Abstract: Methods and compounds useful for inhibiting a phoshpolipase A2 are provided, the methods comprising contacting the phoshpolipase A2 with a compound having the structure A, or pharmaceutically acceptable salts thereof: wherein R1 is H, F, NH2, or COOH; R2 is, H, linear saturated or unsaturated alkyl, alkenyl, or alkynyl; each of R3 and R4 is independently H, linear saturated or unsaturated alkyl, alkenyl, alkynyl, phenyl, or substituted phenyl; R5 is H, (C1-C6) alkyl such as methyl or ethyl; X is aryl or substituted aryl, such as phenyl or a substituted phenyl; and Y is O or S.

Abstract: The disclosure provides a series of 2-oxoamides based on dipeptides and pseudodipeptides, which were synthesized and their activities toward two human intracellular phospholipases A2 (GIVA CPLA 2 and GVIA 1PLA 2) and one human secretory phospholipase A2 (GV sPLA 2) were evaluated. Derivatives containing a free carboxyl group are selective GIVA cPLA 2 inhibitors. A derivative based on the ethyl ester of an ether pseudodipeptide is the first 2-oxoamide, which preferentially inhibits GVIA iPLA 2. The effect of 2-oxoamides on the generation of arachidonic acid from RAW 264.7 macrophages was also studied. It was found that selective GIVA cPLA 2 inhibitors preferentially inhibited cellular arachidonic acid release; in which one pseudodipeptide gave an IC50 value of 2 ?M.

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).

Abstract: The disclosure provides a series of 2-oxoamides based on dipeptides and pseudodipeptides, which were synthesized and their activities toward two human intracellular phospholipases A2 (GIVA CPLA2 and GVIA 1PLA2) and one human secretory phospholipase A2 (GVsPLA2) were evaluated. Derivatives containing a free carboxyl group are selective GIVA cPLA2 inhibitors. A derivative based on the ethyl ester of an ether pseudodipeptide is the first 2-oxoamide, which preferentially inhibits GVIA iPLA2. The effect of 2-oxoamides on the generation of arachidonic acid from RAW 264.7 macrophages was also studied. It was found that selective GIVA cPLA2 inhibitors preferentially inhibited cellular arachidonic acid release; in which one pseudodipeptide gave an IC50 value of 2 ?M.

Abstract: Methods and compounds useful for inhibiting a phospholipase A2 are provided, the methods comprising contacting the phospholipase A2 with a compound having the structure A, or pharmaceutically acceptable salts thereof: wherein R1 is H, F, NH2, or COOH; R2 is, H, linear saturated or unsaturated alkyl, alkenyl, or alkynyl; each of R3 and R4 is independently H, linear saturated or unsaturated alkyl, alkenyl, alkynyl, phenyl, or substituted phenyl; R5 is H, (C1-C6) alkyl such as methyl or ethyl; X is aryl or substituted aryl, such as phenyl or a substituted phenyl; and Y is O or S.

Abstract: Specific, highly potent 2-oxo-amide based inhibitors of phospholipase A2 (PLA2) activity are provided. A role for PLA2 activity in spinally mediated inflammatory processes is established, and a method for treating hyperalgesia and other inflammatory conditions associated with PLA2 activity is provided.

Abstract: Novel perfluoroketone compounds of formula [I] and [Ia] are described. Also described are uses thereof, such as for inhibition of phospholipase A2 activity. Therapeutic uses thereof are also described, such as for the treatment of neural conditions and/or inflammatory conditions, such as demyelinating (e.g., multiple sclerosis) and neural injury (e.g., spinal cord injury).

Abstract: Phospholipase A2 (PLA2) forins 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).