3-甲氧基-5-(三氟甲基)苯甲酰氯 | 916420-92-3

• 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: 3-甲氧基-5-(三氟甲基)苯甲酰氯
• 英文名称: 3-methoxy-5-(trifluoromethyl) benzoyl chloride
• 英文别名: 3-Methoxy-5-(trifluoromethyl)benzoyl chloride
• CAS: 916420-92-3
• 化学式: C₉H₆ClF₃O₂
• mdl: MFCD09025410
• 分子量: 238.594
• InChiKey: IHMFMHOCMZSKNI-UHFFFAOYSA-N

物化性质

• 沸点：
  255.2±40.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  3-甲氧基-5-(三氟甲基)苯甲酰氯 在 吡啶 、 ammonium hydroxide 、 氯化亚砜 、 水 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 异丙醇 、 甲苯 为溶剂， 反应 24.0h， 生成 2-[3-methoxy-5-(trifluoromethyl)phenyl]-4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidine
  参考文献：
  名称：

  Crystal Structures of PI3Kα Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design

  摘要：

  The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3K alpha-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R-1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3K alpha-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3K alpha inhibitors.

  DOI：

  10.1021/ml400378e
• 作为产物：
  描述：

  3-甲氧基-5-(三氟甲基)苯甲酸 在 氯化亚砜 作用下， 反应 6.0h， 生成 3-甲氧基-5-(三氟甲基)苯甲酰氯
  参考文献：
  名称：

  Crystal Structures of PI3Kα Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design

  摘要：

  The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3K alpha-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R-1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3K alpha-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3K alpha inhibitors.

  DOI：

  10.1021/ml400378e

文献信息

• 3-AMINO-PYRIDINES AS GPBAR1 AGONISTS
  申请人：Bissantz Caterina

  公开号：US20120232051A1

  公开（公告）日：2012-09-13

  This invention relates to novel 3-aminopyridines of the formula wherein B 1 , B 2 and R 1 to R 6 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及以下结构的新型3-氨基吡啶： 其中B1、B2和R1至R6如描述和索赔中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗诸如2型糖尿病等疾病的药物。
• 3-amino-pyridines as GPBAR1 agonists
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US10385022B2

  公开（公告）日：2019-08-20

  This invention relates to novel 3-aminopyridines of the formula wherein B1, B2 and R1 to R6 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.

  本发明涉及新型 3-氨基吡啶，其式为 其中 B1、B2 和 R1 至 R6 如说明书和权利要求书中所定义，以及其药学上可接受的盐类。这些化合物是 GPBAR1 激动剂，可用作治疗 II 型糖尿病等疾病的药物。
• Optimization of a 1,3,4-oxadiazole series for inhibition of Ca2+/calmodulin-stimulated activity of adenylyl cyclases 1 and 8 for the treatment of chronic pain
  作者：Jatinder Kaur、Monica Soto-Velasquez、Zhong Ding、Ahmadreza Ghanbarpour、Markus A. Lill、Richard M. van Rijn、Val J. Watts、Daniel P. Flaherty

  DOI：10.1016/j.ejmech.2018.11.036

  日期：2019.1

  Adenylyl cyclases type 1 (AC1) and 8 (AC8) are group 1 transmembrane adenylyl cyclases (AC) that are stimulated by Ca2+/calmodulin. Studies have shown that mice depleted of AC1 have attenuated inflammatory pain response, while AC1 /AC8 double-knockout mice display both attenuated pain response and opioid dependence. Thus, AC1 has emerged as a promising new target for treating chronic pain and opioid abuse. We discovered that the 1,3,4-oxadiazole scaffold inhibits Ca2+/calmodulin-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in cells stably expressing either AC1 or AC8. We then carried out structure-activity relationship studies, in which we designed and synthesized 65 analogs, to modulate potency and selectivity versus each AC isoform in cells. Furthermore, molecular docking of the analogs into an AC1 homology model suggests the molecules may bind at the ATP binding site. Finally, a prioritized analog was tested in a mouse model of inflammatory pain and exhibited modest analgesic properties. In summary, our data indicate the 1,3,4-oxadiazoles represent a novel scaffold for the cellular inhibition of Ca2+/calmodulin-stimulated AC1- and AC8 CAMP and warrant further exploration as potential lead compounds for the treatment of chronic inflammatory pain. (C) 2018 Elsevier Masson SAS. All rights reserved.
• US8987307B2
  申请人：——

  公开号：US8987307B2

  公开（公告）日：2015-03-24
• [EN] 3-AMINO-PYRIDINES AS GPBAR1 AGONISTS<br/>[FR] 3-AMINOPYRIDINES EN TANT QU'AGONISTES DE GPBAR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012117000A1

  公开（公告）日：2012-09-07

  This invention relates to novel 3-aminopyridines of the formula (I) wherein B1, B2 and R1 to R6 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.