The University of Edinburgh

Malcolm Walkinshaw

Julien Michel

Jordi Juarez-Jimenez

Dahlia Doughty Shenton

Charis Georgiou

Charalampos Ioannidis

Alessio De Simone

Alison Hulme

Arun Gupta

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 &#x2014;R, -haloalkyl, -hydroxyalkyl, &#x2014;OR, &#x2014;C(O)R, &#x2014;CO2R, &#x2014;C(O)N(R)2, &#x2014;NRC(O)R, and &#x2014;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 &#x2014;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&#x2014;CH&#x2014; 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 &#x2014;H, C-alkyl, optionally substituted with one substituent selected from HN(O)C&#x2014; or EtO(O)C&#x2014;; 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 &#x2014;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 &#x2014;OH; and m is 1 or 2; and n is 1 or 2.

Compounds for the modulation of cyclophilins function

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Edinburgh, United Kingdom

Malcolm Walkinshaw