title: Sulfonamide-based non-alkyne LpxC inhibitors as Gram-negative antibacterial agents.
abstract: We attempted to optimize sulfonamide-based non-alkyne LpxC inhibitors by focusing on improvements in enzyme inhibitory and antibacterial activity. It was discovered that inhibitors possessing 2-aryl benzofuran as a hydrophobe exhibited good activity. In particular, compound 21 displayed impressive antibacterial activity (E. coli MIC=0.063μg/mL, K. pneumoniae MIC=0.5μg/mL, and P. aeruginosa MIC=0.5μg/mL), and is a promising lead for further exploration as an antibacterial agent.
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
authors.forename: Iwase
authors.initials: I
authors.lastname: Kazuhiko
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takaya
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kishii
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kohno
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. Electronic address: haruaki.kurasaki@mb.kyorin-pharm.co.jp.
authors.forename: Haruaki
authors.initials: H
authors.lastname: Kurasaki
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013449:Sulfonamides; D000581:Amidohydrolases; C097307:UDP-3-O-acyl-N-acetylglucosamine deacetylase
keywords: Antibacterial; Benzofuran; Gram-negative; LpxC; Sulfonamide