1-(4,5-Dihydroxyhexyl)theobromine | 6493-08-9

• 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: 1-(4,5-Dihydroxyhexyl)theobromine
• 英文别名: 1-(4,5-dihydroxy-hexyl)-3,7-dimethyl-3,7-dihydro-purine-2,6-dione；1-(4,5-Dihydroxyhexyl)-3,7-dimethylxanthin；1-(4,5-Dihydroxyhexyl)theobromin；Pentoxifylline metabolite M-3；1-(4,5-dihydroxyhexyl)-3,7-dimethylpurine-2,6-dione
• CAS: 6493-08-9
• 化学式: C₁₃H₂₀N₄O₄
• 分子量: 296.326
• InChiKey: ZJBOLBRXIQZJSF-UHFFFAOYSA-N

物化性质

• 熔点：
  157-160 °C
• 沸点：
  580.6±60.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  98.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(5-羟基己基)-3,7-二甲基嘌呤-2,6-二酮 在 cDNA-expressed human CYP₃A₄ 作用下， 以 phosphate buffer 为溶剂， 生成 1-(4,5-Dihydroxyhexyl)theobromine
  参考文献：
  名称：

  CYP3A4-Mediated Oxidation of Lisofylline to Lisofylline 4,5-Diol in Human Liver Microsomes

  摘要：

  The cytochrome P450s responsible for the conversion of lisofylline, a drug being developed to prevent the complications of high-dose chemotherapy, to lisofylline 4,5-diol, one of two principal metabolites in human liver microsomes, were evaluated. Lisofylline diol formation in microsomes prepared from five adult human livers was biphasic, with respective K-m values of 0.0230 +/- 0.015 and 4.23 +/- 2.8 mM (mean +/- SD) and respective V-max values of 0.0565 +/- 0.052 and 0.429 +/- 0.15 nmol/min/mg of protein. Through studies with isoform selective chemical inhibitors, CYP3A4 was implicated as the low K-m enzyme from 89.0 +/- 11.2% inhibition of lisofylline 4,5-diol formation by troleandomycin at 50 mu M substrate and CYP2A6 was implicated as the high K-m enzyme. The formation of lisofylline 4,5-diol by these enzymes was confirmed with cDNA-expressed human CYP3A4 and CYP2A6.

  DOI：

  10.1021/js970382f

文献信息

• [EN] SUBSTITUTED XANTHINE DERIVATIVES<br/>[FR] DÉRIVÉS DE XANTHINE SUBSTITUÉS
  申请人：CONCERT PHARMACEUTICALS INC

  公开号：WO2013013052A1

  公开（公告）日：2013-01-24

  The present invention in one embodiment relates to a compound of Formula (I); or a pharmaceutically acceptable salt thereof, wherein: each of R1 and R2 is independently selected from -CH3 and -CD3; R3 is hydrogen or deuterium; each of Z1, Z2 and Z3 is independently selected from hydrogen and deuterium; each Z4 is hydrogen or deuterium; each Z5 is hydrogen or deuterium; and each Z6 is hydrogen or deuterium.

  在一个实施例中，本发明涉及一种化合物，其化学式为（I）；或其药用可接受的盐，其中：R1和R2中的每一个可独立选择自-CH3和-CD3；R3是氢或氘；Z1、Z2和Z3中的每一个可独立选择自氢和氘；每个Z4是氢或氘；每个Z5是氢或氘；每个Z6是氢或氘。
• Substituted xanthine derivatives
  申请人：Tung Roger D.

  公开号：US20090239886A1

  公开（公告）日：2009-09-24

  This invention relates to novel compounds that are substituted xanthine derivatives and pharmaceutically acceptable salts thereof. For example, this invention relates to novel substituted xanthine derivatives that are derivatives of pentoxifylline. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions for which pentoxifylline and related compounds are beneficial.

  本发明涉及新型化合物，即取代黄嘌呤衍生物及其药学上可接受的盐。例如，本发明涉及新型取代黄嘌呤衍生物，它们是戊酰异丙基黄嘌呤的衍生物。本发明还提供了包含本发明中的一种或多种化合物和载体的组合物，以及把所述化合物和组合物用于治疗戊酰异丙基黄嘌呤和相关化合物有益的疾病和病况的方法。
• SUBSTITUTED XANTHINE DERIVATIVES
  申请人：Aslanian Ara

  公开号：US20140296263A1

  公开（公告）日：2014-10-02

  The present invention in one embodiment relates to a compound of Formula (I); or a pharmaceutically acceptable salt thereof, wherein: each of R 1 and R 2 is independently selected from —CH 3 and —CD 3 ; R 3 is hydrogen or deuterium; each of Z 1 , Z 2 and Z 3 is independently selected from hydrogen and deuterium; each Z 4 is hydrogen or deuterium; each Z 5 is hydrogen or deuterium; and each Z 6 is hydrogen or deuterium.

  本发明在一种实施例中涉及化合物(I)的一种；或其药学上可接受的盐，其中：R1和R2各自独立地选自—CH3和—CD3；R3是氢或氘；Z1、Z2和Z3各自独立地选自氢和氘；每个Z4是氢或氘；每个Z5是氢或氘；每个Z6是氢或氘。
• Use of xanthines for the preparation of a medicament effective for inhibiting the replication of human retroviruses
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0484785A2

  公开（公告）日：1992-05-13

  A family of compounds effective in inhibiting replication of a human retrovirus is comprised of 7-(oxoalkyl) 1,3-dialkyl xanthines of the formula: in which R1 and R2 are the same or different and are selected from the group consisting of straight-chain or branched alkyl radicals with 2 to 6 carbon atoms, cyclohexyl, alkoxyalkyl and hydroxyalkyl radicals, and A represents a hydrocarbon radical with up to 4 carbon atoms which can be substituted by a methyl group. Another family of effective compounds is comprised of compounds of the formula: wherein at least one of R1 and R3 is either a) a branched hydroxyalkyl group of the formula in which R4 stands for an alkyl group with 1 to 3 carbon atoms and n stands for a whole number from 2 to 5, the other R1 or R3 group that may optionally be present stands for a hydrogen atom or on aliphatic hydrocarbon group R5 with up to 6 carbon atoms, whose carbon chain may be interrupted by up to 2 oxygen atoms or may be substituted with a hydroxy or oxo group, or b) an oxoallyl group of the formula wherein R6 is C1 -C6 and p is 2, 3 or 4, the remaining R1 or R3 being as defined above, and R2 is an alkyl group C1-C4.The inhibition of replication of human retroviruses is indicated in humans infected by human immunodeficiency virus (HIV) or susceptible to HIV infection.

  一种能有效抑制人类逆转录病毒复制的化合物家族由式 7-(氧代烷基)1,3-二烷基黄嘌呤组成： 其中 R1 和 R2 相同或不同，且选自由 2 至 6 个碳原子的直链或支链烷基、环己基、烷氧基烷基和羟基烷基组成的组，A 代表最多 4 个碳原子的烃基，可被甲基取代。另一个有效化合物家族由以下式子的化合物组成： 其中 R1 和 R3 中至少有一个是 a) 式中的支链羟烷基 其中 R4 代表具有 1 至 3 个碳原子的烷基，n 代表 2 至 5 的整数，另一个可选的 R1 或 R3 基团代表氢原子或具有最多 6 个碳原子的脂肪族烃基 R5，其碳链可被最多 2 个氧原子打断，或可被羟基或氧代基团取代，或 b) 式中的氧代烯丙基 其中 R6 为 C1 -C6，p 为 2、3 或 4，其余 R1 或 R3 如上定义，R2 为 C1-C4 烷基。抑制人类逆转录病毒的复制适用于感染人类免疫缺陷病毒（HIV）或易感染 HIV 的人类。
• Use of xanthines for the preparation of a medicament effective for inhibiting the effects of allograft reaction in humans
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0493682A2

  公开（公告）日：1992-07-08

  A family of compounds effective in inhibiting the effects of allograft reaction, such as graft versus host reaction (GVHR), in a human is comprised of 7-(oxoalkyl) 1,3-dialkyl xanthines of the formula in which R1 and R2 are the same or different and are selected from the group consisting of straight-chain or branched alkyl radicals with 2 to 6 carbon atoms, cyclohexyl, alkoxyalkyl and hydroxyalkyl radicals, and A represents a hydrocarbon radical with up to 4 carbon atoms which can be substituted by a methyl group. Another family of effective compounds is comprised of compounds of the formula wherein at least one of R1 and R3 is either a) a branched hydroxyalkyl group of the formula in which R4 stands for an alkyl group with 1 to 3 carbon atoms and n stands for a whole number from 2 to 5, the other R1 or R3 group that may optionally be present stands for a hydrogen atom or an aliphatic hydrocarbon group R5 with up to 6 carbon atoms, whose carbon chain may be interrupted by up to 2 oxygen atoms or may be substituted with a hydroxy or oxo group, or b) an oxoallyl group of the formula wherein R6 is C1 -C6 and p is 2, 3 or 4, the remaining R1 or R3 being as defined above, and R2 is an alkyl group C1-C4;The inhibition of GVHR is indicated in human transplant recipients.

  一种能有效抑制异体移植反应（如移植物与宿主反应（GVHR））对人体影响的化合物家族由 7-（氧代烷基）1,3-二烷基黄嘌呤组成，其式为 其中 R1 和 R2 相同或不同，选自由 2 至 6 个碳原子的直链或支链烷基、环己基、烷氧基烷基和羟基烷基组成的组，A 代表可被甲基取代的最多 4 个碳原子的烃基。另一族有效化合物包括如下式的化合物 其中 R1 和 R3 中至少有一个是 a) 式中的支链羟烷基 其中 R4 代表具有 1 至 3 个碳原子的烷基，n 代表 2 至 5 的整数，另一个可选的 R1 或 R3 基团代表氢原子或具有最多 6 个碳原子的脂肪族烃基 R5，其碳链可被最多 2 个氧原子打断，或可被羟基或氧代基团取代，或 b) 式中的氧代烯丙基 其中 R6 为 C1 -C6，p 为 2、3 或 4，其余 R1 或 R3 如上定义，R2 为 C1-C4 烷基；GVHR 的抑制作用适用于人体移植受者。