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【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
Extended Information