Avexxin as

University of California

George Kokotos

Berit Johansen

Inger-Reidun Aukrust

Edward A Dennis

Violetta Constantinou-Kokotou

Efrosini Barbayianni

Marcel Sandberg

Victoria Magrioti

Thomas Brimert

Samuel David

Marcel Sanderberg

Johan Evenäs

Michael Tsakos

Kildahl-Andersen Geir

Tony L Yaksh

Ruben Lopez-Vales

Daren Stephens

Athena Kalyvas

Karin Killermann Lucas

Camilla Svensson

David A Six

A compound of formula (I) wherein X is 0, C=0 or S; Y is N or CH; Rand Rare each independently H, &#x2014;(CH)COOH, &#x2014;(CH)CON(R)or &#x2014;(CH)COOCalkyl; or Rand Rtogether form a 6-membered phenyl ring fused to the five membered ring; each Ris independently selected from H, halo (e.g. fluoro or chloro), Caryl, Carylalkyl, Calkenyl; OCalkyl, OCalkenyl or a Calkyl group; each Ris H or Calkyl; each p is 0 to 3; n is 1 to 4; or a salt, ester, solvate, N-oxide, or prodrug thereof, e.g. a salt thereof.

Anti-inflammatory and antitumor 2-oxothiazoles and 2-oxothiophenes compounds

A compound of formula (I) wherein X is O, C&#x2550;O or S;

A compound of formula (I') wherein Ris H, Calkyl, &#x2014;(CH)COOH, &#x2014;(CH)COOCalkyl, &#x2014;(CH)CONH, &#x2014;(CH)CONHCalkyl, &#x2014;(CH)CON(Calkyl), Ris as defined for R; or and Rtaken together with the atoms joining them can form a 6-membered aromatic or non aromatic, saturated or unsaturated, carbocyclic or heteroatom containing (e.g. O, N or S containing) ring optionally substituted by up to 4 groups R; each Ris defined as for Ror is oxo; Ris Calkyl Ar is a Caryl group, wherein the aryl group may be optionally substituted (preferably in the meta or para position relative to O) with one or more Rgroups; each Ris halo, OH, CN, nitro, NH, NHCalkyl, N(Calkyl), haloCalkyl, Caryl group, Carylalkyl, a Calkyl group, C-mono or multiply unsaturated alkenyl group, OCalkyl group, SCalkyl group &#x2014;OCalkyl-O&#x2014;Calkyl, &#x2014;Calkyl-O&#x2014;Calkyl, &#x2014;OC-mono or multiply unsaturated alkenyl group, OAr, O(CH)Ar, SAror S(CH)Ar; wherein Aris phenyl, optionally substituted with one or more of halo, trihalomethyl, C-alkoxy, or Calkyl; each q is 1 to 3, preferably 1; each p is 0 to 3; or a salt, ester, solvate, N-oxide, or prodrug thereof. 

2-oxothiatole compounds having activity as cPLAinhibitors for the treatment of inflammatory disorders and hyperproliferative disorders

The invention provides compounds of formula (I) 

2-oxothiazole compounds and method of using same for chronic inflammatory disorders

Anti-inflammatory and antitumor 2-oxothiazoles ABD 2-oxothiophenes compounds

2-oxothiatole compounds having activity as CPLA2 inhibitors for the treatment of inflammatory disorders and hyperproliferative disorders

Methods and compounds useful for inhibiting a phoshpolipase Aare provided, the methods comprising contacting the phoshpolipase Awith a compound having the structure A, or pharmaceutically acceptable salts thereof: wherein Ris H, F, NH, or COOH; Ris, H, linear saturated or unsaturated alkyl, alkenyl, or alkynyl; each of Rand Ris independently H, linear saturated or unsaturated alkyl, alkenyl, alkynyl, phenyl, or substituted phenyl; Ris H, (C-C) 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. 

Amides as inhibitors of human secreted phospholipase A2

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 &#x3bc;M.

2-oxamide inhibitors of phospholipase A2 activity and cellular arachidonate release based on dipeptides and pseudopeptides

Phospholipase A(PLA) forms are expressed in spinal cord whose inhibition induces a potent antihyperalgesia. PLAinhibitor 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 PLA(cPLA) and/or Group VIA calcium independent PLA(iPLA) and/or Group V secreted PLA(sPLA). Pharmaceutical compositions of compounds having cPLAinhibitory activity (but not iPLAor sPLAinhibitory activity) are useful in treating multiple sclerosis, while compositions of compounds having sPLAinhibitory activity (as well as iPLAand CPLAactivity) are useful in treating spinal cord injuries (with related functional recovery).

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

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

Compositions and methods for inhibition of phospholipase A2 mediated inflammation

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Athens, Greece

George Kokotos