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【结 构 式】 
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【药物名称】GNTI 【化学名称】17-(Cyclopropylmethyl)-4,5alpha-epoxy-3,14-dihydroxy-5'-guanidino-6,7-didehydroindolo[2',3':6,7]morphinan 【CA登记号】219655-56-8, 219655-57-9 (trifluoroacetate) 【 分 子 式 】C27H29N5O3 【 分 子 量 】471.56388 |
【开发单位】University of Minnesota (Originator) 【药理作用】Antiobesity Drugs, Antipsychotic Drugs, METABOLIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, Treatment of Nutritional Disorders, Treatment of Opioid Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, kappa-Opioid Antagonists |
合成路线1
Fischer indole cyclization of naltrexone (I) with 4-nitrophenylhydrazine (II) provided 5'-nitronaltrindole (III). Subsequent reduction of the nitro group of (III) by means of hydrazine hydrate and Raney Nickel gave the 5'-amino derivative (IV). Mercury-assisted condensation of (IV) with di(tert-butoxy-carbonyl)thiourea (V) afforded the protected guanidine (VI). Finally, the Boc groups of (VI) were cleaved by treatment with trifluoroacetic acid to furnish the title compound.
| 【1】 Jones, R.M.; Hjorth, S.A.; Schwartz, T.W.; Portoghese, P.S.; Mutational evidence for a common kappa antagonist binding pocket in the wild-type kappa and mutant mu[K303E] opioid receptors. J Med Chem 1998, 41, 25, 4911. |
| 【2】 Sercel, A.D.; Stevens, W.C. Jr.; Ingals, S.; et al.; Naltrindole analogs as potent and selective kappa-opioid receptor antagonists. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 267. |
| 【3】 Stevens, W.C.; Jones, R.M.; Subramanian, G.; Metzger, T.G.; Ferguson, D.M.; Portoghese, P.S.; Potent and selective indolomorphinan antagonists of the kappa-opioid receptor. J Med Chem 2000, 43, 14, 2759. |
| 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) | 25079 | (1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one; Naltrexone | 16590-41-3 | C20H23NO4 | 详情 | 详情 |
| (II) | 34400 | 1-(4-nitrophenyl)hydrazine; 4-Nitrophenylhydrazine | 100-16-3 | C6H7N3O2 | 详情 | 详情 |
| (III) | 34703 | (1S,2S,13R,21R)-22-(cyclopropylmethyl)-7-nitro-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C26H25N3O5 | 详情 | 详情 | |
| (IV) | 34704 | (1S,2S,13R,21R)-7-amino-22-(cyclopropylmethyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C26H27N3O3 | 详情 | 详情 | |
| (V) | 21843 | tert-butyl [(tert-butoxycarbonyl)amino]carbothioylcarbamate | 145013-05-4 | C11H20N2O4S | 详情 | 详情 |
| (VI) | 34705 | tert-butyl (Z)-[(tert-butoxycarbonyl)amino][[(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2,16-dihydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-7-yl]amino]methylidenecarbamate | C37H45N5O7 | 详情 | 详情 |