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【结 构 式】 
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【药物名称】CGS-8216 【化学名称】2,5-Dihydro-2-phenyl-3H-pyrazolo[4,3-c]quinolin-3-one 【CA登记号】77779-60-3 【 分 子 式 】C16H11N3O 【 分 子 量 】261.28557 |
【开发单位】Novartis (Originator), Pfizer (Originator) 【药理作用】Antidepressants, Antipsoriatics, Anxiolytics, DERMATOLOGIC DRUGS, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, GABA(A) BZ Site Receptor Antagonists, Non-Steroidal Antiinflammatory Drugs |
合成路线1
The condensation of aniline (I) with diethyl ethoxymethylenemalonate (II) by heating at 90 C gives diethyl anilinomethylenemalonate (III), which is cyclized to ethyl 4-hydroxyquinoline-3-carboxylate (IV) by heating at 240 C in diphenyl ether-biphenyl. The reaction of (IV) with hot POCl3 affords ethyl 4-chloro-quinoline-3-carboxylate (V), which is finally cyclized with phenylhydrazine (VI) by heating at 105 C in xylene. (VI) is prepared in the usual way starting from aniline (I) by diazotation with NaNO2-HCl to phenyldiazonium chloride (VII), and reduction with SnCl2-HCl.
| 【1】 Yokoyama, N.; EP 0022078 . |
| 【2】 Yokoyama, N.; US 4312870 . |
| 【3】 Ritter, B.; Yokoyama, N.; Neubert, A.D.; 2-Arylpyrazolo[4,3-c]quinolin-3-ones: A partial novel agonist and antagonist of benzodiazepines. J Med Chem 1982, 25, 4, 337-339. |
| 【4】 Serradell, M.N.; Grau, M.; Castaner, J.; Blancafort, P.; CGS-8216 and CGS-9896. Drugs Fut 1983, 8, 2, 99. |
| 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) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (II) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (III) | 35953 | diethyl 2-(anilinomethylene)malonate | C14H17NO4 | 详情 | 详情 | |
| (IV) | 35954 | ethyl 4-hydroxy-3-quinolinecarboxylate | C12H11NO3 | 详情 | 详情 | |
| (V) | 35955 | ethyl 4-chloro-3-quinolinecarboxylate | C12H10ClNO2 | 详情 | 详情 | |
| (VI) | 11818 | Phenyl hydrazine; 1-Phenylhydrazine | 100-63-0 | C6H8N2 | 详情 | 详情 |
| (VII) | 25897 | benzenediazonium chloride | C6H5ClN2 | 详情 | 详情 |