INDOLE AND INDOLIZIDINE DERIVATIVES FOR THE TREATMENT OF MIGRAINE

摘要

Described herein are compounds useful in the treatment of migraine, which have general formula (I) wherein: X is selected from the group consisting of N, CH; R1 represents a 5- to 7-membered monocyclic or benzo-fused heterocyclic ring, which may be unsaturated, and which may contain one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, amino and mono- or di-lower alkyl amino; Ak represents a C1-3alkylene chain which may be substituted with R2, where R2 represents lower alkyl; R3 and R4 are independently selected from the group consisting of H, lower alkyl, lower alkenyl, cycloalkyl and optionally-substituted benzyl; or one pair of R2 and R3 or R3 and R4 together may form an alkylene or alkenylene bridge which, with the nitrogen atom, form a 3- to 7-membered ring which may contain one or more substituents selected from the group consisting of lower alkyl, hydroxy, hydroxymethyl, alkoxymethyl, amino and substituted amino; R5 is selected from the group consisting of H, lower alkyl and a 4- to 7-membered carbocyclic or heterocyclic group, which may be unsaturated; and a salt, solvate or prodrug thereof. Also disclosed are novel compounds of formula (II) wherein: X is selected from the group consisting of N and CH; R6 represents a 5- to 7-membered monocyclic or benzo-fused heterocyclic ring, which may be unsaturated, and which may contain one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, amino and mono- or di-lower alkyl amino; Ak represents a C1-3alkylene chain which may be substituted with R7, where R7 represents lower alkyl; R8 and R9 are independently selected from the group consisting of H, lower alkyl, lower alkenyl, cycloalkyl and optionally-substituted benzyl; R10 is selected from the group consisting of H, lower alkyl and a 4- to 7-membered carbocyclic or heterocyclic group, which may be unsaturated, and a salt, solvate or prodrug thereof.