GW-544, GW-409544X

N-[1-甲基-3-氧基-3-苯基-1(Z)-丙基]-O-[2-(5-甲基-2-苯洛克唑-4-基)乙基]-L-酪氨酸Chemical Name: N-[1-Methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine
CAS No. 258345-41-4
项目整合开发状态: Phase I
项目研究机构: GlaxoSmithKline (Originator), Ligand (Codevelopment)
合成路线:The cyclization of methyl 4-bromo-3-oxopentanoate (I) with benzamide (II) and sodium hydrogen phosphate in refluxing ethanol gives methyl 2-(5-methyl-2-phenyloxazol-4-yl)acetate (III),which is reduced with LiAlH4 in THF to yield the ethanol derivative (IV).The reaction of (IV) with methanesulfonyl chloride and TEA in dichloromethane affords the mesylate (V),which is condensed with N-(tert-butoxycarbonyl)-L-tyrosine (VI) by means of NaOH in hot DMSO/water to provide the 4-O-substituted tyrosine (VII),which is deprotected by means of HCl in dioxane to give intermediate (VIII) with a free amino group.Finally,this compound is condensed with benzoylacetone (IX) by means of trimethyl orthoformate in refluxing methanol to afford the target N-substituted tyrosine derivative.