4-trifluoromethyl-4-phenylpiperidine | 1254981-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-trifluoromethyl-4-phenylpiperidine
• 英文别名: 4-phenyl-4-(trifluoromethyl)piperidine
• CAS: 1254981-45-7
• 化学式: C₁₂H₁₄F₃N
• 分子量: 229.245
• InChiKey: UNZWJLQWPUTIDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-氯-3-(环丙基甲基)-7-碘-[1,2,4]三唑并[4,3-A]吡啶 、 4-trifluoromethyl-4-phenylpiperidine 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以39%的产率得到8-chloro-3-(cyclopropylmethyl)-7-(4-trifluoromethyl-4-phenyl-piperidin-1-yl)-1,2,4-triazolo[4,3-a]pyridine
  参考文献：
  名称：

  Discovery of 3-Cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): A Positive Allosteric Modulator of the Metabotropic Glutamate 2 Receptor

  摘要：

  Advanced leads from a series of 1,2,4-triazolo[4,3-a]pyridines with mGlu2 receptor PAM activity are reported. By modification of the analogous imidazo[1,2-a]pyridine series, the newly reported leads have improved potency, in vitro ADMET, and hERG as well as good in vivo PK profile. The optimization of the series focused on improving metabolic stability while controlling lipophilicity by introducing small modifications to the scaffold substituents. Analysis of this series combined with our previously reported mGlu2 receptor PAMs showed how lipophilic ligand efficiency was improved during the course of the program. Among the best compounds, example 20 (JNJ-42153605) showed a central in vivo efficacy by inhibition of REM sleep state at a dose of 3 mg/kg po in the rat sleep-wake EEG paradigm, a phenomenon shown earlier to be mGlu2 mediated. In mice, compound 20 reversed PCP-induced hyperlocomotion with an ED50 of 5.4 mg/kg sc, indicative of antipsychotic activity.

  DOI：

  10.1021/jm3010724
• 作为产物：
  描述：

  4-phenyl-4-trifluoromethyl-piperidine-2,6-dione 在 硼烷四氢呋喃络合物 、 盐酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 21.0h， 以64%的产率得到4-trifluoromethyl-4-phenylpiperidine
  参考文献：
  名称：

  [EN] 1,2,4-TRIAZOLO [4,3-A] PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
  [FR] DÉRIVÉS DE 1,2,3-TRIAZOLO[4,3-A]PYRIDINE ET LEUR UTILISATION POUR LE TRAITEMENT OU LA PRÉVENTION DE TROUBLES NEUROLOGIQUES ET PSYCHIATRIQUES

  摘要：

  公开号：

  WO2010130424A9

文献信息

• PYRIDAZINE COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3118200A1

  公开（公告）日：2017-01-18

  The present provides a pyridazine compound having an inhibiting effect on Stearoyl-CoA desaturase (SCD) (in particular, SCD1). The present provides a compound represented by formula (where each symbol is as defined as in the Specification) or a salt thereof

  本发明提供了一种对硬脂酰辅酶A去饱和酶（SCD）（特别是SCD1）具有抑制作用的吡啶啉化合物。本发明提供了一种由以下公式表示的化合物（其中每个符号如规范中定义）或其盐。
• Discovery of Novel and Potent Stearoyl Coenzyme A Desaturase 1 (SCD1) Inhibitors as Anticancer Agents
  作者：Keisuke Imamura、Naoki Tomita、Youichi Kawakita、Yoshiteru Ito、Kouji Ono、Noriyuki Nii、Tohru Miyazaki、Kazuko Yonemori、Michiko Tawada、Hiroyuki Sumi、Yoshihiko Satoh、Yukiko Yamamoto、Ikuo Miyahisa、Masako Sasaki、Yoshinori Satomi、Megumi Hirayama、Ryuichi Nishigaki、Hironobu Maezaki

  DOI：10.1016/j.bmc.2017.05.016

  日期：2017.7

  A lead compound A was identified previously as an stearoyl coenzyme A desaturase (SCD) inhibitor during research on potential treatments for obesity. This compound showed high SCD1 binding affinity, but a poor pharmacokinetic (PK) profile and limited chemical accessibility, making it suboptimal for use in anticancer research. To identify potent SCD1 inhibitors with more promising PK profiles, we newly

  在对肥胖症的潜在治疗方法进行研究期间，先前已将先导化合物A确定为硬脂酰辅酶A去饱和酶（SCD）抑制剂。该化合物显示出高的SCD1结合亲和力，但药代动力学（PK）谱较差，化学可及性有限，使其在抗癌研究中不理想。为了鉴定具有更富前景的PK谱的有效SCD1抑制剂，我们基于分子模型研究，新设计了一系列“非螺” 4,4-二取代哌啶衍生物。结果，我们发现了化合物1a，其保留了中等的SCD1结合亲和力。通过分析Hansch–Fujita和Hammett常数，加快了1a附近的优化，以获得4-苯基-4-（三氟甲基）哌啶衍生物1n。对1n的唑部分进行微调，得到化合物1o（T-3764518），该化合物保留了纳摩尔摩尔亲和力并表现出出色的PK分布。口服化合物1o反映了良好的药效和PK曲线，在HCT116小鼠异种移植模型中显示出显着的药效学（PD）标记降低（0.3 mg / kg，bid），在786-小鼠中抑制了肿瘤生长（以1
• 1,2,3-TRIAZOLO [4,3-A] PYRIDINE DERIVATIVES AND THIER USE FOR THE TREATMENT OF PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
  申请人：Cid-Nunez Jose Maria

  公开号：US20120184525A1

  公开（公告）日：2012-07-19

  The present invention relates to novel triazolo[4,3- a ]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor 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. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

  本发明涉及一种新型的三唑并[4,3-a]吡啶衍生物，其化学式为（I），其中所有基团均如权利要求中所定义。本发明中的化合物是代谢型谷氨酸受体亚型2（“mGluR2”）的正向变构调节剂，可用于治疗或预防与谷氨酸功能障碍有关的神经和精神障碍以及涉及代谢型受体的mGluR2亚型的疾病。本发明还涉及包含这些化合物的制药组合物，制备这些化合物和组合物的过程，以及使用这些化合物预防或治疗涉及mGluR2的神经和精神障碍和疾病的方法。
• 1,2,4-Triazolo [4,3-A] Pyridine Derivatives and Their Use For The Treatment of Prevention of Neurological and Psychiatric Disorders
  申请人：JANSSEN PHARMACEUTICALS, INC.

  公开号：US20150141403A1

  公开（公告）日：2015-05-21

  The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor 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. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

  本发明涉及一种新型的三唑并[4,3-a]吡啶衍生物，其化学式为（I），其中所有基团如权利要求所定义。本发明的化合物是代谢型谷氨酸受体亚型2（“mGluR2”）的正向变构调节剂，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。本发明还涉及包含这种化合物的制药组合物、制备这种化合物和组合物的过程，以及使用这种化合物预防或治疗涉及mGluR2的神经和精神障碍和疾病的方法。
• 1,2,4-triazolo [4,3-A] pyridine derivatives and their use for the treatment of neurological and psychiatric disorders
  申请人：JANSSEN PHARMACEUTICALS, INC.

  公开号：US10071095B2

  公开（公告）日：2018-09-11

  The present invention relates to methods of treating various central nervous system disorders using novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor 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. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

  本发明涉及使用式 (I) 的新型三唑并[4,3-a]吡啶衍生物治疗各种中枢神经系统疾病的方法 其中所有基团如权利要求中定义。根据本发明的化合物是代谢型谷氨酸受体亚型 2（"mGluR2"）的正异位调节剂，可用于治疗或预防与谷氨酸功能障碍相关的神经和精神疾病以及代谢型受体 mGluR2 亚型参与的疾病。本发明还涉及包含此类化合物的药物组合物、制备此类化合物和组合物的工艺，以及使用此类化合物预防或治疗涉及 mGluR2 的神经和精神障碍及疾病。