Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure-activity relationship for anti-inflammatory drug was written by Hayashi, Shigeo;Ueno, Naomi;Murase, Akio;Nakagawa, Yoko;Takada, Junji. And the article was included in European Journal of Medicinal Chemistry in 2012.Synthetic Route of C7H6N2 This article mentions the following:
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 tumor 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 clin. 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 analogs 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 analogs toward potent and selective COX-2 inhibition in vitro, and identified 2-{6-fluoro-2-[(4-methyl-2-pyridinyl)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 edema formation in the foot of SPF/VAF male SD rats as a peripheral inflammation model in vivo. In the experiment, the researchers used many compounds, for example, 4-Methylpicolinonitrile (cas: 1620-76-4Synthetic Route of C7H6N2).
4-Methylpicolinonitrile (cas: 1620-76-4) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. Halopyridines are particularly attractive synthetic building blocks in a variety of cross-coupling methods, including the Suzuki-Miyaura cross-coupling reaction.Synthetic Route of C7H6N2