|
【结 构 式】 
|
【药物名称】Leteprinim potassium, AIT0082, AIT-082, Neotrofin, Neotrophin 【化学名称】4-[3-(6-Oxo-1,6-dihydro-9H-purin-9-yl)propionamido]benzoic acid potassium salt 【CA登记号】192564-13-9, 138117-50-7 (free acid) 【 分 子 式 】C15H12KN5O4 【 分 子 量 】365.39599 |
【开发单位】Spectrum Pharmaceuticals (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , Antiparkinsonian Drugs, Cognition Disorders, Treatment of, Extrapyramidal Disorders, Treatment of, Lesions of the Spinal Cord and Related Structures, Treatment of, NEUROLOGIC DRUGS, Neurologic Drugs (Miscellaneous), ONCOLYTIC DRUGS, Treatment of Disorders Associated with Cancer Therapy, Neurotrophic Agents |
合成路线1
The condensation of adenine (I) with ethyl acrylate (II) by means of sodium ethoxide in methanol gives 3-(9-adenyl)propionic acid ethyl ester (III), which is treated with NaNO2/acetic acid yielding 3-(6-oxo-1,6-dihydro-9H-purin-9-yl)propionic acid ethyl ester (IV). The hydrolysis of (IV) with KOH in water affords the corresponding free acid (V), which is esterified with 4-chlorophenyl trifluoroacetate (VI) in pyridine giving the expected 4-chlorophenyl ester (VII). The condensation of ester (VII) with ethyl 4-aminobenzoate (VIII) by heating (35-40 C) in DMSO yields 4-[3-(6-oxo-1,6-dihydro-9H-purin-9-yl)propionamido]benzoic acid ethyl ester (IX), which is finally hydrolyzed with KOH in water.
| 【1】 Graul, A.; Castañer, J.; AIT-082. Drugs Fut 1997, 22, 9, 945. |
| 【2】 Glasky, A.J.; Multi-functional pharmaceutical cpds. and methods of use. WO 9114434 . |
| 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) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (II) | 10164 | ethyl acrylate | 140-88-5 | C5H8O2 | 详情 | 详情 |
| (III) | 16493 | ethyl 3-(6-amino-9H-purin-9-yl)propanoate | C10H13N5O2 | 详情 | 详情 | |
| (IV) | 16494 | ethyl 3-(6-oxo-1,6-dihydro-9H-purin-9-yl)propanoate | C10H12N4O3 | 详情 | 详情 | |
| (V) | 16495 | 3-(6-oxo-1,6-dihydro-9H-purin-9-yl)propionic acid | C8H8N4O3 | 详情 | 详情 | |
| (VI) | 16496 | 4-[(2,2,2-trifluoroacetyl)oxy]benzoic acid | C9H5F3O4 | 详情 | 详情 | |
| (VII) | 16497 | 4-[[3-(6-oxo-1,6-dihydro-9H-purin-9-yl)propanoyl]oxy]benzoic acid | C15H12N4O5 | 详情 | 详情 | |
| (VIII) | 16498 | Benzocaine; ethyl 4-aminobenzoate | 94-09-7 | C9H11NO2 | 详情 | 详情 |
| (IX) | 16499 | ethyl 4-[[3-(6-oxo-1,6-dihydro-9H-purin-9-yl)propanoyl]amino]benzoate | C17H17N5O4 | 详情 | 详情 |