|
【结 构 式】 
|
【药物名称】Trichlorfon, Metriphonate, Metrifonate, Bayer-L-1359, Bay-a-9826, Bilarcil, Memobay, ProMem 【化学名称】(2,2,2-Trichloro-1-hydroxyethyl)phosphonic acid dimethyl ester 【CA登记号】52-68-6 【 分 子 式 】C4H8Cl3O4P 【 分 子 量 】257.43876 |
【开发单位】Bayer (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , ANTIINFECTIVE THERAPY, Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Treatment of Helminthic Diseases, Butyrylcholinesterase Inhibitors |
合成路线1
Metrifonate is easily synthesized in a one-step spontaneous exothermic condensation of equimolar amounts of chloral hydrate with dimethylhydrogenphosphite, which in turn is accessible by reacting PCl3 with methanol. Contrary to similar reactions described earlier (1950-1952) in two Soviet papers and a U.S. process patent, no catalyst is needed if the aldehyde compound is chloral. Therefore, metrifonate can be readily crystallized directly from the reaction mixture.
| 【1】 Mucke, H.A.M.; Metrifonate. Drugs Fut 1998, 23, 5, 491. |
| 【2】 Giang, P.A.; Barthel, W.F.; Hall, S.A.; Dialkylalpha-hydroxyphosphonates derived from chloral. J Am Chem Soc 1954, 76, 4186-7. |
合成路线2
Metrifonate is totally unique among the acetylcholinesterase inhibitors currently used or proposed for the treatment of Alzheimer's disease because it is an inactive prodrug. The active compound dichlorvos, (2,2-dichlorovinyl dimethylphosphate; DDVP), is formed in a nonenzymatic reaction by hydrolysis and elimination of HCl followed by rearrangement of an intermediate according to Scheme.
| 【1】 Mucke, H.A.M.; Metrifonate. Drugs Fut 1998, 23, 5, 491. |
| 【2】 Giang, P.A.; Barthel, W.F.; Hall, S.A.; Dialkylalpha-hydroxyphosphonates derived from chloral. J Am Chem Soc 1954, 76, 4186-7. |