4-(4-bromophenyl)-tetrahydro-2H-pyran-4-carboxylic acid methyl ester | 894399-90-7

• 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: 4-(4-bromophenyl)-tetrahydro-2H-pyran-4-carboxylic acid methyl ester
• 英文别名: 4-(4-bromophenyl)tetrahydropyran-4-carboxylic acid methyl ester；4-(4-Bromo-phenyl)-tetrahydro-pyran-4-carboxylic acid methyl ester；methyl 4-(4-bromophenyl)oxane-4-carboxylate
• CAS: 894399-90-7
• 化学式: C₁₃H₁₅BrO₃
• 分子量: 299.164
• InChiKey: QAOQGIOUFOTDFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-bromophenyl)-tetrahydro-2H-pyran-4-carboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 4-(4-bromophenyl)tetrahydro-2H-pyran-4-carboxylic acid chloride
  参考文献：
  名称：

  异羟肟酸酯AR-42的手性衍生物有效抑制I类HDAC酶和癌细胞的增殖。

  摘要：

  在多发性骨髓瘤，白血病和淋巴瘤的临床试验中，AR-42是组蛋白脱乙酰基酶（HDAC）的口服活性抑制剂。它几乎没有氢键供体和受体，但是是手性的2-芳基丁酸酯，可能易于消旋。我们报道了非手性AR-42类似物，其包含通过季碳原子连接的环烷基，对人类I类HDAC的效力提高了40倍（例如，JT86，IC 500.7 nM，HDAC1），对五种人类癌细胞系的细胞毒性增加了25倍，而对正常人类细胞的毒性降低了多达70倍。JT86在促进MM96L黑色素瘤细胞中乙酰化组蛋白H4积累方面比racAR-42强9倍。分子模型和结构-活性之间的关系支持四氢吡喃与HDAC1的结合，而四氢吡喃则是对酶表面水的疏水屏蔽。这种有效的I类HDAC抑制剂可在AR-42活跃的疾病（癌症，寄生虫感染，炎性疾病）中显示出益处。

  DOI：

  10.1021/acs.jmedchem.0c00230
• 作为产物：
  描述：

  2,2'-二溴二乙醚 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-(4-bromophenyl)-tetrahydro-2H-pyran-4-carboxylic acid methyl ester
  参考文献：
  名称：

  WO2006/68213

  摘要：

  公开号：

文献信息

• [EN] 1,3-DISUBSTITUTED-4-PHENYL-1 H-PYRIDIN-2-ONES<br/>[FR] 4-PHÉNYLE-1H-PYRIDINE-2-ONES 1,3-DISUBSTITUÉES
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2009033703A1

  公开（公告）日：2009-03-19

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors - subtype 2 ('mGluR2') which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新颖化合物，特别是根据式（I）的新型吡啶酮衍生物，其中所有基团如申请和权利要求中所定义。根据本发明的化合物是代谢型受体-亚型2（'mGluR2'）的阳性变构调节剂，用于治疗或预防与谷氨酸功能障碍相关的神经和精神疾病以及涉及代谢型受体mGluR2亚型的疾病。具体来说，这些疾病是中枢神经系统疾病，包括焦虑、精神分裂症、偏头痛、抑郁症和癫痫等。该发明还涉及制备这种化合物和组合物的药物组合物和过程，以及利用这种化合物预防和治疗涉及mGluR2的疾病。
• Glycine Derivative and Use Thereof
  申请人：Hirano Noriyuki

  公开号：US20080085910A1

  公开（公告）日：2008-04-10

  A glycine derivative which is, e.g., the following compound (Chemical formula (1)). It is highly effective in the treatment and prevention of inflammatory bowel diseases. Compared to conventional compounds, the compound is excellent in absorbability in oral administration and in vivo stability. The compound can be orally administered and can retain an excellent therapeutic or preventive effect over a longer period.

  一种甘氨酸衍生物，例如以下化合物（化学式（1））。它在治疗和预防炎症性肠病方面非常有效。与传统化合物相比，该化合物在口服吸收和体内稳定性方面表现出色。该化合物可以口服给药，并能在较长时间内保持出色的治疗或预防效果。
• Therapeutic or prophylactic agent for multiple sclerosis
  申请人：Toray Industries, Inc.

  公开号：US07879837B2

  公开（公告）日：2011-02-01

  A therapeutic or prophylactic agent for multiple sclerosis is disclosed. The therapeutic or prophylactic agent comprises as an effective ingredient a glycine derivative having a specific structure or a pharmaceutically acceptable salt thereof, for example, the below-described compound [(E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid]. The therapeutic or prophylactic agent for multiple sclerosis according to the present invention shows the excellent absorbability and in vivo stability when orally administered, and exhibits high therapeutic or prophylactic effects.

  本发明揭示了一种治疗或预防多发性硬化的药剂。该治疗或预防药剂包含一种具有特定结构的甘氨酸衍生物或其药学上可接受的盐作为有效成分，例如下述化合物 [(E)-2-(2,6-二氯苯甲酰氨基)-5-[4-(异丙基嘧啶-2-基氨基)苯基]戊-4-烯酸]。本发明的治疗或预防多发性硬化的药剂口服时表现出优异的吸收性和体内稳定性，并表现出高疗效或预防效果。
• 1,3-DISUBSTITUTED-4-PHENYL-1H-PYRIDIN-2-ONES
  申请人：Cid-Nunez Jose Maria

  公开号：US20100240706A1

  公开（公告）日：2010-09-23

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors—subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新型化合物，特别是根据公式(I)定义的新型吡啶酮衍生物，其中所有基团均如本申请和权利要求中所定义。本发明的化合物是代谢型受体亚型2（“mGluR2”）的阳性变构调节剂，可用于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及涉及代谢型受体亚型mGluR2的疾病。特别地，这些疾病是选择自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病的一组。本发明还涉及制备此类化合物和组合物的制药组合和过程，以及使用此类化合物预防和治疗涉及mGluR2的上述疾病。
• Therapeutic or prophylactic agent for leukemia
  申请人：Toray Industries, Inc.

  公开号：US07893046B2

  公开（公告）日：2011-02-22

  A therapeutic or prophylactic agent for leukemia is disclosed. The therapeutic or prophylactic agent comprises as an effective ingredient a glycine derivative having a specific structure or a pharmaceutically acceptable salt thereof, for example, the below-described compound [(E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid]. The therapeutic or prophylactic agent for leukemia according to the present invention shows the excellent absorbability and in vivo stability when orally administered, and exhibits prominent therapeutic or prophylactic effects.

  本发明揭示了一种治疗或预防白血病的药剂。该治疗或预防药剂包含一种具有特定结构的甘氨酸衍生物或其药学上可接受的盐作为有效成分，例如下述化合物[(E)-2-(2,6-二氯苯甲酰胺基)-5-[4-(异丙基嘧啶-2-基)苯基]戊-4-烯酸]。本发明的白血病治疗或预防药剂在口服后表现出优异的吸收性和体内稳定性，并展现出显著的治疗或预防效果。