GI-264879A, -Drug Synthesis Database

【结构式】

【药物名称】GI-264879A

【化学名称】N1-[1(S)-Benzyl-2-methoxyethyl]-N2-[3,3-di(1-naphthyl)propionyl]-D-argininamide trifluoroacetate

【CA登记号】181110-62-3 (free base)

【分子式】C₄₁H₄₄F₃N₅O₅

【分子量】743.83353

【开发单位】GlaxoSmithKline (Originator)

【药理作用】Antiobesity Drugs, METABOLIC DRUGS, Treatment of Nutritional Disorders, Neuropeptide Y1 (NPY Y1) Antagonists

合成路线1

Coupling of Fmoc-D-arginine(PMC) (I) with phenylalaninol methyl ether (II) in the presence of EDC and HOBt provided amide (III). Cleavage of the Fmoc group by using piperidine in DMF afforded amine (IV), which was subsequently coupled with dinaphthylpropionic acid (V), yielding diamide (VI). The pentamethylchromansulfonyl protecting group (PMC) was finally removed by treatment with trifluoroacetic acid in the presence of ethanedithiol and anisole.

参考文献中间体

【1】 Daniels, A.J.; Heyer, D.; Leban, J.J. (Glaxo Wellcome plc); Modified peptides. WO 9622305 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	49886	(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoic acid	C₃₅H₄₄N₄O₇S	详情	详情
(II)	49881	(2S)-1-methoxy-3-phenyl-2-propanamine; (1S)-1-benzyl-2-methoxyethylamine	C₁₀H₁₅NO	详情	详情
(III)	49882	9H-fluoren-9-ylmethyl (1R)-1-([[(1S)-1-benzyl-2-methoxyethyl]amino]carbonyl)-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butylcarbamate	C₄₅H₅₇N₅O₇S	详情	详情
(IV)	49883	(2R)-2-amino-N-[(1S)-1-benzyl-2-methoxyethyl]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanamide	C₃₀H₄₇N₅O₅S	详情	详情
(V)	49884	3,3-di(1-naphthyl)propionic acid	C₂₃H₁₈O₂	详情	详情
(VI)	49885	(2R)-N-[(1S)-1-benzyl-2-methoxyethyl]-2-[[3,3-di(1-naphthyl)propanoyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanamide	C₅₃H₆₃N₅O₆S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)