N-(2-(2-phenyl-2H-tetrazol-5-yl)phenyl)-1-naphthamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(2-(2-phenyl-2H-tetrazol-5-yl)phenyl)-1-naphthamide
• 英文别名: N-[2-(2-phenyltetrazol-5-yl)phenyl]naphthalene-1-carboxamide
• 化学式: C₂₄H₁₇N₅O
• 分子量: 391.432
• InChiKey: XSDIDNPDOVZCQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(2-nitrophenyl)-2-phenyl-2H-tetrazole 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 20.0 ℃ 、300.01 kPa 条件下， 反应 1.0h， 生成 N-(2-(2-phenyl-2H-tetrazol-5-yl)phenyl)-1-naphthamide
  参考文献：
  名称：

  Structure activity relationships, multidrug resistance reversal and selectivity of heteroarylphenyl ABCG2 inhibitors

  摘要：

  An overexpression of the transmembrane ATP-binding cassette transporter G2 (ABCG2, BCRP) in cancer tissues is supposed to play a role in the multidrug resistance (MDR) of tumors resulting in an inefficient chemotherapy. Therefore, co-administration of selective and non-toxic ABCG2 inhibitors is a promising strategy for improving the efficacy of chemotherapy by blocking ABCG2-mediated export of the cytostatic drugs. In the present study, we designed a small library of 38 novel compounds containing a heteroaryl-phenyl scaffold possessing several (bioisosteric) moieties, and twelve new precursors. We investigated the library for ABCG2 inhibition, for the selectivity against MDR-involved efflux pump ABCBI (P-gp) and for toxicity. Structure activity relationship (SAR) studies revealed that, at least a phenylheteroaryl-phenylamide scaffold is necessary for observing an ABCG2 inhibition. 4-Methoxy-N-(2(2-(6-methoxypyridin-3-yl)-2H-tetrazol-5-yl)phenyl)benzamide (43) exhibited a high potency (IC50 = 61 nM)), selectivity, low intrinsic toxicity and reversed the ABCG2-mediated drug resistance in presence of only 0.1 mu M. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.01.012

文献信息

• Structure activity relationships, multidrug resistance reversal and selectivity of heteroarylphenyl ABCG2 inhibitors
  作者：Sebastian C. Köhler、Sahel Vahdati、Matthias S. Scholz、Michael Wiese

  DOI：10.1016/j.ejmech.2018.01.012

  日期：2018.2

  An overexpression of the transmembrane ATP-binding cassette transporter G2 (ABCG2, BCRP) in cancer tissues is supposed to play a role in the multidrug resistance (MDR) of tumors resulting in an inefficient chemotherapy. Therefore, co-administration of selective and non-toxic ABCG2 inhibitors is a promising strategy for improving the efficacy of chemotherapy by blocking ABCG2-mediated export of the cytostatic drugs. In the present study, we designed a small library of 38 novel compounds containing a heteroaryl-phenyl scaffold possessing several (bioisosteric) moieties, and twelve new precursors. We investigated the library for ABCG2 inhibition, for the selectivity against MDR-involved efflux pump ABCBI (P-gp) and for toxicity. Structure activity relationship (SAR) studies revealed that, at least a phenylheteroaryl-phenylamide scaffold is necessary for observing an ABCG2 inhibition. 4-Methoxy-N-(2(2-(6-methoxypyridin-3-yl)-2H-tetrazol-5-yl)phenyl)benzamide (43) exhibited a high potency (IC50 = 61 nM)), selectivity, low intrinsic toxicity and reversed the ABCG2-mediated drug resistance in presence of only 0.1 mu M. (C) 2018 Elsevier Masson SAS. All rights reserved.