Sulfonamide-based non-alkyne LpxC inhibitors as Gram-negative antibacterial agents.

Journal: Bioorganic & medicinal chemistry letters
PMID:

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

  • Tetsuya Kawai
    Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
  • Iwase Kazuhiko
    Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
  • Noriko Takaya
    Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
  • Yuko Yamaguchi
    Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
  • Ryuta Kishii
    Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
  • Yasushi Kohno
    Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
  • Haruaki Kurasaki
    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.