(1S,2S)-2-(3-thienyl)cyclopropane-1-carboxylic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S,2S)-2-(3-thienyl)cyclopropane-1-carboxylic acid
• 英文别名: (1S,2S)-2-thiophen-3-ylcyclopropane-1-carboxylic acid
• 化学式: C₈H₈O₂S
• 分子量: 168.216
• InChiKey: ZZCJDGURVYEFFD-RQJHMYQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,2S)-2-(3-thienyl)cyclopropane-1-carboxylic acid 在 氯甲酸乙酯 、 三乙胺 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 18.0h， 生成 2-trimethylsilylethyl N-[(1S,2R)-2-thiophen-3-ylcyclopropyl]carbamate
  参考文献：
  名称：

  探索A3腺苷受体结合位点的远端区域：在空间上受约束的N6-（2-苯乙基）腺苷衍生物作为有效的配体。

  摘要：

  我们合成了N（6）-（1S，2R）-（2-苯基-1-环丙基）腺苷的苯环取代类似物，其与人A（3）AR的结合力强，Ki值为0.63 nM。测量了这些结构变化对人和大鼠腺苷受体的亲和力以及对hA（3）AR的内在功效的影响。3-硝基苯基类似物色谱分离成纯的非对映异构体，在A（3）AR结合中表现出10倍的立体选择性，有利于1S，2R异构体。分子模型在苯基部分周围的假定的A（3）AR结合位点中定义了疏水区（Phe168）。杂芳族基团（3-噻吩基）可以取代苯基部分，并保留A（3）AR结合的高亲和力。包括其他相关的N（6）取代腺苷衍生物进行比较。尽管N（6）-（2-苯基-1-环丙基）衍生物是完全的A（3）AR激动剂，但其他几种衍生物的功效也大大降低。N（6）-环丙基腺苷是一种A（3）AR拮抗剂，在环丙基部分的2位添加一个或两个苯环可恢复功效。N（6）-（2,2-二苯基乙基）腺苷是一种A（3）AR拮抗剂，

  DOI：

  10.1016/j.bmc.2004.02.037
• 作为产物：
  描述：

  methyl (E)-3-(thiophen-3-yl)acrylate 在 palladium diacetate 、 sodium hydroxide 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (1S,2S)-2-(3-thienyl)cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  trans-2-Aryl-N,N-dipropylcyclopropylamines:  Synthesis and Interactions with 5-HT_1A Receptors

  摘要：

  Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [H-3]-8-OH-DPAT from rat brain 5-HT1A receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7I) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT1A receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT1A receptor affinity. The racemic mixtures of the interesting 7j and 7I were resolved into the enantiomers; 7j and 7I exhibited a high enantiomeric 5-HT1A receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7I were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (LR,2R)-7j behaved as a partial agonist whereas (1R,2S)-7I appeared as an efficacious 5-HT1A receptor agonist, stimulating both autoreceptors and postsynaptic receptors.

  DOI：

  10.1021/jm9507136

文献信息

• A novel route to cyclopropyl ketones, aldehydes, and carboxylic acids.
  作者：Karen E. Rodriques

  DOI：10.1016/s0040-4039(00)79644-4

  日期：1991.3

  Cyclopropanation of α,β-unsaturated N-methoxy-N-methyl amides provided the cyclopropyl amides in far superior yields to those obtained with the corresponding ketones. The desired ketones are then readily accessible by the addition of organometallic reagents. Access to a variety functional groups, including aldehydes and carboxylic acids, is also described.

  α，β-不饱和N-甲氧基-N-甲基酰胺的环丙烷化提供的环丙基酰胺的收率远高于用相应的酮获得的收率。然后通过添加有机金属试剂可以容易地获得所需的酮。还描述了对包括醛和羧酸在内的各种官能团的获取。
• [EN] NOVEL MORPHINANS USEFUL FOR TREATING MEDICAL DISORDERS<br/>[FR] NOUVEAUX MORPHINANES UTILES POUR LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：HUMANWELL PHARMACEUTICAL US

  公开号：WO2020205735A1

  公开（公告）日：2020-10-08

  The present invention related to novel morphinans, compositions comprising the novel morphinans, and their uses as agonists of the kappa opioid receptor.

  本发明涉及新型吗啡酮类化合物，包括这些新型吗啡酮类化合物的组合物，以及它们作为κ阿片受体激动剂的用途。
• Morphinans useful for treating medical disorders
  申请人：Humanwell Pharmaceutical US

  公开号：US11214577B2

  公开（公告）日：2022-01-04

  The present invention related to novel morphinans, compositions comprising the novel morphinans, and their uses as agonists of the kappa opioid receptor.

  本发明涉及新型吗啡烷、包含新型吗啡烷的组合物及其作为卡巴阿片受体激动剂的用途。
• Improvement of the Metabolic Stability of GPR88 Agonist RTI-13951-33: Design, Synthesis, and Biological Evaluation
  作者：Md Toufiqur Rahman、Ann M. Decker、Sami Ben Hamida、David A. Perrey、Hetti Handi Chaminda Lakmal、Rangan Maitra、Emmanuel Darcq、Brigitte L. Kieffer、Chunyang Jin

  DOI：10.1021/acs.jmedchem.2c01983

  日期：2023.2.23
• NOVEL MORPHINANS USEFUL FOR TREATING MEDICAL DISORDERS
  申请人：Humanwell Pharmaceutical US

  公开号：US20200308185A1

  公开（公告）日：2020-10-01

  The present invention related to novel morphinans, compositions comprising the novel morphinans, and their uses as agonists of the kappa opioid receptor.