AR-H040922, H-409/22

Chemical Name: Nalpha-(2,2-Diphenylacetyl)-N1-[1(R)-(4-hydroxyphenyl)ethyl]-D-argininamide
项目整合开发状态: Phase II
项目研究机构: AstraZeneca (Originator)
合成路线:The protected (R)-ornithine (I) was converted to the active ester (III) upon coupling with 2-nitrophenol (II) in the presence of DCC and pyridine.Subsequent reaction of the nitrophenyl ester (III) with (R)-4-hydroxy-alpha-methylbenzylamine (IV) produced the corresponding amide (V).After acid cleavage of the Boc protecting group of (V),the resulting amine (VI) was acylated with diphenylacetyl chloride (VII) to give (VIII).Removal of the N-benzyloxycarbonyl group of (VIII) was achieved by catalytic hydrogenation over Pd/C.The resultant amine (IX) was then converted to the protected guanidine (XI) by reaction with N,N'-bis(benzyloxycarbonyl)-S-methylisothiourea (X).The protecting groups of (X) were finally removed by hydrogenation over Pd/C.