Suberoylanilide hydroxamic acid, Suberanilohydroxamic acid, SW-064652, SAHA
伏立诺他Chemical Name: N-Hydroxy-N'-phenyloctanediamide; 8-(Phenylamino)-8-oxooctanohydroxamic acid
CAS No. 149647-78-9
项目整合开发状态: Phase II/III
项目研究机构: Aton Pharma (Orphan Drug), Columbia University (Originator), Sanofi-Aventis (Originator), National Cancer Institute (Not Determined), Aton Pharma (Licensee)
合成路线:1.A mixture of diacid dichloride (I),aniline (II),hydroxylamine (III) and KOH in 50% THF/water gives,after chromatographic purification,the title product with yields of 15-30%.
合成路线:2.The reaction of the diacid monoester (IV) with oxalyl chloride in benzene gives the corresponding acyl chloride (V),which is treated with aniline (II) and pyridine in THF,yielding the monoester monoamide (VI).The hydrolysis of the ester group of (VI) with OH in refluxing methanol affords the monoamide carboxylic acid (VII),which is condensed with O-benzylhydroxylamine (VIII) by means of DCC in pyridine to provide the protected hydroxamic acid (IX).Finally,this compound is debenzylated with H2 over Pd/C in methanol to furnish the target hydroxamic acid with yields of 35-65%.3.A mixture of diacid dichloride (I),aniline (II) and O-benzylhydroxylamine (VIII) in pyridine gives,after chromatographic purification,the protected hydroxamic acid (IX),which is debenzylated as before to provide the target hydroxamic acid with yields of 20-35%.4.The reaction of acid dichloride (I) with aniline (II) and O-(trimethylsilyl)hydroxylamine (X) by means of TEA in chloroform gives the trimethylsilyl protected compound (XI),which is desilylated with NH4Cl in hot methanol to afford the target hydroxamic acid with yields of 20-33%.
📌 参考资料/链接：
参考文献标题:Novel potent inducers of terminal differentiation and methods of use thereof
文献作者:Breslow,R.; Rifkind,R.A.; Jursic,B.(Columbia University; Sloan-Kettering Institute)
参考来源:WO 9307148
📄 详细内容
合成路线:5.The condensation of diacid (XII) with aniline (II) by heating at 190 C gives the monoamide (VII),which is esterified by means of Dowex 50W-X2 in refluxing methanol to yield the monoamide monoester (XIII).Finally,this compound is treated with hydroxylamine and NaOMe in methanol to afford the target hydroxamic acid with overall yields of around 37%.
参考文献标题:The synthesis of N-hydroxy-N'-phenyloctanediamide and its inhibitory effect on proliferation of AXC rat prostate cancer cells
文献作者:Stowell,J.C.; Huot,R.I.; Van Voast,L.
参考来源:J Med Chem 1995,38(8),1411
合成路线:6.The reaction of acid (XII) with refluxing acetic anhydride gives the cyclic anhydride (XIV),which is treated with aniline (II) in THF to yield the monoamide (VII).The reaction of (VII) with ethyl chloroformate and TEA in THF affords the mixed anhydride (XV),which is finally treated with hydroxylamine in methanol to afford the target hydroxamic acid with overall yields of around 58%.
参考文献标题:A new facile and expeditious synthesis of N-hydroxy-N'-phenyloctanediamide,a potent inducer of terminal cytodifferentiation
文献作者:Mai,A.; et al.
参考来源:Org Prep Proced Int 2001,33(4),391
产品链接: CAS No. 149647-78-9››