Bioorganic and Medicinal Chemistry Letters p. 6492 - 6499 (2013)
Update date:2022-09-26
Suryadevara, Praveen Kumar
Racherla, Kishore Kumar
Olepu, Srinivas
Norcross, Neil R.
Tatipaka, Hari Babu
Arif, Jennifer A.
Planer, Joseph D.
Lepesheva, Galina I.
Verlinde, Christophe L.M.J.
Buckner, Frederick S.
Gelb, Michael H.
New dialkylimidazole based sterol 14α-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 <1 nM) against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate.
View MoreJiaxing Anrui Material Technology Co., Ltd.
Contact:86-573-82651652 13305832579
Address:Room 407, Technology Building, 1369 Chennan Road, Jiaxing City, Zhejiang, China
FOSHAN NANHAI ZHONGNAN PHARMACEUTICAL FACTORY
Contact:0086-0757-85609331
Address:XIAHENGTIAN INDUSTRIAL ZONE,SHAYONG VILLAGE,LISHUI TOWN
Jintan City Mego Chemical Co., Ltd
Contact:+86-0519-82814387
Address:23# Dengguan Town, Jintan, Jiangsu Province, China
WUXI KINGHAN BIO-MEDICAL&CHEMICAL INC.
Contact:13861062998
Address:Room 1316,No.1619 Huishan Avenue,Wuxi,China
Contact:86-25-58619180
Address:Nanjing High-Tech Zone 10 Xinghuo Road Pukou District Nanjing, Jiangsu 210061 The People's Republic of China
Doi:10.1134/S1070363206070280
(2006)Doi:10.1021/ja049846j
(2004)Doi:10.1039/c39840000990
(1984)Doi:10.1021/acs.joc.8b01294
(2018)Doi:10.1016/j.ejmech.2006.12.012
(2007)Doi:10.1002/anie.200701203
(2007)