N-(2-chlorobenzyl)-N-[2-(cyclopentylamino)-2-oxo-1-phenylethyl]propynamide | 1281933-52-5

• 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: N-(2-chlorobenzyl)-N-[2-(cyclopentylamino)-2-oxo-1-phenylethyl]propynamide
• 英文别名: N-[(2-chlorophenyl)methyl]-N-[2-(cyclopentylamino)-2-oxo-1-phenylethyl]prop-2-ynamide
• CAS: 1281933-52-5
• 化学式: C₂₃H₂₃ClN₂O₂
• 分子量: 394.901
• InChiKey: GKCXHHLJOZQQLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  环戊异腈 、 苯甲醛 、 丙炔酸 、 邻氯苯甲胺 以 甲醇 为溶剂， 反应 48.0h， 以61%的产率得到N-(2-chlorobenzyl)-N-[2-(cyclopentylamino)-2-oxo-1-phenylethyl]propynamide
  参考文献：
  名称：

  Discovery and Preclinical Evaluation of a Novel Class of Cytotoxic Propynoic Acid Carbamoyl Methyl Amides (PACMAs)

  摘要：

  Herein, we discovered a series of propynoic acid carbamoyl methyl-amides (PACMAs) with potent cytotoxicity against a panel of cancer cell lines. These compounds interrupted cell cycle progression at low micromolar concentrations and induced early and late stage apoptosis. A representative compound suppressed tumor growth without apparent toxicity in an MDA-MB-435 mouse xenograft Model. We used a Kinexus 628-antibody microarray and the Ingenuity Pathway Analysis (IPA) bioinformatics tools to better understand their mechanisms. The IPA analysis revealed the initiation of Nrf2-mediated oxidative stress through modulating the expression of SOD1 and STIP1 by compound 1. The involvement of the oxidative stress pathway was further validated by measuring the levels of the PACMA-induced mitochondrial superoxide species. To our knowledge, this is the first report on the discovery and biological evaluations of PACMAs as anticancer agents. Their broad-spectrum in vitro cytotoxicity, possibly through an oxidative stress-mediated pathway, and in vivo efficacy warrant further preclinical investigations.

  DOI：

  10.1021/jm101655d

文献信息

• Propynoic Acid Carbamoyl Methyl-Amides and Pharmaceutical Compositions and Methods Based Thereon
  申请人：NEAMATI Nouri

  公开号：US20130071328A1

  公开（公告）日：2013-03-21

  This invention discloses a series of novel propynoic acid carbamoyl methyl-amides (PACMAs), methods for synthesizing the PACMAs and pharmaceutical compositions containing the PACMAs. These novel compounds and compositions show cytotoxicity in cancer cells and are useful as lead compounds for anti-cancer drugs or pharmaceutical agents. This invention also discloses treatment methods that uses the PACMAs and pharmaceutical compositions as well as methods for promoting the release and nuclear localization of the transcription factor Nrf2.
• Discovery and Preclinical Evaluation of a Novel Class of Cytotoxic Propynoic Acid Carbamoyl Methyl Amides (PACMAs)
  作者：Roppei Yamada、Xuefei Cao、Alexey N. Butkevich、Melissa Millard、Srinivas Odde、Nick Mordwinkin、Rambabu Gundla、Ebrahim Zandi、Stan G. Louie、Nicos A. Petasis、Nouri Neamati

  DOI：10.1021/jm101655d

  日期：2011.4.28

  Herein, we discovered a series of propynoic acid carbamoyl methyl-amides (PACMAs) with potent cytotoxicity against a panel of cancer cell lines. These compounds interrupted cell cycle progression at low micromolar concentrations and induced early and late stage apoptosis. A representative compound suppressed tumor growth without apparent toxicity in an MDA-MB-435 mouse xenograft Model. We used a Kinexus 628-antibody microarray and the Ingenuity Pathway Analysis (IPA) bioinformatics tools to better understand their mechanisms. The IPA analysis revealed the initiation of Nrf2-mediated oxidative stress through modulating the expression of SOD1 and STIP1 by compound 1. The involvement of the oxidative stress pathway was further validated by measuring the levels of the PACMA-induced mitochondrial superoxide species. To our knowledge, this is the first report on the discovery and biological evaluations of PACMAs as anticancer agents. Their broad-spectrum in vitro cytotoxicity, possibly through an oxidative stress-mediated pathway, and in vivo efficacy warrant further preclinical investigations.