- 作者: 林和盛
- 作者服務機構: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana, U.S.A.
- 中文摘要: A series of nonpeptide angiotensin II receptor antagonists was synthesized via palladium-assisted cross coupling of aryl stannane and cycloalkenyl triflates and subsequent alkylation of silyl-protected imidazole. Our compounds, which have a terminal five- to seven-membered cycloalkenyl ring, are compared to DuPont EXP7711, an N- [ (2'-carboxybiphenylyl)methyl ] imidazole, which has a terminal phenyl moiety. Physicochemical properties of the compounds, such as lipophilicity, steric bulk, conformation, and the relative spatial proximity of the 2-carboxyl and the middle phenyl, are quantitated by computational chemistry. Potency in terms of binding affinity to AT/sub 1/ receptors in rat adrenal glomerulosa and rabbit aorta is maximized when the terminal ring is aromatic.
- 英文摘要: --
- 中文關鍵字: Renin Angiotensin System; Hypertension; Imidazole; Molecular Modeling; Palladium-Assisted Coupling; Synthesis
- 英文關鍵字: 腎酵素血管緊縮素系統;高血壓;咪唑;分子模擬;鈀-輔助耦合;合成