trans-2,2-dimethyl-3-(3-chlorophenyl)cyclopropanecarboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: trans-2,2-dimethyl-3-(3-chlorophenyl)cyclopropanecarboxylic acid
• 英文别名: (1S,3S)-3-(3-chlorophenyl)-2,2-dimethylcyclopropane-1-carboxylic acid
• 化学式: C₁₂H₁₃ClO₂
• 分子量: 224.687
• InChiKey: BPQATEPQCCWLDZ-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.16
• 重原子数：
  15.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  37.3
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  trans-2,2-dimethyl-3-(3-chlorophenyl)cyclopropanecarboxylic acid 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 生成 1-[(1S,3R)-3-(3-Chloro-phenyl)-2,2-dimethyl-cyclopropyl]-ethanone
  参考文献：
  名称：

  Aminoimidazoles as bioisosteres of acylguanidines: novel, potent, selective and orally bioavailable inhibitors of the sodium hydrogen exchanger isoform-1

  摘要：

  dInhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to limit damage to the myocardium under ischemic conditions in animals. While most known NHE-1 inhibitors are acylguanidines, this report describes the design and synthesis of a series of heterocyclic inhibitors of NHE-1 including aminoimidazoles with undiminished in vitro activity and oral bioavailability. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.066
• 作为产物：
  描述：

  3-氯苯乙烯 在 三氟甲磺酸酐 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 trans-2,2-dimethyl-3-(3-chlorophenyl)cyclopropanecarboxylic acid
  参考文献：
  名称：

  A new facile method for the stereoselective synthesis of trans-2-aryl-3,3-dimethylcyclopropane-1-carboxylic acids

  摘要：

  A new facile method for the preparation of trans-2-aryl-3,3-dimethylcyclopropane-1-carboxylic acids was developed. The new method involved [2+2]-cycloaddition of styrenes with NN,2-trimethylpropionamide followed by bromination and rearrangement of the resulting 3-aryl-2,2-dimethylcyclobutanones, affording the title compounds in two steps in 60-84% overall yields. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01224-2

文献信息

• Heterocyclic sodium/proton exchange inhibitors and method
  申请人：Ahmad Saleem

  公开号：US06887870B1

  公开（公告）日：2005-05-03

  Heterocyclic are provided which are sodium/proton exchange (NHE) inhibitors which have the structure wherein n is 1 to 5; X is N or C—R 5 wherein R 5 is H, halo, alkenyl, alkynyl, alkoxy, alkyl, aryl or heteroaryl; Z is a heteroaryl gorup, R 1 , R 2 , R 3 and R 4 are as defined herein, and where X is N. R 1 is preferably aryl or heteroaryl, and are useful as antianginal and cardioprotective agents. In addition, a method is provided for preventing or treating angina pectoris, cardiac dysfunction, myocardial necrosis, and arrhythmia employing the above heterocyclic derivatives.

  提供了杂环化合物，这些化合物是钠/质子交换（NHE）抑制剂，其结构如下： 其中n为1至5；X为N或C—R5，其中R5为H、卤素、烯基、炔基、烷氧基、烷基、芳基或杂芳基；Z为杂芳基团，R1、R2、R3和R4如本文所定义，且其中X为N。R1最好为芳基或杂芳基，并且可用作抗心绞痛和心脏保护剂。此外，提供了一种方法，用于预防或治疗心绞痛、心脏功能障碍、心肌坏死和心律失常，采用上述杂环衍生物。
• Arylcyclopropanecarboxyl Guanidines as Novel, Potent, and Selective Inhibitors of the Sodium Hydrogen Exchanger Isoform-1
  作者：Saleem Ahmad、Lidia M. Doweyko、Sundeep Dugar、Nyeemah Grazier、Khehyong Ngu、Shung C. Wu、Kenneth J. Yost、Bang-Chi Chen、Jack Z. Gougoutas、John D. DiMarco、Shih-Jung Lan、Brian J. Gavin、Alice Y. Chen、Charles R. Dorso、Randy Serafino、Mark Kirby、Karnail S. Atwal

  DOI：10.1021/jm010100v

  日期：2001.9.1

  A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC(50) = 3.5 microM) shows inhibitory activity comparable to cariporide (IC(50) = 3.4 microM). Structure-activity relationships are

  合成了一系列新的芳基环丙烷羧基胍，并评估了其对钠氢交换异构体-1（NHE-1）的活性。在表达人NHE-1亚型的AP1细胞系中进行的生物学分析中，起始环丙烷3a（IC（50）= 3.5 microM）表现出与甲立哌啶相当的抑制活性（IC（50）= 3.4 microM）。通过筛选芳基和环丙基环上的取代基的作用，使用结构活性关系优化各种酰基胍对NHE-1的亲和力。已证明在苯环上引入适当的疏水基团和在环丙烷环上引入宝石二甲基基团最多可将NHE-1抑制活性提高3个数量级（化合物7f，IC（50）= 0.003 microM）。此外，宝石二甲基系列类似物似乎在大鼠中显示出改善的口服生物利用度和更长的血浆半衰期。此外，与卡立哌利德相比，苯并二氢呋喃基铅类似物1（BMS-284640）表现出的NHE-1抑制活性提高了380倍以上，并且对NHE-1的选择性提高了。
• Nitrile Biotransformation for Highly Enantioselective Synthesis of 3-Substituted 2,2-Dimethylcyclopropanecarboxylic Acids and Amides
  作者：Mei-Xiang Wang、Guo-Qiang Feng

  DOI：10.1021/jo026490q

  日期：2003.1.1

  2-dimethylcyclopropanecarbonitriles appeared inert toward the biocatalyst, a number of racemic trans-isomers efficiently underwent a highly enantioselective hydrolysis to produce (+)-(1R,3R)-3-aryl-2,2-dimethylcyclopropanecarboxylic acids and (-)-(1S,3S)-3-aryl-2,2-dimethylcyclopropanecarboxamides in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the

  使用含有腈水合酶/酰胺酶的红球菌研究了不同构型的2,2-二甲基-3-取代的环丙烷甲腈的生物转化。AJ270全细胞催化剂在非常温和的条件下。尽管所有的cis-3-芳基-2,2-二甲基环丙烷甲腈对生物催化剂均呈惰性，但许多外消旋反式异构体均经过高度对映选择性水解，生成（+）-（1R，3R）-3-芳基-大多数情况下，以高收率得到2,2-二甲基环丙烷羧酸和（-）-（1S，3S）-3-芳基-2,2-二甲基环丙烷甲酰胺。腈类生物转化的整体对映选择性源于1R-对映选择性腈水合酶和酰胺酶的联合作用，后者是主要因素。从空间和电子效应的角度讨论了底物对反应效率和对映选择性的影响。与化学转化相结合，腈的生物转化提供了两种对映体形式的光学纯的双键取代的光学纯的双甲基取代的环丙烷羧酸和酰胺（包括菊酸）的合成。
• Aminoimidazoles as bioisosteres of acylguanidines: novel, potent, selective and orally bioavailable inhibitors of the sodium hydrogen exchanger isoform-1
  作者：Saleem Ahmad、Khehyong Ngu、Donald W Combs、Shung C Wu、David S Weinstein、Wen Liu、Bang-Chi Chen、Gamini Chandrasena、Charles R Dorso、Mark Kirby、Karnail S Atwal

  DOI：10.1016/j.bmcl.2003.09.066

  日期：2004.1

  dInhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to limit damage to the myocardium under ischemic conditions in animals. While most known NHE-1 inhibitors are acylguanidines, this report describes the design and synthesis of a series of heterocyclic inhibitors of NHE-1 including aminoimidazoles with undiminished in vitro activity and oral bioavailability. (C) 2003 Elsevier Ltd. All rights reserved.
• A new facile method for the stereoselective synthesis of trans-2-aryl-3,3-dimethylcyclopropane-1-carboxylic acids
  作者：Bang-Chi Chen、Khehyong Ngu、Peng Guo、Wen Liu、Joseph E Sundeen、David S Weinstein、Karnail S Atwal、Saleem Ahmad

  DOI：10.1016/s0040-4039(01)01224-2

  日期：2001.9

  A new facile method for the preparation of trans-2-aryl-3,3-dimethylcyclopropane-1-carboxylic acids was developed. The new method involved [2+2]-cycloaddition of styrenes with NN,2-trimethylpropionamide followed by bromination and rearrangement of the resulting 3-aryl-2,2-dimethylcyclobutanones, affording the title compounds in two steps in 60-84% overall yields. (C) 2001 Elsevier Science Ltd. All rights reserved.