A new family of H3 receptor antagonists based on the natural product Conessine.
A new family of Histamine H(3) receptor antagonists (5a-t) has been prepared based on the structure of the natural product Conessine, a known H(3) antagonist. Several members of the new series are highly potent and selective binders of rat and human H(3) receptors and display inverse agonism at the human H(3) receptor. Compound 5n exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H(3) receptor in an in-vivo pharmacological model.
Santora
Vincent J
VJ
Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA.
Covel
Jonathan A
JA
Hayashi
Rena
R
Hofilena
Brian J
BJ
Ibarra
Jason B
JB
Pulley
Michelle D
MD
Weinhouse
Michael I
MI
Sengupta
Dipanjan
D
Duffield
Jonathan J
JJ
Semple
Graeme
G
Webb
Robert R
RR
Sage
Carleton
C
Ren
Albert
A
Pereira
Guilherme
G
Knudsen
Jens
J
Edwards
Jeffrey E
JE
Suarez
Marissa
M
Frazer
John
J
Thomsen
William
W
Hauser
Erin
E
Whelan
Kevin
K
Grottick
Andrew J
AJ
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D017442:Histamine Agonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000588:Amines; D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; C007111:conessine