Development of androgen-antagonistic coumarinamides with a unique aromatic folded pharmacophore was written by Koga, Hitomi;Negishi, Mai;Kinoshita, Marie;Fujii, Shinya;Mori, Shuichi;Ishigami-Yuasa, Mari;Kawachi, Emiko;Kagechika, Hiroyuki;Tanatani, Aya. And the article was included in International Journal of Molecular Sciences in 2020.Synthetic Route of C8H4ClNO This article mentions the following:
First-generation nonsteroidal androgen receptor (AR) antagonists, such as flutamide (2a) and bicalutamide (3), are effective for most prostate cancer patients, but resistance often appears after several years due to the mutation of AR. Second-generation AR antagonists are effective against some of these castration-resistant prostate cancers, but their structural variety is still limited. In this study, we designed and synthesized 4-methyl-7-(N-alkyl-arylcarboxamido)coumarins as AR antagonist candidates and evaluated their growth-inhibitory activity toward androgen-dependent SC-3 cells. Coumarinamides with a secondary amide bond did not show inhibitory activity, but their N-methylated derivatives exhibited AR-antagonistic activity. Especially, 19b and 31b were more potent than the lead compound 7b, which was comparable to hydroxyflutamide (2b). Conformational anal. showed that the inactive coumarinamides with a secondary amide bond have an extended structure with a trans-amide bond, while the active N-methylated coumarinamides have a folded structure with a cis-amide bond, in which the two aromatic rings are placed face-to-face. Docking study suggested that this folded structure is important for binding to AR. Selected coumarinamide derivatives showed AR-antagonistic activity toward LNCaP cells with T877A AR, and they had weak progesterone receptor (PR)-antagonistic activity. The folded coumarinamide structure appears to be a unique pharmacophore, different from those of conventional AR antagonists. In the experiment, the researchers used many compounds, for example, 3-Cyanobenzoyl chloride (cas: 1711-11-1Synthetic Route of C8H4ClNO).
3-Cyanobenzoyl chloride (cas: 1711-11-1) belongs to organic chlorides. An organic chloride is an organic compound containing at least one covalently bonded atom of chlorine. Their wide structural variety and divergent chemical properties lead to a broad range of names and applications. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Synthetic Route of C8H4ClNO
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics