- Ortho-Carbaborane derivatives of indomethacin as cyclooxygenase (COX)-2 selective inhibitors
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A series of novel indomethacin analogues with carbaboranes as three-dimensional substitutes for the chlorophenyl ring have been prepared. Their cyclooxygenase (COX) inhibition and enzyme selectivity has been tested and compared to the corresponding adamantyl analogues. Surprisingly, only the ortho-carbaborane derivatives were active compounds. Preliminary biological studies gave an interesting insight into the validity of employing carbaboranes as pharmacophores.
- Scholz, Matthias,Blobaum, Anna L.,Marnett, Lawrence J.,Hey-Hawkins, Evamarie
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p. 4830 - 4837
(2012/09/22)
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- Synthesis and biological evaluation of indomethacin analogs possessing a N-difluoromethyl-1,2-dihydropyrid-2-one ring system: A search for novel cyclooxygenase and lipoxygenase inhibitors
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A novel class of indomethacin analogs were synthesized wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety (5-LOX pharmacophore) was attached at its C-4 or C-5 position via either a CO (14a-b) or CH2 (19a-b) linker to the indole N1-position. In this regard, replacement of the 4-chlorobenzoyl group present in indomethacin by N-difluoromethyl-1,2- dihydropyrid-2-one-4-(or 5-)carbonyl and N-difluoromethyl-1,2-dihydropyrid-2- one-4-yl(or 5-yl)methylene moieties furnished compounds showing no inhibitory activities against the COX-2/5-LOX enzymes (except for the weak but selective COX-2 inhibitor 19a, COX-2 IC50 = 31 μM), and moderate in vivo anti-inflammatory activities (except for the methylene compound 19a that was inactive). These structure-activity data indicate replacement of the 4-chlorobenzoyl group present in indomethacin by a N-difluoromethyl-1,2- dihydropyrid-2-one ring system connected by a CO or CH2 linker is not a suitable approach for the design of dual COX-2/5-LOX inhibitory analogs of indomethacin.
- Chowdhury, Morshed A.,Huang, Zhangjian,Abdellatif, Khaled R.A.,Dong, Ying,Yu, Gang,Velázquez, Carlos A.,Knaus, Edward E.
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experimental part
p. 5776 - 5780
(2010/12/18)
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- Aromatic enamide/ene metathesis toward substituted indoles and its application to the synthesis of indomethacins
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A. steric and electronic effect: on enamide/ene metathesis, a novel preparation of 2-substituted indoles and 3-substituted indoles using enamide-ene metathesis as a key reaction, and its application to the synthesis of indoniethacin are described. Wiley-VCH Verlag GmbH & Co. KGaA.
- Kasaya, Yayoi,Hoshi, Kosuke,Terada, Yukiyoshi,Nishida, Atsushi,Shuto, Satoshi,Arisawa, Mitsuhiro
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experimental part
p. 4606 - 4613
(2009/12/27)
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- Esters and amides of substituted pyrrole acetic acids
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Esters and amides of substituted pyrrole acetic acids are useful in the treatment of colonic polyps.
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