trans-2,2-Dimethyl-3-<4-methoxy-phenyl>-cyclopropan-carbonsaeure-(1)

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: trans-2,2-Dimethyl-3-<4-methoxy-phenyl>-cyclopropan-carbonsaeure-(1)
• 英文别名: (1S,3S)-3-(4-methoxyphenyl)-2,2-dimethylcyclopropane-1-carboxylic acid
• 化学式: C₁₃H₁₆O₃
• 分子量: 220.268
• InChiKey: HUYGRUXPOKDGSO-WDEREUQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trans-2,2-Dimethyl-3-<4-methoxy-phenyl>-cyclopropan-carbonsaeure-(1) 在 臭氧 、 溶剂黄146 作用下， 生成 trans-caronic acid
  参考文献：
  名称：

  Farkas,J.; Novak,J.J.K., Collection of Czechoslovak Chemical Communications, 1960, vol. 25, p. 1815 - 1823

  摘要：

  DOI：
• 作为产物：
  描述：

  diethyl 2,2-dimethyl-3-(p-methoxyphenyl)cyclopropane-1,1-dicarboxylate 在 potassium cyanide 、 sodium hydroxide 、 乙醇 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 生成 trans-2,2-Dimethyl-3-<4-methoxy-phenyl>-cyclopropan-carbonsaeure-(1)
  参考文献：
  名称：

  Discovery of +(2-{4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]phenyl}-cyclopropyl)acetic acid as potent and selective αvβ3 inhibitor: Design, synthesis, and optimization

  摘要：

  The integrin alpha(v)beta(3) is expressed in a number of cell types and is thought to play a major role in several pathological conditions. Various small molecules that inhibit the integrin have been shown to suppress tumor growth and retinal angiogenesis. The tripeptide Arg-Gly-Asp (RGD), a common binding motif in several ligands that bind to alpha(v)beta(3), has been depeptidized and optimized in our efforts toward discovering a small molecule inhibitor. We recently disclosed the synthesis and biological activity of several small molecules that did not contain any peptide bond and mimic the tripeptide RGD. The phenethyl group in one of the lead compounds was successfully replaced with a cyclopropyl moiety. The new lead compound was optimized for potency, selectivity, and for its ADME properties. We describe herein the discovery, synthesis, and optimization of cyclopropyl containing analogs that are potent and selective inhibitors of alpha(v)beta(3). (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.020

文献信息

• 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。
• Smejkai,J.; Farkas,J., Collection of Czechoslovak Chemical Communications, 1963, vol. 28, p. 1557 - 1568
  作者：Smejkai,J.、Farkas,J.

  DOI：——

  日期：——
• Discovery of +(2-{4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]phenyl}-cyclopropyl)acetic acid as potent and selective αvβ3 inhibitor: Design, synthesis, and optimization
  作者：Srinivasan R. Nagarajan、Hwang-Fun Lu、Alan F. Gasiecki、Ish K. Khanna、Mihir D. Parikh、Bipinchandra N. Desai、Thomas E. Rogers、Michael Clare、Barbara B. Chen、Mark A. Russell、Jeffery L. Keene、Tiffany Duffin、V. Wayne Engleman、Mary B. Finn、Sandra K. Freeman、Jon A. Klover、G. Alan Nickols、Maureen A. Nickols、Kristen E. Shannon、Christina A. Steininger、William F. Westlin、Marisa M. Westlin、Melanie L. Williams

  DOI：10.1016/j.bmc.2007.03.020

  日期：2007.5

  The integrin alpha(v)beta(3) is expressed in a number of cell types and is thought to play a major role in several pathological conditions. Various small molecules that inhibit the integrin have been shown to suppress tumor growth and retinal angiogenesis. The tripeptide Arg-Gly-Asp (RGD), a common binding motif in several ligands that bind to alpha(v)beta(3), has been depeptidized and optimized in our efforts toward discovering a small molecule inhibitor. We recently disclosed the synthesis and biological activity of several small molecules that did not contain any peptide bond and mimic the tripeptide RGD. The phenethyl group in one of the lead compounds was successfully replaced with a cyclopropyl moiety. The new lead compound was optimized for potency, selectivity, and for its ADME properties. We describe herein the discovery, synthesis, and optimization of cyclopropyl containing analogs that are potent and selective inhibitors of alpha(v)beta(3). (c) 2007 Elsevier Ltd. All rights reserved.
• Farkas,J.; Novak,J.J.K., Collection of Czechoslovak Chemical Communications, 1960, vol. 25, p. 1815 - 1823
  作者：Farkas,J.、Novak,J.J.K.

  DOI：——

  日期：——