176174-97-3Relevant academic research and scientific papers
Thiazole analogues of the NSAID indomethacin as selective COX-2 inhibitors
Woods, Keith W.,McCroskey, Richard W.,Michaelides, Michael R.,Wada, Carol K.,Hulkower, Keren I.,Bell, Randy L.
, p. 1325 - 1328 (2007/10/03)
The carboxyl group of the NSAID indomethacin was replaced with a variety of substituted thiazoles to obtain a series of potent, selective inhibitors of COX-2. Additional substitutions were made at the 1-position and 5-position of the indole of indomethacin.
Synthesis of indomethacin analogues for evaluation as modulators of MRP activity
Maguire, Anita R.,Plunkett, Stephen J.,Papot, Sébastien,Clynes, Martin,O'Connor, Robert,Touhey, Samantha
, p. 745 - 762 (2007/10/03)
Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. Copyright
Ester and amide derivatives of the nonsteroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors
Kalgutkar, Amit S.,Marnett, Alan B.,Crews, Brenda C.,Remmel, Rory P.,Marnett, Lawrence J.
, p. 2860 - 2870 (2007/10/03)
Recent studies from our laboratory have shown that derivatization of the carboxylate moiety in substrate analogue inhibitors, such as 5,8,11,14- eicosatetraynoic acid, and in nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin and meclofenamic acid, results in the generation of potent and selective cyclooxygenase-2 (COX-2) inhibitors (Kalgutkar et al. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 925-930). This paper summarizes details of the structure-activity studies involved in the transformation of the arylacetic acid NSAID, indomethacin, into a COX-2-selective inhibitor. Many of the structurally diverse indomethacin esters and amides inhibited purified human COX-2 with IC50 values in the low-nanomolar range but did not inhibit ovine COX-1 activity at concentrations as high as 66 μM. Primary and secondary amide analogues of indomethacin were more potent as COX-2 inhibitors than the corresponding tertiary amides. Replacement of the 4- chlorobenzoyl group in indomethacin esters or amides with the 4-bromobenzyl functionality or hydrogen afforded inactive compounds. Likewise, exchanging the 2-methyl group on the indole ring in the ester and amide series with a hydrogen also generated inactive compounds. Inhibition kinetics revealed that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Conversion of indomethacin into ester and amide derivatives provides a facile strategy for generating highly selective COX-2 inhibitors and eliminating the gastrointestinal side effects of the parent compound.
Heterocyclic compounds as COX-2 inhibitors
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, (2008/06/13)
The present invention relates to COX-2 inhibitors of the formula: STR1 wherein, A=halogen, C1 -C6 alkyl, SR1 or OR1 ; B=O, or H,H; X=Br or Cl; L=5-,6- or 7-membered heteroatom containing rings and is preferrably a 5-membered heteroaromatics such as thiazole, oxazole, imidazole, or oxadiazole; n=1-6, wherein the (C) is optionally branched; R=optionally substituted aryl wherein aryl is selected from phenyl, pyridyl, naphthyl, benzothienyl, or quinoxolyl, alkyl, carboxyl, esters, amino, amide, or urea; and R1 =alkyl. The compounds are useful as research tools and could be useful as potential therapeutic agents in the inhibition of the PGHS-2 isozyme and in the treatment of inflammation in mammals including humans or other conditions associated with the production of prostaglandins.
