S-methyl 4-methyl-4-[methyl(phenyl)amino]pent-2-ynethioate | 1038439-98-3

• 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: S-methyl 4-methyl-4-[methyl(phenyl)amino]pent-2-ynethioate
• 英文别名: S-methyl 4-methyl-4-(N-methylanilino)pent-2-ynethioate
• CAS: 1038439-98-3
• 化学式: C₁₄H₁₇NOS
• 分子量: 247.361
• InChiKey: FSUYJHAYAWXTRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  S-methyl 4-methyl-4-[methyl(phenyl)amino]pent-2-ynethioate 、 碘甲烷 以 乙酸乙酯 为溶剂， 生成 Trimethyl-(2-methyl-5-methylsulfanyl-5-oxopent-3-yn-2-yl)azanium;iodide
  参考文献：
  名称：

  Aldehyde dehydrogenase inhibitors: α,β-Acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but irreversible apoptogens for cancer epithelial cells from human prostate in culture

  摘要：

  The pharmacomodulation of the N atom of alpha,beta-acetylenic aminothiolesters or the replacement of the thiolester moiety by more electroplfflic groups did not permit any clear rationale to be established for improving the selective growth-inhibitory activity of this family of compounds over that of the previously synthesized alpha,beta-acetylenic aminothiolesters DIMATE and MATE [G. Quash, G. Fournet, J. Chantepie, J. Gore, C. Ardiet, D. Ardail, Y. Michal, U. Reichert, Biochem Phannacol 64 (2002) 1279-92]. Hence DIMATE and MATE were investigated more thoroughly for selectivity and growth-inhibitory activity using human prostate epithelial normal cells (HPENC) on the one hand and human prostate epithelial cancer cells (DU145) on the other. Unequivocal evidence was obtained showing that both compounds were reversible growth inhibitors of HPENC but irreversible growth inhibitors of DU145. Growth-inhibition of DU145 was due to the induction of early apoptosis as revealed by the flow cytometric analytical profile of inhibitor-treated cells, of the decrease in the redox potential and increase in superoxide anion content of their mitochondria. Of the two intracellular enzymes: aldehyde dehydrogenases 1 and 3 (ALDH1 and ALDH3) targeted by DIMATE and MATE, ALDH3 was inhibited to the same extent by both compounds whereas ALDH1 was less susceptible to inhibition by MATE. As the induction of ALDH3 by xenobiotics is hormone-dependent, MATE, the more selective of the two inhibitors, is a useful tool not only for examining the role of the ALDH3 isoform in hormone-sensitive and resistant prostate cancer cells in culture but also for investigating if it can inhibit the growth of xenografts of prostate cancer in immunodeficient mice. (C) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.06.004
• 作为产物：
  描述：

  4-methyl-4-(N-methylanilino)pent-2-ynethioic S-acid 、 碘甲烷 生成 S-methyl 4-methyl-4-[methyl(phenyl)amino]pent-2-ynethioate
  参考文献：
  名称：

  Aldehyde dehydrogenase inhibitors: α,β-Acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but irreversible apoptogens for cancer epithelial cells from human prostate in culture

  摘要：

  The pharmacomodulation of the N atom of alpha,beta-acetylenic aminothiolesters or the replacement of the thiolester moiety by more electroplfflic groups did not permit any clear rationale to be established for improving the selective growth-inhibitory activity of this family of compounds over that of the previously synthesized alpha,beta-acetylenic aminothiolesters DIMATE and MATE [G. Quash, G. Fournet, J. Chantepie, J. Gore, C. Ardiet, D. Ardail, Y. Michal, U. Reichert, Biochem Phannacol 64 (2002) 1279-92]. Hence DIMATE and MATE were investigated more thoroughly for selectivity and growth-inhibitory activity using human prostate epithelial normal cells (HPENC) on the one hand and human prostate epithelial cancer cells (DU145) on the other. Unequivocal evidence was obtained showing that both compounds were reversible growth inhibitors of HPENC but irreversible growth inhibitors of DU145. Growth-inhibition of DU145 was due to the induction of early apoptosis as revealed by the flow cytometric analytical profile of inhibitor-treated cells, of the decrease in the redox potential and increase in superoxide anion content of their mitochondria. Of the two intracellular enzymes: aldehyde dehydrogenases 1 and 3 (ALDH1 and ALDH3) targeted by DIMATE and MATE, ALDH3 was inhibited to the same extent by both compounds whereas ALDH1 was less susceptible to inhibition by MATE. As the induction of ALDH3 by xenobiotics is hormone-dependent, MATE, the more selective of the two inhibitors, is a useful tool not only for examining the role of the ALDH3 isoform in hormone-sensitive and resistant prostate cancer cells in culture but also for investigating if it can inhibit the growth of xenografts of prostate cancer in immunodeficient mice. (C) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.06.004

文献信息

• Combination comprising an aminothiolester compound or a pharmaceutically acceptable salt thereof and a compound able to increase the H2O2 level in cancer cells of a subject
  申请人：ADVANCED BIODESIGN

  公开号：US10406125B2

  公开（公告）日：2019-09-10

  The present invention relates to a combination comprising an aminothiolester compound or a pharmaceutically acceptable salt thereof, in particular the S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, and more particularly the 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate, and a compound able to increase H2O2 level in cancer cells of a subject, in particular for use for the treatment of cancer in a subject, wherein cancer cells of said subject do not overproduce H2O2 in comparison to a control value and have a level of GSH below 5 nmol for 25000 cells.

  本发明涉及一种组合物，包括氨基硫醇酯化合物或其药学上可接受的盐，特别是 4-(二甲基氨基)-4-甲基-2-戊炔硫酸 S-甲酯或其药学上可接受的盐，尤其是 4-(二甲基氨基)-4-甲基-2-戊炔硫酸 S-甲酯富马酸盐、以及一种能提高受试者癌细胞中 H2O2 水平的化合物，特别是用于治疗受试者癌症的化合物，其中所述受试者的癌细胞与对照值相比不会过量产生 ，并且每 25000 个细胞的 GSH 水平低于 5 nmol。
• AMINOTHIOLESTER COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, FOR USE IN THE TREATMENT OF CANCER
  申请人：Advanced Biodesign

  公开号：EP3362056B1

  公开（公告）日：2021-02-24
• COMBINATION COMPRISING AN AMINOTHIOLESTER COMPOUND OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND A COMPOUND ABLE TO INCREASE THE H2O2 LEVEL IN CANCER CELLS OF A SUBJECT
  申请人：Advanced Biodesign

  公开号：EP3362094B1

  公开（公告）日：2021-02-17
• [EN] COMBINATION COMPRISING AN AMINOTHIOLESTER COMPOUND OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND A COMPOUND ABLE TO INCREASE THE H2O2 LEVEL IN CANCER CELLS OF A SUBJECT<br/>[FR] COMBINAISON COMPRENANT UN COMPOSÉ AMINOTHIOLESTER OU UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI ET UN COMPOSÉ CAPABLE D'AUGMENTER LE TAUX DE H2O2 DANS DES CELLULES CANCÉREUSES D'UN SUJET
  申请人：ADVANCED BIODESIGN

  公开号：WO2017064241A1

  公开（公告）日：2017-04-20

  Combination comprising an aminothiolester compound or a pharmaceutically acceptable salt thereof and a compound able to increase the H 2 0 2 level in cancer cells of a subject, for use as a medicament The present invention relates to a combination comprising an aminothiolester compound or a pharmaceutically acceptable salt thereof, in particular the S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, and more particularly the 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate, and a compound able to increase H 2 0 2 level in cancer cells of a subject, in particular for use for the treatment of cancer in a subject, wherein cancer cells of said subject do not overproduce H 2 0 2 in comparison to a control value and have a level of GSH below 5 nmol for 25000 cells.
• [EN] AMINOTHIOLESTER COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, FOR USE IN THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS D'AMINOTHIOLESTERS OU SELS DE QUALITÉ PHARMACEUTIQUE DE CEUX-CI POUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：ADVANCED BIODESIGN

  公开号：WO2017064247A1

  公开（公告）日：2017-04-20

  The present invention relates to the treatment of cancer in a subject, wherein cancer cells of said subject overproduce H 2 0 2 and have a level of GSH below 0,5 nmol for 25 000 cells, with aminothiolester compounds or pharmaceutically acceptable salts thereof, in particular with S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, more particularly with 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate. It also relates to a method for selecting a subject suffering from a cancer and who will most likely benefit from a treatment with aminothiolester compounds or pharmaceutically acceptable salts thereof, in particular with S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, more particularly with 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate.