(1S,2R,3S,4R,5S)-4-(6-(butylamino)-2-((5-chlorothiophen-2-yl)ethynyl)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide

• 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: (1S,2R,3S,4R,5S)-4-(6-(butylamino)-2-((5-chlorothiophen-2-yl)ethynyl)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
• 英文别名: (1S,2R,3S,4R,5S)-4-[6-(butylamino)-2-[2-(5-chlorothiophen-2-yl)ethynyl]purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
• 化学式: C₂₃H₂₅ClN₆O₃S
• 分子量: 501.009
• InChiKey: AQICAVVSPZOFNC-VYYPKGNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (1'S,2'R,3'S,4'R,5'S)-4'-[6-chloro-2-iodopurin-9-yl]-2',3'-isopropylidenebicyclo[3.1.0]hexane-1'-carboxylic acid ethyl ester 在 trans-bis(triphenylphosphine)palladium dichloride 、 三氟甲磺酸 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 (1S,2R,3S,4R,5S)-4-(6-(butylamino)-2-((5-chlorothiophen-2-yl)ethynyl)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
  参考文献：
  名称：

  Rigidified A₃ Adenosine Receptor Agonists: 1-Deazaadenine Modification Maintains High in Vivo Efficacy

  摘要：

  Substitution of rigidified A(3) adenosine receptor (AR) agonists with a 2-((5-chlorothiophen-2-y1)ethynyl) or a 2-(4-(5-chlorothiophen-2-y1)-1H-1,2,3-triazol-1-yl)) group provides prolonged protection in a model of chronic neuropathic pain. These agonists contain a bicyclo[3.1.0]hexane ((N)-methanocarba) ring system in place of ribose, which adopts a receptor-preferred conformation. N-6-Small alkyl derivatives were newly optimized for A(3)AR affinity and the effects of a 1-deaza-adenine modification probed. 1-Deaza-N-6-ethyl alkyne 20 (MRS7144, K-i 1.7 nM) and 1-aza N-6-propyl alkyne 12 (MRS7154, K-i 1.1 nM) were highly efficacious in vivo. Thus, the presence of N1 is not required for nanomolar binding affinity or potent, long-lasting functional activity. Docking of 1-deaza compounds to a receptor homology model confirmed a similar binding mode as previously reported 1-aza derivatives. This is the first demonstration in nonribose adenosine analogues that the 1-deaza modification can maintain high A(3)AR affinity, selectivity, and efficacy.

  DOI：

  10.1021/acsmedchemlett.5b00150