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【结 构 式】 
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【药物名称】Proxodolol 【化学名称】(±)-1-(tert-Butylamino)-3-[2-(3-methyl-1,2,4-oxadiazol-5-ylmethoxy)phenoxy]-2-propanol hydrochloride 【CA登记号】152289-59-3, 158446-41-4 (error in CA), 152289-58-2 (free base) 【 分 子 式 】C17H26ClN3O4 【 分 子 量 】371.86747 |
【开发单位】Center for Chemistry of Drugs (Originator) 【药理作用】Angina pectoris, Treatment of, Antiglaucoma Agents, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, OCULAR MEDICATIONS, Ophthalmic Drugs, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, beta-Adrenoceptor Antagonists |
合成路线1
Proxodolol (V) was obtained as shown in Scheme 21696501a: Monoalkylation of pyrocatechol with chloroacetic acid gives 2-hydroxyphenoxyacetic acid (I), which is cyclized on heating into 1,4-benzodioxan-2-one (II). Condensation of (II) with acetamidoxime, giving 2-methyl-5-(2-hydroxyphenoxymethyl)-1,2,4-oxadiazole (III), followed by alkylation with epichlorohydrin yields the corresponding diether (IV), which smoothly reacts with tert-BuNH2, and the amine (V) is converted into its hydrochloride by reaction with HCl.
| 【1】 Mashkovski, M.D.; Sokolov, S.D.; Vinogradova, S.M.; Yuzhakov, S.D.; Yermakova, V.N.; Proxodolol. Drugs Fut 1997, 22, 5, 499. |
| 【2】 Sokolov, S.D.; Vinogradova, S.M.; Azarevich, O.G.; Berg, M.V.; Mashkovski, M.D.; Yuzhakov, S.D.; Morozov, A.V. (Center for Chemistry of Drugs); The hydrochlorides of derivs. of 5-phenoxymethyl-1,2, 4-oxadiaxole, possessing beta- and alpha-adrenoblocking activities. SU 1132505 . |
| 【3】 Sokolov, S.D.; Vinogradova, S.M.; Azarevich, O.G. (Center for Chemistry of Drugs); The method for producing of 5-(2-hydroxyphenoxymethyl)-1,2,4-oxadiazoles. SU 1139129 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 | |
| 11599 | o-Dihydroxybenzene; Catechol; Pyrocatechol | 120-80-9 | C6H6O2 | 详情 | 详情 | |
| 11847 | 2-Chloroacetic acid; Chloroacetic Acid | 79-11-8 | C2H3ClO2 | 详情 | 详情 | |
| 64134 | N'-hydroxyethanimidamide | C2H6N2O | 详情 | 详情 | ||
| (I) | 16894 | 2-Hydroxyphenoxyacetic acid; o-Hydroxyphenoxyacetic acid; 2-(2-hydroxyphenoxy)acetic acid | 6324-11-4 | C8H8O4 | 详情 | 详情 |
| (II) | 16895 | 1,4-BENZODIOXAN-2-ONE; 1,4-benzodioxin-2(3H)-one | 4385-48-2 | C8H6O3 | 详情 | 详情 |
| (III) | 16896 | 2-[(3-methyl-1,2,4-oxadiazol-5-yl)methoxy]phenol | C10H10N2O3 | 详情 | 详情 | |
| (IV) | 16897 | 2-[(3-methyl-1,2,4-oxadiazol-5-yl)methoxy]phenyl 2-oxiranylmethyl ether; 3-methyl-5-[[2-(2-oxiranylmethoxy)phenoxy]methyl]-1,2,4-oxadiazole | C13H14N2O4 | 详情 | 详情 | |
| (V) | 16898 | 1-(tert-butylamino)-3-[2-[(3-methyl-1,2,4-oxadiazol-5-yl)methoxy]phenoxy]-2-propanol hydrochloride | C17H26ClN3O4 | 详情 | 详情 |