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【结 构 式】 
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【药物名称】GW-7854 【化学名称】3-[3-[1-(N-Isopropyl-N-phenylcarbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]ureido]benzoic acid 【CA登记号】184945-01-5 【 分 子 式 】C34H31N5O6 【 分 子 量 】605.65607 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antiobesity Drugs, METABOLIC DRUGS, Treatment of Nutritional Disorders, CCK1 (CCKA) Agonists, CCK2 (CCKB/Gastrin) Antagonists |
合成路线1
N-Phenyl-1,2-phenylenediamine (I) was alkylated with bromoacetanilide (II) in the presence of potassium carbonate in DMF, and the resulting alkylated phenylenediamine (III) was condensed with diacid chloride (IV) in THF to afford dioxobenzodiazepine (V). Reduction of the hydrazone function with zinc-acetic acid provided amine (VI) (1). Urea (VIII) was then prepared by treatment of amine (VI) with isocyanate (VII) in dichloromethane, and finally, ethyl ester was hydrolyzed on treatment with K2CO3 in a refluxing mixture of methanol and THF.
| 【1】 Hirst, G.C.; et al.; Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity (II): Optimization of the C3 amino substituent. J Med Chem 1996, 39, 26, 5236. |
| 【2】 Finch, H.; Shah, P.; Carr, R.A.E. (Glaxo Wellcome plc); 1,5-Benzodiazepine derivs. having CCK and/or gastrin antagonistic activity. US 5585376; US 5646140; WO 9424149; WO 9424151 . |
| 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) | 18990 | N-(2-aminophenyl)-N-phenylamine; N(1)-phenyl-1,2-benzenediamine | 534-85-0 | C12H12N2 | 详情 | 详情 |
| (II) | 18991 | 2-bromo-N-isopropyl-N-phenylacetamide | C11H14BrNO | 详情 | 详情 | |
| (III) | 18992 | 2-(2-anilinoanilino)-N-isopropyl-N-phenylacetamide | C23H25N3O | 详情 | 详情 | |
| (IV) | 17971 | 2-(2-phenylhydrazono)malonoyl dichloride | C9H6Cl2N2O2 | 详情 | 详情 | |
| (V) | 18994 | 2-[2,4-dioxo-5-phenyl-3-[(Z)-2-phenylhydrazono]-4,5-dihydro-1H-1,5-benzodiazepin-1(2H)-yl]-N-isopropyl-N-phenylacetamide | C32H29N5O3 | 详情 | 详情 | |
| (VI) | 18995 | 2-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl)-N-isopropyl-N-phenylacetamide | C26H26N4O3 | 详情 | 详情 | |
| (VII) | 18996 | ethyl 3-isocyanatobenzoate | 67531-68-4 | C10H9NO3 | 详情 | 详情 |
| (VIII) | 18997 | ethyl 3-[[([1-[2-(isopropylanilino)-2-oxoethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]amino)carbonyl]amino]benzoate | C36H35N5O6 | 详情 | 详情 |