231297-58-8Relevant articles and documents
Stereoselective construction of deoxy-cruciferane alkaloids by NHC-catalyzed intramolecular annulation of homoenolate with quinazolinone
Ahire, Milind M.,Pol, Mahesh D.,Kavale, Dattatry S.,Gonnade, Rajesh G.,Mhaske, Santosh B.
, p. 7135 - 7139 (2019)
Chiral N-heterocyclic carbene (NHC)-catalyzed intramolecular [3 + 2] annulation of enals with an unactivated imine moiety of quinazolinone via formal homoenolate cycloaddition has been demonstrated. It is an excellent approach for stereoselective syntheses of deoxy-cruciferane alkaloids comprising a biologically important pyrroloindoline scaffold. Notably, this is the first report on the NHC-catalyzed asymmetric intramolecular homoenolate annulation with cyclic N-acyl amidine.
Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure-activity relationship for anti-inflammatory drug
Hayashi, Shigeo,Ueno, Naomi,Murase, Akio,Nakagawa, Yoko,Takada, Junji
experimental part, p. 179 - 195 (2012/07/27)
Cyclooxygenase (COX) is a key rate-limiting enzyme for prostaglandin (PG) production cascades in the human body. The mechanisms of both the anti-inflammation effects and the side-effects of traditional COX inhibitors are associated with the existence of two COX isoforms. Thus while COX-1 is predominantly expressed ubiquitously and constitutively, and it serves a housekeeping role in processes such as gastrointestinal (GI) mucosa protection, COX-2 is absent or exhibits a low level of expression in most tissues, and is highly upregulated in response to endotoxin, virus, inflammatory or tissue-injury stimuli/signals, and tumour promoter in the various types of organs, tissues, and cells. Furthermore, COX-2 contribution to PGE2 and PGI2 production evokes and sustains systemic or peripheral inflammatory disease, but it is not involved in the COX-1-mediated GI tract events. Also, hypersensitivity of aspirin owing to its inhibitory action against COX-1 is a significant concern clinically. Consequently, highly selective COX-2 inhibitors have been needed for the treatment of inflammatory- and inflammation related-diseases that include pyrexia, inflammation, pain, rheumatoid arthritis, osteoarthritis, and cancers. In this study, a series of novel [2-{[(4-substituted or 4,5-disubstituted)-pyridin-2-yl]carbonyl}-(5- or 6-substituted or 5,6-disubstituted)-1H-indol-3-yl]acetic acid analogues was designed, synthesized, and evaluated to identify potent and selective COX-2 inhibitors as potential agents against inflammatory diseases. As significant findings, the present study clarified unique structure-activity relationship of the analogues toward potent and selective COX-2 inhibition in vitro, and identified 2-{6-fluoro-2-[4-methyl-2-pridinyl)carbonyl]-1H-indol-3-yl}acetic acid as a potent and selective COX-2 inhibitor in vitro that demonstrated orally potent anti-inflammation efficacy against carrageenan-induced oedema formation in the foot of SPF/VAF male SD rats as a peripheral inflammation model in vivo.
Tetrazolylalkyl indole compounds as anti-inflammatory and analgesic agents
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, (2008/06/13)
This invention provides a compound of the following formula: or the pharmaceutically acceptable salts thereof wherein Z is tetrazolyl optionally substituted with a substituent selected from C1-4 alkyl and halosubstituted C1-4 alkyl;A is C1-6 alkylene; Q is selected from the following groups: (a) optionally substituted phenyl; (b) an optionally substituted, partially saturated, fully saturated or fully unsaturated five to six membered monocyclic group having one to three heteroatoms; and (c) an optionally substituted, bicyclic group consisting of two fused partially saturated, fully saturated or fully unsaturated five or six membered rings independently and optionally having one to four heteroatoms; X is halogen, C1-4 alkyl, halosubstituted C1-4 alkyl, OH, C1-4 alkoxy or the like; and n is 0, 1, 2, 3 or 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.
