|
【结 构 式】 
|
【药物名称】RPR-117820A 【化学名称】(+)-2(S)-[2-Cyano-5-(4-pyridylmethoxy)phenoxy]-2-(2-methylphenyl)acetic acid sodium salt 【CA登记号】181038-01-7 【 分 子 式 】C22H17N2NaO4 【 分 子 量 】396.38159 |
【开发单位】Aventis Pharma (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Endothelin ETA Receptor Antagonists |
合成路线1
The alkylation of 2-fluoro-4-hydroxybenzonitrile (I) with 4-picolyl chloride (II) afforded ether (III). This was coupled with (R,S)-2-hydroxy-2-(2-methylphenyl)acetic acid (IV) in the presence of NaH in DMSO to produce the racemic adduct (V). Resolution of (V) was then achieved by fractional crystallization of the diastereoisomeric salts with (-)-ephedrine to furnish the desired (S)-enantiomer, which was finally isolated as the corresponding sodium salt.
| 【1】 Astles, P.C.; Brown, T.J.; Halley, F.; et al.; Selective ETA antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives. J Med Chem 2000, 43, 5, 900. |
| 【2】 Porter, B.; Astles, P.C.; Bridge, A.W.; McLay, I.M.; Van Sickle, A.P.; Walsh, R.J.A.; McCarthy, C.; Morley, A.D.; Halley, F.; Harris, N.V.; Majid, T.N.; Smith, C. (Rhône-Poulenc Rorer Ltd.); Substd. phenyl cpds. as endothelin antagonists. US 6048893; US 6124343; WO 9622978 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 20094 | 2,4-dihydroxybenzaldehyde | 95-01-2 | C7H6O3 | 详情 | 详情 |
| (II) | 10844 | 4-(Chloromethyl)pyridine | 10445-91-7 | C6H6ClN | 详情 | 详情 |
| (III) | 38985 | 2-fluoro-4-(4-pyridinylmethoxy)benzonitrile | C13H9FN2O | 详情 | 详情 | |
| (IV) | 38977 | 2-hydroxy-2-(2-methylphenyl)acetic acid | C9H10O3 | 详情 | 详情 | |
| (V) | 38986 | 2-[2-cyano-5-(4-pyridinylmethoxy)phenoxy]-2-(2-methylphenyl)acetic acid | C22H18N2O4 | 详情 | 详情 |