Phospholipase A2 inhibitors and their use in treating neurological injury and disease

US8420852B2 · kind B2 · utility

Assignee

• The Regents of the University of California · US

Inventors

• Edward A. Dennis · Village of La Jolla, US
• Daren Stephens · Morrisville, US
• Samuel David · Dorval, CA
• Ruben Lopez-Vales · Sankt Moritz, CH
• Athena Kalyvas · Laval, CA
• George Kokotos · Athens, GR
• Violetta Constantinou-Kokotou · Athens, GR
• Efrosini Barbayianni · Athens, GR
• Victoria Magrioti · Athens, GR

Key dates

• Filing date: Jul 3, 2008
• Grant date: Apr 16, 2013
• Expiry date: Jul 3, 2028

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P25/00
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Phospholipase A2 (PLA2) forms are expressed in spinal cord whose inhibition induces a potent antihyperalgesia. PLA2 inhibitor compounds are provided that include a common motif consisting of a 2-oxoamide with a hydrocarbon tail and a four carbon tether. The compounds block Group IVA calcium dependent PLA2 (cPLA2) and/or Group VIA calcium independent PLA2 (iPLA2) and/or Group V secreted PLA2 (sPLA2). Pharmaceutical compositions of compounds having cPLA2 inhibitory activity (but not iPLA2 or sPLA2 inhibitory activity) are useful in treating multiple sclerosis, while compositions of compounds having sPLA2 inhibitory activity (as well as iPLA2 and CPLA2 activity) are useful in treating spinal cord injuries (with related functional recovery).