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【结 构 式】 
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【药物名称】IDR-16084, GYKI-16084, Uroflux 【化学名称】(+)-(R)-2-[3-(Benzo-1,4-dioxan-2-ylmethylamino)propyl]pyridazin-3(2H)-one hydrochloride 【CA登记号】185739-21-3 (free base) 【 分 子 式 】C16H20ClN3O3 【 分 子 量 】337.8091 |
【开发单位】Gedeon Richter (Originator), Ivax (Originator) 【药理作用】Benign Prostatic Hyperplasia Therapy, RENAL-UROLOGIC DRUGS, alpha1-Adrenoceptor Antagonists, alpha2-Adrenoceptor Antagonists |
合成路线1
The enantiomerically pure benzodioxane derivative (VIII) was obtained in a straightforward route including five steps starting from pyrocatechin (I). Racemic (VI) was then resolved by means of crystallization with (-)-O,O'-dibenzoyl-L-tartaric acid.
| 【1】 Matyus, P.; GYKI-16084. Drugs Fut 1999, 24, 10, 1072. |
| 【2】 3(2H)-Pyridazinone derivs. and pharmaceutical compsns. containing these cpds.. WO 9638441 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 18522 | 3-amino-1-propanol | 156-87-6 | C3H9NO | 详情 | 详情 | |
| (I) | 11599 | o-Dihydroxybenzene; Catechol; Pyrocatechol | 120-80-9 | C6H6O2 | 详情 | 详情 |
| (II) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (III) | 28714 | 2,3-dihydro-1,4-benzodioxin-2-ylmethanol | 3663-82-9 | C9H10O3 | 详情 | 详情 |
| (IV) | 20959 | 2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylbenzenesulfonate | C16H16O5S | 详情 | 详情 | |
| (V) | 20960 | 3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol | C12H17NO3 | 详情 | 详情 | |
| (VI) | 28715 | 3-chloro-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-propanamine | C12H16ClNO2 | 详情 | 详情 | |
| (VII) | 16186 | (2R,3R)-2,3-bis(benzoyloxy)butanedioic acid | C18H14O8 | 详情 | 详情 | |
| (VIII) | 28716 | 3-chloro-N-[(2R)-2,3-dihydro-1,4-benzodioxin-2-ylmethyl]-1-propanamine | C12H16ClNO2 | 详情 | 详情 |
合成路线2
The pyridazinone intermediate (XII) was prepared from dihydroxypyridazine (IX) in three synthetic steps.
| 【1】 Matyus, P.; GYKI-16084. Drugs Fut 1999, 24, 10, 1072. |
| 【2】 3(2H)-Pyridazinone derivs. and pharmaceutical compsns. containing these cpds.. WO 9638441 . |
合成路线3
Finally, N-alkylation of the potassium salt of (XII) with the base form of (VIII) was performed in dimethyl sulfoxide to afford GYKI-16084.
| 【1】 Matyus, P.; GYKI-16084. Drugs Fut 1999, 24, 10, 1072. |
| 【2】 3(2H)-Pyridazinone derivs. and pharmaceutical compsns. containing these cpds.. WO 9638441 . |