6-(benzamidomethylthio)purine | 80693-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-(benzamidomethylthio)purine
• 英文别名: N-{[(7H-Purin-6-yl)sulfanyl]methyl}benzamide；N-(7H-purin-6-ylsulfanylmethyl)benzamide
• CAS: 80693-21-6
• 化学式: C₁₃H₁₁N₅OS
• 分子量: 285.329
• InChiKey: LUAQVBIWUIAIRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-氯甲基-苯甲酰胺 、 6-甲巯基嘌呤 在 三乙胺 作用下， 生成 6-(benzamidomethylthio)purine 、 9-Phenyl-8,9-dihydro-7H-6-thia-2,3,5,8,9a-pentaaza-benzo[cd]azulen-9-ol
  参考文献：
  名称：

  6-硫嘌呤的前药：增强了通过皮肤的递送。

  摘要：

  已经制备并评估了6-巯基嘌呤，其核糖苷和2-氨基-6-巯嘌呤核糖苷的软烷基化衍生物，以改善硫代嘌呤通过皮肤的递送。通过在中性或碱性条件下将硫嘌呤与酰基杂烷基卤化物烷基化来制备软烷基化衍生物。使用扩散池测量衍生物通过无毛小鼠皮肤的渗透。所有衍生物在其通过皮肤的扩散过程中都经历了广泛的降解，因此即使在核糖苷的情况下，母体硫嘌呤也是受体相中观察到的主要产物。新戊酰氧基甲基衍生物显示出最大的潜力，可增强硫嘌呤通过皮肤的渗透。在6-巯基嘌呤衍生物中，VII和XI最有效。

  DOI：

  10.1002/jps.2600720413

文献信息

• Prodrugs of 6-mercaptopurine and 6-mercaptopurine ribosides and
  申请人：Merck & Co., Inc.

  公开号：US04443435A1

  公开（公告）日：1984-04-17

  Novel, transient prodrug forms of biologically active agents containing mercapto groups have (i) the structural formula (I): ##STR1## wherein X is O, S, or NR.sup.5 ; R.sup.1 S is the residue of any biologically active agent R.sup.1 SH; R.sup.2 is selected from the group consisting of straight or branched chain alkyl having from 1 to 20 carbon atoms; aryl having from 6 to 10 carbon atoms; cycloalkyl having from 3 to 8 carbon atoms; alkenyl having from 2 to 20 carbon atoms; cycloalkenyl having from 4 to 8 carbon atoms; alkynyl having from 2 to 20 carbon atoms; aralkyl, alkaryl, aralkenyl, aralkynyl, alkenylaryl, alkynylaryl, loweralkanoyloxyalkyl, carboxyalkyl, and lower alkanoyloxyalkyl wherein alkyl, aryl, alkenyl and alkynyl are as defined above; saturated or unsaturated monoheterocyclic or polyheterocyclic, or fused heterocyclic, either directly bonded to the carbonyl function or linked thereto via an alkylene bridge, containing from 1 to 3 of any one or more of the heteroatoms N, S or O in each heterocyclic ring thereof and each such ring being from 3- to 8- membered; and mono- or polysubstituted derivatives of the above, each of said substituents being selected from the group consisting of lower akyl, lower alkoxy, lower acyl, lower acyloxy, halo, haloloweralkyl, cyano, carbethoxy, loweralkylthio, amino, nitro, loweralkylamino, diloweralkylamino, carboxyl, carbamyl, loweralkylcarbamyl, diloweralkylcarbamyl and ##STR2## wherein R.sup.4 is hydrogen or alkyl having from 1 to 10 carbons; R.sup.3 is hydrogen, R.sup.2, lower acyl, cyano, haloloweralkyl, carbamyl, loweralkylcarbamyl, diloweralkylcarbamyl, --CH.sub.2 ONO.sub.2 and --CH.sub.2 OCOR.sup.2 ; R.sup.5 is hydrogen or lower alkyl; and further wherein R.sup.2 and R.sup.3 may be taken together to form a cyclizing moiety selected from the group consisting of ##STR3## with the proviso that when R.sup.1 S is the residue of a sulfur containing amino acid, then X cannot be NR.sup.5 ; (ii) the structural formula (I) wherein ##STR4## is the residue of any naturally occurring protein amino acid, the residue of any N-substituted naturally occurring amino acid, which N-substituent is lower alkyl or any amino acid protective group cleavable via hydrogenolysis or hydrolysis, or the residue of an N,N-lower dialkyl of C.sub.4 -C.sub.7 cycloalkylamino acid; and (iii) the non-toxic, pharmaceutically acceptable salts thereof.

  含有巯基的生物活性剂的新型、短暂的前药形式具有以下结构式(I)： ##STR1## 其中，X为O、S或NR.sup.5; R.sup.1 S为任何生物活性剂R.sup.1 SH的残基; R.sup.2选自以下组合：直链或支链烷基，其碳原子数为1到20；含有6到10个碳原子的芳基；含有3到8个碳原子的环烷基；含有2到20个碳原子的烯基；含有4到8个碳原子的环烯基；含有2到20个碳原子的炔基；aralkyl、alkaryl、aralkenyl、aralkynyl、alkenylaryl、alkynylaryl、loweralkanoyloxyalkyl、carboxyalkyl和lower alkanoyloxyalkyl，其中alkyl、aryl、烯基和炔基如上所定义；饱和或不饱和的单杂环或多杂环，或融合的杂环，直接与羰基功能键相结合或通过烷基桥连接到其中，每个杂环环中都包含1到3个任何一个或多个杂原子N、S或O，并且每个这样的环都是3到8个成员的；上述化合物的单取代或多取代衍生物，每个取代基选自以下组合：lower alkyl、lower alkoxy、lower acyl、lower acyloxy、halo、haloloweralkyl、cyano、carbethoxy、loweralkylthio、amino、nitro、loweralkylamino、diloweralkylamino、carboxyl、carbamyl、loweralkylcarbamyl、diloweralkylcarbamyl和 ##STR2## 其中，R.sup.4为氢或具有1到10个碳的烷基；R.sup.3为氢、R.sup.2、lower acyl、cyano、haloloweralkyl、carbamyl、loweralkylcarbamyl、diloweralkylcarbamyl、--CH.sub.2 ONO.sub.2和--CH.sub.2 OCOR.sup.2；R.sup.5为氢或低碳烷基；进一步，R.sup.2和R.sup.3可以结合形成选自以下组合的环化基团： ##STR3## 但是，当R.sup.1 S是含硫氨基酸的残基时，X不能是NR.sup.5；(ii)结构式(I)其中 ##STR4## 为任何天然存在的蛋白质氨基酸的残基，任何N-取代的天然存在的氨基酸的残基，其N-取代基为低碳烷基或可以通过氢解或水解脱离的任何氨基酸保护基，或C.sub.4-C.sub.7环烷基氨基酸的N,N-低二烷基的残基；(iii)其非毒性的、药学上可接受的盐。
• Novel prodrugs of biologically active agents containing mercapto groups, process for preparing and therapeutically effective composition containing the same
  申请人：Merck & Co., Inc.

  公开号：EP0038541B1

  公开（公告）日：1986-08-13
• US4443435A
  申请人：——

  公开号：US4443435A

  公开（公告）日：1984-04-17
• Prodrugs of 6-Thiopurines: Enhanced Delivery Through the Skin
  作者：K.B. Sloan、M. Hashida、J. Alexander、N. Bodor、T. Higuchi

  DOI：10.1002/jps.2600720413

  日期：1983.4

  improve the delivery of the thiopurines through the skin. The soft-alkylated derivatives were prepared by the alkylation of the thiopurines with acylheteroalkyl halides under neutral or basic conditions. The penetration of the derivatives through hairless mouse skin was measured using diffusion cells. All of the derivatives underwent extensive degradation during their diffusion through skin so that the

  已经制备并评估了6-巯基嘌呤，其核糖苷和2-氨基-6-巯嘌呤核糖苷的软烷基化衍生物，以改善硫代嘌呤通过皮肤的递送。通过在中性或碱性条件下将硫嘌呤与酰基杂烷基卤化物烷基化来制备软烷基化衍生物。使用扩散池测量衍生物通过无毛小鼠皮肤的渗透。所有衍生物在其通过皮肤的扩散过程中都经历了广泛的降解，因此即使在核糖苷的情况下，母体硫嘌呤也是受体相中观察到的主要产物。新戊酰氧基甲基衍生物显示出最大的潜力，可增强硫嘌呤通过皮肤的渗透。在6-巯基嘌呤衍生物中，VII和XI最有效。