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【结 构 式】

【药物名称】CGS-21680

【化学名称】2-[2-[4-(2-Carboxyethyl)phenyl]ethylamino]adenosin-5'-oic acid ethylamide
      2-[4-(2-Carboxyethyl)phenylethylamino]-5'-(N-ethyl)carboxamidoadenosine

【CA登记号】120225-54-9

【 分 子 式 】C23H29N7O6

【 分 子 量 】499.53088

【开发单位】Novartis (Originator)

【药理作用】Antipsychotic Drugs, CARDIOVASCULAR DRUGS, DERMATOLOGIC DRUGS, Hypertension, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Wound-Healing Agents, Adenosine A2A Agonists

合成路线1

The intermediate amine (V) was prepared via a Heck reaction between p-bromophenylacetonitrile (I) and tert-butyl acrylate (II) to afford the p-(cyanomethyl)cinnamate (III) . Catalytic double bond hydrogenation in (III) provided the saturated cyano ester (IV), which was then reduced to amine (V) by using NaBH4 in the presence of CoCl2. Alternatively, simultaneous double bond and cyano group reduction was accomplished by hydrogenation of (III) in the presence of Pd/C and HCl.

1 Hutchison, A.J.; Williams, M.; de Jesus, R.; Yokoyama, R.; Oei, H.H.; Ghai, G.R.; Webb, R.L.; Zoganas, H.C.; Stone, G.A.; Jarvis, M.F.; 2-(Arylalkylamino)adenosin-5'-uronamides: A new class of highly selective adenosine A2 receptor ligands. J Med Chem 1990, 33, 7, 1919.
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) 45829 2-(4-bromophenyl)acetonitrile; 4-Bromobenzyl cyanide 16532-79-9 C8H6BrN 详情 详情
(II) 12760 tert-butyl acrylate 1663-39-4 C7H12O2 详情 详情
(III) 62371 tert-butyl (E)-3-[4-(2-nitriloethyl)phenyl]-2-propenoate C15H17NO2 详情 详情
(IV) 62372 tert-butyl 3-[4-(2-nitriloethyl)phenyl]propanoate C15H19NO2 详情 详情
(V) 62373 tert-butyl 3-[4-(2-aminoethyl)phenyl]propanoate C15H23NO2 详情 详情

合成路线2

Acetonide (VII) was prepared by treatment of 2-chloroadenosine (VI) with 2,2-dimethoxypropane and camphorsulfonic acid. Subsequent oxidation of (VII) with KMnO4 under basic conditions produced the carboxylic acid (VIII). After activation of (VIII) as the corresponding acid chloride (IX), reaction with ethylamine afforded amide (X). Condensation of amine (V) with the chloroadenosine derivative (X) at 130 C furnished the diaminopurine adduct (XI). Finally, simultaneous cleavage of the tert-butyl ester and acetonide groups of (XI) upon acidic treatment provided the title compound

1 Hutchison, A.J.; Williams, M.; de Jesus, R.; Yokoyama, R.; Oei, H.H.; Ghai, G.R.; Webb, R.L.; Zoganas, H.C.; Stone, G.A.; Jarvis, M.F.; 2-(Arylalkylamino)adenosin-5'-uronamides: A new class of highly selective adenosine A2 receptor ligands. J Med Chem 1990, 33, 7, 1919.
2 Hutchison, A.J. (Novartis AG); Certain adenosine 5'-carboxamide derivs.. AU 8811233; EP 0277917; JP 1988201196 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 62373 tert-butyl 3-[4-(2-aminoethyl)phenyl]propanoate C15H23NO2 详情 详情
(VI) 62374 (2R,3R,4S,5R)-2-(6-amino-2-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol C10H12ClN5O4 详情 详情
(VII) 62375 [(3aR,4R,6R,6aR)-6-(6-amino-2-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol C13H16ClN5O4 详情 详情
(VIII) 62376 (3aR,4S,6R,6aR)-6-(6-amino-2-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid C13H14ClN5O5 详情 详情
(IX) 62377 (3aR,4S,6R,6aR)-6-(6-amino-2-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carbonyl chloride C13H13Cl2N5O4 详情 详情
(X) 62378 (3aR,4S,6R,6aR)-6-(6-amino-2-chloro-9H-purin-9-yl)-N-ethyl-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide C15H19ClN6O4 详情 详情
(XI) 62379 tert-butyl 3-(4-{2-[(9-{(3aR,4R,6S,6aR)-6-[(ethylamino)carbonyl]-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl}-6-amino-9H-purin-2-yl)amino]ethyl}phenyl)propanoate C30H41N7O6 详情 详情
Extended Information