【药物名称】SB-683698, TR-14035
化学结构式(Chemical Structure):
参考文献No.40019
标题:Inhibitors of alpha4 mediated cell adhesion
作者:Gudmundsson, K.S.; Sircar, I.; Martin, R. (Tanabe Seiyaku Co., Ltd.)
来源:WO 9936393
合成路线图解说明:

Treatment of N-Boc-4-bromo-L-phenylalanine (I) with ethanolic or methanolic HCl gave aminoester (II). Subsequent condensation of (II) with 2,6-dichlorobenzoyl chloride (III) produced amide (IV). Lithiation of 1,3-dimethoxybenzene (V) with n-butyllithium, followed by reaction with trimethyl borate and aqueous hydrolysis yielded boronic acid (VI). Suzuki coupling of bromide (IV) with boronic acid (VI) in the presence of palladium catalyst furnished biphenyl derivative (VII). Finally, hydrolysis of the ethyl ester of (VII) with LiOH provided the title carboxylic acid.

参考文献No.546368
标题:Discovery of TR-14035: An orally active dual alpha4beta7/alpha4beta1 integrin antagonist
作者:Hattfield, L.D.; Sircar, I.; McNutly, A.; Naubauer, B.
来源:218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999,Abst MEDI 59
合成路线图解说明:

In an alternative procedure, N-Boc-L-tyrosine methyl ester (VIII) was treated with trifluoromethanesulfonic anhydride to afford triflate (IX). Suzuki coupling of (IX) with boronic acid (VI) produced biphenyl (X). After deprotection of the Boc group of (X) with trifluoroacetic acid, the resulting aminoester (XI) was acylated with acid chloride (III) to give amide (XII). The title compound was then obtained by hydrolysis of the methyl ester of (XII) with LiOH.

参考文献No.547517
标题:SAR of TR-14035: An orally active dual alpha4beta7/alpha4beta1 integrin antagonist
作者:Sircar, I.; Liang, J.T.; Mart韓, R.; et al.
来源:218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999,Abst MEDI 60
合成路线图解说明:

In an alternative procedure, N-Boc-L-tyrosine methyl ester (VIII) was treated with trifluoromethanesulfonic anhydride to afford triflate (IX). Suzuki coupling of (IX) with boronic acid (VI) produced biphenyl (X). After deprotection of the Boc group of (X) with trifluoroacetic acid, the resulting aminoester (XI) was acylated with acid chloride (III) to give amide (XII). The title compound was then obtained by hydrolysis of the methyl ester of (XII) with LiOH.

参考文献No.668944
标题:Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: Discovery of TR-14035, a dual alpha4beta7/alpha4beta1 integrin antagonist
作者:Sircar, I.; Gudmundsson, K.S.; Martin, R.; Liang, J.; Nomura, S.; Jayakumar, H.; Teegarden, B.R.; Nowlin, D.M.; Cardarelli, P.M.; Mah, J.R.; Connell, S.; Griffith, R.C.; Lazarides, E.
来源:Bioorg Med Chem 2002,10(6),2051
合成路线图解说明:

Treatment of N-Boc-4-bromo-L-phenylalanine (I) with ethanolic or methanolic HCl gave aminoester (II). Subsequent condensation of (II) with 2,6-dichlorobenzoyl chloride (III) produced amide (IV). Lithiation of 1,3-dimethoxybenzene (V) with n-butyllithium, followed by reaction with trimethyl borate and aqueous hydrolysis yielded boronic acid (VI). Suzuki coupling of bromide (IV) with boronic acid (VI) in the presence of palladium catalyst furnished biphenyl derivative (VII). Finally, hydrolysis of the ethyl ester of (VII) with LiOH provided the title carboxylic acid.

合成路线图解说明:

In an alternative procedure, N-Boc-L-tyrosine methyl ester (VIII) was treated with trifluoromethanesulfonic anhydride to afford triflate (IX). Suzuki coupling of (IX) with boronic acid (VI) produced biphenyl (X). After deprotection of the Boc group of (X) with trifluoroacetic acid, the resulting aminoester (XI) was acylated with acid chloride (III) to give amide (XII). The title compound was then obtained by hydrolysis of the methyl ester of (XII) with LiOH.

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us