Journal of Medicinal Chemistry p. 613 - 624 (2015)
Update date:2022-08-16
Topics:
?ink, Roman
Sosi?, Izidor
?ivec, Matej
Fernandez-Menendez, Raquel
Turk, Samo
Pajk, Stane
Alvarez-Gomez, Daniel
Lopez-Roman, Eva Maria
Gonzales-Cortez, Carolina
Rullas-Triconado, Joaquin
Angulo-Barturen, Inigo
Barros, David
Ballell-Pages, Lluís
Young, Robert J.
Encinas, Lourdes
Gobec, Stanislav
Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.
View MoreLiaoyang Xinyou Chemical Products Co.,Ltd.
Contact:+86-419-5165433 13604191870
Address:Huishang Road6-1, Hongwei District, Liaoyang, Liaoning, China
Henan zhongda Biological Engineering Co., Ltd
Contact:86-28-18109029985
Address:shenzhou road,xuedian industrial estate,zhengzhou city,henan province CHN
Beijing Hope Pharmaceutical Co., Ltd.
Contact:86-10-67886402
Address:309,Block 1 District B,No.12 Hongda North Road , Beijing Economic-Technological Development Area, Beijing, China
Ningbo Inno Pharmchem Co., Ltd.
Contact:86-574-87319282
Address:6F-5,NO.163 RUIQING RD.,NINGBO 315000 CHINA
website:http://www.acrospharmatech.com
Contact:+1-3234804688
Address:Flat/RM 1502,Easey Commercial building 253-261 Hennessy Road,Wanchai,HongKong
Doi:10.1016/0040-4039(95)00167-B
(1995)Doi:10.1021/acs.bioconjchem.8b00361
(2018)Doi:10.1039/a905974a
(1999)Doi:10.1039/C6RA27003D
(2017)Doi:10.1002/cssc.201300120
(2013)Doi:10.1021/jo01348a521
(1966)