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

摘要

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).