A novel class of H3 antagonists derived from the natural product guided synthesis of unnatural analogs of the marine bromopyrrole alkaloid dispyrin.
This Letter describes the natural product guided synthesis of unnatural analogs of the marine bromopyrrole alkaloid dispyrin, and the resulting SAR of H(3) antagonism. Multiple rounds of iterative parallel synthesis improved human H(3) IC(50) approximately 33-fold, and afforded a new class of H(3) antagonists based on the novel bromotyramine core of dispyrin.
Kennedy
J Phillip
JP
Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
Conn
P Jeffrey
PJ
Lindsley
Craig W
CW
D000470:Alkaloids / Q000737:chemistry; D000818:Animals; D001688:Biological Products / Q000737:chemistry; D001966:Bromine; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D011161:Porifera; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D018100:Receptors, Histamine H3 / Q000187:drug effects; D013329:Structure-Activity Relationship; D013566:Sympathomimetics; D014439:Tyramine
D000470:Alkaloids; D001688:Biological Products; D054828:Histamine H3 Antagonists; D011758:Pyrroles; D018100:Receptors, Histamine H3; D013566:Sympathomimetics; C519748:dispyrin; D001966:Bromine; D014439:Tyramine