COMPOUNDS FOR THE MODULATION OF CYCLOPHILINS FUNCTION

• Main Authors: HULME, Alison, MICHEL, Julien, DOUGHTY SHENTON, Dahlia, JUAREZ-JIMENEZ, Jordi, IOANNIDIS, Charalampos, DE SIMONE, Alessio, WALKINSHAW, Malcolm, GEORGIOU, Charis, GUPTA, Arun
• Format: Patent
• Language: English; French; German
• Published: 07.07.2021
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

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.