3, 4, 3-LI(1, 2-Me-3, 2-HOPO), -Drug Synthesis Database

【结构式】

【药物名称】3, 4, 3-LI(1, 2-Me-3, 2-HOPO)

【化学名称】N,N'-(1,4-Butylene)bis[N-(1-hydroxy-6-oxo-1,6-dihydropyridin-2-ylcarbonyl)imino]bis(1,3-propylene)bis(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamide)

【CA登记号】

【分子式】C₃₆H₄₂N₈O₁₂

【分子量】778.78254

【开发单位】University of California, Berkeley (Originator)

【药理作用】Antagonists to Metals, Specific Antidotes, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Metal Chelators

合成路线1 合成路线2

合成路线1

6-Hydroxypicolinic acid (I) is oxidized to the N-hydroxy pyridinone (II) employing peracetic acid (obtained by mixing Ac2O and H2O2) in the presence of TFA. Protection of the N-hydroxy group of (II) with benzyl chloride affords the N-benzyloxy pyridinone (III). The carboxy group of (III) is then activated as the corresponding acid chloride (IV) by treatment with oxalyl chloride.

参考文献中间体

【1】 Xu, J.; et al.; Synthesis and initial evaluation for in vivo chelation of Pu(IV) of a mixed octadentate spermine-based ligand containing 4-carbamoyl-3-hydroxy-1-methyl-2(1H)-pyridinone and 6-carbamoyl-1-hydroxy-2(1H)-pyridinone. J Med Chem 2002, 45, 18, 3963.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	61990	6-hydroxy-2-pyridinecarboxylic acid	C₆H₅NO₃	详情	详情
(II)	61991	1-hydroxy-6-oxo-1,6-dihydro-2-pyridinecarboxylic acid	C₆H₅NO₄	详情	详情
(III)	61992	1-(benzyloxy)-6-oxo-1,6-dihydro-2-pyridinecarboxylic acid	C₁₃H₁₁NO₄	详情	详情
(IV)	61993	1-(benzyloxy)-6-oxo-1,6-dihydro-2-pyridinecarbonyl chloride	C₁₃H₁₀ClNO₃	详情	详情

合成路线2

Acylation of the primary amino groups of spermine (V) by the N acyl thiazolide (VI) furnishes diamide (VII). This is further coupled with acid chloride (IV) producing tetraamide (VIII). Finally, deprotection of the O-benzyl groups under acidic conditions gives rise to the title compound.

参考文献中间体

【1】 Xu, J.; et al.; Synthesis and initial evaluation for in vivo chelation of Pu(IV) of a mixed octadentate spermine-based ligand containing 4-carbamoyl-3-hydroxy-1-methyl-2(1H)-pyridinone and 6-carbamoyl-1-hydroxy-2(1H)-pyridinone. J Med Chem 2002, 45, 18, 3963.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	61993	1-(benzyloxy)-6-oxo-1,6-dihydro-2-pyridinecarbonyl chloride	C₁₃H₁₀ClNO₃	详情	详情
(V)	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
(VI)	48345	3-(benzyloxy)-1-methyl-4-[(2-thioxo-1,3-thiazolidin-3-yl)carbonyl]-2(1H)-pyridinone	C₁₇H₁₆N₂O₃S₂	详情	详情
(VII)	61994	3-(benzyloxy)-N-{3-[(4-{[3-({[3-(benzyloxy)-1-methyl-2-oxo-1,2-dihydro-4-pyridinyl]carbonyl}amino)propyl]amino}butyl)amino]propyl}-1-methyl-2-oxo-1,2-dihydro-4-pyridinecarboxamide	C₃₈H₄₈N₆O₆	详情	详情
(VIII)	61995	1-(benzyloxy)-N-[3-({[3-(benzyloxy)-1-methyl-2-oxo-1,2-dihydro-4-pyridinyl]carbonyl}amino)propyl]-N-[4-([3-({[3-(benzyloxy)-1-methyl-2-oxo-1,2-dihydro-4-pyridinyl]carbonyl}amino)propyl]{[1-(benzyloxy)-6-oxo-1,6-dihydro-2-pyridinyl]carbonyl}amino)but	C₆₄H₆₆N₈O₁₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)