4-氯-3-(乙氧羰基)苯硼酸 | 874219-46-2

• 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 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氯-3-(乙氧羰基)苯硼酸
• 中文别名: 3-乙氧羰基-4-氯苯硼酸；4-氯-3-乙氧基羰基苯硼酸
• 英文名称: (4-chloro-3-(ethoxycarbonyl)phenyl)boronic acid
• 英文别名: (4-chloro-3-ethoxycarbonylphenyl)boronic acid
• CAS: 874219-46-2
• 化学式: C₉H₁₀BClO₄
• mdl: MFCD08235062
• 分子量: 228.44
• InChiKey: HYQMEDIXHJXOND-UHFFFAOYSA-N

物化性质

• 熔点：
  162-164

计算性质

• 辛醇/水分配系数(LogP)：
  2.65
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2931900090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5-[2-(4-bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-one 、 4-氯-3-(乙氧羰基)苯硼酸 生成 4,3'-Dichloro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-propyl]-biphenyl-3-carboxylic acid
  参考文献：
  名称：

  1,1,1-TRIFLUORO-2-HYDROXYPROPYL COMPOUNDS

  摘要：

  本发明涉及公式I的化合物，其中R1a到R1e和R2到R5如说明书和权利要求所定义，并且它们的药学上可接受的盐。这些化合物是糖皮质激素受体拮抗剂，可用于治疗和/或预防疾病，如糖尿病、血脂异常、肥胖症、高血压、心血管疾病、肾上腺失衡或抑郁症。

  公开号：

  US20100249139A1
• 作为产物：
  描述：

  5-溴-2-氯苯甲酸乙酯 在 1,1'-双(二苯基膦)二茂铁 、 sodium periodate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 ammonium acetate 、 potassium acetate 作用下， 以 1,4-二氧六环 、 水 、 丙酮 为溶剂， 反应 41.0h， 生成 4-氯-3-(乙氧羰基)苯硼酸
  参考文献：
  名称：

  Metal-Free Coupling of Saturated Heterocyclic Sulfonylhydrazones with Boronic Acids

  摘要：

  The coupling of aromatic moieties with saturated heterocyclic partners is currently an area of significant interest for the pharmaceutical industry. Herein, we present a procedure for the metal-free coupling of 4-, 5-, and 6-membered saturated heterocyclic p-methoxyphenyl (PMP) sulfonylhydrazones with aryl and heteroaromatic boronic acids. This procedure enables a simple, two-step synthesis of a range of functionalized sp(2)-sp(3) linked bicyclic building blocks, including oxetanes, piperidines, and azetidines, from their parent ketones.

  DOI：

  10.1021/jo402526z

文献信息

• 1,1,1-TRIFLUORO-2-HYDROXYPROPYL COMPOUNDS
  申请人：Hunziker Daniel

  公开号：US20100249139A1

  公开（公告）日：2010-09-30

  The present invention relates to compounds of formula I wherein R 1a to R 1e and R 2 to R 5 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are glucocorticoid receptor antagonists useful for the treatment and/or prevention of diseases such as diabetes, dyslipidemia, obesity, hypertension, cardiovascular diseases, adrenal imbalance or depression.

  本发明涉及以下式I的化合物 其中R 1a 至R 1e 和R 2 至R 5 如描述和权利要求中所定义，并且其药学上可接受的盐。这些化合物是糖皮质激素受体拮抗剂，可用于治疗和/或预防疾病，如糖尿病、血脂异常、肥胖、高血压、心血管疾病、肾上腺失调或抑郁症。
• Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents
  作者：Seneha Santoshi、Naresh Kumar Manchukonda、Charu Suri、Manya Sharma、Balasubramanian Sridhar、Silja Joseph、Manu Lopus、Srinivas Kantevari、Iswar Baitharu、Pradeep Kumar Naik

  DOI：10.1007/s10822-014-9820-5

  日期：2015.3

  We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity. The predictive binding free energy (ΔGbind, pred) of these derivatives (ranging from −5.568 to −5.970 kcal/mol) based on linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model showed improved binding affinity with tubulin compared to the lead compound, natural α-noscapine (−5.505 kcal/mol). Guided by the computational findings, these new biaryl type α-noscapine congeners were synthesized from 9-bromo-α-noscapine using optimized Suzuki reaction conditions for further experimental evaluation. The derivatives showed improved inhibition of the proliferation of human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human lung adenocarcinoma cells (A549), compared to natural noscapine. The cell cycle analysis in MCF-7 further revealed that these compounds alter the cell cycle profile and cause mitotic arrest at G2/M phase more strongly than noscapine. Tubulin binding assay revealed higher binding affinity to tubulin, as suggested by dissociation constant (Kd) of 126 ± 5.0 µM for 5a, 107 ± 5.0 µM for 5c, 70 ± 4.0 µM for 5d, and 68 ± 6.0 µM for 5e compared to noscapine (Kd of 152 ± 1.0 µM). In fact, the experimentally determined value of ΔGbind, expt (calculated from the Kd value) are consistent with the predicted value of ΔGbind, pred calculated based on LIE–SGB. Based on these results, one of the derivative 5e of this series was used for further toxicological evaluation. Treatment of mice with a daily dose of 300 mg/kg and a single dose of 600 mg/kg indicates that the compound does not induce detectable pathological abnormalities in normal tissues. Also there were no significant differences in hematological parameters between the treated and untreated groups. Hence, the newly designed noscapinoid, 5e is an orally bioavailable, safe and effective anticancer agent with a potential for the treatment of cancer and might be a candidate for clinical evaluation.

  我们通过将双芳基药性体（许多微管靶向天然抗癌化合物的主要结构成分）插入诺卡平的支架结构，战略性地设计了一系列诺卡平衍生物。通过分子对接、分子动力学模拟和结合自由能计算，研究了这些衍生物与α、β-微管蛋白异源二聚体的分子相互作用。预测的结合亲和力表明，新设计的 noscapinoids 能以更大的亲和力与微管蛋白结合。这些衍生物的预测结合自由能（ΔGbind，pred）（从-5.568到-5.970 kcal/mol）基于线性相互作用能（LIE）方法和表面广义博恩（SGB）连续溶解模型，与先导化合物天然α-莨菪碱（-5.505 kcal/mol）相比，与小管蛋白的结合亲和力有所提高。在计算结果的指导下，我们采用优化的铃木反应条件，从 9-溴-α-莨菪碱合成了这些新的双芳基型 α-莨菪碱同系物，并进行了进一步的实验评估。与天然莨菪碱相比，这些衍生物对人类乳腺癌细胞（MCF-7）、人类宫颈癌细胞（HeLa）和人类肺腺癌细胞（A549）增殖的抑制效果更好。在 MCF-7 细胞中进行的细胞周期分析进一步显示，这些化合物改变了细胞周期轮廓，并比诺卡品更强烈地导致有丝分裂停滞在 G2/M 期。5a的解离常数（Kd）为126 ± 5.0 µM，5a的解离常数（Kd）为107 ± 5.0 µM。0 µM，5d 为 70 ± 4.0 µM ，5e 为 68 ± 6.0 µM ，而诺卡平（Kd 为 152 ± 1.0 µM）。事实上，实验测定的 ΔGbind, expt 值（根据 Kd 值计算得出）与根据 LIE-SGB 计算得出的 ΔGbind, pred 预测值一致。基于这些结果，该系列中的一种衍生物 5e 被用于进一步的毒理学评估。对小鼠进行每日剂量为 300 mg/kg 和单次剂量为 600 mg/kg 的处理表明，该化合物不会在正常组织中诱发可检测到的病理异常。此外，治疗组和未治疗组之间的血液学参数也没有明显差异。因此，新设计的 5e 是一种口服生物利用度高、安全有效的抗癌剂，具有治疗癌症的潜力，可能成为临床评估的候选药物。
• 2,3-diaryl- or heteroaryl-substituted 1,1,1-trifluoro-2-hydroxypropyl compounds
  申请人：Hoffmann-La Roche Inc.

  公开号：US08268820B2

  公开（公告）日：2012-09-18

  The present invention relates to compounds of formula I wherein R1a to R1c, R2, R3 and R5 are as defined in the description and claims and R4 signifies a bicyclic heteroaryl group or a cyanophenyl group, as well as pharmaceutically acceptable salts thereof. The compounds are glucocorticoid receptor antagonists useful for the treatment and/or prevention of diseases such as diabetes, dyslipidemia, obesity, hypertension, cardiovascular diseases, adrenal imbalance or depression.

  本发明涉及以下式子的化合物：其中R1a至R1c、R2、R3和R5如说明书和权利要求中所定义，R4表示双环杂芳基或氰基苯基，以及其药学上可接受的盐。这些化合物是糖皮质激素受体拮抗剂，可用于治疗和/或预防糖尿病、血脂异常、肥胖症、高血压、心血管疾病、肾上腺失调或抑郁症等疾病。
• 2,3-DIARYL- OR HETEROARYL-SUBSTITUTED 1,1,1-TRIFLUORO-2-HYDROXYPROPYL COMPOUNDS
  申请人：Hunziker Daniel

  公开号：US20100249124A1

  公开（公告）日：2010-09-30

  The present invention relates to compounds of formula I wherein R 1a to R 1c , R 2 , R 3 and R 5 are as defined in the description and claims and R 4 signifies a bicyclic heteroaryl group or a cyanophenyl group, as well as pharmaceutically acceptable salts thereof. The compounds are glucocorticoid receptor antagonists useful for the treatment and/or prevention of diseases such as diabetes, dyslipidemia, obesity, hypertension, cardiovascular diseases, adrenal imbalance or depression.

  本发明涉及公式I的化合物，其中R1a到R1c，R2，R3和R5如描述和权利要求中所定义，R4表示一个双环杂芳基或氰基苯基，以及其药学上可接受的盐。这些化合物是糖皮质激素受体拮抗剂，可用于治疗和/或预防糖尿病、血脂异常、肥胖症、高血压、心血管疾病、肾上腺失衡或抑郁症等疾病。
• 1-HYDROXYIMINO-3-PHENYL-PROPANES
  申请人：Bissantz Caterina

  公开号：US20120010190A1

  公开（公告）日：2012-01-12

  This invention relates to novel 1-hydroxyimino-3-phenyl-propanes of the formula wherein R 1 to R 10 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may be used as medicaments for the treatment of diseases such as type II diabetes.

  本发明涉及一种新的1-羟基亚胺基-3-苯基-丙烷的化合物，其结构式如下： 其中R1至R10的定义见说明书和权利要求书，以及其制备的药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗2型糖尿病等疾病的药物。