3-(4-(trifluoromethyl)phenyl)isoindolin-1-one | 1357261-47-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 3-(4-(trifluoromethyl)phenyl)isoindolin-1-one
• 英文别名: 3-[4-(Trifluoromethyl)phenyl]isoindoline-1-one；3-[4-(trifluoromethyl)phenyl]-2,3-dihydroisoindol-1-one
• CAS: 1357261-47-2
• 化学式: C₁₅H₁₀F₃NO
• 分子量: 277.246
• InChiKey: RRXULQPNOAYJOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-(trifluoromethyl)phenyl)isoindolin-1-one 在 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)isoindoline-2-carboxamide
  参考文献：
  名称：

  Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists

  摘要：

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).

  DOI：

  10.1021/jm2013634
• 作为产物：
  描述：

  4-三氟甲基苯基溴化镁 在 三乙基硅烷 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 3-(4-(trifluoromethyl)phenyl)isoindolin-1-one
  参考文献：
  名称：

  EP3750885

  摘要：

  公开号：

文献信息

• COMPOUND HAVING BET INHIBITORY ACTIVITY AND PREPARATION METHOD AND USE THEREFOR
  申请人：Shanghai Haihe Pharmaceutical Co., Ltd.

  公开号：EP3750885A1

  公开（公告）日：2020-12-16

  The invention relates to the field of pharmaceutical chemistry. Specifically, the present invention relates to a series of BET (bromodomain and extra-terminal domain) inhibitors having a novel structure, particularly inhibitors targeting BRD4 (Bromodomain-containing protein 4), and a preparation method and use therefor. The structure thereof is shown in the following general formula (I). Said compounds or a stereoisomer, racemate, geometric isomer, tautomer, prodrug, hydrate, solvate, or crystal form thereof, or a pharmaceutically acceptable salt thereof, and the pharmaceutical compsosition thereof can be used for the treatment and/or prevention of related diseases mediated by bromodomain proteins.

  本发明涉及药物化学领域。具体地说，本发明涉及一系列具有新型结构的 BET（溴基二甲基和端外域）抑制剂，特别是针对 BRD4（含溴基二甲基蛋白 4）的抑制剂，以及其制备方法和用途。其结构如下通式（I）所示。所述化合物或其立体异构体、外消旋体、几何异构体、同分异构体、原药、水合物、溶液或晶体形式，或其药学上可接受的盐，以及其药物组合物可用于治疗和/或预防由溴基团蛋白介导的相关疾病。
• EP3750885
  申请人：——

  公开号：——

  公开（公告）日：——
• Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists
  作者：Nuria A. Tamayo、Yunxin Bo、Vijay Gore、Vu Ma、Nobuko Nishimura、Phi Tang、Hong Deng、Lana Klionsky、Sonya G. Lehto、Weiya Wang、Brad Youngblood、Jiyun Chen、Tiffany L. Correll、Michael D. Bartberger、Narender R. Gavva、Mark H. Norman

  DOI：10.1021/jm2013634

  日期：2012.2.23

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).