarylene or a 5-10 membered heterocyclene, each comprising at least one heteroatom selected from N, S and O; Ring D is an optionally substituted benzofused 9-11 membered heterocyclyl or optionally substituted ben2ofused 9-11 membered heteroaryl comprising at least one heteroatom selected from N or O; L is a linker selected from branched and unbranched C1-C4 alkylene, —S(0)2-NH—, —C(0)-NH—, —NH—C(0)-NH—, —S(0)2-NH—C(0)-NH—, —S(0)2-NH—C(0)- and —CH═CH—; wherein Rings B and C, and Rings C and D, are connected to each other via a C—C bond at any of the available C atoms on each respective ring; and J in each occurrence is independently selected from H, optionally substituted C₁-C₆alkyl or optionally substituted haloC₁-C₆alkyl.

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First Claim