Design, synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic terminus

注册 English

Design, synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic terminus

Shi Ding , Wen-Ke Wang , Qiao Cao , Wen-Jing Chu , Le-Fu Lan , Wen-Hao Hu , Yu-She Yang

Citation: Shi Ding, Wen-Ke Wang, Qiao Cao, Wen-Jing Chu, Le-Fu Lan, Wen-Hao Hu, Yu-She Yang. Design, synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic terminus[J]. Chinese Chemical Letters, 2015, 26(6): 763-767. doi: 10.1016/j.cclet.2015.03.029 shu

shu

Design, synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic terminus

通讯作者: Yu-She Yang,

基金项目:

Manufacturing Program, China (No. 2014ZX09507009-016). (No. 2014ZX09507009-016)

摘要: In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coli and Pseudomonas aeruginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes (rat andmouse), which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.

关键词:

English

Design, synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic terminus

1.
a State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
2.
b Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China

Corresponding author: Yu-She Yang,

Received Date: 18 December 2014
Available Online: 28 March 2015

Abstract: In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coli and Pseudomonas aeruginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes (rat andmouse), which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.

Key words:

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