| 摘要 |
<p>A thrombin inhibitor or a pharmaceutically acceptable salt thereof has the formula (I) AS-Z-P wherein: AS is an S subsite blocking segment; P is a fibrinogen recognition exosite blocking segment and Z is a S' subsite blocking segment which links AS and P. The S' subsite blocking segment has the sequence: Xaa-Gly-Yaa-Gly-bAla wherein: Xaa is a residue selected from glycine, L-alanine, D-alanine, 2-aminoisobutyric acid, L-a-aminobutyric acid, D-a-aminobutyric acid, L-norvaline, D-norvaline, L-norleucine, D-norleucine, L-cysteine, L-penicillamine, D-penicillamine, L-methionine, D-methionine, L-valine, D-valine, L-tert butylglycine, D-tert butylglycine, L-isoleucine, D-isoleucine, L-leucine, D-leucine, cyclohexylglycine, L-b-cyclohexylalanine, D-b-cyclohexylalanine, L-phenylglycine, D-phenylglycine, L-phenylalanine, D-phenylalanine, L-homophenylalanine, D-homophenylalanine, L-histidine, D-histidine, L-tryptophan, D-tryptophan, L-b-(2- thienyl)-alanine and D-b-(2-thienyl)-alanine; Yaa is a residue selected from glycine, L-alanine, D-alanine, 2-aminoisobutyric acid, L-a-aminobutyric acid, D-a-aminobutyric acid, L-norvaline, D-norvaline, L-norleucine, D-norleucine, L-cysteine, L-penicillamine, D-penicillamine, L-methionine, D-methionine, L-valine, D-valine, L-tert-butylglycine, D-tert-butylglycine, L-isoleucine, D-isoleucine, L-leucine, D-leucine, cyclohexylglycine, L-b-cyclohexylalanine, D-b-cyclohexylalanine, L-phenylglycine, D-phenylglycine, L-phenylalanine, D-phenylalanine, homophenylalanine, histidine, L-tryptophan, D-tryptophan, L-b-(2-thienyl)-alanine, and D-b-(2-thienyl)-alanine. AS can have the sequence: Bbs-Arg-(D-Pip) wherein Bbs is 4-tertbutylbenzenesulphonyl and D-Pip is D-pipecolic acid. P can have the sequence: Asp-Tyr-Glu-Pro-Ile-Pro-Glu-Glu-Ala-Cha- (D-Glu)-OH wherein Cha is b-cyclohexylalanine. A pharmaceutical composition thereof is useful for treating vascular diseases.</p> |
