【结 构 式】 |
【药物名称】FR-168888 【化学名称】N''-[3-(Hydroxymethyl)-5-(1H-pyrrol-1-yl)benzoyl]guanidine methanesulfonate 【CA登记号】168620-46-0, 168620-45-9 (free base), 168620-05-1 (HCl) 【 分 子 式 】C14H18N4O5S 【 分 子 量 】354.38736 |
【开发单位】Fujisawa (Originator) 【药理作用】Angina pectoris, Treatment of, Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Na+/H+ Exchange (NHE) Inhibitors |
合成路线1
The condensation of dimethyl 5-aminoisophthalate (I) with 2,5-dimethoxytetrahydrofuran (II) in refluxing AcOH provided the pyrrolyl derivative (III). Partial hydrolysis of (III) with methanolic KOH then gave mono ester (IV). After activation of the carboxy group of (IV) as the corresponding mixed anhydride with isobutyl chloroformate, reduction employing NaBH4 furnished alcohol (V). The ester group of (V) was then displaced with guanidine-HCl (VI) in the presence of NaOMe to yield the title benzoyl guanidine, which was isolated as the methanesulfonate salt.
【1】 Kuno, A.; Inoue, Y.; Takasugi, H.; Mizuno, H.; Yamasaki, K. (Fujisawa Pharmaceutical Co., Ltd.); Guanidine derivs. as inhibitors of Na+/H+ exchange in cells. EP 0699185; JP 1996511243; US 5824691; WO 9426709 . |
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) | 35226 | dimethyl 5-aminoisophthalate | 99-27-4 | C10H11NO4 | 详情 | 详情 |
(II) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
(III) | 35227 | dimethyl 5-(1H-pyrrol-1-yl)isophthalate | C14H13NO4 | 详情 | 详情 | |
(IV) | 35228 | 3-(methoxycarbonyl)-5-(1H-pyrrol-1-yl)benzoic acid | C13H11NO4 | 详情 | 详情 | |
(V) | 35229 | methyl 3-(hydroxymethyl)-5-(1H-pyrrol-1-yl)benzoate | C13H13NO3 | 详情 | 详情 | |
(VI) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |