Syntheses and SH-enzyme inhibitory activities of new epoxysuccinic acid piperazine derivatives against mu-calpain and cathepsin B.
New chiral epoxysuccinic acid derivatives 5 approximately 23 bearing various amino acids and N-substituted piperazines were synthesized to evaluate their inhibitory activities against mu-calpain and cathepsin B. After screening these compounds, 1-[(2S,3S)-epoxysuccinyl-L-leucyl]-4-(2-chlorophenyl)piperazine 9 proved to exhibit fairly strong inhibitory activity against both cysteine proteases. L-Valyl derivative 19 exhibited selective inhibitory activity against cathepsin B in comparison with that against mu-calpain.
Inoue
J
J
Kobe Creative Center, Senju Pharmaceutical CO., LTD., Hyogo, Japan.
Yoshida
Y
Y
Nakamura
M
M
Cui
Y S
YS
Nagao
Y
Y
D002154:Calpain / Q000037:antagonists & inhibitors*; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D019802:Succinic Acid / Q000737:chemistry
D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D010879:Piperazines; D019802:Succinic Acid; D002154:Calpain; D002401:Cathepsin B