【结 构 式】 |
【药物名称】 【化学名称】N-(N-Phenylcarbamoyl)-L-seryl-L-leucyl-L-valine ethyl ester 【CA登记号】189110-11-0 【 分 子 式 】C23H36N4O6 【 分 子 量 】464.56657 |
【开发单位】Kirin Brewery (Originator) 【药理作用】ONCOLYTIC DRUGS, Apoptosis Inducers |
合成路线1
The title compound was obtained by the solid-phase method using a peptide synthesizer. Starting from Fmoc-valine linked to Wang resin (I), cleavage of the Fmoc group with piperidine in DMF provided the deprotected valine-resin (II), which was then coupled with Fmoc-leucine (III) by means of 1-hydroxybenzotriazole and diisopropylcarbodiimide. The resulting dipeptide resin (IV) was deprotected with piperidine in DMF to give (V), and further coupling with protected serine (VI) yielded (VII). After Fmoc-deprotection, the tripeptide-resin (VIII) was coupled with phenyl isocyanate (IX), affording urea (X). Cleavage from the resin with simultaneous deprotection using trifluoroacetic acid furnished the tripeptide urea (XI). This was finally esterified by treatment with ethanolic HCl to provide the target ethyl ester.
【1】 Sawa, E.; et al.; Structural modification of Fas C-terminal tripeptide and its effects on the inhibitory activity of Fas/FAP-1 binding. J Med Chem 1999, 42, 17, 3289. |
【2】 Kataoka, S.; Nishitoba, T.; Takahashi, M.; Sawa, E.; Kamishohara, M. (Kirin Brewery Co., Ltd.); Novel peptide cpds. and medicinal compsns. thereof. JP 1999171896; WO 9711091 . |
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) | 19932 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid | C20H21NO4 | 详情 | 详情 | |
(II) | 21056 | (R)-(-)-Valine; D-Valine; (R)-alpha-Aminoisovaleric acid | 640-68-6 | C5H11NO2 | 详情 | 详情 |
(III) | 19934 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
(IV) | 33117 | (2S)-2-[((2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoyl)amino]-3-methylbutyric acid | C26H32N2O5 | 详情 | 详情 | |
(V) | 33123 | (2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutyric acid | 35436-83-0 | C11H22N2O3 | 详情 | 详情 |
(VI) | 33118 | (2S)-3-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | 71989-33-8 | C22H25NO5 | 详情 | 详情 |
(VII) | 33119 | (5S,8S,11S)-5-(tert-butoxymethyl)-1-(9H-fluoren-9-yl)-8-isobutyl-11-isopropyl-3,6,9-trioxo-2-oxa-4,7,10-triazadodecan-12-oic acid | C33H45N3O7 | 详情 | 详情 | |
(VIII) | 33120 | (2S)-2-[((2S)-2-[[(2S)-2-amino-3-(tert-butoxy)propanoyl]amino]-4-methylpentanoyl)amino]-3-methylbutyric acid | C18H35N3O5 | 详情 | 详情 | |
(IX) | 11289 | 1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate | 103-71-9 | C7H5NO | 详情 | 详情 |
(X) | 33121 | (2S)-2-[((2S)-2-[[(2S)-2-[(anilinocarbonyl)amino]-3-(tert-butoxy)propanoyl]amino]-4-methylpentanoyl)amino]-3-methylbutyric acid | C25H40N4O6 | 详情 | 详情 | |
(XI) | 33122 | (2S)-2-[[(2S)-2-([(2S)-2-[(anilinocarbonyl)amino]-3-hydroxypropanoyl]amino)-4-methylpentanoyl]amino]-3-methylbutyric acid | C21H32N4O6 | 详情 | 详情 |