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【结 构 式】 
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【药物名称】Buspirone hydrochloride, APC-6003(oral), APC-6002(topical), MJ-9022-1, Buspimen, Bespar, Narol, BuSpar 【化学名称】8-[4-[4-(2-Pyrimidinyl)piperazin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione monohydrochloride 【CA登记号】33386-08-2, 36505-84-7 (free base) 【 分 子 式 】C21H32ClN5O2 【 分 子 量 】421.97449 |
【开发单位】Bristol-Myers Squibb (Originator), Almirall Prodesfarma (Licensee), Meiji Seika (Licensee), Menarini (Licensee), Elan Transdermal Technologies (Codevelopment) 【药理作用】Anxiolytics, Attention Deficit Hyperactivity Disorder (ADHD), Treatment of, Generalized Anxiety Disorder (GAD), Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT1A Partial Agonists |
合成路线1
The condensation of 1-(2-pyrimidinyl)piperazine (I) with 3-chloro-1-cyanopropane (II) by means of Na2CO3 in n-butanol gives 4-(2-pyrimidinyl)-1-(3-cyanopropyl)piperazine (III). This product is reduced with LiAlH4 or with H2 and Raney-Ni yielding 4-(2-pyrimidinyl)-1-(4-aminobutyl)piperazine (IV), which is finally condensed with 8-oxaspiro[4.5]decane-7,9-dione-(3,3-tetramethylene-glutaric anhydride) (V) in pyridine.
| 【1】 Wu, Y.H.; et al.; N-(Heteroarcyclic)piperazizylalkylazaspiroalkanediones. DE 2057845; FR 2073406; GB 1332194; US 3717634 . |
| 【2】 Wu, Y.H.; et al.; Psychosedative agents. 2. 8-(4-substituted-1-piperazinylalkyl)-8-azaspiro-[4,5]decane-7,9-diones. J Med Chem 1972, 15, 5, 477-479. |
| 【3】 Castaner, J.; Thorpe, P.; Buspirone. Drugs Fut 1976, 1, 9, 409. |
| 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) | 11175 | 2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine | 20980-22-7 | C8H12N4 | 详情 | 详情 |
| (II) | 11179 | 4-Chlorobutanenitrile; 4-Chlorobutyronitrile | 628-20-6 | C4H6ClN | 详情 | 详情 |
| (III) | 11180 | 4-[4-(2-Pyrimidinyl)piperazino]butanenitrile | C12H17N5 | 详情 | 详情 | |
| (IV) | 11181 | 4-[4-(2-Pyrimidinyl)piperazino]butylamine; 4-[4-(2-Pyrimidinyl)piperazino]-1-butanamine | 33386-20-8 | C12H21N5 | 详情 | 详情 |
| (V) | 34125 | 8-oxaspiro[4.5]decane-7,9-dione | 5662-95-3 | C9H12O3 | 详情 | 详情 |