Aplysamine-1 and related analogs as histamine H3 receptor antagonists.
Aplysamine-1 (1), a marine natural product, was synthesized and screened for in vitro activity at the human and rat histamine H3 receptors. Aplysamine-1 (1) was found to possess a high binding affinity for the human H3 receptor (Ki = 30+/-4 nM). Synthetic analogs of 1, including des-bromoaplysamine-1 (10) and dimethyl-{2-[4-(3-piperidin-1-yl-propoxy)-phenyl]-ethyl}-amine (13), were potent H3 antagonists.
Swanson
Devin M
DM
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. dswanso1@prdus.jnj.com
Wilson
Sandy J
SJ
Boggs
Jamin D
JD
Xiao
Wei
W
Apodaca
Richard
R
Barbier
Ann J
AJ
Lovenberg
Timothy W
TW
Carruthers
Nicholas I
NI
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D008024:Ligands; D018100:Receptors, Histamine H3; C509742:aplysamine-1; D014443:Tyrosine