PD-116948, DPCPX, CPX

1,3-二丙基-8-环戊基黄嘌呤Chemical Name: 8-Cyclopentyl-1,3-dipropylxanthine; 8-Cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione
CAS No. 102146-07-6
项目整合开发状态: Phase II
项目研究机构: SciClone (Orphan Drug), National Institutes of Health (Originator), SciClone (Licensee)
合成路线:CPX has been obtained by two related ways:1) Nitrosation of 6-amino-1,3-dipropyluracil (I) with NaNO2 in acetic acid gives the 5-nitrosouracil derivative (II),which is reduced with H2 over Pd/C in ethanol to yield 5,6-diamino-1,3-dipropyluracil (III).Acylation of (III) with cyclopentanecarboxylic acid (IV) by heating up to the mixture's melting point or by treatment with diisopropylcarbodiimide (DIC) gives the amide (V),which is finally cyclized by means of NaOH in refluxing water or refluxing methanol/water.2) Acylation of the 5-nitrosouracil (II) with cyclopentanecarbonyl chloride (VI) by means of lithium hexamethyldisilazane (LHMDS) in THF gives the amide (VII),which is submitted to a reductive cyclization with Sn(OAc)2 in the same solvent.
📌 参考资料/链接:
参考文献标题:8-Aryl- and 8-cycloalkyl-1,3-dipropylxanthines: Further potent and selective antagonists for A1-adenosine receptors
文献作者:Shamim,M.T.; Ukena,D.; Padgett,W.L.; Hong,O.; Daly,J.W.
参考来源:J Med Chem 1988,31(3),613

📄 详细内容


合成路线:CPX has been obtained by two related ways:1) Nitrosation of 6-amino-1,3-dipropyluracil (I) with NaNO2 in acetic acid gives the 5-nitrosouracil derivative (II),which is reduced with H2 over Pd/C in ethanol to yield 5,6-diamino-1,3-dipropyluracil (III).Acylation of (III) with cyclopentanecarboxylic acid (IV) by heating up to the mixture's melting point or by treatment with diisopropylcarbodiimide (DIC) gives the amide (V),which is finally cyclized by means of NaOH in refluxing water or refluxing methanol/water.2) Acylation of the 5-nitrosouracil (II) with cyclopentanecarbonyl chloride (VI) by means of lithium hexamethyldisilazane (LHMDS) in THF gives the amide (VII),which is submitted to a reductive cyclization with Sn(OAc)2 in the same solvent.

参考文献标题:1,3,8-Trisubstituted xanthines.Effects of substitution pattern upon adenosine receptor A1/A2 affinity
文献作者:Erickson,R.H.; Hiner,R.N.; Feeney,S.W.; Blake,P.R.; Rzeszotarski,W.J.; Hicks,R.P.; Costello,D.G.; Abreu,M.E.
参考来源:J Med Chem 1991,34(4),1431


合成路线:CPX has been obtained by two related ways:1) Nitrosation of 6-amino-1,3-dipropyluracil (I) with NaNO2 in acetic acid gives the 5-nitrosouracil derivative (II),which is reduced with H2 over Pd/C in ethanol to yield 5,6-diamino-1,3-dipropyluracil (III).Acylation of (III) with cyclopentanecarboxylic acid (IV) by heating up to the mixture's melting point or by treatment with diisopropylcarbodiimide (DIC) gives the amide (V),which is finally cyclized by means of NaOH in refluxing water or refluxing methanol/water.2) Acylation of the 5-nitrosouracil (II) with cyclopentanecarbonyl chloride (VI) by means of lithium hexamethyldisilazane (LHMDS) in THF gives the amide (VII),which is submitted to a reductive cyclization with Sn(OAc)2 in the same solvent.

参考文献标题:Convenient one-pot synthesis of xanthines from 6-amino-5-nitrosouracils
文献作者:Schow,S.R.; Lum,R.T.; Melville,C.R.; Nelson,M.G.; Moore,A.G.
参考来源:Synthesis 1999,(7),1123


合成路线:CPX has been obtained by two related ways:1) Nitrosation of 6-amino-1,3-dipropyluracil (I) with NaNO2 in acetic acid gives the 5-nitrosouracil derivative (II),which is reduced with H2 over Pd/C in ethanol to yield 5,6-diamino-1,3-dipropyluracil (III).Acylation of (III) with cyclopentanecarboxylic acid (IV) by heating up to the mixture's melting point or by treatment with diisopropylcarbodiimide (DIC) gives the amide (V),which is finally cyclized by means of NaOH in refluxing water or refluxing methanol/water.2) Acylation of the 5-nitrosouracil (II) with cyclopentanecarbonyl chloride (VI) by means of lithium hexamethyldisilazane (LHMDS) in THF gives the amide (VII),which is submitted to a reductive cyclization with Sn(OAc)2 in the same solvent.
参考文献标题:CPX
文献作者:Castar,J.; Mart韓,L.; Sorbera,L.A.
参考来源:Drugs Fut 2000,25(10),1011


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