4-(4-溴苯基)四氢-2H-吡喃-4-羧酸 | 1152567-60-6

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 烃类卤化物
• 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-(4-溴苯基)四氢-2H-吡喃-4-羧酸
• 中文别名: 4-(4-溴苯基)四氢吡喃-4-甲酸
• 英文名称: 4-(4-bromophenyl)tetrahydro-2H-pyran-4-carboxylic acid
• 英文别名: 4-(4-Bromophenyl)oxane-4-carboxylic acid
• CAS: 1152567-60-6
• 化学式: C₁₂H₁₃BrO₃
• mdl: MFCD10693768
• 分子量: 285.137
• InChiKey: VTAWBRQRLDUOOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-(4-溴苯基)四氢-2H-吡喃-4-羧酸 在 四(三苯基膦)钯 氯化亚砜 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4-(4-Cyanophenyl)-N,N-dimethyl-tetrahydro-2H-pyran-4-carboxamide
  参考文献：
  名称：

  HETEROAROMATIC COMPOUNDS FOR USE AS HIF INHIBITORS

  摘要：

  本申请涉及新型取代芳基化合物，其制备方法，它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防过度增殖和血管生成性疾病以及那些由于代谢适应缺氧状态而引起的疾病。这种治疗可以作为单独治疗进行，也可以与其他药物或进一步的治疗措施结合使用。

  公开号：

  US20110301122A1
• 作为产物：
  描述：

  4-溴苯乙酸甲酯 在 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 mineral oil 为溶剂， 反应 21.17h， 生成 4-(4-溴苯基)四氢-2H-吡喃-4-羧酸
  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

文献信息

• [EN] BIARYLAMIDE INHIBITORS OF LEUKOTRIENE PRODUCTION<br/>[FR] INHIBITEURS BIARYLAMIDE DE PRODUCTION DE LEUKOTRIÈNES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012082817A1

  公开（公告）日：2012-06-21

  The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, C, R1a, R1b, R2, R3, R4a and R4b are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式(I)的化合物及其药学上可接受的盐，其中A、B、C、R1a、R1b、R2、R3、R4a和R4b如本文所定义。该发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和疾病的方法，制备这些化合物的方法以及在这些过程中有用的中间体。
• HETEROCYCLIC COMPOUNDS AS INHIBITORS OF LEUKOTRIENE PRODUCTION
  申请人：BARTOLOZZI Alessandra

  公开号：US20130196967A1

  公开（公告）日：2013-08-01

  The present invention relates to compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R 1 -R 7 , A and HET are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式(I)的化合物： 或其药用可接受的盐，其中R1-R7、A和HET按本文定义。本发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和失调的方法，以及制备这些化合物和在这些过程中有用的中间体的方法。
• [EN] GEM-DISUBSTITUTED HETEROCYCLIC COMPOUNDS AND THEIR USE AS IDH INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES À DOUBLE SUBSTITUTION GEM ET LEUR UTILISATION EN TANT QU'INHIBITEURS D'IDH
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2021089395A1

  公开（公告）日：2021-05-14

  The present invention relates to certain gem-disubstituted heterocyclic compounds, which modulate the activity of Isocitrate Dehydrogenase (IDH). The compounds of this invention are therefore useful in treating diseases caused by mutated IDH1 and/or mutated IDH2 enzyme and/or IDH1 wild type (wt) enzyme. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.

  本发明涉及某些宝石二取代杂环化合物，其调节异柠檬酸脱氢酶（IDH）的活性。因此，本发明的化合物在治疗由突变的IDH1和/或突变的IDH2酶和/或IDH1野生型（wt）酶引起的疾病方面是有用的。本发明还提供了制备这些化合物的方法，包括这些化合物的药物组合物，以及利用包含这些化合物的药物组合物治疗疾病的方法。
• Design, Synthesis, and Biological Evaluation of Sulfonyl Acrylonitriles as Novel Inhibitors of Cancer Metastasis and Spread
  作者：Yi Shen、Craig A. Zificsak、Jill E. Shea、Xuegang Lao、Oana Bollt、Xiufen Li、Joseph G. Lisko、Jay P. Theroff、Courtney L. Scaife、Mark A. Ator、Bruce A. Ruggeri、Bruce D. Dorsey、Scott K. Kuwada

  DOI：10.1021/jm501437v

  日期：2015.2.12

  The spread of intra-abdominal cancers is a vexing clinical problem for which there is no widely effective treatment. We discovered previously that (2E)-3-[(4-tert-butylphenyl)sulfonyl]acrylonitrile (1) induced cancer cell apoptosis during adhesion to normal mesothelial cells which line the peritoneum. We recently demonstrated that the sulfonylacrylonitrile portion of 1 and hydrophobic aryl substitution were essential for pro-apoptotic activity in cancer cells. Here we synthesized a diverse series of analogues of 1 in order to improve the efficacy and pharmaceutical properties. Analogues and 1 were compared in their ability to cause cancer cell death during adhesion to normal mesothelial cell monolayers. Potent analogues identified in the in vitro assay were validated and found to exhibit improved inhibition of intra-abdominal cancer in two clinically relevant murine models of ovarian and pancreatic cancer spread and metastasis, highlighting their potential clinical use as an adjunct to surgical resection of cancers.
• 2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety
  作者：Robert L. Dow、Mark Ammirati、Scott W. Bagley、Samit K. Bhattacharya、Leonard Buckbinder、Christian Cortes、Ayman F. El-Kattan、Kristen Ford、Gary B. Freeman、Cristiano R. W. Guimarães、Shenping Liu、Mark Niosi、Athanasia Skoura、David Tess

  DOI：10.1021/acs.jmedchem.8b00152

  日期：2018.4.12

  Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a number of biological processes and/or diseases, including diabetes, cancer, inflammation, and angiogenesis. With a majority of the members of our lead series (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought design avenues that would eliminate this risk. One such approach arose from the observation that carboxylic acid-based intermediates employed in our discovery efforts retained high MAP4K4 inhibitory potency and were devoid of the TDI risk. The medicinal chemistry effort that led to the discovery of this central nervous system-impaired inhibitor together with its preclinical safety profile is described.