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Palladium-Catalyzed alpha-Arylation of Cyclic beta-Dicarbonyl Compounds for the Synthesis of Ca(V)1.3 Inhibitors
- Title
- Palladium-Catalyzed alpha-Arylation of Cyclic beta-Dicarbonyl Compounds for the Synthesis of Ca(V)1.3 Inhibitors
- Authors
- Yun, Jisu; Jeong, Dayeon; Xie, Zhong; Lee, Sol; Kim, Jiho; Surmeier, D. James; Silverman, Richard B.; Kang, Soosung
- Ewha Authors
- 강수성
- SCOPUS Author ID
- 강수성
- Issue Date
- 2022
- Journal Title
- ACS OMEGA
- ISSN
- 2470-1343
- Citation
- ACS OMEGA vol. 7, no. 16, pp. 14252 - 14263
- Publisher
- AMER CHEMICAL SOC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Cyclic alpha-aryl beta-dicarbonyl derivatives are important scaffolds in medicinal chemistry. Palladium-catalyzed coupling reactions of haloarenes were conducted with diverse five- to seven-membered cyclic beta-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 Cs2CO3 were 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 Ca(V)1.3 Ca2+ channel inhibitors. Among the synthesized molecules, 14e was the most potent Ca(V)1.3 inhibitor with an IC50 of 1.42 mu M.
- DOI
- 10.1021/acsomega.2c00889
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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