Synthesis and evaluation of potent pyrrolidine H(3) antagonists.
The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable, to afford several compounds with high affinity and selectivity for the H(3) receptor.
Vasudevan
Anil
A
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60031, USA. anil.vasudevan@abbott.com
Conner
Scott E
SE
Gentles
Robert G
RG
Faghih
Ramin
R
Liu
Huaqing
H
Dwight
Wesley
W
Ireland
Lynne
L
Kang
Chae Hee
CH
Esbenshade
Timothy A
TA
Bennani
Youssef L
YL
Hancock
Arthur A
AA
D000215:Acylation; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship
D006633:Histamine Antagonists; D008024:Ligands; D011759:Pyrrolidines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3