methyl 2-o-tolyl-4-carboxybenzoate | 216237-17-1

• 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: methyl 2-o-tolyl-4-carboxybenzoate
• 英文别名: methyl 2-(2-methylphenyl)-4-carboxybenzoate；6-(methoxycarbonyl)-2'-methyl(1,1'-biphenyl)-3-carboxylic Acid；2-(2-methylphenyl)-4-carboxybenzoic acid,methyl ester；4-Methoxycarbonyl-3-(2-methylphenyl)benzoic acid
• CAS: 216237-17-1
• 化学式: C₁₆H₁₄O₄
• 分子量: 270.285
• InChiKey: VVBPSBHOVOBNIR-UHFFFAOYSA-N

物化性质

• 沸点：
  459.8±45.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-o-tolyl-4-carboxybenzoate 在 硼烷四氢呋喃络合物 、 三溴化磷 、 lithium bromide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 4-bromomethyl-2-(2-methylphenyl)benzoic acid methyl ester
  参考文献：
  名称：

  Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase

  摘要：

  Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.

  DOI：

  10.1021/jm980298s
• 作为产物：
  描述：

  碘代对苯二甲酸二甲酯 在 氢氧化钾 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 3.0h， 生成 methyl 2-o-tolyl-4-carboxybenzoate
  参考文献：
  名称：

  Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase

  摘要：

  Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.

  DOI：

  10.1021/jm980298s

文献信息

• Substituted phenyl farnesyltransferase inhibitors
  申请人：——

  公开号：US20020019527A1

  公开（公告）日：2002-02-14

  Compounds of formula (I) 1 or pharmaceutically acceptable salts thereof, inhibit farnesyltransferase. Methods for making the compounds, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds are disclosed.

  式(I)的化合物或其药学上可接受的盐，抑制法尼基转移酶。公开了制备这些化合物的方法，含有这些化合物的药物组合物，以及使用这些化合物进行治疗的方法。
• Peptidomimetic inhibitors of farnesyltransferase with high in vitro activity and significant cellular potency
  作者：Cristiano Bolchi、Marco Pallavicini、Chiara Rusconi、Luisa Diomede、Nicola Ferri、Alberto Corsini、Laura Fumagalli、Alessandro Pedretti、Giulio Vistoli、Ermanno Valoti

  DOI：10.1016/j.bmcl.2007.09.015

  日期：2007.11

  amidified with 2-hydroxymethyl- and 2-aminomethylpyridodioxane, respectively, are described as inhibitors of Ras protein farnesyltransferase (FTase). Of the sixteen compounds, resulting from the substitution pattern of benzamide and the configuration of the two stereocenters, seven inhibited FTase activity with potencies in the nanomolar range. They were all 2-oxymethylpyridodioxane ethers and, among

  描述了分别被2-羟甲基-和2-氨基甲基吡啶二恶烷醚化和酰胺化的蛋氨酸的2-o-甲苯基或2-o-茴香基取代的4-羟基-和4-羧基苯甲酰胺是Ras蛋白法呢基转移酶（FTase）的抑制剂。在16种化合物中，由于苯甲酰胺的取代模式和两个立构中心的构型，其中7种抑制FTase活性，其效力在纳摩尔范围内。它们都是2-氧甲基吡啶二恶烷醚，并且其中四个邻甲苯基取代的立体异构体还对人主动脉平滑肌细胞产生微摩尔抗增殖作用，从而干扰了拉斯法呢基化。对接分析表明，氧甲基吡啶二恶烷和氨基甲基吡啶二恶烷衍生物之间的酶相互作用存在显着差异。
• Process for the preparation of farnesyltransferase inhibitors
  申请人：Abbott Laboratories

  公开号：US06248919B1

  公开（公告）日：2001-06-19

  A process for the preparation of preparation of farnesyltransferase inhibitors of formula (I) or pharmaceutically acceptable salts or prodrugs thereof, is disclosed.

  揭示了一种制备式(I)的法尼西尔转移酶抑制剂或其药学上可接受的盐或前药的过程。
• New Ras CAAX mimetics: Design, synthesis, antiproliferative activity, and RAS prenylation inhibition
  作者：Cristiano Bolchi、Marco Pallavicini、Laura Fumagalli、Nicola Ferri、Alberto Corsini、Chiara Rusconi、Ermanno Valoti

  DOI：10.1016/j.bmcl.2009.07.065

  日期：2009.9

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing cysteine (C) by 2-hydroxymethylbenzodioxane or 2-aminomethylbenzodioxane, respectively etherified and amidified with 2'-methyl or 2'-methoxy substituted 2-carboxy-4-hydroxybiphenyl and 2,4-dicarboxybiphenyl. These pluri-substituted biphenyl systems, used as internal spacer and AA dipeptide bioisoster, were linked to the methyl ester Of L-methionine, glycine or L-leucine by an amide bond. The resultant twelve pairs of stereoisomers at the dioxane C-2 were tested for anti proliferative effect finding the maximum activity for derivatives with methyleneoxy linker between benzodioxane and 2'-methylbiphenyl. Of these compounds, the one with terminal methionine and S configuration proved a good Ras prenylation inhibitor in a cell-based assay. (C) 2009 Elsevier Ltd. All rights reserved.
• INHIBITORS OF PROTEIN ISOPRENYL TRANSFERASES
  申请人：UNIVERSITY OF PITTSBURGH

  公开号：EP0986384B1

  公开（公告）日：2012-02-22