Bioorganic and Medicinal Chemistry Letters p. 3500 - 3503 (2008)
Update date:2022-07-29
Topics:
McAtee, John J.
Dodson, Jason W.
Dowdell, Sarah E.
Girard, Gerald R.
Goodman, Krista B.
Hilfiker, Mark A.
Sehon, Clark A.
Sha, Deyou
Wang, Gren Z.
Wang, Ning
Viet, Andrew Q.
Zhang, Daohua
Aiyar, Nambi V.
Behm, David J.
Carballo, Luz H.
Evans, Christopher A.
Fries, Harvey E.
Nagilla, Rakesh
Roethke, Theresa J.
Xu, Xiaoping
Yuan, Catherine C.K.
Douglas, Stephen A.
Neeb, Michael J.
This work describes the development of potent and selective human Urotensin-II receptor antagonists starting from lead compound 1, (3,4-dichlorophenyl)methyl{2-oxo-2-[3-phenyl-2-(1-pyrrolidinylmethyl)-1-piperidinyl]ethyl}amine. Several problems relating to oral bioavailability, cytochrome P450 inhibition, and off-target activity at the kappa opioid receptor and cardiac sodium channel were addressed during lead development. hUT binding affinity relative to compound 1 was improved by more than 40-fold in some analogs, and a structural modification was identified which significantly attenuated both off-target activities.
View MoreContact:410-273-7300; 800-221-3953
Address:4609 Richlynn Dr., PO Box 369, Belcamp, MD, 21017-0369, USA
Nantong LiKai Chemical Co.,Ltd
Contact:+86-513-89068669
Address:Jincheng Science Park
SPRING CHEMICAL INDUSTRY CO.,LTD
Contact:86-187-66672125
Address:linchi industry park.zouping
HANGZHOU YUNUO CHEMICAL CO.,LTD
website:http://www.yunuochem.com
Contact:0571-83715115
Address:hangzhou
Jingzhou TianHe Sci&Tech Chemical Co., Ltd.
Contact:86-716-8331612
Address:Jiangjin Road, #18, High-grade technology industries development district, Jingzhou city, Hubei province
Doi:10.1039/jr9500000859
(1950)Doi:10.1021/ol802939u
(2009)Doi:10.1002/anie.201004619
(2010)Doi:10.1016/S0040-4039(00)94312-0
(1983)Doi:10.1002/ejoc.201701477
(2018)Doi:10.1021/jo00236a001
(1988)