2-(4-iodophenyl)-2-phenyl-1,3,2-oxazaborolidin-3-ium-2-uide | 1435463-77-6

• 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: 2-(4-iodophenyl)-2-phenyl-1,3,2-oxazaborolidin-3-ium-2-uide
• 英文别名: 2-(4-Iodophenyl)-2-phenyl-1-oxa-3-azonia-2-boranuidacyclopentane；2-(4-iodophenyl)-2-phenyl-1-oxa-3-azonia-2-boranuidacyclopentane
• CAS: 1435463-77-6
• 化学式: C₁₄H₁₅BINO
• 分子量: 350.995
• InChiKey: KBSYJUUWVAIJOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.44
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  25.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,4-二碘苯 、 苯硼酸频哪醇酯 在 正丁基锂 作用下， 以 乙醚 、 正己烷 、 乙腈 为溶剂， 反应 5.75h， 生成 2-(4-iodophenyl)-2-phenyl-1,3,2-oxazaborolidin-3-ium-2-uide
  参考文献：
  名称：

  Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport

  摘要：

  2-Aminoethyl diphenylborinate (2-APB) is a known modulator of the IP3 receptor, the calcium ATPase SERCA, the calcium release-activated calcium channel Orai and TRP channels. More recently, it was shown that 2-APB is an efficient inhibitor of the epithelial calcium channel TRPV6 which is overexpressed in prostate cancer. We have conducted a structure-activity relationship study of 2-APB congeners to understand their inhibitory mode of action on TRPV6. Whereas modifying the aminoethyl moiety did not significantly change TRPV6 inhibition, substitution of the phenyl rings of 2-APB did. Our data show that the diaryl borinate moiety is required for biological activity and that the substitution pattern of the aryl rings can influence TRPV6 versus SOCE inhibition. We have also discovered that 2-APB is hydrolyzed and transesterified within minutes in solution. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.037

文献信息

• Synthesis and Pharmacological Characterization of 2-Aminoethyl Diphenylborinate (2-APB) Derivatives for Inhibition of Store-Operated Calcium Entry (SOCE) in MDA-MB-231 Breast Cancer Cells
  作者：Achille Schild、Rajesh Bhardwaj、Nicolas Wenger、Dominic Tscherrig、Palanivel Kandasamy、Jan Dernič、Roland Baur、Christine Peinelt、Matthias A. Hediger、Martin Lochner

  DOI：10.3390/ijms21165604

  日期：——

  significant therapeutic interest, as enhanced SOCE has been associated with several cancers, and mutations in STIM and Orai have been linked to immunodeficiency, autoimmune, and muscular diseases. 2-Aminoethyl diphenylborinate (2-APB) is a known modulator and depending on its concentration can inhibit or enhance SOCE. We have synthesized several novel derivatives of 2-APB, introducing halogen and other

  钙离子调节多种生理功能，包括细胞分化，增殖，肌肉收缩，神经传递和受精。内质网（ER）是主要的细胞内Ca2 +储存，诱导ER储存耗尽的细胞事件（例如，肌醇1,4,5-三磷酸（IP3）受体的激活）触发了重新填充过程，即储存操纵的钙进入（ SOCE）。它要求位于ER膜中的Ca2 +感应基质相互作用分子（STIM）与质膜（PM）中形成Orai蛋白的通道之间存在复杂的相互作用。生成的活性STIM / Orai复合物形成高度选择性的Ca2 +通道，可促进可测量的Ca2 +流入细胞质，随后通过浆/内质网钙ATPase（SERCA）连续补充ER。由于增强的SOCE与几种癌症有关，并且STIM和Orai的突变与免疫缺陷，自身免疫和肌肉疾病有关，因此STIM和Orai引起了广泛的治疗兴趣。2-氨基乙基二苯基硼酸酯（2-APB）是一种已知的调节剂，取决于其浓度，可以抑制或增强SOCE。我们已经合成了2-APB的
• Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport
  作者：Alexandre Hofer、Gergely Kovacs、Anna Zappatini、Michele Leuenberger、Matthias A. Hediger、Martin Lochner

  DOI：10.1016/j.bmc.2013.03.037

  日期：2013.6

  2-Aminoethyl diphenylborinate (2-APB) is a known modulator of the IP3 receptor, the calcium ATPase SERCA, the calcium release-activated calcium channel Orai and TRP channels. More recently, it was shown that 2-APB is an efficient inhibitor of the epithelial calcium channel TRPV6 which is overexpressed in prostate cancer. We have conducted a structure-activity relationship study of 2-APB congeners to understand their inhibitory mode of action on TRPV6. Whereas modifying the aminoethyl moiety did not significantly change TRPV6 inhibition, substitution of the phenyl rings of 2-APB did. Our data show that the diaryl borinate moiety is required for biological activity and that the substitution pattern of the aryl rings can influence TRPV6 versus SOCE inhibition. We have also discovered that 2-APB is hydrolyzed and transesterified within minutes in solution. (C) 2013 Elsevier Ltd. All rights reserved.