6-[(2,2-Diphenylethyl)amino]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-N-(2-[({[1-(2-pyridinyl)-4-piperidinyl]amino}carbonyl)amino]ethyl)-9H-purine-2-carboxamide | 380221-63-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-[(2,2-Diphenylethyl)amino]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-N-(2-[({[1-(2-pyridinyl)-4-piperidinyl]amino}carbonyl)amino]ethyl)-9H-purine-2-carboxamide
• 英文别名: 6-(2,2-diphenylethylamino)-9-((2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxytetrahydrofuran-2-yl)-N-(2-(3-(1-(pyridin-2-yl)piperidin-4-yl)ureido)ethyl)-9H-purine-2-carboxamide；UK-432,097；UK-432097；UK432,097；UK432097；6-[(2,2-diphenylethyl)amino]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-N-{2-[({[1-(2-pyridinyl)-4-piperidinyl]amino}carbonyl)amino]ethyl}-9H-purine-2-carboxamide；6-(2,2-Diphenylethylamino)-9-[(2r,3r,4s,5s)-5-(Ethylcarbamoyl)-3,4-Dihydroxy-Oxolan-2-Yl]-N-[2-[(1-Pyridin-2-Ylpiperidin-4-Yl)carbamoylamino]ethyl]purine-2-Carboxamide；6-(2,2-diphenylethylamino)-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]-N-[2-[(1-pyridin-2-ylpiperidin-4-yl)carbamoylamino]ethyl]purine-2-carboxamide
• CAS: 380221-63-6
• 化学式: C₄₀H₄₇N₁₁O₆
• 分子量: 777.883
• InChiKey: ZOTHAEBAWXWVID-HXEFRTELSA-N

物化性质

• 密度：
  1.46±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO: 2mg/mL, clear

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  57
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  221
• 氢给体数：
  7
• 氢受体数：
  12

制备方法与用途

UK-432097 是一种高效且选择性的 A2AAR 激动剂，其对人类 A2AAR 的 pKi 值为 8.4。这种化合物具有抗炎和抗聚集特性，并且在 COPD（慢性阻塞性肺疾病）研究中展现出潜力。

反应信息

• 作为产物：
  描述：

  4-氨基-1-(2-吡啶)哌啶盐酸盐 在 甲烷磺酸 、 乙醇 、 水 、 三乙胺 、 N,N-二异丙基乙胺 、 乙酰氯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 14.0h， 生成 6-[(2,2-Diphenylethyl)amino]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-N-(2-[({[1-(2-pyridinyl)-4-piperidinyl]amino}carbonyl)amino]ethyl)-9H-purine-2-carboxamide
  参考文献：
  名称：

  吸入A 2a激动剂的多公斤路线的路线选择和工艺开发UK-432,097

  摘要：

  本文介绍了合成，合成复杂核苷类似物A 2a激动剂UK-432,097（1）的选择，工艺开发和放大，最终生产了超过25 kg的API。该过程的关键步骤是（1）立体选择性糖苷化反应；（2）可扩展的漂白剂-TEMPO氧化；（3）最终原料药的异常高温结晶过程。还介绍了按比例放大路线时遇到的问题以及如何克服这些问题。

  DOI：

  10.1021/op200365n

文献信息

• 2-aminocarbonyl-9H-purine derivatives
  申请人：——

  公开号：US20020058641A1

  公开（公告）日：2002-05-16

  The present invention relates to compounds of the formula. 1 and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.

  本发明涉及公式.1的化合物及其药学上可接受的盐和溶剂化物，以及制备这些化合物所使用的中间体、含有这些化合物的组合物的制备方法和用途。
• 2-Aminocarbonyl-9H-purine derivatives
  申请人：Pfizer Inc

  公开号：US20040077584A1

  公开（公告）日：2004-04-22

  The present invention relates to compounds of the formula: 1 and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.

  本发明涉及公式1的化合物：1及其药学上可接受的盐和溶剂，以及制备这些化合物的中间体、含有这些化合物的组合物的制备过程和用途。
• Use of adenosine receptor signaling to regulate P-gp function
  申请人：CORNELL UNIVERSITY

  公开号：US10953015B2

  公开（公告）日：2021-03-23

  The present invention relates to a method of inhibiting p-glycoprotein (P-gp) expression in a cell. The method involves contacting a cell expressing P-gp with a composition comprising an effective amount of an A2A adenosine receptor (A2A AR) agonist to inhibit P-gp expression in the cell. Methods of enhancing the bioavailability of a chemotherapeutic in a subject having multi-drug resistant (MDR) cancer and methods of increasing P-gp-mediated efflux in a cell are also disclosed.

  本发明涉及一种抑制细胞中 p-糖蛋白（P-gp）表达的方法。 该方法包括将表达 P-gp 的细胞与包含有效量的 A2A 腺苷受体（A2A AR）激动剂的组合物接触，以抑制细胞中 P-gp 的表达。 本发明还公开了提高具有多重耐药性（MDR）癌症患者的化疗药物生物利用度的方法，以及增加细胞中 P-gp 介导的外流的方法。
• Combination of an adenosine A2A-receptor agonist and tiotropium or a derivative thereof for treating obstructive airways and other inflammatory diseases
  申请人：Boehringer Ingelheim Pharma KG

  公开号：US20030013675A1

  公开（公告）日：2003-01-16

  A combination of therapeutic agents useful in the treatment of obstructive airways and other inflammatory diseases comprising (i) an adenosine A 2A receptor agonist; and (ii) an anti-cholinergic agent, preferably comprising a member selected from the group consisting of tiotropium and derivatives thereof; the combination being therapeutically effective in the treatment of the diseases when administered by inhalation; as well as to a method of treating the obstructive airways and other inflammatory diseases comprising administering separately, simultaneously or sequentially to the mammal by inhalation a therapeutically effective amount of the combination of therapeutic agents; as well as to a pharmaceutical composition comprising a pharmaceutically acceptable carrier together with the combination of therapeutic agents; as well as to a product containing the compounds of the combination for separate, simultaneous or sequential administration by inhalation to a mammal for the treatment of obstructive airways and other inflammatory diseases. It is preferred that the anti-cholinergic agent component be tiotropium bromide.

  一种用于治疗阻塞性气道和其他炎症性疾病的治疗剂组合，包括(i) 一种腺苷 A 2A 受体激动剂；以及(ii) 抗胆碱能药物，优选包含选自由噻托溴铵及其衍生物组成的组中的成员；当通过吸入给药时，该组合对治疗疾病有效；以及治疗阻塞性气道和其他炎症性疾病的方法，包括通过吸入给哺乳动物分别、同时或依次给药治疗有效量的治疗剂组合；以及包含药学上可接受的载体和治疗剂组合物的药物组合物；以及包含组合物化合物的产品，用于通过吸入对哺乳动物单独、同时或连续给药，以治疗阻塞性气道和其他炎症性疾病。抗胆碱能药物成分最好是噻托溴铵。
• Use of compounds in a dry powder inhaler
  申请人：——

  公开号：US20030064034A1

  公开（公告）日：2003-04-03

  The present invention relates to an inhaled formulation comprising a compound selected from a particular class of 5,6-dihydro-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridines which is capable of delivering the compound as fine, solid particles to the lung and the use of such a formulation in the treatment of certain diseases such as respiratory diseases. By the use of such formulations, it is possible to eliminate the unwanted cough response associated with the use of these compounds in solution metered dose inhalers, which response can prevent the administration of a therapeutically effective dose and, in the long term, undermine patient compliance.

  本发明涉及一种吸入制剂，该制剂包含选自5,6-二氢-9H-吡唑并[lsqb;3,4-c]并[rsqb;-1,2,4-三唑并[lsqb;4,3-a]并[rsqb;吡啶]特定类别的化合物，该化合物能够以细小的固体颗粒形式输送到肺部，以及将这种制剂用于治疗某些疾病，如呼吸系统疾病。通过使用这种制剂，可以消除与在溶液计量吸入器中使用这些化合物有关的不希望出现的咳嗽反应，这种反应会妨碍给药治疗有效剂量，而且从长远来看，会影响患者的依从性。