2. Academic Validation
  3. Discovery of LFF571: an investigational agent for Clostridium difficile infection

Discovery of LFF571: an investigational agent for Clostridium difficile infection

  • J Med Chem. 2012 Mar 8;55(5):2376-87. doi: 10.1021/jm201685h.
Matthew J LaMarche 1,  Jennifer A Leeds,  Adam Amaral,  Jason T Brewer,  Simon M Bushell,  Gejing Deng,  Janetta M Dewhurst,  Jian Ding,  JoAnne Dzink-Fox,  Gabriel Gamber,  Akash Jain,  Kwangho Lee,  Lac Lee,  Troy Lister,  David McKenney,  Steve Mullin,  Colin Osborne,  Deborah Palestrant,  Michael A Patane,  Elin M Rann,  Meena Sachdeva,  Jian Shao,  Stacey Tiamfook,  Anna Trzasko,  Lewis Whitehead,  Aregahegn Yifru,  Donghui Yu,  Wanlin Yan,  Qingming Zhu
Affiliations

Affiliation

  • 1 Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. matthew.lamarche@novartis.com
PMID: 22315981 DOI: 10.1021/jm201685h
Abstract

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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z