AZETIDINE DERIVATIVE FOR THE TREATMENT OF PERIPHERAL NEUROPATHIES

摘要

A compound of formula A1 or A2 for use in the treatment of a demyelinating peripheral neuropathy: wherein A is COOR5, OPO(OR5)2, PO(OR5)2, SO2OR5, POR5OR5 or 1H-tetrazol-5-yl, R5 being H or an ester-forming group, optionally C1-6alkyl; W is a bond, C1-3alkylene or C2-3alkenylene; Y is C6-10aryl or C2-9heteroaryl eg C3-9heteroaryl, optionally substituted by 1 to 3 radicals selected from halogen, OH, NO2, C1-6alkyl, C1-6alkoxy; halo-substituted C1-6alkyl and halo-substituted C1-6alkoxy; Z is chosen from: wherein the asterisks of Z indicate the point of attachment between—C(R3)(R4)—and A of Formula Ia or Ib, respectively; R6 is chosen from hydrogen and C1-6alkyl; and J1 and J2 are independently methylene or a heteroatom chosen from S, O and NR5; wherein R5 is chosen from hydrogen and C1-6alkyl; and any alkylene of Z can be further substituted by one to three radicals chosen from halo, hydroxy, C1-6alkyl; or R6 can be attached to a carbon atom of Y to form a 5-7 member ring; R1 is C6-10aryl or C2-9heteroaryl eg C3-9heteroaryl, optionally substituted by C1-6alkyl, C6-10aryl, C6-10arylC1-4alkyl, C3-9heteroaryl, C3-9heteroarylC1-4alkyl, C3-8cycloalkyl, C3-8cycloalkylC1-4alkyl, C3-8heterocycloalkyl or C3-8heterocycloalkylC1-4alkyl; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R1 may be substituted by 1 to 5 groups selected from halogen, C1-6alkyl, C1-6alkoxy and halo substituted-C1-6alkyl or—C1-6alkoxy; R2 is H, C1-6alkyl, halo substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl; and each of R3 and R4, independently, is H, halogen, OH, C1-6alkyl, C1-6alkoxy or halo substituted C1-6alkyl or C1-6alkoxy; and the N-oxide derivatives thereof or prodrugs thereof, or a pharmacologically acceptable salt, solvate or hydrate thereof.