1,3-dimethyl-8-morpholin-4-yl-3,7-dihydropurine-2,6-dione | 30958-49-7

• 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: 1,3-dimethyl-8-morpholin-4-yl-3,7-dihydropurine-2,6-dione
• 英文别名: 1,3-dimethyl-8-morpholino-7H-purine-2,6-dione；1,3-dimethyl-8-(morpholin-4-yl)xanthine；8-morpholinotheophylline；1,3-dimethyl-8-morpholin-4-yl-3,7(9)-dihydro-purine-2,6-dione；8-morpholino-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione；8-Morpholinotheophyllin；1,3-dimethyl-8-morpholin-4-yl-7H-purine-2,6-dione
• CAS: 30958-49-7
• 化学式: C₁₁H₁₅N₅O₃
• mdl: MFCD01879277
• 分子量: 265.272
• InChiKey: RVMJTHOVOXFBQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  81.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,3-dimethyl-8-morpholin-4-yl-3,7-dihydropurine-2,6-dione 在 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 丙醇 、 丙酮 为溶剂， 反应 30.0h， 生成 7-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-1,3-dimethyl-8-(morpholin-4-yl)-3,7-dihydropurine-2,6-dione hydrochloride
  参考文献：
  名称：

  New 7-arylpiperazinylalkyl-8-morpholin-4-yl-purine-2,6-dione derivatives with anxiolytic activity – Synthesis, crystal structure and structure–activity study

  摘要：

  On the basis of our earlier studies with serotonin (5-HT) receptor ligands in the group of long-chain arylpiperazines (LCAPs), a new series of 7-arylpiperazinylalkyl-8-morpholin-4-yl-purine-2,6-dione derivatives (5-12) has been designed, synthesised and studied in vitro for their affinity for 5-HT1A, 5-HT2A, 5-HT6 and 5-HT7 receptors. The introduction of o-OCH3 and m-Cl into the phenylpiperazinyl moiety as well as the elongation of the linker between purine-2,6-dione core and arylpiperazine fragment modified the affinity for the tested 5-HT receptors. The structures of compounds 9-11 (hydrochloride salts) were confirmed by an X-ray diffraction method. All molecules adopted a different conformation in the crystal. The strongest observed type of interaction is a charge assisted hydrogen bond N+-H center dot center dot center dot Cl-. Additionally, the pi-pi interactions between 1,3-dimethyl-3,7-dihydropurine-2,6-dione cores of the neighbouring molecules were also observed. As it is observed in the presented crystal structures, the morpholine ring (a potential donor and acceptor of the hydrogen bonds) seems to be an attractive substituent, that may support binding to the non-specific sites of 5-HT receptors. Another interesting feature is the mutual orientation of rings in the arylpiperazine fragment, with plausible influence on ligand-receptor recognition. For compound 10, with strong 5-HT,A binding affinity, the mutual orientation of rings is determined by the intramolecular weak C-H center dot center dot center dot O hydrogen bond. This observation may contribute to a better understanding of the more selective binding of o-OCH3 arylpiperazine derivatives to the 5-HT1A receptor. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2014.03.018
• 作为产物：
  描述：

  茶碱 在 溴 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 1,3-dimethyl-8-morpholin-4-yl-3,7-dihydropurine-2,6-dione
  参考文献：
  名称：

  The synthesis, characterization and biological evaluation of a new nitric oxide donor agent

  摘要：

  对一种新的黄嘌呤一氧化氮供体（TSP-81）的合成进行了讨论。 讨论。所设计的化合物包括两个结构分子，即 茶碱（1,3-二甲基黄嘌呤）和对乙酰氨基酚（4-羟基乙酰苯胺） 通过一氧化氮供体烷基链作为间隔物连接起来。该化合物 通过微量分析（CHN）、1H-NMR、13C-NMR、FT-IR、UV-VIS、TG 和 DTG 表征。热学特性表明，TSP-81 在分解时会熔化、 最重要的是第二步（记录的重量损失为 17.6%）。 重量损失为 17.6 %）和第三步（重量损失为 30.4 %）。 30.4 %).毒性程度、抗炎作用和释放一氧化氮的能力 还对 TSP-81 的毒性、抗炎效果和释放一氧化氮的能力进行了评估。生物 实验证明，TSP-81 具有更强的生物特性，如较低的毒性和较高的抗炎性。 与茶碱和对乙酰氨基酚相比，TSP-81 具有更强的生物特性，如更低的毒性和更高的抗炎效果。 茶碱和对乙酰氨基酚（用作母体分子的药物）相比，TSP-81 表现出更强的生物特性，如更低的毒性和更高的抗炎效果。TSP-81 TSP-81 的活性大约是茶碱的 2 倍，是对乙酰氨基酚的 4 倍。 在减少棉粒-肉芽肿形成方面，TSP-81 的活性约为茶碱的 2 倍，对乙酰氨基酚的 4 倍。 此外，一氧化氮（NO）的释放似乎对增强抗炎作用有重要贡献。 此外，一氧化氮（NO）的释放似乎对增强抗炎效果有重要作用。

  DOI：

  10.2298/jsc130124131p

文献信息

• Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity
  作者：Grażyna Chłoń-Rzepa、Adam Bucki、Marcin Kołaczkowski、Anna Partyka、Magdalena Jastrzębska-Więsek、Grzegorz Satała、Andrzej J. Bojarski、Justyna Kalinowska-Tłuścik、Grzegorz Kazek、Barbara Mordyl、Monika Głuch-Lutwin、Anna Wesołowska

  DOI：10.3109/14756366.2015.1088844

  日期：2016.11.1

  and 8-dipropylamine (45-47) analogs with four and five carbon aliphatic linkers. The selected compounds 24, 31, 34, 39, 41, 43, 45, and 46 in the functional in vitro evaluation for all targeted receptors showed significant partial D2 agonist, partial 5-HT1A agonist, and 5-HT2A antagonist properties. The advantageous in vitro affinity of compound 34 for 5-HT1A and D2 receptors has been explained by

  合成了一系列在8位上具有多个8-氨基取代基的7-芳基哌嗪基烷基-1,3-二甲基-嘌呤-2,6-二酮衍生物，并分别合成了它们的5-HT1A，5-HT2A，5-HT6、5-HT7 ，并确定D2受体的亲和力。结合研究允许鉴定一些有效的5-HT1A / 5-HT2A / 5-HT7 / D2配体。由于它们的多受体特性，最有趣的是具有四个和五个碳脂族连接子的8-哌啶（30-35）和8-二丙胺（45-47）类似物。在针对所有靶向受体的功能性体外评估中，所选化合物24、31、34、39、41、43、45和46显示出显着的部分D2激动剂，部分5-HT1A激动剂和5-HT2A拮抗剂特性。化合物34对5-HT1A和D2受体的有利的体外亲和力已通过分子模型进行了解释，考虑到它对后者的部分激动剂活性。在行为研究中，化合物32和34显示出类似抗精神病药的特性，从而大大降低了d-苯异丙胺诱导的小鼠活动过度。
• SMALL MOLECULE BICYCLIC AND TRICYCLIC CFTR CORRECTORS
  申请人：DISCOVERYBIOMED, INC.

  公开号：US20150307503A1

  公开（公告）日：2015-10-29

  Novel CFTR corrector compounds that are effective in rescuing halide efflux, delF508-CFTR protein processing, and apical functional chloride ion transport in a cell are provided. Also provided are methods for treating protein folding disorders (e.g., cystic fibrosis). The methods include administering a CFTR corrector compound or pharmaceutically acceptable salt or prodrug thereof. Methods of rescuing halide efflux in a cell, correcting a processing defect of a delF508-CFTR protein in a cell, and correcting functional delF508-CFTR chloride channels in a cell are also provided.

  提供了一种在细胞中有效拯救卤化物流出、修复delF508-CFTR蛋白加工和顶端功能氯离子传输的新型CFTR校正化合物。还提供了治疗蛋白质折叠障碍（例如囊性纤维化）的方法。该方法包括给予CFTR校正化合物或其药用可接受的盐或前药。还提供了在细胞中拯救卤化物流出、纠正细胞中delF508-CFTR蛋白的加工缺陷以及纠正细胞中功能性delF508-CFTR氯通道的方法。
• Piperazine derivatives of theophylline
  申请人：Laroche-Navarron, S.A.

  公开号：US04400381A1

  公开（公告）日：1983-08-23

  New compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamine, n-lower alkylamine, and aryl piperazino; Z.sub.1 and Z.sub.2 are each independently selected from the group consisting of CH.sub.2, CHOB and C.dbd.O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z.sub.1 is CHOB; m is an integer from 0-4 but cannot be zero when Z.sub.2 is CHOB, or when m is hydrogen; R.sub.1, R.sub.2 and R.sub.3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; and R.sub.4 and R.sub.5 are each independently lower alkyl, with the proviso that both R.sub.4 and R.sub.5 cannot be methyl when M is hydrogen; are antihistamines and are therefore useful in the treatment of respiratory diseases including asthma, hay fever, allergies and the common cold. They are also vasodilators.

  公式为 ##STR1## 的新化合物及其药物可接受的酸盐，其中M选自氢，吗啡啶，苄基氨基，二元低烷基胺，一元低烷基胺和芳基哌嗪；Z.sub.1和Z.sub.2各自独立地选自CH.sub.2，CHOB和C.dbd.O的群，其中B选自氢和脂肪酰基；Y为氧或硫；n为0-4的整数，但当Z.sub.1为CHOB时，n不能为零；m为0-4的整数，但当Z.sub.2为CHOB或m为氢时，m不能为零；R.sub.1，R.sub.2和R.sub.3各自独立地为氢，卤素，羟基，三氟甲基，烷基或烷氧基；R.sub.4和R.sub.5各自独立地为低烷基，但当M为氢时，R.sub.4和R.sub.5不能同时为甲基。这些化合物是抗组胺剂，因此在治疗呼吸系统疾病包括哮喘，花粉热，过敏和普通感冒方面有用。它们也是血管扩张剂。
• Copper-Catalyzed Electrophilic Amination of Heteroaromatic and Aromatic C−H Bonds via TMPZnCl•LiCl Mediated Metalation
  作者：Stacey McDonald

  DOI：10.15227/orgsyn.092.0356

  日期：——
• Purines, pyrimidines, and condensed systems based on these compounds. 13. Transformation of fervenuli-1-oxide to 8-alkylaminotheophyllines under the action of alkylamines
  作者：A. V. Gulevskaya、A. F. Pozharskii、S. V. Shvidchenko

  DOI：10.1007/bf01171171

  日期：1994.9