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【结 构 式】 
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【药物名称】TQX-173 【化学名称】7-Chloro-4-oxo-8-(4H-1,2,4-triazol-4-yl)-4,5-dihydro[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylic acid 【CA登记号】308137-55-5 【 分 子 式 】C12H6ClN7O3 【 分 子 量 】331.67972 |
【开发单位】Università degli Studi di Firenze (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, AMPA Antagonists |
合成路线1
Diazotization of substituted aniline (I) followed by reaction with ethyl 2-chloro-3-oxobutanoate (II) in MeOH yields hydrazono chloroacetate derivative (III), which is converted into oxamidrazonate (IV) by means of NH3 (gas). Treatment of derivative (IV) with ethyloxalyl chloride (V) affords ethoxalyl derivative (VI), which is then heated until cyclization occurs, providing derivative (VII). Reduction of triazole dicarboxylate (VII) with iron in HOAc gives tricyclic compound (VIII), which is nitrated by means of HNO3 to afford nitro derivative (IX). Reduction of the nitro group of (IX) by means of iron in HOAc provides the corresponding 8-amino derivative (X), which is treated with diformylhydrazine and trimethylsilyl chloride (TMSCl) in pyridine to furnish ethyl carboxylate (XI). Finally, saponification of (XI) with NaOH in EtOH gives the desired compound.
| 【1】 Catarzi, D.; et al.; 4,5-Dihydro-1,2,4-triazolo[1,5-a]quinoxalin-4-ones: Excitatory amino acid antagonists with combined glycine/NMDA and AMPA receptor affinity. J Med Chem 1999, 42, 13, 2478. |
| 【2】 Colotta, V.; Carlà, V.; Costagli, C.; Filacchioni, G.; Varano, F.; Cecchi, L.; Galli, A.; Catarzi, D.; 7-Chloro-4,5-dihydro-8-(1,2,4-triazol-4-yl)-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates as novel highly selective AMPA receptor antagonists. J Med Chem 2000, 43, 21, 3824. |
| 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) | 47585 | 1-Amino-4-chloro-2-nitrobenzene; 2-Nitro-4-chloroaniline; p-chloro-o-nitroaniline; 4-chloro-2-nitroaniline; 4-chloro-2-nitrophenylamine | 89-63-4 | C6H5ClN2O2 | 详情 | 详情 |
| (II) | 21337 | ethyl 2-chloro-3-oxobutanoate | 609-15-4 | C6H9ClO3 | 详情 | 详情 |
| (III) | 47586 | N-(4-chloro-2-nitrophenyl)-2-ethoxy-2-oxoethanehydrazonoyl chloride | C10H9Cl2N3O4 | 详情 | 详情 | |
| (IV) | 47587 | N'-(4-chloro-2-nitrophenyl)-2-ethoxy-2-oxoethanehydrazonamide | C10H11ClN4O4 | 详情 | 详情 | |
| (V) | 11043 | Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride | 4755-77-5 | C4H5ClO3 | 详情 | 详情 |
| (VI) | 47588 | ethyl 2-([1-[(E)-2-(4-chloro-2-nitrophenyl)hydrazono]-2-ethoxy-2-oxoethyl]amino)-2-oxoacetate | C14H15ClN4O7 | 详情 | 详情 | |
| (VII) | 47589 | diethyl 1-(4-chloro-2-nitrophenyl)-1H-1,2,4-triazole-3,5-dicarboxylate | C14H13ClN4O6 | 详情 | 详情 | |
| (VIII) | 47590 | ethyl 7-chloro-4-oxo-4,5-dihydro[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate | C12H9ClN4O3 | 详情 | 详情 | |
| (IX) | 47591 | ethyl 7-chloro-8-nitro-4-oxo-4,5-dihydro[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate | C12H8ClN5O5 | 详情 | 详情 | |
| (X) | 47592 | ethyl 8-amino-7-chloro-4-oxo-4,5-dihydro[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate | C12H10ClN5O3 | 详情 | 详情 | |
| (XI) | 47593 | ethyl 7-chloro-4-oxo-8-(4H-1,2,4-triazol-4-yl)-4,5-dihydro[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate | C14H10ClN7O3 | 详情 | 详情 |