- FUSED PYRAZOLE DERIVATIVE HAVING AUTOTAXIN INHIBITORY ACTIVITY
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The present invention provides a compound of formula (I), wherein R1, R2, R3, R4a, R4b, R5a and R5b are as defined in the description, which has an autotaxin inhibitory activity,
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Paragraph 0296; 0297
(2017/01/09)
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- SUBSTITUTED 2-AMINOPYRIDINE PROTEIN KINASE INHIBITOR
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Disclosed are a 2-aminopyridine derivative having protein kinase inhibition activity, a preparation method and a pharmaceutical composition thereof Also disclosed are uses of the compounds and the pharmaceutical compositions thereof in the preparation of drugs for treating and/or preventing protein kinase-related diseases.
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Paragraph 0196
(2015/12/19)
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- Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure-activity relationship for anti-inflammatory drug
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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.
- Hayashi, Shigeo,Ueno, Naomi,Murase, Akio,Nakagawa, Yoko,Takada, Junji
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experimental part
p. 179 - 195
(2012/07/27)
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- 1-(4-BENZYL-PIPERAZIN-1-YL)-3-PHENYL-PROPENONE DERIVATIVES
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A compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein the symbols have meaning as defined, which are antagonists of CCR-1 and which find use pharmaceutically for treatment of diseases and conditions in which CCR-1 is i
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- Preparation of 6-chloro-5-fluoroindole via the use of palladium and copper-mediated heterocyclisations
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The title indole, the heterocyclic core of the 5-HT2C receptor agonist Ro 60-0175, was prepared by a modification to the Stille indole synthesis, or by the method of Gonzalez and co-workers.
- Adams, David R.,Duncton, Matthew A.J.,Roffey, Jonathan R.A.,Spencer, John
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p. 7581 - 7583
(2007/10/03)
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