(6-(Benzyl(methyl)amino)pyridin-3-yl)boronic acid | 1356239-98-9

• 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: (6-(Benzyl(methyl)amino)pyridin-3-yl)boronic acid
• 英文别名: [6-[benzyl(methyl)amino]pyridin-3-yl]boronic acid
• CAS: 1356239-98-9
• 化学式: C₁₃H₁₅BN₂O₂
• 分子量: 242.085
• InChiKey: MPRLSUCCTBCVJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  56.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-(4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile 、 (6-(Benzyl(methyl)amino)pyridin-3-yl)boronic acid 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 以65%的产率得到2-(3-(3-methoxy-5-methylphenyl)-4-(2-(6-(benzyl(methyl)amino)pyridin-3-yl)pyridin-4-yl)-1H-pyrazole-1-yl)acetonitrile
  参考文献：
  名称：

  Synthesis and in Vitro Screening of Phenylbipyridinylpyrazole Derivatives as Potential Antiproliferative Agents

  摘要：

  一系列苯基双吡啶基吡唑化合物通过2-(4-(2-氯吡啶-4-基)-3-(3-甲氧基-5-甲基苯基)-1H-吡唑-1-基)乙腈（4）与不同的6-取代吡啶-3-基硼酸的反应合成。最终化合物5a–j在美国国家癌症研究所（NCI）以10 µM的浓度筛选了超过60种肿瘤细胞系。根据NCI的结果，化合物5c和5h对NCI细胞系展现出广泛的活性，平均抑制率分别为53%和58%。化合物5e的表现有所不同，其在10 µM浓度下对白血病SR细胞系的生长抑制率达到96%，表现出高度选择性和效能。标准COMPARE分析在GI50水平上进行，结果显示当前三种化合物与三种已知抗癌药物之间的成对相关系数(PCC)高于0.6。化合物5e与美巴龙（NSC S336628）表现出较高的相关性，PCC值为0.631。化合物5h与二氯烯丙基溶碱素的PCC值为0.626，而化合物5i与二氯烯丙基溶碱素和N,N-二苄基道努霉素（NSC S268242）的PCC值分别为0.601和0.604。这三种标准药物通过两种主要机制发挥抗癌活性，即抑制拓扑异构酶 II 和抑制嘧啶核苷酸的生物合成，因此，化合物5a–j是针对不同人类恶性肿瘤的有希望的治疗剂。此外，还考虑了这些新合成衍生物的药物相似性和毒性预测。

  DOI：

  10.3390/molecules20011031

文献信息

• Design, synthesis and SAR investigation of thienosultam derivatives as ADAMTS-5 (aggrecanase-2) inhibitors
  作者：Masakazu Atobe、Naomi Maekawara、Masashi Kawanishi、Hiroko Suzuki、Eiichi Tanaka、Shiro Miyoshi

  DOI：10.1016/j.bmcl.2013.01.120

  日期：2013.4

  A series of 1,1-dioxothieno[2,3-d]isothiazole (thienosultam) derivatives were designed and synthesized as novel ADAMTS-5 inhibitors for an investigation into a side chain of thienosultam for the S1' pocket. The resulting compounds (19 and 24) show high ADAMTS-5 inhibition and other MMP selectivity, and these compounds show good oral bioavailability. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and in Vitro Screening of Phenylbipyridinylpyrazole Derivatives as Potential Antiproliferative Agents
  作者：Mohammad Al-Sanea、Ahmed Elkamhawy、Ahmed Zakaria、Byung Park、Youngjoo Kwon、So Lee、Sang Lee、In Kim

  DOI：10.3390/molecules20011031

  日期：——

  A series of phenylbipyridinylpyrazoles was synthesized through the reaction of 2-(4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile (4) with different 6-substituted pyridine-3-ylboronic acids. The final compounds 5a–j were screened at 10 µM against over 60 tumor cell lines at the U.S. National Cancer Institute (NCI). In light of the NCI results, compounds 5c and 5h showed a broad spectrum of activity against NCI cell lines with mean growth of 53% and 58%, respectively. Compound 5e behaved differently as it showed high degree of selectivity and potency by inhibiting 96% of growth of leukemia SR cell line at 10 µM. Standard COMPARE analyses were performed at the GI50 level and the results exhibit high correlation in the form of pairwise correlation coefficient (PCC) of more than 0.6 between three of the current compounds and three standard known anticancer agents. Compound 5e demonstrated high correlation levels with merbarone (NSC S336628) with a PCC value of 0.631. Compound 5h showed a considerably high PCC value of 0.626 with dichloroallyl lawsone, while compound 5i, showed PCC values of 0.601 and 0.604 with both dichloroallyl lawsone and N,N-dibenzyldaunomycin (NSC S268242), respectively. These three standard agents have anticancer activity via two major mechanism of actions, inhibition of topoisomerase II and inhibition of biosynthesis of pyrimidine nucleotides, therefore, compounds 5a–j are promising therapeutic agents for targeting different human malignancies. Prediction of drug-likeness and toxicity of these newly synthesized derivatives were also considered.

  一系列苯基双吡啶基吡唑化合物通过2-(4-(2-氯吡啶-4-基)-3-(3-甲氧基-5-甲基苯基)-1H-吡唑-1-基)乙腈（4）与不同的6-取代吡啶-3-基硼酸的反应合成。最终化合物5a–j在美国国家癌症研究所（NCI）以10 µM的浓度筛选了超过60种肿瘤细胞系。根据NCI的结果，化合物5c和5h对NCI细胞系展现出广泛的活性，平均抑制率分别为53%和58%。化合物5e的表现有所不同，其在10 µM浓度下对白血病SR细胞系的生长抑制率达到96%，表现出高度选择性和效能。标准COMPARE分析在GI50水平上进行，结果显示当前三种化合物与三种已知抗癌药物之间的成对相关系数(PCC)高于0.6。化合物5e与美巴龙（NSC S336628）表现出较高的相关性，PCC值为0.631。化合物5h与二氯烯丙基溶碱素的PCC值为0.626，而化合物5i与二氯烯丙基溶碱素和N,N-二苄基道努霉素（NSC S268242）的PCC值分别为0.601和0.604。这三种标准药物通过两种主要机制发挥抗癌活性，即抑制拓扑异构酶 II 和抑制嘧啶核苷酸的生物合成，因此，化合物5a–j是针对不同人类恶性肿瘤的有希望的治疗剂。此外，还考虑了这些新合成衍生物的药物相似性和毒性预测。