N-(1,3-benzodioxol-5-ylmethyl)-N-[ 2-(benzylamino)-1-(2-fluorophenyl)-2-oxoethyl]propynamide | 1032662-75-1

• 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-(1,3-benzodioxol-5-ylmethyl)-N-[ 2-(benzylamino)-1-(2-fluorophenyl)-2-oxoethyl]propynamide
• 英文别名: N-(1,3-benzodioxol-5-ylmethyl)-N-[2-(benzylamino)-1-(2-fluorophenyl)-2-oxoethyl]prop-2-ynamide
• CAS: 1032662-75-1
• 化学式: C₂₆H₂₁FN₂O₄
• 分子量: 444.462
• InChiKey: QFHKUOFFJYSOLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4-亚甲二氧基苄胺 、 苄异腈 、 2-氟苯甲醛 、 丙炔酸 以 甲醇 为溶剂， 反应 48.0h， 以92%的产率得到N-(1,3-benzodioxol-5-ylmethyl)-N-[ 2-(benzylamino)-1-(2-fluorophenyl)-2-oxoethyl]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

• [EN] COMPOUNDS WHICH CAN BE USED FOR THE TREATMENT OF CANCERS<br/>[FR] COMPOSÉS POUVANT ÊTRE UTILISÉS POUR LE TRAITEMENT DE CANCERS
  申请人：CYTOMICS SYSTEMS

  公开号：WO2009150248A1

  公开（公告）日：2009-12-17

  The present invention relates to a compound of general formula (I) : and also to the pharmaceutically acceptable salts thereof, to the isomers or isomer mixtures thereof in all proportions, in particular to an enantiomer mixture, and especially to a racemic mixture. The present invention also relates to the use of these compounds as a medicament, and in particular for the treatment of cancer, and also to the compositions containing them.

  本发明涉及一般式（I）的化合物，以及其药学上可接受的盐，所有比例的异构体或异构体混合物，特别是对映异构体混合物，尤其是消旋混合物。本发明还涉及将这些化合物用作药物，特别是用于癌症治疗，以及含有它们的组合物。
• Compounds which can be used for the Treatment of Cancers
  申请人：Carniato Denis

  公开号：US20110104162A1

  公开（公告）日：2011-05-05

  The present invention relates to a compound of general formula (I): and also to the pharmaceutically acceptable salts thereof, to the isomers or isomer mixtures thereof in all proportions, in particular to an enantiomer mixture, and especially to a racemic mixture. The present invention also relates to the use of these compounds as a medicament, and in particular for the treatment of cancer, and also to the compositions containing them.

  本发明涉及一般式(I)的化合物，以及其药学上可以接受的盐，所有比例的异构体或异构体混合物，特别是对映异构体混合物，尤其是外消旋混合物。本发明还涉及这些化合物作为药物的用途，特别是用于癌症治疗，以及含有它们的组合物。
• 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.
• US8519188B2
  申请人：——

  公开号：US8519188B2

  公开（公告）日：2013-08-27
• [EN] PROPYNOIC ACID CARBAMOYL METHYL-ALMIDES AND PHARMACEUTICAL COMPOSITIONS AND METHODS BASED THEREON<br/>[FR] CARBAMOYL MÉTHYL-AMIDES D'ACIDE PROPYNOÏQUE ET COMPOSITIONS PHARMACEUTIQUES ET PROCÉDÉS À BASE DE CEUX-CI
  申请人：UNIV SOUTHERN CALIFORNIA

  公开号：WO2012129452A2

  公开（公告）日：2012-09-27

  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.