Small molecules and a pharmacophore model for inhibition of botulinum toxin and methods of making and using thereof

US7574340B2 · kind B2 · utility

Assignee

• The United States of America as represented by the Secretary of the Army · US

Inventors

• Sina Bavari · Dillsburg, US
• James J. Schmidt · Mount Airy, US
• James C. Burnett · Richmond, US
• Rick Gussio · Frederick, US

Key dates

• Filing date: Sep 8, 2004
• Grant date: Aug 11, 2009
• Expiry date: Apr 15, 2025

Classification

• Technology area (CPC G): Physics
• CPC primary: G16C20/40
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed herein is a pharmacophore model for inhibiting Botulinum neurotoxin A metalloprotease activity which comprises a first plane A, a second plane B, a first hydrophobic moiety C, a second hydrophobic moiety D and a positive ionizable substituent E. The pharmacophore model may further comprise a heteroatom in the first plane A. In some embodiments, the distance between the center of the first plane A and the center of the second plane B is about 6.5 to about 9.5 Å. In some embodiments, the distance between the center of the first hydrophobic moiety C and the center of the second hydrophobic moiety D is about 8.0 to about 16.0 Å. In some embodiments, the distance between the center of the first plane to the center of the first hydrophobic moiety C is about 3.0 to about 5.0 Å. In some embodiments, the distance between the center of the second plane to the center of the second hydrophobic moiety C is about 3.0 to about 5.0 Å. In some embodiments, the distance between the center of the first plane to the center of the positive ionizable substituent is about 6.5 to about 9.5 Å.