Side-chain modified analogues of histaprodifen: asymmetric synthesis and histamine H1-receptor activity.
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%).
Patil
Rameshwar
R
Institut für Organische Chemie, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
Elz
Sigurd
S
Reiser
Oliver
O
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
D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; C118994:histaprodifen; D006632:Histamine