(1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)cyclopropanecarboxylic acid | 947767-40-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)cyclopropanecarboxylic acid
• 英文别名: (1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-thiophene-2-ylcyclopropanecarboxylic acid；(1R,2R)-2-[(1,3-dioxoisoindol-2-yl)methyl]-1-thiophen-2-ylcyclopropane-1-carboxylic acid
• CAS: 947767-40-0
• 化学式: C₁₇H₁₃NO₄S
• 分子量: 327.361
• InChiKey: YLNPBWUBSHRYNJ-BTDLBPIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)cyclopropanecarboxylic acid 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (1S,2R)-2-[(1,3-dioxoisoindol-2-yl)methyl]-1-thiophen-2-ylcyclopropane-1-carbonyl chloride
  参考文献：
  名称：

  WO2007/98356

  摘要：

  公开号：
• 作为产物：
  描述：

  (+)-1-(thiophen-2-yl)-3-oxa-bicyclo[3.1.0]hexan-2-one 、 potassium phtalimide 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以31%的产率得到(1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)cyclopropanecarboxylic acid
  参考文献：
  名称：

  Characterization of Thien-2-yl 1S,2R-Milnacipran Analogues as Potent Norepinephrine/Serotonin Transporter Inhibitors for the Treatment of Neuropathic Pain

  摘要：

  Thien-2-yl 1S,2R-milnacipran analogues were synthesized and characterized as norepinephrine/serotonin transporter inhibitors. These compounds possessed higher potencies than IS,2R-milnacipran (2R-1) while maintaining low molecular weight and moderate lipophilicity, which are the important features for the pharmacological and pharmacokinetic characteristics of milnacipran (1). Thus, compound 5c exhibited IC50 values of 2.3 and 32 nM, respectively, at NET and SERT, which were more than 10-fold better than those of 1 (NET IC50 = 77 nM, SERT IC50 = 420 nM). Moreover, 5c achieved the same efficacy as 1, but with much lower doses, in a rodent spinal nerve ligation pain model. In addition, 5c displayed desirable pharmacokinetic properties in several species, including high oral availability and significant brain penetration.

  DOI：

  10.1021/jm8009537

文献信息

• Studies on the structure–activity relationship of bicifadine analogs as monoamine transporter inhibitors
  作者：Mingzhu Zhang、Florence Jovic、Troy Vickers、Brian Dyck、Junko Tamiya、Jonathan Grey、Joe A. Tran、Beth A. Fleck、Rebecca Pick、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2008.05.077

  日期：2008.7

  Compounds with various activities and selectivities were discovered through structure -activity relationship studies of bicifadine analogs as monoamine transporter inhibitors. The norepinephrine-selective 2-thienyl compound S-6j was efficacious in a rodent pain model. (C) 2008 Elsevier Ltd. All rights reserved.
• WO2007/98356
  申请人：——

  公开号：——

  公开（公告）日：——
• Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors
  作者：Troy Vickers、Brian Dyck、Junko Tamiya、Mingzhu Zhang、Florence Jovic、Jonathan Grey、Beth A. Fleck、Anna Aparicio、Michael Johns、Liping Jin、Hui Tang、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2008.04.045

  日期：2008.6

  A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as monoamine transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26 nM at NET and SERT, respectively. (C) 2008 Elsevier Ltd. All rights reserved.
• Characterization of Thien-2-yl 1<i>S</i>,2<i>R</i>-Milnacipran Analogues as Potent Norepinephrine/Serotonin Transporter Inhibitors for the Treatment of Neuropathic Pain
  作者：Brian Dyck、Junko Tamiya、Florence Jovic、Rebecca R. Pick、Margaret J. Bradbury、Julie O’Brien、Jenny Wen、Michael Johns、Ajay Madan、Beth A. Fleck、Alan C. Foster、Binfeng Li、Mingzhu Zhang、Joe A. Tran、Troy Vickers、Jonathan Grey、John Saunders、Chen Chen

  DOI：10.1021/jm8009537

  日期：2008.11.27

  Thien-2-yl 1S,2R-milnacipran analogues were synthesized and characterized as norepinephrine/serotonin transporter inhibitors. These compounds possessed higher potencies than IS,2R-milnacipran (2R-1) while maintaining low molecular weight and moderate lipophilicity, which are the important features for the pharmacological and pharmacokinetic characteristics of milnacipran (1). Thus, compound 5c exhibited IC50 values of 2.3 and 32 nM, respectively, at NET and SERT, which were more than 10-fold better than those of 1 (NET IC50 = 77 nM, SERT IC50 = 420 nM). Moreover, 5c achieved the same efficacy as 1, but with much lower doses, in a rodent spinal nerve ligation pain model. In addition, 5c displayed desirable pharmacokinetic properties in several species, including high oral availability and significant brain penetration.