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【结 构 式】 
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【药物名称】 【化学名称】N1-[3-[3-(2-Chlorophenylsulfonyloxy)-5-methylphenoxy]propylideneamino]guanidine hydrochloride 【CA登记号】 【 分 子 式 】C17H20Cl2N4O4S 【 分 子 量 】447.34335 |
【开发单位】3-Dimensional (Originator) 【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Thrombin Inhibitors |
合成路线1
Orcinol (I) is first derivatized to (III) by reaction with sulfonyl chloride (II) in a mixture of aqueous NaHCO3 (sat) and Et2O. Monosulfonate (III) undergoes Mitsunobu reaction with monobenzylated diol (IV) in the presence of PPh3 and DEAD in dichloromethane to yield derivative (V), which is then debenzylated by hydrogenolysis over Pd/C in MeOH, or in THF/HCl/dioxane, to afford (VI). Alcohol (VI) is oxidized with SO3·pyr complex in DMSO/dichloromethane in the presence of DIEA to provide aldehyde (VIII), which finally reacts with aminoguanidine nitrate in EtOH in the presence of HCl/dioxane.
| 【1】 Soll, R.M.; Lu, T.; Tomczuk, B.; et al.; Amidinohydrazones as guanidine bioisosteres: Application to a new class of potent, selective and orally bioavailable, non-amide-based small-molecule thrombin inhibitors. Bioorg Med Chem Lett 2000, 10, 1, 1. |
| 【2】 Soll, R.M.; Lu, T.; Fedde, C.L.; Tomczuk, B.E.; Illig, C. (3-Dimensional Pharmaceuticals, Inc.); Amidinohydrazones as protease inhibitors. EP 0906091; JP 2000507588; US 5891909; WO 9736580 . |
| 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) | 27257 | 5-Methyl-1,3-benzenediol; Orcinol | 505-15-4 | C7H8O2 | 详情 | 详情 |
| (II) | 30817 | 2-chlorobenzenesulfonyl chloride | 2905-23-9 | C6H4Cl2O2S | 详情 | 详情 |
| (III) | 30818 | 3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate | C13H11ClO4S | 详情 | 详情 | |
| (IV) | 14687 | 3-(benzyloxy)-1-propanol; 3-(Benzyloxy)propanol | 4799-68-2 | C10H14O2 | 详情 | 详情 |
| (V) | 30819 | 3-[3-(benzyloxy)propoxy]-5-methylphenyl 2-chlorobenzenesulfonate | C23H23ClO5S | 详情 | 详情 | |
| (VI) | 30820 | 3-(3-hydroxypropoxy)-5-methylphenyl 2-chlorobenzenesulfonate | C16H17ClO5S | 详情 | 详情 | |
| (VII) | 30821 | 3-methyl-5-(3-oxopropoxy)phenyl 2-chlorobenzenesulfonate | C16H15ClO5S | 详情 | 详情 | |
| (VIII) | 10015 | 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide | 79-17-4 | CH6N4 | 详情 | 详情 |