Design, synthesis and antimycobacterial activity of less lipophilic Q203 derivatives containing alkaline fused ring moieties. Issue 5 (1st March 2019)

• Record Type: Journal Article
• Authors: Wang, Apeng; Wang, Hongjian; Geng, Yunhe; Fu, Lei; Gu, Jian; Wang, Bin; Lv, Kai; Liu, Mingliang; Tao, Zeyu; Ma, Chao; Lu, Yu
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 5(2019)
• Page Start: 813
• Page End: 821
• Publication Date: 2019-03-01
• Subjects: Tuberculosis -- Imidazo[1, 2-a]pyridine-3-carboxamides -- hERG K+ channel inhibition -- Pharmacokinetics -- Structure-activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.01.022
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: We report herein the design and synthesis of a series of less lipophilic Q203 derivatives containing an alkaline fused ring moiety. Most of them show considerable potency against MTB H37Rv strain (MIC < 0.25 μM). Nine compounds (13, 15, 19, 21, 23, 25, 29, 35, 36 ) have the same excellent activity against both drug-sensitive and -resistant strains (MIC < 0.035 μM) as Q203 and PBTZ169. Especially, compound29 also displays acceptable safety, greater absorption in plasma and aqueous solubility than Q203, suggesting its promising potential to be lead compound for future antitubercular drug discovery.