Exploration of peptidyl hydrazones as water-soluble calpain inhibitors.
A series of peptidyl hydrazones was synthesized, and their inhibitory activity against mu-calpain and water-solubility were measured. Among these compounds, N,N-dimethyl glycyl hydrazone 6, which inhibited mu-calpain with IC(50) of 0.37 microM, possessed the appropriate water-solubility. Furthermore, hydrazone 6 was found to possess the excellent in vitro metabolic stability.
Nakamura
Masayuki
M
Research Laboratory, Senju Pharmaceutical Co., Ltd., 1-5-4 Murotani Nishiku, Kobe 651-2241, Japan. masayuki-nakamura@senju.co.jp
Inoue
Jun
J
D001711:Biotransformation; D002154:Calpain / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D014867:Water / Q000737:chemistry
D015853:Cysteine Proteinase Inhibitors; D006835:Hydrazones; D014867:Water; D002154:Calpain