公开(公告)号：US20210238130A1

公开(公告)日：2021-08-05

申请号：US17269338

申请日：2019-08-29

申请人： The University Court of The University of Edinburgh

发明人： Julien MICHEL ,  Alessio DE SIMONE ,  Charalampos IOANNIDIS ,  Jordi JUAREZ-JIMENEZ ,  Charis GEORGIOU ,  Arun GUPTA ,  Alison HULME ,  Malcolm WALKINSHAW ,  Dahlia DOUGHTY SHENTON

IPC分类号： C07C275/24 ,  C07D257/04 ,  C07C323/60 ,  C07D491/08 ,  C07D207/16 ,  C07D403/12

摘要： 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: R1 and R2 are 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 R2 could also be a sulphide; each R is independently hydrogen, C1-6 aliphatic, C3-10 aryl, 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; R3 is Formula (Ia) selected from the group consisting of —OEt, and wherein R5 and R6 are independently selected from the group consisting of H, halide, methoxy, thiomethyl, morpholine and trifluoromethyl; R4 is selected from the group consisting of C1-6-alkyl-, and R4.1—CH2— wherein, R4.1 is C3-6-cycloalkyl-, a 5-6 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, sulphur; optionally substituted with one R4.1.1 wherein, R4.1.1 is selected from —H, C1-4-alkyl, optionally substituted with one substituent selected from H2N(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 —NH2, 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.