Lys-Spm, ORI-1202, -Drug Synthesis Database

【结构式】

【药物名称】Lys-Spm, ORI-1202

【化学名称】L-Lysine N-[3-[4-(3-aminopropylamino)butylamino]propyl]amide

【CA登记号】134951-06-7

【分子式】C₁₆H₃₈N₆O

【分子量】330.52086

【开发单位】MediQuest Therapeutics (Originator)

【药理作用】ONCOLYTIC DRUGS, Polyamine Biosynthesis Inhibitors

合成路线1 合成路线2

合成路线1

Di-Boc-protected L-lysine p-nitrophenyl active ester (I) was coupled to spermine (II), yielding the primary amide (III) along with some by-products. The crude reaction mixture was fully protected using an excess of di-tert-butyl dicarbonate, and the desired compound (IV) was then isolated by column chromatography. Finally, the Boc-protecting groups of (IV) were removed by acidic treatment to provide the title spermine lysinamide.

参考文献中间体

【1】 Burns, M.R.; O'Day, C.L.; Bergstrom, D.E.; Webb, H.K.; Vermeulin, N.M.J. (Oridigm Corp.); Novel polyamine analogues as therapeutic and diagnostic agents. EP 1085011 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	46325	4-nitrophenyl (2S)-2,6-bis[(tert-butoxycarbonyl)amino]hexanoate	C₂₂H₃₃N₃O₈	详情	详情
(II)	46326	N-(3-aminopropyl)-N-[4-[(3-aminopropyl)amino]butyl]amine; N(1),N(4)-bis(3-aminopropyl)-1,4-butanediamine	C₁₀H₂₆N₄	详情	详情
(III)	46327	tert-butyl (5S)-6-[[3-([4-[(3-aminopropyl)amino]butyl]amino)propyl]amino]-5-[(tert-butoxycarbonyl)amino]-6-oxohexylcarbamate	C₂₆H₅₄N₆O₅	详情	详情
(IV)	46328	tert-butyl 3-([(2S)-2,6-bis[(tert-butoxycarbonyl)amino]hexanoyl]amino)propyl[4-((tert-butoxycarbonyl)[3-[(tert-butoxycarbonyl)amino]propyl]amino)butyl]carbamate	C₄₁H₇₈N₆O₁₁	详情	详情

合成路线2

The N-hydroxysuccinimide ester of di-carbobenzyloxy-L-lysine (IV) was coupled to spermine (II), yielding amide (V). The N- carbobenzyloxy groups were then deprotected by catalytic hydrogenolysis in the presence of Pearlman’s catalyst.

参考文献中间体

【1】 Cai, F.; Carlson, C.L.; Vanderwerf, S.M.; Devens, B.H.; Webb, H.K.; O'Day, C.L.; Burns, M.R.; Weeks, R.S.; Novel lysine-spermine conjugate inhibits polyamine transport and inhibits cell growth when given with DFMO. Exp Cell Res 2000, 261, 1, 293.
【2】 Burns, M.R.; et al.; Amino acid/spermine conjugates: Polyamine amides as potent spermidine uptake inhibitors. J Med Chem 2001, 44, 22, 3632.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	52059	benzyl (1S)-5-[[(benzyloxy)carbonyl]amino]-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]pentylcarbamate	C₂₆H₂₉N₃O₈	详情	详情
(II)	46326	N-(3-aminopropyl)-N-[4-[(3-aminopropyl)amino]butyl]amine; N(1),N(4)-bis(3-aminopropyl)-1,4-butanediamine	C₁₀H₂₆N₄	详情	详情
(III)	52305		C₃₂H₅₀N₆O₅	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)