Thrombin inhibitors based on the amino acid sequence of hirudin

US6060451A · kind A · utility

Assignee

• National Research Council of Canada · CA

Inventors

• John DiMaio · Montréal, CA
• Yasuo Konishi · Toyoake, JP
• Feng Ni · Longbeilingcun, CN
• Torsten Steinmetzer · Jena, DE

Key dates

• Filing date: Mar 20, 1995
• Grant date: May 9, 2000
• Expiry date: Mar 20, 2015

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A thrombin inhibitor comprising a first bulky hydrophobic portion interacting with the catalytic site of thrombin responsible for proteolysis and a second portion at least maintaining the hydrophobic and acidic character of amino acids 55 to 60 of native hirudin at the C-terminal non-catalytic region of N-acetyl-hirudin45-65. Between the first and second portions is a divalent linker moiety having a chain length of at least 10 carbon atoms. Connecting the first bulky hydrophobic portion and the linker is a peptidomimetic bond. Preferably, the bulky hydrophobic portion comprises at least one amino acid of D-configuration. The compounds are useful in the treatment of thrombotic disorders.