| dc.contributor.author |
Kokotos, G |
en |
| dc.contributor.author |
Six, DA |
en |
| dc.contributor.author |
Loukas, V |
en |
| dc.contributor.author |
Smith, T |
en |
| dc.contributor.author |
Constantinou-Kokotou, V |
en |
| dc.contributor.author |
Hadjipavlou-Litina, D |
en |
| dc.contributor.author |
Kotsovolou, S |
en |
| dc.contributor.author |
Chiou, A |
en |
| dc.contributor.author |
Beltzner, CC |
en |
| dc.contributor.author |
Dennis, EA |
en |
| dc.date.accessioned |
2014-06-06T06:46:02Z |
|
| dc.date.available |
2014-06-06T06:46:02Z |
|
| dc.date.issued |
2004 |
en |
| dc.identifier.issn |
00222623 |
en |
| dc.identifier.uri |
http://dx.doi.org/10.1021/jm030485c |
en |
| dc.identifier.uri |
http://62.217.125.90/xmlui/handle/123456789/2765 |
|
| dc.subject.other |
2 oxoamide derivative |
en |
| dc.subject.other |
3 [1 (2 oxopentadecanoyl)pyrrolidin 2 yl]propionic acid |
en |
| dc.subject.other |
3 [2 (2 oxododecanoyl)pyrrolidin 2 yl]propionic acid |
en |
| dc.subject.other |
4 (hexadecanoylamino)butyric acid |
en |
| dc.subject.other |
4 [(2 oxododecanoyl)amino]octanoic acid |
en |
| dc.subject.other |
4 [(2 oxohexadecanoyl)amino]butanoic acid |
en |
| dc.subject.other |
4 [(2 oxooctanoyl)amino] 5 phenylpentanoic acid |
en |
| dc.subject.other |
4 [(2 oxooctanoyl)amino]butanoic acid |
en |
| dc.subject.other |
4 [(2 oxopentadecanoyl)amino] 5 phenylpentanoic acid |
en |
| dc.subject.other |
4 [(2 oxopentadecanoyl)amino]pentanoic acid |
en |
| dc.subject.other |
4 [(2 oxopentanodecanoyl)amino]octanoic acid |
en |
| dc.subject.other |
4 aminobutyric acid |
en |
| dc.subject.other |
5 (decyloxy) 4 [(2 oxododecanoyl)amino]pentanoic acid |
en |
| dc.subject.other |
6 methyl 4 [(2 oxododecanoyl)amino]heptanoic acid |
en |
| dc.subject.other |
6 methyl 4 [(2 oxopentadecanoyl)amino]heptanoic acid |
en |
| dc.subject.other |
arachidonic acid |
en |
| dc.subject.other |
ax 001 |
en |
| dc.subject.other |
ax 002 |
en |
| dc.subject.other |
ax 003 |
en |
| dc.subject.other |
ax 004 |
en |
| dc.subject.other |
ax 005 |
en |
| dc.subject.other |
ax 006 |
en |
| dc.subject.other |
ax 007 |
en |
| dc.subject.other |
ax 008 |
en |
| dc.subject.other |
ax 009 |
en |
| dc.subject.other |
ax 010 |
en |
| dc.subject.other |
ax 011 |
en |
| dc.subject.other |
ax 012 |
en |
| dc.subject.other |
ax 013 |
en |
| dc.subject.other |
ax 014 |
en |
| dc.subject.other |
ax 015 |
en |
| dc.subject.other |
ax 016 |
en |
| dc.subject.other |
ax 017 |
en |
| dc.subject.other |
ax 018 |
en |
| dc.subject.other |
ax 019 |
en |
| dc.subject.other |
ax 024 |
en |
| dc.subject.other |
ax 026 |
en |
| dc.subject.other |
ax 027 |
en |
| dc.subject.other |
methyl 4 [(2 oxohexadecanoyl)amino]butanoate |
en |
| dc.subject.other |
norleucine |
en |
| dc.subject.other |
phospholipase A2 |
en |
| dc.subject.other |
phospholipase A2 inhibitor |
en |
| dc.subject.other |
prostaglandin E2 |
en |
| dc.subject.other |
unclassified drug |
en |
| dc.subject.other |
analgesic activity |
en |
| dc.subject.other |
animal cell |
en |
| dc.subject.other |
animal experiment |
en |
| dc.subject.other |
animal model |
en |
| dc.subject.other |
antiinflammatory activity |
en |
| dc.subject.other |
article |
en |
| dc.subject.other |
controlled study |
en |
| dc.subject.other |
cytosol |
en |
| dc.subject.other |
drug potency |
en |
| dc.subject.other |
drug synthesis |
en |
| dc.subject.other |
enzyme inhibition |
en |
| dc.subject.other |
in vitro study |
en |
| dc.subject.other |
in vivo study |
en |
| dc.subject.other |
mouse |
en |
| dc.subject.other |
nonhuman |
en |
| dc.subject.other |
rat |
en |
| dc.subject.other |
structure activity relation |
en |
| dc.subject.other |
Amides |
en |
| dc.subject.other |
Animals |
en |
| dc.subject.other |
Anti-Inflammatory Agents, Non-Steroidal |
en |
| dc.subject.other |
Butyric Acids |
en |
| dc.subject.other |
Cell Line |
en |
| dc.subject.other |
Edema |
en |
| dc.subject.other |
Heptanoic Acids |
en |
| dc.subject.other |
Macrophage Activation |
en |
| dc.subject.other |
Mice |
en |
| dc.subject.other |
Octanoic Acids |
en |
| dc.subject.other |
Pain Measurement |
en |
| dc.subject.other |
Phospholipases A |
en |
| dc.subject.other |
Rats |
en |
| dc.subject.other |
Rats, Inbred F344 |
en |
| dc.subject.other |
Stereoisomerism |
en |
| dc.subject.other |
Structure-Activity Relationship |
en |
| dc.title |
Inhibition of group IVA cytosolic phospholipase A2 by novel 2-oxoamides in vitro, in cells, and in vivo |
en |
| heal.type |
journalArticle |
en |
| heal.identifier.primary |
10.1021/jm030485c |
en |
| heal.publicationDate |
2004 |
en |
| heal.abstract |
The Group IVA cytosolic phospholipase A2 (GIVA PLA2) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA2 [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on γ-aminobutyric acid and γ-norleucine are potent inhibitors of GIVA PLA2. Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E2 in cells, and demonstrate potent in vivo anti-inflammatory and analgesic activity. |
en |
| heal.journalName |
Journal of Medicinal Chemistry |
en |
| dc.identifier.issue |
14 |
en |
| dc.identifier.volume |
47 |
en |
| dc.identifier.doi |
10.1021/jm030485c |
en |
| dc.identifier.spage |
3615 |
en |
| dc.identifier.epage |
3628 |
en |