MRS-1595
Chemical Name: N-(3,4-Dimethyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy]acetamide
项目整合开发状态: Preclinical
项目研究机构: National Institutes of Health (Originator), University of Virginia (Originator)
合成路线:Alkylation of 4-hydroxybenzaldehyde (I) with iodoacetic acid in the presence of K2CO3 afforded ether (II).Subsequent condensation of (II) with 5,6-diamino-1,3-dipropyluracil (III) gave imine (IV).Oxidative ring closure by means of FeCl3 in boiling EtOH,with concomitant esterification,furnished xanthine (V).The ethyl ester of (V) was then displaced by hydrazine to yield hydrazide (VI).Finally,condensation of (VI) with dimethylmaleic anhydride (VII) gave rise to the corresponding maleimide.
📌 参考资料/链接：
参考文献标题:Acyl-hydrazide derivatives of a xanthine carboxylic congener (XCC) as selective antagonists at human A2B adenosine receptors
文献作者:Karton,Y.; Melman,N.; Ji,X.-D.; Jacobson,K.A.; Linden,J.; Kim,Y.-C.
参考来源:Drug Dev Res 1999,47(4),178
📄 详细内容
合成路线:Alkylation of 4-hydroxybenzaldehyde (I) with iodoacetic acid in the presence of K2CO3 afforded ether (II).Subsequent condensation of (II) with 5,6-diamino-1,3-dipropyluracil (III) gave imine (IV).Oxidative ring closure by means of FeCl3 in boiling EtOH,with concomitant esterification,furnished xanthine (V).The ethyl ester of (V) was then displaced by hydrazine to yield hydrazide (VI).Finally,condensation of (VI) with dimethylmaleic anhydride (VII) gave rise to the corresponding maleimide.
合成路线:Alkylation of 4-hydroxybenzaldehyde (I) with iodoacetic acid afforded 4-formylphenoxyacetic acid (II).This was condensed with 5,6-diamino-1,3-dipropyluracil (III) to produce imine (IV),which was oxidatively cyclized to xanthine (V) in the presence of ferric chloride.After activation of (V) as the corresponding acid chloride (VI),coupling with 4-aminobenzonitrile (VII) furnished the title amide.
参考文献标题:Functionalized congeners of 1,3-dialkylxanthines: preparation of analogues with high affinity for adenosine receptors
文献作者:Jacobson,K.A.; Kirk,K.L.; Padgett,W.L.; Daly,J.W.
参考来源:J Med Chem 1985,28(9),1334-40