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Side-chain modified analogues of histaprodifen: asymmetric synthesis and histamine H1-receptor activity
Rameshwar Patil1, Sigurd Elz, Oliver Reiser
1Institut für Organische Chemie, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
Abstract:
New analogues of histaprodifen with polar side chains have been stereoselectively synthesized and evaluated as histamine H(1)-receptor agonists. As a key transformation the asymmetric aminohydroxylation has been used, which was successfully realized for the first time on an imidazolyl derivative. While all chiral analogues proved to be weak H(1)-receptor antagonists, an achiral keto derivative of histaprodifen turned out to be the first 2-acylated histamine congener displaying partial H(1)-receptor agonism (relative potency 12%).
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