ABT-518-药物合成数据库

【药物名称】ABT-518

化学结构式(Chemical Structure):

参考文献No.	44475
标题:	Reverse hydroxamate inhibitors of matrix metalloproteinases
作者:	Curtin, M.L.; Davidsen, S.K.; Michaelides, M.R.; Steinman, D.H.; Dai, Y.; Heyman, H.R.; Holmes, J.H. (Abbott Laboratories Inc.)
来源:	WO 0044739

合成路线图解说明: The condensation of 4-(trifluoromethoxy)phenol (I) with 4-fluorophenyl(methyl)sulfone (II) by means of K2CO3 in hot DMSO gives the diphenyl ether (III), which is condensed with 2,2-dimethyl-1,3-dioxolane-(R)-carboxylic acid methyl ester (IV) by means of BuLi in THF to afford the ethanone (V). The reduction of (V) with NaBH4 in ethanol yields the ethanol derivative (VI), which is dehydrated to the ethylene (VII) by means of MsCl, TEA and NaHCO3. The addition of hydroxylamine to the double bond of (VII) provides the hydroxyamine derivative (VIII) as a diastereomeric mixture that is separated by flash chromatography, affording the desired enantiomer (IX). Finally, this compound is formylated by treatment with 2,2,2-trifluoroethyl formate (X) (obtained by reaction of 2,2,2-trifluoroethanol (XI) with hot formic acid (XII)) in refluxing MTBE.

参考文献No.	646941
标题:	Phenoxyphenyl sulfone N-forylhydroxylamines (retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors
作者:	Wada, C.K.; Holms, J.H.; Curtin, M.L.; Dai, Y.; Florjancic, A.S.; Garland, R.B.; Guo, Y.; Heyman, H.R.; Stacey, J.R.; Steinman, D.H.; Albert, D.H.; Bouska, J.J.; Elmore, I.N.; Goodfellow, C.L.; Marcotte, P.A.; Tapang, P.; Morgan, D.W.; et al.
来源:	J Med Chem 2002,45(1),219

合成路线图解说明: The condensation of 4-(trifluoromethoxy)phenol (I) with 4-fluorophenyl(methyl)sulfone (II) by means of K2CO3 in hot DMSO gives the diphenyl ether (III), which is condensed with 2,2-dimethyl-1,3-dioxolane-(R)-carboxylic acid methyl ester (IV) by means of BuLi in THF to afford the ethanone (V). The reduction of (V) with NaBH4 in ethanol yields the ethanol derivative (VI), which is dehydrated to the ethylene (VII) by means of MsCl, TEA and NaHCO3. The addition of hydroxylamine to the double bond of (VII) provides the hydroxyamine derivative (VIII) as a diastereomeric mixture that is separated by flash chromatography, affording the desired enantiomer (IX). Finally, this compound is formylated by treatment with 2,2,2-trifluoroethyl formate (X) (obtained by reaction of 2,2,2-trifluoroethanol (XI) with hot formic acid (XII)) in refluxing MTBE.