Novel heterocyclic analogs of the new potent class of calcium entry blockers: 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines

Abstract
Several heterocyclic analogues of the potent 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines were synthesized and evaluated for their antagonistic calcium activities in comparison with the 1-sulfonylindolizine SR 33557 and the usual calcium antagonist references verapamil, cis-(+)-diltiazem, and nifedipine. The bicyclic nine-membered rings were, in general, more potent than the bicyclic 10-membered or five-membered rings. Among the bicyclic nine-membered rings, the indole nucleus appeared to be extremely favorable to support the calcium antagonistic activity. In particular, compound 36, with an IC50 value for the inhibition of [3H]nitrendipine equal to 0.072 nM, is among the most potent calcium antagonist known. This compound has been selected for clinical development.

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