Structure-activity relationship studies of chloromethyl ketone derivatives for selective human chymase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 3, 2000, Pages 199-201

  Hayashi, Yoshio ^a,b   Iijima, Kiyoko ^b   Katada, Jun ^b   Kiso, Yoshiaki ^a  

^a KYOTO PHARMACEUTICAL UNIVERSITY   (Japan)

^b Life Science Research Center   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CATHEPSIN G; CHLOROMETHYL KETONE 21; CHYMASE; CHYMOTRYPSIN A; ELASTASE; PEPTIDE CHLOROMETHYL KETONE; TRYPSIN; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; DRUG INHIBITION; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; STRUCTURE ACTIVITY RELATION;

CHYMASES; HUMANS; KETONES; MAGNETIC RESONANCE SPECTROSCOPY; SERINE ENDOPEPTIDASES; SERINE PROTEINASE INHIBITORS; SPECTROMETRY, MASS, FAST ATOM BOMBARDMENT; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034615120     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00659-9     Document Type: Article

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18. Enzyme assay: The inhibitory effects of each compound on the enzymatic activities of five serine proteases were evaluated using the purified enzymes and the chromogenic substrates. Enzymes and those substrates used here were as follows, N-succinyl-Ala-Ala-Pro-Phe-pNA (1.5 mM) for human recombinant chymase and bovine pancreatic α-chymotrypsin (Sigma Type I-S; 47 ng/mL); N-succinyl-Ala-Ala-Pro-Phe-pNA (3 mM) for human leukocyte cathepsin G (Elastin Products Co., Inc.; 2.5 U/mL); N-succinyl-Ala-Ala-Ala-pNA (1 mM) for porcine pancreatic elastase (Sigma Type III; 0.8 mg/mL); Bz-L-Arg-pNA (1 mM) for porcine pancreatic trypsin (Wako Pure Chemicals; 1 U/mL). All experiments were carried out in 50 mM Hepes buffer (pH 7.4) containing 0.1 mM NaCl, except for the buffer used for chymase, which contained 50 mM Tris-HCl (pH 8.0) and 1 M KCl.
19. 2: C, 65.61; H, 5.51; N, 4.03. Found: C, 65.41; H, 5.53; N, 3.89.