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【结 构 式】 
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【分子编号】38281 【品名】5-amino-1,3,4-thiadiazole-2-sulfonamide 【CA登记号】 |
【 分 子 式 】C2H4N4O2S2 【 分 子 量 】180.21152 【元素组成】C 13.33% H 2.24% N 31.09% O 17.76% S 35.59% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of 5-amino-1,3,4-thiadiazol-2-sulfonamide (I) with the protected guanidinoacetic acid (II) by means of EDC in acetonitrile gives the corresponding amide (III), which is then deprotected with HCl in hot dioxane.
| 【1】 Mincione, F.; Briganti, F.; Mincione, G.; Scozzafava, A.; Menabuoni, L.; Supuran, C.T.; Carbonic anhydrase inhibitors: Synthesis of water-soluble, aminoacyl/dipeptidyl sulfonamides possessing long-lasting intraocular pressure-lowering properties via the topical route. J Med Chem 1999, 42, 18, 3690. |
| 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) | 38281 | 5-amino-1,3,4-thiadiazole-2-sulfonamide | C2H4N4O2S2 | 详情 | 详情 | |
| (II) | 38282 | 2-[[imino[(tritylsulfanyl)amino]methyl](methyl)amino]acetic acid | C23H23N3O2S | 详情 | 详情 | |
| (III) | 38283 | N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]-2-[[imino[(tritylsulfanyl)amino]methyl](methyl)amino]acetamide | C25H25N7O3S3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The condensation of 5-amino-1,3,4-thiadiazol-2-sulfonamide (I) with the protected guanidinodipeptide (II) by means of EDC in acetonitrile gives the corresponding amide (III), which is then deprotected with HCl in hot dioxane.
| 【1】 Mincione, F.; Briganti, F.; Mincione, G.; Scozzafava, A.; Menabuoni, L.; Supuran, C.T.; Carbonic anhydrase inhibitors: Synthesis of water-soluble, aminoacyl/dipeptidyl sulfonamides possessing long-lasting intraocular pressure-lowering properties via the topical route. J Med Chem 1999, 42, 18, 3690. |
| 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) | 38281 | 5-amino-1,3,4-thiadiazole-2-sulfonamide | C2H4N4O2S2 | 详情 | 详情 | |
| (II) | 38284 | 4-imino-5-methyl-7-oxo-1,1,1-triphenyl-2-thia-3,5,8-triazaundecan-11-oic acid | C26H28N4O3S | 详情 | 详情 | |
| (III) | 38285 | N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]-4-imino-5-methyl-7-oxo-1,1,1-triphenyl-2-thia-3,5,8-triazaundecan-11-amide | C28H30N8O4S3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)Removal of acetyl group of acetazolamide (I) by refluxing with concentrated HCl affords 5-amino-1,3,4-thiadiazole-2-sulfonamide (II), which is then coupled to Boc-protected beta-alanine (III) by means of EDC and Et3N in acetonitrile to yield the protected derivative (IV). Finally, (IV) is treated with TFA in CH2Cl2 for Boc removal to provide the target compound. Alternatively, conversion of (II) into the desired compound can be achieved by first condensation of (II) with 3-phthalimidopropionyl chloride (V) in pyridine to give the N-phthalimido derivative (VI), which is then subjected to hydrazinolysis and finally treated with TFA.
| 【6】 Barboiu, M.; et al.; Carbonic anhydrase inhibitors. Synthesis of topically effective intraocular pressure lowering agents derived from 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide. J Enzym Inhib 1999, 15, 1, 23. |
| 【1】 Jitianu, A.; Ilies, M.A.; Scozzafava, A.; Supuran, C.T.; Complexes with biologically active ligands. Part 8. Synthesis and carbonic anhydrase inhibitory activity of 5-benzoylamido- and 5-(3-nitrobenzoylamido)-1,3,4-thiadiazole-2-sulfonamide and their metal complexes. Main Group Met Chem 1997, 20, 147-153. |
| 【2】 Mincione, F.; Briganti, F.; Mincione, G.; Scozzafava, A.; Menabuoni, L.; Supuran, C.T.; Carbonic anhydrase inhibitors: Synthesis of water-soluble, aminoacyl/dipeptidyl sulfonamides possessing long-lasting intraocular pressure-lowering properties via the topical route. J Med Chem 1999, 42, 18, 3690. |
| 【3】 Scozzafava, A.; et al.; Carbonic anhydrase inhibitors. Synthesis of water-soluble, topically effective intraocular pressure-lowering aromatic/heterocyclic sulfonamides containing cationic or anionic moieties. Is the tail more important than the ring?. J Med Chem 2000, 42, 14, 2641. |
| 【4】 Scozzafava, A.; Menabuoni, L.; Briganti, F.; Mincione, G.; Mincione, F.; Supuran, C.T.; Carbonic anhydrase inhibitors - Part 78. Synthesis of water-soluble sulfonamides incorporating beta-alanyl moieties, possessing long lasting-intraocular pressure lowering properties via the topical route. Eur J Med Chem 2000, 35, 3, 309. |
| 【5】 Scozzafava, A.; Mincione, G.; Briganti, F.; Menabuoni, L.; Muncione, F.; Supuran, C.T.; Borras, J.; Carbonic anhydrase inhibitors: Synthesis of water-soluble, topically effective intraocular pressure lowering aromatic/heterocyclic sulfonamides containing 8-quinoline-sulfonyl moieties: Is the tail more important than the ring?. Bioorg Med Chem 1999, 7, 11, 2397. |
| 【7】 Ilies, M.A.; Briganti, F.; Scozzafava, A.; Supuran, C.T.; Carbonic anhydrase inhibitors: Synthesis of membrane impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes. J Med Chem 2000, 43, 2, 292. |
| 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) | 44871 | N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]acetamide | 59-66-5 | C4H6N4O3S2 | 详情 | 详情 |
| (II) | 38281 | 5-amino-1,3,4-thiadiazole-2-sulfonamide | C2H4N4O2S2 | 详情 | 详情 | |
| (III) | 44872 | 3-(tert-butoxycarbonyl)-1-triazanecarboxylic acid | C6H13N3O4 | 详情 | 详情 | |
| (IV) | 44873 | tert-butyl 3-([[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]amino]carbonyl)-1-triazanecarboxylate | C8H15N7O5S2 | 详情 | 详情 | |
| (V) | 44875 | 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-hydrazinecarbonyl chloride | C9H6ClN3O3 | 详情 | 详情 | |
| (VI) | 44874 | N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-hydrazinecarboxamide | C11H9N7O5S2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)The title bis-amide was prepared by condensation of the dianhydride (I) with 5-amino-1,3,4-thiadiazole-2-sulfonamide (II).
| 【1】 Supuran, C.T.; Muncione, F.; Scozzafava, A.; Mincione, G.; Menabuoni, L.; Carbonic anhydrase inhibitors: Synthesis of sulfonamides incorporating DTPA tails and of their zinc complexes with powerful topical antiglaucoma properties. Bioorg Med Chem Lett 2001, 11, 4, 575. |
合成路线5
该中间体在本合成路线中的序号：(I)The title compound is prepared by acylation of 5-amino-1,3,4-thiadiazole-2-sulfonamide (I) with valproyl chloride (II) in acetonitrile in the presence of triethylamine.
| 【1】 Abbate, F.; Scozzafava, A.; Supuran, C.T.; Masereel, B. ; Rolin, S.; Carbonic anhydrase inhibitors: Anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. J Med Chem 2002, 45, 2, 312. |