Compounds for the modulation of cyclophilins function

Abstract

The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof useful as inhibitors of Cyclophilins and modulators of cyclophilin-like proteins. The invention also relates to uses of said compounds in the treatment of various disorders. Formula (I), wherein: Rand Rare each independently is selected from the group consisting of —R, -haloalkyl, -hydroxyalkyl, —OR, —C(O)R, —CO2R, —C(O)N(R)2, —NRC(O)R, and —N(R)2; wherein Rcould also be a sulphide; each R is independently hydrogen, Caliphatic, Caryl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, sulphur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms selected from nitrogen, oxygen, or sulphur; Ris Formula (Ia) selected from the group consisting of —OEt, and wherein Rand Rare independently selected from the group consisting of H, halide, methoxy, thiomethyl, morpholine and trifluoromethyl; Ris selected from the group consisting of C-alkyl-, and R—CH— wherein, Ris C-cycloalkyl-, a 5-6 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, sulphur; optionally substituted with one Rwherein, Ris selected from —H, C-alkyl, optionally substituted with one substituent selected from HN(O)C— or EtO(O)C—; X is carbon or nitrogen; A is selected from the group consisting of 6 membered unsaturated ring, with 1-3 nitrogen atoms, which is optionally substituted by —NH, and Formula (Ib), wherein ring B is a fused 5-10 membered saturated or partially unsaturated heterocyclic mono-bicyclic ring having 1-3 heteroatoms selected from nitrogen, oxygen or sulphur, which is optionally substituted by —OH; and m is 1 or 2; and n is 1 or 2.