- 5-Isoquinolinesulfonamide derivatives. III. Synthesis and vasodilatory activity of 1-(5-isoquinolinesulfonyl)piperazine derivatives
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On the basis of a hypothesis that cyclization and alkylation of the diamine part in formula 1 may give highly active compounds, a new series of 5-isoquinolinesulfonamide derivatives, shown as formula 2, were prepared from cyclic diamines. Their vasodilatory effects were subsequently evaluated in vivo according to the increase in arterial blood flow after the formulas were injected locally to the femoral and/or vertebral arteries of dogs. Cyclization of the diamine structure in formula 1 gave very potent vasodilators: 6 and 14. Acylation and sulfonylation of terminal amino nitrogen afforded much less potent compounds. In contrast to the hypothesis, alkylation on the ring carbon and the terminal nitrogen of the cyclic amine afforded less active compounds except for compound 11. The most active compounds, 6, 11 and 14, showed more potent vasodilatory effects and more selective activity to the vertebral artery than either trapidil or diltiazem.
- Morikawa,Sone,Asano
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p. 770 - 773
(2007/10/02)
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- Isoquinolinesulfonyl derivatives and process for the preparation thereof
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A 5-isoquinolinesulfonyl derivative of Formula (I): STR1 wherein l is zero or one; m and n each is an integer of one to nine; m+n is an integer of at least one; R1 is a hydrogen atom, a C1-10 alkyl group, a C5-6 cycloalkyl group or an aryl group; or R2 and R3 each is a hydrogen atom, a C1-10 alkyl group, a C5-6 cycloalkyl group, an aryl group or an aralkyl group; R2 and R3 are C1-6 alkylene groups and linked directly or through an oxygen atom to form a 5- to 7-membered heterocyclic ring with the adjacent nitrogen atom; or the STR2 group is a STR3 group wherein R4 and R5 each is a hydrogen atom, a C1-10 alkyl group, an aryl group or an aralkyl group and R6 is a hydrogen atom, a C1-10 alkyl group, and aryl group, an aralkyl group, a benzoyl group, a cinnamyl group, a cinnamoyl group, a furoyl group or a STR4 group wherein R7 is a C1-8 alkyl group; and the pharmaceutically acceptable salt thereof; and a process for the preparation thereof. The compounds of this invention have a relaxatory action for vascular smooth muscle and are useful as a vasodilator and a hypotensor.
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