Palladium-Catalyzed α-Arylation of Cyclic β-Dicarbonyl Compounds for the Synthesis of CaV1.3 Inhibitors
- 등재 SCIE, SCOPUS
- OA유형 All Open Access, Green
- 발행기관 American Chemical Society
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190487
- 본문언어 영어
- Published As https://doi.org/10.1021/acsomega.2c00889
초록/요약
Cyclic α-aryl β-dicarbonyl derivatives are important scaffolds in medicinal chemistry. Palladium-catalyzed coupling reactions of haloarenes were conducted with diverse five- to seven-membered cyclic β-dicarbonyl derivatives including barbiturate, pyrazolidine-3,5-dione, and 1,4-diazepane-5,7-dione. The coupling reactions of various para- or meta-substituted aryl halides occurred efficiently when Pd(t-Bu3P)2, Xphos, and Cs2CO3were used under 1,4-dioxane reflux conditions. Although the couplings of ortho-substituted aryl halides with pyrazolidine-3,5-dione and 1,4-diazepane-5,7-dione were moderate, the coupling with barbiturate was limited. Using the optimized reaction conditions, we synthesized several 5-aryl barbiturates as new scaffolds of CaV1.3 Ca2+channel inhibitors. Among the synthesized molecules, 14e was the most potent CaV1.3 inhibitor with an IC50of 1.42 μM. © 2022 American Chemical Society. All rights reserved.
more