Journal of Medicinal Chemistry p. 2376 - 2387 (2012)
Update date:2022-08-05
Topics:
Lamarche, Matthew J.
Leeds, Jennifer A.
Amaral, Adam
Brewer, Jason T.
Bushell, Simon M.
Deng, Gejing
Dewhurst, Janetta M.
Ding, Jian
Dzink-Fox, Joanne
Gamber, Gabriel
Jain, Akash
Lee, Kwangho
Lee, Lac
Lister, Troy
McKenney, David
Mullin, Steve
Osborne, Colin
Palestrant, Deborah
Patane, Michael A.
Rann, Elin M.
Sachdeva, Meena
Shao, Jian
Tiamfook, Stacey
Trzasko, Anna
Whitehead, Lewis
Yifru, Aregahegn
Yu, Donghui
Yan, Wanlin
Zhu, Qingming
Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.
View MoreJiangsu Zhenfang Chemical CO.,LTD.(Suzhou Zhenfang Chemical Factory)
Contact:+86-512-69598882
Address:Room1201, Jiayuan Road No.1018, Xiangcheng District, Suzhou, China
Shandong united-rising pharmaceutical cooperation.,ltd.
Contact:008653187965009
Address:171No., Jing5 Road, Shizhong District, Jinan, China
Hangzhou Deli Chemical Co.,Ltd.
website:http://www.dlchemical.com
Contact:86 571 28006267
Address:Tangxi Industrial Area, Yuhang District, Hangzhou
Shantou Baokang Pharmaceutical Co., Ltd.
Contact:+86-754-88873487
Address:5/F B Block Huangshan Bldg Huangshan Rd Shantou
Shanghai Run-Biotech Co., Ltd.
website:http://www.run-biotech.com
Contact:+86-21-31576854/57171705 / 57171706
Address:second floor, building 3, No.999, jiangyue Road, minghang District, Shanghai, China
Doi:10.1016/j.ica.2011.11.038
(2012)Doi:10.1002/1099-0690(200109)2001:18<3559::AID-EJOC3559>3.0.CO;2-V
(2001)Doi:10.7164/antibiotics.29.1286
(1976)Doi:10.1021/jo00214a021
(1985)Doi:10.1039/C39760000835
(1976)Doi:10.1016/S0040-4039(00)92580-2
(1976)