title: Side-chain modified analogues of histaprodifen: asymmetric synthesis and histamine H1-receptor activity.
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%).
authors.affiliation: Institut für Organische Chemie, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Rameshwar
authors.initials: R
authors.lastname: Patil
authors.forename: Sigurd
authors.initials: S
authors.lastname: Elz
authors.forename: Oliver
authors.initials: O
authors.lastname: Reiser
mesh_terms: D000215:Acylation; D000818:Animals; D006168:Guinea Pigs; D006632:Histamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017442:Histamine Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007082:Ileum / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; C118994:histaprodifen; D006632:Histamine