CH-2856, FE-999024, -Drug Synthesis Database

【结构式】

【药物名称】CH-2856, FE-999024

【化学名称】4-Chloro-D-phenylalanyl-3-(1-naphthyl)-L-alanine 3-guanidinopropylamide

【CA登记号】168825-65-8

【分子式】C₂₆H₃₁ClN₆O₂

【分子量】495.02897

【开发单位】Ferring (Originator)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, GASTROINTESTINAL DRUGS, Pancreatic Disorders, Treatment of, RESPIRATORY DRUGS, Serine Protease Inhibitors

合成路线1 合成路线2

合成路线1

1,3-Diaminopropane (I) is mono-protected with benzyl chloroformate, producing carbamate (II). Coupling of (II) with N,N'-bis-Boc-S-methylisothiourea (III) yields the Boc-protected guanidine (IV). The benzyloxycarbonyl group of (IV) is then removed by catalytic hydrogenolysis to furnish the noragmatine derivative (V)

参考文献中间体

【1】 Szelke, M.; Evans, D.M.; Jones, D.M. (Ferring AB); Kininogen inhibitors. WO 9507291 .

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)	19331	3-aminopropylamine; 1,3-propanediamine	109-76-2	C₃H₁₀N₂	详情	详情
(II)	62059	benzyl 3-aminopropylcarbamate		C₁₁H₁₆N₂O₂	详情	详情
(III)	22345	tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₁₂H₂₂N₂O₄S	详情	详情
(IV)	62060	benzyl 3-({[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl}amino)propylcarbamate		C₂₂H₃₄N₄O₆	详情	详情
(V)	26836	tert-butyl (Z)-[(3-aminopropyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₁₄H₂₈N₄O₄	详情	详情

合成路线2

Coupling between N-Boc-D-(4-chlorophenyl)alanine succinimidyl ester (VI) and L-naphthylalanine methyl ester (VII) affords the protected dipeptide (VIII). The methyl ester group of (VIII) is hydrolyzed by means of LiOH to produce the carboxylic acid (IX), which is subsequently coupled to the di-Boc-protected noragmatine (V), yielding amide (X). Finally, acidic cleavage of the Boc protecting groups of (X) leads to the title compound

参考文献中间体

【1】 Szelke, M.; Evans, D.M.; Jones, D.M. (Ferring AB); Kininogen inhibitors. WO 9507291 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	26836	tert-butyl (Z)-[(3-aminopropyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate	C₁₄H₂₈N₄O₄	详情	详情
(VI)	62061	tert-butyl (1R)-1-(4-chlorobenzyl)-2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethylcarbamate	C₁₈H₂₁ClN₂O₆	详情	详情
(VII)	62062	methyl (2S)-2-amino-3-(1-naphthyl)propanoate	C₁₄H₁₅NO₂	详情	详情
(VIII)	62063	methyl (2S)-2-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propanoyl]amino}-3-(1-naphthyl)propanoate	C₂₈H₃₁ClN₂O₅	详情	详情
(IX)	62064	(2S)-2-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propanoyl]amino}-3-(1-naphthyl)propanoic acid	C₂₇H₂₉ClN₂O₅	详情	详情
(X)	62065	tert-butyl (1R,4S,11Z)-11-[(tert-butoxycarbonyl)amino]-1-(4-chlorobenzyl)-15,15-dimethyl-4-(1-naphthylmethyl)-2,5,13-trioxo-14-oxa-3,6,10,12-tetraaza-11-hexadecen-1-ylcarbamate	C₄₁H₅₅ClN₆O₈	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)