MRS 5465 | 1312015-12-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: MRS 5465
• 英文别名: (1R,2R,3S,4R,5S)-4-(2-chloro-6-(cyclohexylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol；MRS5465；(1R,2R,3S,4R,5S)-4-[2-chloro-6-(cyclohexylamino)purin-9-yl]bicyclo[3.1.0]hexane-2,3-diol
• CAS: 1312015-12-5
• 化学式: C₁₇H₂₂ClN₅O₂
• 分子量: 363.847
• InChiKey: FWCAXXBWEDQGJG-HNTFPEDGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  96.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (1R,2R,3S,4R,5S)-4-(2-chloro-6-(cyclohexylamino)-9H-purin-9-yl)-2',3'-O-(isopropylidene)-bicyclo[3.1.0]hexane 在 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以84%的产率得到MRS 5465
  参考文献：
  名称：

  Truncated (N)-Methanocarba Nucleosides as A₁ Adenosine Receptor Agonists and Partial Agonists: Overcoming Lack of a Recognition Element

  摘要：

  A(1) adenosine receptor (AR) agonists are neuroprotective, cardioprotective, and anxiolytic. (N)-Methanocarba adenine nucleosides designed to bind to human A(1)AR were truncated to eliminate 5'-CH2OH. This modification previously converted A(3)AR agonists into antagonists, but the comparable effect at A(1)AR is unknown. In comparison to ribosides, affinity at the A(1)AR was less well preserved than that at the A(3)AR, although a few derivatives were moderately A(1)AR selective, notably full agonist 21 (N-6-dicyclopropyl-methyl, K-i 47.9 nM). Thus, at the A(1)AR, recognition elements for nucleoside binding depend more on 5' region interactions, and in their absence, A(3)AR selectivity predominates. Based on the recently reported agonist-bound AR structure, this difference between subtypes likely correlates with an essential His residue in transmembrane domain 6 of A(1) but not A(3)AR The derivatives ranged from partial to full agonists in A(1)AR-mediated adenylate cyclase inhibition. Truncated derivatives have more druglike physical properties than other A(1)AR agonists; this approach is appealing for preclinical development.

  DOI：

  10.1021/ml200114q

文献信息

• ADENOSINE RECEPTOR AGONISTS, PARTIAL AGONISTS, AND ANTAGONISTS
  申请人：Jacobson Kenneth A.

  公开号：US20120252823A1

  公开（公告）日：2012-10-04

  Disclosed are A 3 adenosine receptor antagonists and/or partial agonists and A 1 adenosine receptor agonists and/or partial agonists of formula (I): wherein R 1 to R 5 are as described herein, as well as pharmaceutical compositions thereof and methods of use thereof. The A 3 AR antagonists or partial agonists find use in treating a number of diseases such as cancer, glaucoma, and inflammatory diseases, as well as in preventing cardiac ischemia. Also disclosed are radiolabeled compounds of formula (I) and the use thereof in diagnostic imaging of tissues and organs. The A 1 AR agonists and partial agonists find use in treating diseases such as seizures, convulsion, stroke, diabetes, pain, arrhythmias, depression, and anxiety and in cardioprotection or neuroprotection.

  本发明涉及式(I)的A3腺苷受体拮抗剂和/或部分激动剂以及A1腺苷受体激动剂和/或部分激动剂，其中R1至R5如本文所述，以及其制药组合物和使用方法。A3AR拮抗剂或部分激动剂可用于治疗诸如癌症、青光眼和炎症性疾病等多种疾病，以及预防心脏缺血。本发明还涉及式(I)的放射性标记化合物及其在组织和器官的诊断成像中的应用。A1AR激动剂和部分激动剂可用于治疗癫痫、惊厥、中风、糖尿病、疼痛、心律失常、抑郁症和焦虑症以及心脏保护或神经保护。
• US9181253B2
  申请人：——

  公开号：US9181253B2

  公开（公告）日：2015-11-10
• Truncated (N)-Methanocarba Nucleosides as A₁ Adenosine Receptor Agonists and Partial Agonists: Overcoming Lack of a Recognition Element
  作者：Dilip K. Tosh、Khai Phan、Francesca Deflorian、Qiang Wei、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/ml200114q

  日期：2011.8.11

  A(1) adenosine receptor (AR) agonists are neuroprotective, cardioprotective, and anxiolytic. (N)-Methanocarba adenine nucleosides designed to bind to human A(1)AR were truncated to eliminate 5'-CH2OH. This modification previously converted A(3)AR agonists into antagonists, but the comparable effect at A(1)AR is unknown. In comparison to ribosides, affinity at the A(1)AR was less well preserved than that at the A(3)AR, although a few derivatives were moderately A(1)AR selective, notably full agonist 21 (N-6-dicyclopropyl-methyl, K-i 47.9 nM). Thus, at the A(1)AR, recognition elements for nucleoside binding depend more on 5' region interactions, and in their absence, A(3)AR selectivity predominates. Based on the recently reported agonist-bound AR structure, this difference between subtypes likely correlates with an essential His residue in transmembrane domain 6 of A(1) but not A(3)AR The derivatives ranged from partial to full agonists in A(1)AR-mediated adenylate cyclase inhibition. Truncated derivatives have more druglike physical properties than other A(1)AR agonists; this approach is appealing for preclinical development.