1,7-dicarba-closo-dodecarborane-1-carboxylic acid chloride | 40101-88-0

• 英文名称: 1,7-dicarba-closo-dodecarborane-1-carboxylic acid chloride
• 英文别名: 1,7-dicarba-closododecaborane-1-carbonyl chloride；m-carboranyl-C-carboxylic acid chloride；m-carborane-1-carboxylic chloride；m-carborane-1-carbonyl chloride
• CAS: 40101-88-0
• 化学式: C₃H₁₁B₁₀ClO
• 分子量: 206.683
• InChiKey: ONZUNUPZJSCMRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  2-氨基-4,5-二甲基噻唑 、 1,7-dicarba-closo-dodecarborane-1-carboxylic acid chloride 在 三乙胺 作用下， 以 乙腈 为溶剂， 以26 %的产率得到(Z)-N-[4,5-dimethylthiazole-2(3H)-ylidene](1,7-dicarba-closo-dodecaboranyl)-1-carboxamide
  参考文献：
  名称：

  高亲和力碳硼烷大麻素受体 2 型 PET 配体 [18F]LUZ5-d8 的开发

  摘要：

  深入探索了用于正电子发射断层扫描 (PET) 成像的 2 型大麻素受体 (CB 2 R) 放射性配体的开发。为了克服低代谢稳定性并同时增加已知CB 2 R放射性配体的结合亲和力，使用碳硼烷部分作为生物等排体。在这里，我们报道了基于碳硼烷的 1,8-萘啶酮和噻唑作为新型 CB 2 R 配体的合成和表征。所有测试的化合物均显示出低纳摩尔 CB 2 R 亲和力，与 ( Z )- N -[3-(4-氟丁基)-4,5-二甲基噻唑-2(3 H )-亚基]-(1,7-二碳酰氯) -十二硼烷)-甲酰胺 ( LUZ5 ) 表现出最高的亲和力 (0.8 nM)。使用自动放射合成仪以高放射化学产率和纯度获得化合物[ 18 F]LUZ5- d 8 。体内评估显示，与[ 18 F ]JHU94620 相比，[ 18 F ] LUZ5 - d 8的代谢稳定性得到改善。大鼠的 PET 实验显示，脾脏的摄取量较高，而大脑

  DOI：

  10.1021/acs.jmedchem.3c00195
• 作为产物：
  描述：

  m-carborane-1-carboxylic acid 在 五氯化磷 作用下， 以 甲苯 为溶剂， 以61 %的产率得到1,7-dicarba-closo-dodecarborane-1-carboxylic acid chloride
  参考文献：
  名称：

  高亲和力碳硼烷大麻素受体 2 型 PET 配体 [18F]LUZ5-d8 的开发

  摘要：

  深入探索了用于正电子发射断层扫描 (PET) 成像的 2 型大麻素受体 (CB 2 R) 放射性配体的开发。为了克服低代谢稳定性并同时增加已知CB 2 R放射性配体的结合亲和力，使用碳硼烷部分作为生物等排体。在这里，我们报道了基于碳硼烷的 1,8-萘啶酮和噻唑作为新型 CB 2 R 配体的合成和表征。所有测试的化合物均显示出低纳摩尔 CB 2 R 亲和力，与 ( Z )- N -[3-(4-氟丁基)-4,5-二甲基噻唑-2(3 H )-亚基]-(1,7-二碳酰氯) -十二硼烷)-甲酰胺 ( LUZ5 ) 表现出最高的亲和力 (0.8 nM)。使用自动放射合成仪以高放射化学产率和纯度获得化合物[ 18 F]LUZ5- d 8 。体内评估显示，与[ 18 F ]JHU94620 相比，[ 18 F ] LUZ5 - d 8的代谢稳定性得到改善。大鼠的 PET 实验显示，脾脏的摄取量较高，而大脑

  DOI：

  10.1021/acs.jmedchem.3c00195

文献信息

• Structure-based drug design of novel carborane-containing nicotinamide phosphoribosyltransferase inhibitors
  作者：Yasunobu Asawa、Kiyotaka Katsuragi、Akira Sato、Atsushi Yoshimori、Sei-ichi Tanuma、Hiroyuki Nakamura

  DOI：10.1016/j.bmc.2019.05.013

  日期：2019.7

  FK866-NAMPT complex (PDB code: 2GVJ) with replacing the boron atom type by the C3 atom type of carboranes predicted that the NAMPT inhibitory activity of 2c was improved by the hydrogen bond formation between the carborane amide and H191 of NAMPT. Although dicarborane compounds 38, 50, 51, and 55 were synthesize aiming to two hydrophobic pockets present in the binding pocket of NAMPT, their inhibitory activity

  根据化合物1的结构设计和合成了一系列含碳硼烷的NAMPT抑制剂，并使用NAMPT比色分析评估了NAMPT的抑制活性。在合成的化合物中，化合物2b和2c表现出显着的NAMPT抑制活性，IC50值分别为0.098±0.008和0.057±0.001 µM。使用FK866-NAMPT配合物（PDB代码：2GVJ）的晶体结构将化合物2与NAMPT的对接模拟，用硼烷的C3原子类型代替硼原子类型，这预示着氢键改善了2c的NAMPT抑制活性在碳硼烷酰胺和NAMPT的H191之间形成。尽管合成了二碳硼烷化合物38、50、51和55，目的是针对NAMPT结合口袋中存在的两个疏水口袋，
• Synthesis and 11C-Radiolabelling of 2-Carboranyl Benzothiazoles
  作者：Kiran Gona、Jaya Thota、Zuriñe Baz、Vanessa Gómez-Vallejo、Jordi Llop

  DOI：10.3390/molecules20057495

  日期：——

  Dicarba-closo-dodecaboranes, commonly known as carboranes, possess unique physico-chemical properties and can be used as hydrophobic moieties during the design of new drugs or radiotracers. In this work, we report the synthesis of two analogues of 2-(4-aminophenyl)benzothiazole (a compound that was found to elicit pronounced inhibitory effects against certain breast cancer cell lines in vitro) in which the phenyl ring has been substituted by a m-carborane cage. Two different synthetic strategies have been used. For the preparation of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-benzo-thiazole, the benzothiazole group was first introduced on one of the cluster carbon atoms of m-carborane and the amine group was further attached in three steps. For the synthesis of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-6-hydroxybenzothiazole, iodination was performed before introducing the benzothiazole group, and the amino group was subsequently introduced in six steps. Both compounds were radiolabelled with carbon-11 using [11C]CH3OTf as the labelling agent. Radiolabelling yields and radiochemical purities achieved should enable subsequent in vitro and in vivo investigations.

  二碳烯-封闭-十二硼烷，通常称为碳烷，具有独特的物理化学特性，可用于新药或放射性示踪剂设计中的疏水部分。在本研究中，我们报告了两种2-(4-氨基苯基)苯并噻唑的类似物的合成（该化合物在体外实验中被发现对某些乳腺癌细胞系具有显著的抑制作用），其中苯环被m-碳烷笼取代。采用了两种不同的合成策略。对于1-(9-氨基-1,7-二碳烯-封闭-十二硼烷-1-基)-苯并噻唑的制备，首先将苯并噻唑基团引入m-碳烷的一个簇碳原子上，然后通过三步进一步连接氨基。对于1-(9-氨基-1,7-二碳烯-封闭-十二硼烷-1-基)-6-羟基苯并噻唑的合成，在引入苯并噻唑基团之前进行了碘化处理，随后氨基通过六步引入。两种化合物均使用[11C]CH3OTf作为标记试剂进行了碳-11放射性标记。实现的放射性标记产率和放射化学纯度应能支持后续的体外和体内研究。
• Synthesis and<i>in vivo</i>evaluation of¹¹C-labeled (1,7-dicarba-<i>closo</i>-dodecaboran-1-yl)-<i>N</i>-{[(2<i>S</i>)-1-ethylpyrrolidin-2-yl]methyl}amide
  作者：Vanessa Gómez-Vallejo、Naiara Vázquez、Kiran Babu Gona、Maria Puigivila、Mikel González、Eneko San Sebastián、Abraham Martin、Jordi Llop

  DOI：10.1002/jlcr.3159

  日期：2014.4

  Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers because of their hydrophobic character, spherical structure, and excellent chemical and photochemical stability. In the present paper, the synthesis and in vivo evaluation of 11C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide, an analog of the D2 receptor ligand [11C]raclopride, is described. The radiosynthesis was approached by reaction of the demethylated precursor with [11C]CH3I in basic media; moderate radiochemical yields (18.2 ± 2.8%, decay corrected), and excellent radiochemical purities (>98%) were obtained in overall synthesis time of ~50 min. In vivo assays showed a biodistribution pattern with significant uptake in liver, kidneys and lungs at short times (t = 4 min) after administration and increasing accumulation in bladder at longer times (t ≥ 14.5 min). Although brain positron emission tomography scans showed good blood brain barrier penetration, the high unspecific uptake observed in different brain regions impedes its applicability as D2 receptor ligand. Copyright © 2013 John Wiley & Sons, Ltd.

  硼簇，特别是二碳闭合十二硼烷，可以作为疏水性药效团用于新药和放射性示踪剂的设计，这得益于它们的疏水特性、球形结构以及优秀的化学和光化学稳定性。本文描述了标记有11C的(1,7-二碳闭合十二硼烷-1-基)-N-[(2S)-1-乙基吡咯烷-2-基]甲基}酰胺的合成及其体内评估，该化合物是D2受体配体[11C]拉克普酮的类似物。放射合成是通过去甲基化前体与[11C]CH3I在碱性介质中反应来实现的；整体合成时间约为50分钟，获得了中等的放射化学产率（18.2 ± 2.8%，衰变校正）和优异的放射化学纯度（>98%）。体内实验显示，给药后短时间（t = 4分钟）在肝脏、肾脏和肺部有显著的摄取，并且在较长时间（t ≥ 14.5分钟）后在膀胱中累积增加。尽管脑正电子发射断层显像扫描显示良好的血脑屏障穿透能力，但在不同脑区观察到的高非特异性摄取限制了其作为D2受体配体的应用。版权 © 2013 John Wiley & Sons, Ltd.
• Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2‐Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres
  作者：Philipp Stockmann、Lydia Kuhnert、Tamara Krajnović、Sanja Mijatović、Danijela Maksimović‐Ivanić、Walther Honscha、Evamarie Hey‐Hawkins

  DOI：10.1002/cmdc.202300506

  日期：2024.1.15

  Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP‐binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP‐mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron‐carbon cluster, namely closo‐dicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2‐phenylquinazolin‐4‐amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta‐methoxylated N‐carboranyl‐2‐phenylquinazolin‐4‐amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP‐mediated mitoxantrone resistance in MDCKII‐hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2‐overexpressing cancers.

  摘要多药耐药性是临床癌症治疗的一大挑战。特别是某些ATP结合盒（ABC）转运蛋白的过度表达，如外排转运蛋白ABCG2（又称乳腺癌耐药蛋白（BCRP）），与癌症治疗中化疗药物耐药性的产生有关，因此靶向抑制BCRP介导的转运可能会导致这种（多药）耐药性（MDR）的逆转。在之前的一项研究中，我们介绍了在聚甲氧基化的 2-苯基喹唑啉-4-胺骨架中引入硼碳簇，即闭合二碳化十二硼烷或碳硼烷，作为无机药基。在这项工作中，研究范围扩展到了相应的酰胺衍生物。由于大多数酰胺衍生物的溶解性较差，只有酰胺衍生物 QCe 和两种胺衍生物 DMQCc 和 DMQCd 得到了进一步研究。硼烷通常被认为是对立体要求较高的苯基模拟物或异构体。因此，我们还研究了最有前途的碳硼烷衍生物的有机苯基和立体要求苛刻的金刚烷基类似物。研究表明，之前描述的五甲氧基化 N-硼烷基-2-苯基喹唑啉-4-胺 DMQCd 在细胞毒性、抑制人类 ABCG2 转运体以及逆转 BCRP 介导的米托蒽醌在 MDCKII-hABCG2 和 HT29 结肠癌细胞中的抗药性方面远远优于其有机类似物。我们的研究结果表明，DMQCd是一种很有希望的候选药物，可用于进一步的体外和体内研究，以联合治疗ABCG2表达缺失的癌症。
• Zvereva, T. D.; Yuvchenko, A. P.; Zhukovskaya, N. A., Journal of general chemistry of the USSR, 1992, vol. 62, p. 705 - 708
  作者：Zvereva, T. D.、Yuvchenko, A. P.、Zhukovskaya, N. A.

  DOI：——

  日期：——