Platelet aggregation inhibitors

US5318899A · kind A · utility

Assignee

• COR Therapeutics, Inc. · US

Inventors

• Robert M. Scarborough · Belmont, US
• David L. Wolf · Palo Alto, US
• Israel Charo · Lafayette, US

Key dates

• Filing date: Feb 20, 1990
• Grant date: Jun 7, 1994
• Expiry date: Feb 20, 2010

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K14/78
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

An assay for screening snake venom for the presence or absence of platelet aggregation inhibitors (PAIs) based on specific receptor binding is described. Using this assay, the identification and characterization of PAIs in a wide range of snake venom samples was accomplished. The isolated and purified PAI from several of these active snake venoms is described and characterized. In addition, PAIs lacking the Arg-Gly-Asp (RGD) adhesion sequence but containing K.sup.* -(G/Sar)-D wherein K.sup.* is a modified lysyl residue of the formula EQU R.sup.1.sub.2 N(CH.sub.2).sub.4 CHNHCO-- wherein each R.sup.1 is independently H, alkyl(1-6C) or at most one R.sup.1 is R.sup.2 --C.dbd.NR.sup.3 wherein R.sup.2 is H, alkyl(1-6C) or is NR.sup.4.sub.2 in which each R.sup.4 is independently H or alkyl(1-6C) and R.sup.3 is H, alkyl(1-6C), phenyl or benzyl, or R.sup.2 --C=NR.sup.3 is a radical selected from the group consisting of: ##STR1## where m is an integer of 2-3, and each R.sup.5 is independently H or alkyl(1-6C); PA0 and wherein one or two (CH.sub.2) may be replaced by O or S provided said O or S is not adjacent to another heteroatom are prepared and shown to specifically inhibit the binding of…