N-[4'-(hydroxymethyl)biphenyl-4-yl]methanesulfonamide | 1268826-43-2

• 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: N-[4'-(hydroxymethyl)biphenyl-4-yl]methanesulfonamide
• 英文别名: N-[4-[4-(hydroxymethyl)phenyl]phenyl]methanesulfonamide
• CAS: 1268826-43-2
• 化学式: C₁₄H₁₅NO₃S
• 分子量: 277.344
• InChiKey: IRSNUHXJCOZMBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  74.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[4'-(hydroxymethyl)biphenyl-4-yl]methanesulfonamide 在 盐酸 、 三乙胺 作用下， 以 水 、 乙腈 为溶剂， 反应 12.0h， 生成 N-{4'-[(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methyl]-[1,1'-biphenyl]-4-yl}methanesulfonamide
  参考文献：
  名称：

  Design, Biological Evaluation, and Molecular Modeling of Tetrahydroisoquinoline Derivatives: Discovery of A Potent P-Glycoprotein Ligand Overcoming Multidrug Resistance in Cancer Stem Cells

  摘要：

  P-Glycoprotein is a well-known membrane transporter responsible for the efflux of an ample spectrum of anticancer drugs. Its relevance in the management of cancer chemotherapy is increased in view of its high expression in cancer stem cells, a population of cancer cells with strong tumor-promoting ability. In the present study, a series of compounds were synthesized through structure modulation of [4'-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-bipheny1-4-ol] (MC70), modifying the phenolic group of the lead compound. Among them, compound 513 emerged for its activity against the transporter (EC50 = 15 nM) and was capable of restoring doxorubicin antiproliferative activity at nontoxic concentration. Its behavior was rationalized through a molecular modeling study consisting of a well-tempered metadynamics simulation, which allowed one to identify the most favorable binding pose, and of a subsequent molecular dynamics run, which indicated a peculiar effect of the compound on the motion pattern of the transporter.

  DOI：

  10.1021/acs.jmedchem.8b01655
• 作为产物：
  描述：

  N-(4-溴苯基)甲基磺酰胺 、 4-羟甲基苯硼酸 在 palladium diacetate 、 二异丙胺 作用下， 以 水 为溶剂， 反应 2.0h， 以80%的产率得到N-[4'-(hydroxymethyl)biphenyl-4-yl]methanesulfonamide
  参考文献：
  名称：

  Design, Biological Evaluation, and Molecular Modeling of Tetrahydroisoquinoline Derivatives: Discovery of A Potent P-Glycoprotein Ligand Overcoming Multidrug Resistance in Cancer Stem Cells

  摘要：

  P-Glycoprotein is a well-known membrane transporter responsible for the efflux of an ample spectrum of anticancer drugs. Its relevance in the management of cancer chemotherapy is increased in view of its high expression in cancer stem cells, a population of cancer cells with strong tumor-promoting ability. In the present study, a series of compounds were synthesized through structure modulation of [4'-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-bipheny1-4-ol] (MC70), modifying the phenolic group of the lead compound. Among them, compound 513 emerged for its activity against the transporter (EC50 = 15 nM) and was capable of restoring doxorubicin antiproliferative activity at nontoxic concentration. Its behavior was rationalized through a molecular modeling study consisting of a well-tempered metadynamics simulation, which allowed one to identify the most favorable binding pose, and of a subsequent molecular dynamics run, which indicated a peculiar effect of the compound on the motion pattern of the transporter.

  DOI：

  10.1021/acs.jmedchem.8b01655

文献信息

• 17β-HSD2 inhibitors for the treatment of osteoporosis: Identification of a promising scaffold
  作者：Marie Wetzel、Sandrine Marchais-Oberwinkler、Rolf W. Hartmann

  DOI：10.1016/j.bmc.2010.12.013

  日期：2011.1

  17 beta-Hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) catalyses the conversion of active 17 beta-hydroxysteroids into the less active 17-ketosteroids thereby controlling the availability of biologically active estrogens (E2) and androgens (T) in the tissues. The skeletal disease osteoporosis occurs mainly in post-menopausal women and in elderly men when the levels of estrogens and androgens, respectively, decrease. Since 17 beta-HSD2 is present in osteoblasts, inhibition of this enzyme may provide a new and promising approach to prevent the onset of osteoporosis, keeping a certain level in estrogens and androgens in bone cells of ageing people. Hydroxynaphthyl, hydroxyphenyl and hydroxymethylphenyl-substituted moieties were synthesised as mimetics of the steroidal substrate. Compound 8 has been identified as promising scaffold for 17 beta-HSD2 inhibitors displaying high activity and good selectivity toward 17 beta-HSD1, ER alpha and ER beta. (C) 2010 Elsevier Ltd. All rights reserved.
• Design, Biological Evaluation, and Molecular Modeling of Tetrahydroisoquinoline Derivatives: Discovery of A Potent P-Glycoprotein Ligand Overcoming Multidrug Resistance in Cancer Stem Cells
  作者：Chiara Riganti、Marialessandra Contino、Stefano Guglielmo、Maria G. Perrone、Iris C. Salaroglio、Vladan Milosevic、Roberta Giampietro、Francesco Leonetti、Barbara Rolando、Loretta Lazzarato、Nicola A. Colabufo、Roberta Fruttero

  DOI：10.1021/acs.jmedchem.8b01655

  日期：2019.1.24

  P-Glycoprotein is a well-known membrane transporter responsible for the efflux of an ample spectrum of anticancer drugs. Its relevance in the management of cancer chemotherapy is increased in view of its high expression in cancer stem cells, a population of cancer cells with strong tumor-promoting ability. In the present study, a series of compounds were synthesized through structure modulation of [4'-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-bipheny1-4-ol] (MC70), modifying the phenolic group of the lead compound. Among them, compound 513 emerged for its activity against the transporter (EC50 = 15 nM) and was capable of restoring doxorubicin antiproliferative activity at nontoxic concentration. Its behavior was rationalized through a molecular modeling study consisting of a well-tempered metadynamics simulation, which allowed one to identify the most favorable binding pose, and of a subsequent molecular dynamics run, which indicated a peculiar effect of the compound on the motion pattern of the transporter.