【结 构 式】 |
【药物名称】NOBEX-AA-007 【化学名称】2-Hydroxy-5-[4-[N-(4-hydroxysuccinyl)sulfamoyl]phenylazo]benzoic acid 【CA登记号】 【 分 子 式 】C17H15N3O8S 【 分 子 量 】421.3884 |
【开发单位】Nobex (Originator) 【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, GASTROINTESTINAL DRUGS, Inflammatory Bowel Disease, Agents for |
合成路线1
The condensation of 4-nitrobenzenesulfonamide (I) with 4-chloro-4-oxobutyric acid methyl ester (II) in refluxing pyridine gives 4-(4-nitrobenzenesulfonamido)-4-oxobutyric acid methyl ester (III), which is reduced with Fe and NH4Cl in methanol/water to yield the corresponding 4-amino derivative (IV). The diazotization of (IV) with NaNO2 and HCl affords the diazonium salt (V), which is condensed with 2-hydroxybenzoic acid (VI) to provide the azo compound (VII). Finally, this compound is hydrolyzed with NaOH to the target succinamic acid derivative.
【1】 Riggs-Sauthier, J.A.; Malson, E.; Harris, M.; Myung, S.; Liddle, R.; Ekwuribe, N.; Synthesis and activity of novel 5-aminosalicylic acid (5-ASA)-containing prodrugs for the treatment of inflammatory bowel disease. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 305. |
【2】 Ekwuribe, N.N.; Malson, E.; Riggs-Sauthier, J. (Nobex Corp.); 5-ASA derivs. having anti-inflammatory and antibiotic activity and methods of treating diseases therewith. US 6458776; WO 0218330 . |
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) | 55807 | 4-Nitrobenzenesulfonamide; p-Nitrobenzenesulfonamide | 6325-93-5 | C6H6N2O4S | 详情 | 详情 |
(II) | 18060 | 4-Chloro-4-oxobutyric acid methyl ester; 3-Carbomethosypropionyl chloride; Methyl 4-chloro-4-oxobutanoate | 1490-25-1 | C5H7ClO3 | 详情 | 详情 |
(III) | 55808 | methyl 4-{[(4-nitrophenyl)sulfonyl]amino}-4-oxobutanoate | C11H12N2O7S | 详情 | 详情 | |
(IV) | 55809 | methyl 4-{[(4-aminophenyl)sulfonyl]amino}-4-oxobutanoate | C11H14N2O5S | 详情 | 详情 | |
(V) | 55810 | 4-{[(4-methoxy-4-oxobutanoyl)amino]sulfonyl}benzenediazonium chloride | C11H12ClN3O5S | 详情 | 详情 | |
(VI) | 15240 | 2-Hydroxybenzoic acid; Salicylic acid | 69-72-7 | C7H6O3 | 详情 | 详情 |
(VII) | 55811 | 2-hydroxy-5-[(E)-2-(4-{[(4-methoxy-4-oxobutanoyl)amino]sulfonyl}phenyl)diazenyl]benzoic acid | C18H17N3O8S | 详情 | 详情 |