3-吡咯硼酸 | 763120-55-4

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 3-吡咯硼酸
• 英文名称: (1H-pyrrol-3-yl)boronic acid
• 英文别名: 3-Pyrrolylboronic acid；1H-pyrrol-3-ylboronic acid
• CAS: 763120-55-4
• 化学式: C₄H₆BNO₂
• mdl: MFCD09751320
• 分子量: 110.908
• InChiKey: ZITITTQOWAPHDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.65
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.2
• 氢给体数：
  3
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  6-(4-(1-(2-(azetidin-1-yl)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(1H-pyrazol-4-yl)pyrimidin-4-amine 、 3-吡咯硼酸 在 tert-butyl 作用下， 生成 6-(4-(1-(2-(azetidin-1-yl)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(1H-pyrrol-3-yl)pyrimidin-4-amine
  参考文献：
  名称：

  US20140343029A1

  摘要：

  公开号：

文献信息

• Nanoscale synthesis and affinity ranking
  作者：Nathan J. Gesmundo、Bérengère Sauvagnat、Patrick J. Curran、Matthew P. Richards、Christine L. Andrews、Peter J. Dandliker、Tim Cernak

  DOI：10.1038/s41586-018-0056-8

  日期：2018.5

  Most drugs are developed through iterative rounds of chemical synthesis and biochemical testing to optimize the affinity of a particular compound for a protein target of therapeutic interest. This process is challenging because candidate molecules must be selected from a chemical space of more than 1060 drug-like possibilities 1 , and a single reaction used to synthesize each molecule has more than 107 plausible permutations of catalysts, ligands, additives and other parameters 2 . The merger of a method for high-throughput chemical synthesis with a biochemical assay would facilitate the exploration of this enormous search space and streamline the hunt for new drugs and chemical probes. Miniaturized high-throughput chemical synthesis3–7 has enabled rapid evaluation of reaction space, but so far the merger of such syntheses with bioassays has been achieved with only low-density reaction arrays, which analyse only a handful of analogues prepared under a single reaction condition8–13. High-density chemical synthesis approaches that have been coupled to bioassays, including on-bead 14 , on-surface 15 , on-DNA 16 and mass-encoding technologies 17 , greatly reduce material requirements, but they require the covalent linkage of substrates to a potentially reactive support, must be performed under high dilution and must operate in a mixture format. These reaction attributes limit the application of transition-metal catalysts, which are easily poisoned by the many functional groups present in a complex mixture, and of transformations for which the kinetics require a high concentration of reactant. Here we couple high-throughput nanomole-scale synthesis with a label-free affinity-selection mass spectrometry bioassay. Each reaction is performed at a 0.1-molar concentration in a discrete well to enable transition-metal catalysis while consuming less than 0.05 milligrams of substrate per reaction. The affinity-selection mass spectrometry bioassay is then used to rank the affinity of the reaction products to target proteins, removing the need for time-intensive reaction purification. This method enables the primary synthesis and testing steps that are critical to the invention of protein inhibitors to be performed rapidly and with minimal consumption of starting materials. A system that combines nanoscale synthesis and affinity ranking enables high-throughput screening of reaction conditions and bioactivity for a given protein target, accelerating the process of drug discovery.

  大多数药物都是通过反复的化学合成和生化测试来开发，以优化特定化合物与治疗感兴趣的蛋白质靶点的亲和力。这一过程颇具挑战性，因为候选分子必须从超过10^60种类药物可能性的化学空间中选出，而用于合成每个分子的单一反应中催化剂、配体、添加剂和其他参数的合理排列组合超过10^7种。将高通量化学合成方法与生化分析方法相结合，将有助于探索这一巨大的搜索空间，并简化新型药物和化学探针的寻找过程。微型化高通量化学合成技术已经能够快速评估反应空间，但迄今为止，这种合成方法与生物分析方法的结合，仅限于低密度反应阵列，即在单一反应条件下仅分析少量类似物。高密度化学合成方法与生物分析方法相结合，包括使用珠子上、表面上、DNA上和质量编码等技术，大大减少了材料需求，但这些方法要求底物与潜在的反应性载体共价连接，必须在高度稀释的情况下进行，并且必须在混合物的形式下运作。这些反应特性限制了过渡金属催化剂的应用，因为过渡金属催化剂很容易受到复杂混合物中存在的多种官能团的毒害，而且对于动力学需要高浓度反应物的反应过程也不适用。本研究将高通量纳摩尔级合成与无标记的亲和选择质谱生物分析相结合，使得每个反应在0.1摩尔浓度的条件下进行，既可能实现过渡金属催化，又使得每个反应消耗的底物不足0.05毫克。然后，使用亲和选择质谱生物分析法对反应产物与靶蛋白的亲和力进行排序，省去了耗时的反应纯化步骤。该方法使得对蛋白质抑制剂发明至关重要的初级合成和测试步骤能够快速完成，且起始材料消耗最小。纳米级合成和亲和力排序相结合的系统可以实现对给定蛋白质靶点的反应条件和生物活性进行高通量筛选，从而加速药物发现过程。
• 吲哚类小分子C-MET抑制剂
  申请人：北京万全德众医药生物技术有限公司

  公开号：CN107311983A

  公开（公告）日：2017-11-03

  本发明属于医药技术领域，提供了用于治疗肺癌、乳腺癌、肾癌、胰腺癌、结肠直肠癌和胃癌等癌症的吲哚类化合物。
• Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7
  作者：Zheng-Song Gu、Wen-Tao Wang、Hao Qian、Ai-Nan Zhou、Hong-Bin Sun、Qing-Wei Zhang、Jian-Qi Li

  DOI：10.1016/j.bmcl.2019.126703

  日期：2019.12

  A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the

  合成了一系列新型的芳烷基哌嗪和哌啶衍生物，并评估了它们对5-羟色胺再摄取的抑制作用和5-HT 1A / 5-HT 7受体的亲和力活性。使用强制游泳测试（FST）和尾部悬浮测试（TST）筛选了选择性化合物的体内抗抑郁活性。结果表明，化合物19a对5-HT 1A / 5-HT 7受体（5-HT 1A，K i  = 12 nM； 5-HT 7，K i  = 3.2 nM）表现出高亲和力，并具有有效的5-羟色胺再摄取抑制作用。 （IC 50 = 14 nM），并在FST和TST模型中显示出明显的抗抑郁样作用。
• Rapid Syntheses of Heteroaryl-Substituted Imidazo[1,5-<i>a</i>]indole and Pyrrolo[1,2-<i>c</i>]imidazole via Aerobic C2–H Functionalizations
  作者：Wei-Jun Kong、Xingrong Chen、Mingming Wang、Hui-Xiong Dai、Jin-Quan Yu

  DOI：10.1021/acs.orglett.7b03596

  日期：2018.1.5

  Here we report an aerobic Pd(0) catalyzed C2–H functionalization of indoles and pyrroles with tethered N-methoxylamide as the directing group. A Pd(0)-initiated mechanism overcomes the directing or poisoning effect from a wide range of heterocycles including pyridine, pyrimidine, and thiazole. The imidazo[1,5-a]indole products are transformed to bioactive analogs after one-step manipulations, demonstrating

  在这里我们报告了一个有氧的Pd（0）催化的吲哚和吡咯的C2-H官能化，其中N-甲氧基酰胺为连接基团。Pd（0）引发的机制克服了包括吡啶，嘧啶和噻唑在内的各种杂环的直接或中毒作用。一步操作后，咪唑并[1,5- a ]吲哚产物转化为生物活性类似物，证明了该反应在药物发现中的潜在效用。
• Identification of Piperidine-3-carboxamide Derivatives Inducing Senescence-like Phenotype with Antimelanoma Activities
  作者：Sangmi Oh、Do Yoon Kwon、Inhee Choi、Young Mi Kim、Ji Young Lee、Jiyoung Ryu、Hangyeol Jeong、Myung Jin Kim、Rita Song

  DOI：10.1021/acsmedchemlett.0c00570

  日期：2021.4.8

  commercially available small-molecule libraries with high-throughput screening and high-content screening image-based technology. Our findings showed an initial hit with the embedded N-arylpiperidine-3-carboxamide scaffold-induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. A focused library containing diversely modified analogues were constructed

  本研究评估了诱导衰老的小分子在治疗黑色素瘤中的潜在用途。我们使用高通量筛选和基于图像的高内涵筛选技术筛选了市售的小分子文库。我们的研究结果表明，嵌入的N -arylpiperidine-3-carboxamide 支架诱导人黑色素瘤 A375 细胞的衰老样表型变化对正常细胞没有严重的细胞毒性。构建并检查了一个包含多种修饰类似物的重点文库，以评估从命中1开始的N-芳基哌啶-3-甲酰胺衍生物的构效关系。这项工作确定了一种具有显着抗增殖活性的新型化合物体外并展示了其中的关键结构部分。