【结 构 式】 |
【药物名称】ONO-BB-039-02 【化学名称】N2-[2(S)-Benzyl-3-sulfanylpropionyl]-L-glutamic acid 1-phenylamide 【CA登记号】126349-24-4 【 分 子 式 】C21H24N2O4S 【 分 子 量 】400.50043 |
【开发单位】Ono (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Enkephalinase Inhibitors, Neprilysin Inhibitors |
合成路线1
Chiral resolution of protected dl-thiopropionic acid derivative (I) is performed by first condensation with (1R,2S)-(-)-2-amino-1,2-diphenyl ethanol in acetonitrile followed by diastereomer separation and finally hydrolysis of the optically active salt to afford the desired stereoisomer (S)-(II). Activation of (S)-(II) with oxalyl chloride in dichloromethane and subsequent coupling to L-isoglutamine derivative (III) in CH2Cl2 in the presence of pyridine provides amide (S)-(IV), which is finally converted into the target product by alkaline hydrolysis with LiOH in THF.
【1】 Katsube, N.; Nakai, H.; Nagao, Y.; Sakai, Y.; Senokuchi, K.; Kawamura, M.; New orally active enkephalinase inhibitors: Their synthesis, biological activity, and analgesic properties. Bioorg Med Chem 1998, 6, 4, 441. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 48898 | 3-(benzoylsulfanyl)-2-benzylpropionic acid | C17H16O3S | 详情 | 详情 | |
(II) | 15141 | (1R,2S)-(-)-2-Amino-1,2-diphenylethanol; (1S,2R)-2-amino-1,2-diphenyl-1-ethanol | 23190-16-1 | C14H15NO | 详情 | 详情 |
(III) | 48899 | (2S)-3-(benzoylsulfanyl)-2-benzylpropionic acid | C17H16O3S | 详情 | 详情 | |
(IV) | 48900 | benzyl (4S)-4-amino-5-anilino-5-oxopentanoate | C18H20N2O3 | 详情 | 详情 | |
(V) | 48901 | benzyl (4S)-5-anilino-4-[[(2S)-3-(benzoylsulfanyl)-2-benzylpropanoyl]amino]-5-oxopentanoate | C35H34N2O5S | 详情 | 详情 |