新产品编号:190349
Chemical Name: 3-[5-[3-[N-(1H-Imidazol-2-yl)carbamoyl]propyl]-4,5-dihydroisoxazo-3-carboxamido]-2(S)-(2,4,6-trimethylphenylsulfonamido)propionic acid
CAS No. 185562-53-2
项目整合开发状态: Biological Testing
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Cycloaddition of 5-hexen-1-ol (I) with (II) in presence of NaHCO3 yields isoxazoline (III).Alternatively (III) can be obtained by treatment of (I) with diethyl nitromalonate (A) in mesitylene.Isoxazoline (III) is then oxidized by means of Jones reagent to provide acid (IV) which is coupled in presence of BOP with the imidazole derivative (V) and hydrolyzed with LiOH affording derivative (VI).Acid (VI) is coupled with derivative (IX) (obtained by reaction of diaminopropionate (VII) with (VIII) in presence of DIEA) by means of BOP,and finally hydrolyzed to afford the desired product.
📌 参考资料/链接：
参考文献标题:Isoxazoline and isoxazole derivs.as integrin receptor antagonists
文献作者:Voss,M.E.; Jadhav,P.K.; Smallheer,J.M.; Batt,D.G.; Pitts,W.J.; Wityak,J.(DuPont Pharmaceuticals Co.)
参考来源:EP 0828737; JP 1999506436; US 5710159; WO 9637492
📄 详细内容
合成路线:Cycloaddition of 5-hexen-1-ol (I) with (II) in presence of NaHCO3 yields isoxazoline (III).Alternatively (III) can be obtained by treatment of (I) with diethyl nitromalonate (A) in mesitylene.Isoxazoline (III) is then oxidized by means of Jones reagent to provide acid (IV) which is coupled in presence of BOP with the imidazole derivative (V) and hydrolyzed with LiOH affording derivative (VI).Acid (VI) is coupled with derivative (IX) (obtained by reaction of diaminopropionate (VII) with (VIII) in presence of DIEA) by means of BOP,and finally hydrolyzed to afford the desired product.
参考文献标题:Heterocyclic integrin inhibitor prodrugs
文献作者:Jadhav,P.; Repta,A.J.; Pitts,W.J.; Hussain,M.A.; Batt,D.G.(DuPont Pharmaceuticals Co.)
参考来源:WO 9843962
合成路线:Cycloaddition of 5-hexen-1-ol (I) with (II) in presence of NaHCO3 yields isoxazoline (III).Alternatively (III) can be obtained by treatment of (I) with diethyl nitromalonate (A) in mesitylene.Isoxazoline (III) is then oxidized by means of Jones reagent to provide acid (IV) which is coupled in presence of BOP with the imidazole derivative (V) and hydrolyzed with LiOH affording derivative (VI).Acid (VI) is coupled with derivative (IX) (obtained by reaction of diaminopropionate (VII) with (VIII) in presence of DIEA) by means of BOP,and finally hydrolyzed to afford the desired product.
参考文献标题:Isoxazolines as potent antagonists of the integrin alphavbeta3
文献作者:Pitts,W.J.; Withyak,J.; Smallheer,J.M.; Tobin,A.E.; Jetter,J.W.; Buynitsky,J.S.; Harlow,P.P.; Solomon,K.A.; Corjay,M.H.; Mousa,S.A.; Wexler,R.R.; Jadhav,P.K.
参考来源:J Med Chem 2000,43(1),27