[Synthetic inhibitors of serine proteinases. 32. Inhibition of trypsin, plasmin and thrombin by amides of N-alpha-substituted 4-amidinophenylalanine. Effect of various amino acids and blocking groups of the n-alpha residue on inhibitory activity].
Cyclic amides of N alpha-arylsulfonylated 4-amidinophenylalanine are specific, highly potent inhibitors of thrombin. Introduction of amino acids between the arylsulfonyl blocking group and amino nitrogen influence particularly the antithrombin activity. By the use of glycine as spacer the compounds become tight binding thrombin inhibitors, while introduction of other omega-amino acids, Gly-Gly, L-Pro, Gly-L-Pro or L-Pro-Gly, reduces the specificity and potency of thrombin inhibition. Substitution of the arylsulfonyl blocking group for a heteroarylsulfonyl residue or an aryl residue causes a decrease in antithrombin activity, while substitution for a benzoyloxycarbonyl blocking group has only slight influence. It is concluded that the N alpha-moiety is of decisive importance for the antithrombin activity of derivatives of 4-amidinophenylalanine.
D000578:Amidines / Q000138:chemical synthesis / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D010450:Endopeptidases / Q000378:metabolism*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis; D012697:Serine Endopeptidases; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors / Q000138:chemical synthesis
D000578:Amidines; D000596:Amino Acids; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D010649:Phenylalanine; D010450:Endopeptidases; D012697:Serine Endopeptidases; D013917:Thrombin; D005341:Fibrinolysin
Synthetische Inhibitoren der Serinproteinasen. 32. Mitteilung2: Hemmung von Trypsin, Plasmin und Thrombin durch Amide des N alpha-substituierten 4-Amidinokphenylalanins. Einfluss verschiedener Aminosäuren und Schutzgruppen im N alpha-Rest auf die Inhibitoraktivität.