Novel H3 receptor antagonists with improved pharmacokinetic profiles.
A new series of H(3) antagonists derived from the natural product Conessine are presented. Several compounds from these new series retain the potency and selectivity of earlier diamine based analogs while exhibiting improved PK characteristics. One compound (3u) demonstrated functional antagonism of the H(3) receptor in an in vivo pharmacological model.
Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA. vsantora@arenapharm.com
Vincent J
VJ
Santora
Jonathan A
JA
Covel
Rena
R
Hayashi
Brian J
BJ
Hofilena
Jason B
JB
Ibarra
Michelle D
MD
Pulley
Michael I
MI
Weinhouse
Graeme
G
Semple
Albert
A
Ren
Guilherme
G
Pereira
Jeffrey E
JE
Edwards
Marissa
M
Suarez
John
J
Frazer
William
W
Thomsen
Erin
E
Hauser
Jodie
J
Lorea
Andrew J
AJ
Grottick
D000470:Alkaloids / Q000493:pharmacokinetics*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006633:Histamine Antagonists / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D051381:Rats; D018100:Receptors, Histamine H3 / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000470:Alkaloids; D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; C007111:conessine