SD-270
Chemical Name: 3-[2-[3-(4-Amidinophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetamido]-N-(2-methylphenylsulfonyl)-L-alanine
CAS No. 223559-85-1, 223559-86-2 (trifluoroacetate)
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The sulfonation of 2(S)-amino-3-(tert-butoxycarbonylamino)propionic acid methyl ester (I) with 3,5-dimethylisoxazol-4-ylsulfonyl chloride (II) by means of triethylamine in dichloromethane gives the corresponding sulfonamide (III),which is deprotected with trifluoroacetic acid yielding the 3-aminopropionic acid derivative (IV).The condensation of (IV) with [3-(4-cyanophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetic acid (V) by means of TBTU and triethylamine in DMF affords the carboxamide (VI).The cyano group of (VI) is treated first with dry HCl and then with NH3,NH4OAc,or CO3(NH4)2 to obtain the amidino group of (VII).Finally,compound (VII) is hydrolyzed with LiOH,6N HCl,or rabbit liver esterase.
合成路线:Condensation of methyl N3-Boc-2,3-diaminopropionate (I) with o-tolylsulfonyl chloride (II) produced sulfonamide (III).Subsequent acid cleavage of the Boc protecting group of (III) gave amine (IV).Coupling of amine (IV) with the previously described (R)-oxazolidineacetic acid (V) using TBTU afforded amide (VI).Pinner reaction of (VI) with methanolic HCl converted nitrile (VI) into imidate (VII),which was further treated with ammonium acetate to furnish amidine (VIII).Finally,selective hydrolysis of the ester function of (VIII) was achieved with either LiOH or with an enzymatic method using rabbit liver esterase.
📌 参考资料/链接：
参考文献标题:Orally active isoxazoline glycoprotein IIb/IIIa antagonists with extended duration of action
文献作者:Olson,R.E.; Sielecki,T.M.; Wityak,J.; Pinto,D.J.; Batt,D.G.; Frietze,W.E.; Liu,J.; Tobin,A.E.; Orwat,M.J.; Di Meo,S.V.; Houghton,G.C.; Lalka,G.K.; Mousa,S.A.; Racanelli,A.L.; Hausner,E.A.; Kapil,R.P.; Rabel,S.R.; et al.
参考来源:J Med Chem 1999,42(7),1178
📄 详细内容
合成路线:Condensation of methyl N3-Boc-2,3-diaminopropionate (I) with o-tolylsulfonyl chloride (II) produced sulfonamide (III).Subsequent acid cleavage of the Boc protecting group of (III) gave amine (IV).Coupling of amine (IV) with the previously described (R)-oxazolidineacetic acid (V) using TBTU afforded amide (VI).Pinner reaction of (VI) with methanolic HCl converted nitrile (VI) into imidate (VII),which was further treated with ammonium acetate to furnish amidine (VIII).Finally,selective hydrolysis of the ester function of (VIII) was achieved with either LiOH or with an enzymatic method using rabbit liver esterase.
参考文献标题:Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa receptor antagonists
文献作者:Sielecki,T.M.; Liu,J.; Mousa,S.A.; Racanelli,A.L.; Hausner,E.A.; Wexler,R.R.; Olson,R.E.
参考来源:Bioorg Med Chem Lett 2001,11(16),2201