| abstract |
Compounds of formula (I) and pharmaceutically accetable salts thereof:n wherein:n Y is N or (when R 3 is hydroxy, C 1-6 alkoxy or C 1-7 acyloxy) CH; one of R 1 and R 2 is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl or R 1 and R 2 together are C 2 -s-polymethylene; R 3 is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 acyloxy; R 4 is a C 3-8 cycloalkyl group or a C 1-6 alkyl group optionally substituted by a group R 7 which is hydroxy, C 1-6 alkoxy, amino optionally substituted by one or two C 1-6 alkyl groups; C 1-7 alkanoylamino, C 3-8 cycloalkyloxy, C 3-8 cycloalkylamino, or 1,3-dioxo-2-isoindoline; n when Y is N, R 5 is hydrogen, C 1-6 alkyl optionally substituted by halogen, hydroxy, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, carboxy or amino optionally substituted by one or two independent C 1-6 alkyl groups, or C 2-6 alkenyl, amino optionally substituted by a C 1-6 alkyl, C 3 -a cycloalkyl or C 1-6 alkenyl group or by a C 1-6 alkanoyl group optionally substituted by up to three halo atoms, by a phenyl group optionally substituted by C 1-6 alkyl, C 1-6 alkoxy or halogen, or aryl or heteroaryl, either being optionally substituted by one or more groups or atoms selected from the class of C 1-6 alkyl, C 1-6 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, C 1-12 carboxylic acyl, or amino or aminocarbonyl optionally substituted by one or two C 1-6 alkyl groups and R 6 is hydrogen or C 1-6 alkyl, or R 5 and R 6 together are -CH 2 -(CH 2 ) n -Z-(CH 2 ) m - wherein m and n are 0 to 2 such that m + n is 1 or 2 and Z is CH 2 , O, S or NR wherein R is hydrogen, C 1-9 alkyl, C 2 - 7 alkanoyl, phenyl C 1-4 -alkyl, naphthylcarbonyl, phenylcarbonyl or benzyl-carbonyl optionally substituted in the phenyl or naphthyl ring by one or two of C 1-6 alkyl, C 1-6 alkoxy or halogen; mono- or bi-cyclic- heteroarylcarbonyl; n when Y is CH, R 5 is NR 8 R 9 wherein R 8 and R 9 are independently C 1-6 alkyl, R 8 is hydrogen and R 9 is C 1-6 alkyl or R 8 and R 9 together are C 4-5 polymethylene; or R 6 and R 8 together are -(CH 2 )p- wherein p is 2 or 3, and R 9 is hydrogen or C 1-6 alkyl; or R 5 is CH 2 R 10 wherein R 10 is hydrogen or C 1-5 alkyl; or R 6 and R 10 are -(CH 2 )q- wherein q is 2 or 3;n X is oxygen or sulphur; or R 5 , R 6 , X and Y (when N) together are tetrahydroisoquinolinone ortetrahydroisoquinolinthione, optionally substituted in the phenyl ring as defined for R above; the nitrogen-containing group is in the 4-position being trans to the R 3 group when R 3 is hydroxy, C 1-6 alkoxy or C 1-7 acyloxy; having K+ channel activator activity, processes for their preparation and their use as pharmaceuticals. |