|
【结 构 式】 
|
【药物名称】ZK-807834, BX-807834, ZK-807191(diHCl), PD-200022, CI-1031 【化学名称】N-[2-(5-Amidino-2-hydroxyphenoxy)-3,5-difluoro-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine 【CA登记号】183305-24-0, 213839-64-6 (diHCl), 183304-36-1 (monoHCl) 【 分 子 式 】C25H24F2N6O5 【 分 子 量 】526.50403 |
【开发单位】Berlex (Originator), Pfizer (Codevelopment) 【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Coagulation Factor Xa Inhibitors |
合成路线1
ZK-807834 is obtained by condensation of the diaryl ether (I) with the phenol (II) by means of K2CO3 to afford the bisaryl ether (III). Reaction of the cyano group of (III), first with HCl in ethanol and then with ammonia, yields the corresponding amidino compound (IV), which is finally demethylated with HBr.
| 【2】 Discovery of N-[2-[5-[amino(imino)methyl]-2-hydroxyphenoxy]-3,5-difluoro-6-[3-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine (ZK-807834): A potent, selective, and orally active inhibitor of the blood coagulation enzyme factor. J Med Chem 1998, 41, 19, 3557. |
| 【1】 Ricart-Diaz, M.; Castaner, J.; ZK-807834. Drugs Fut 2002, 27, 8, 748. |
| 【3】 Buckman, B.O.; Davey, D.D.; Guilford, W.J.; Morrissey, M.M.; Ng, H.P.; Phillips, G.B.; Wu, S.C.; Xu, W. (Berlex Laboratories, Inc.); Benzamidine derivs. their preparation and their use as anti-coagulants. EP 0813525; US 5691364; WO 9628427 . |
| 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) | 54575 | 2-[[2-(5-cyano-2-methoxyphenoxy)-3,5,6-trifluoro-4-pyridinyl](methyl)amino]acetamide | C16H13F3N4O3 | 详情 | 详情 | |
| (II) | 54576 | 2-(3-methoxyphenyl)-1-methyl-4,5-dihydro-1H-imidazole; methyl 3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl ether | C11H14N2O | 详情 | 详情 | |
| (III) | 54578 | 2-[{2-(5-cyano-2-methoxyphenoxy)-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]-4-pyridinyl}(methyl)amino]acetamide | C26H24F2N6O4 | 详情 | 详情 | |
| (IV) | 54579 | 2-[{2-{5-[amino(imino)methyl]-2-methoxyphenoxy}-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]-4-pyridinyl}(methyl)amino]acetamide | C26H27F2N7O4 | 详情 | 详情 | |
| (V) | 54571 | Pentafluoropyridine; Perfluoropyridine | 700-16-3 | C5F5N | 详情 | 详情 |
| (VI) | 54572 | 2-(methylamino)acetamide | C3H8N2O | 详情 | 详情 | |
| (VII) | 54573 | 2-[methyl(2,3,5,6-tetrafluoro-4-pyridinyl)amino]acetamide | C8H7F4N3O | 详情 | 详情 | |
| (VIII) | 54574 | 3-hydroxy-4-methoxybenzonitrile | 52805-46-6 | C8H7NO2 | 详情 | 详情 |
| (IX) | 36250 | 3-methoxybenzonitrile | 1527-89-5 | C8H7NO | 详情 | 详情 |
| (X) | 27777 | N-(2-aminoethyl)-N-methylamine | 109-81-9 | C3H10N2 | 详情 | 详情 |
| (XI) | 54575 | 2-[[2-(5-cyano-2-methoxyphenoxy)-3,5,6-trifluoro-4-pyridinyl](methyl)amino]acetamide | C16H13F3N4O3 | 详情 | 详情 |