1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazole | 908228-44-4

• 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: 1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazole
• 英文别名: 1-[(2-chlorophenyl)methyl]-3,5-dimethylpyrazole
• CAS: 908228-44-4
• 化学式: C₁₂H₁₃ClN₂
• 分子量: 220.702
• InChiKey: PXPUTDXELSBHAY-UHFFFAOYSA-N

物化性质

• 沸点：
  341.7±30.0 °C(Predicted)
• 密度：
  1.15±0.1 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：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazole 在 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 60.0~75.0 ℃ 、900.02 kPa 条件下， 反应 23.83h， 生成 1-(((1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)methyl)(methyl)amino-3-(4-chlorophenoxy)propan-2-ol)
  参考文献：
  名称：

  Development of β-Amino Alcohol Derivatives That Inhibit Toll-like Receptor 4 Mediated Inflammatory Response as Potential Antiseptics

  摘要：

  Toll-like receptor 4 (TLR4) induced proinflammatory signaling has been directly implicated in severe sepsis and represents an attractive therapeutic target. Herein, we report our investigations into the structure-activity relationship and preliminary drug metabolism/pharmacokinetics study of beta-amino alcohol derivatives that inhibit the TLR4 signaling pathway. Lead compounds were identified from in vitro cellular examination with micromolar potency for their inhibitory effects on TLR4 signaling and subsequently assessed for their ability to suppress the TLR4-induced inflammatory response in an ex vivo whole blood model. In addition, the toxicology, specificity, solubility, brain-blood barrier permeability, and drug metabolism of several compounds were evaluated. Although further optimizations are needed, our findings lay the groundwork for the future drug development of this class of small molecule agents for the treatment of severe sepsis.

  DOI：

  10.1021/jm2003365
• 作为产物：
  描述：

  3,5-二甲基吡唑 、 邻氯氯苄 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 4.25h， 生成 1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazole
  参考文献：
  名称：

  一种取代苯酚β-氨基醇类衍生物及其制备方 法和用途

  摘要：

  本发明涉及一种取代苯酚β‑氨基醇类衍生物，其结构如下式所示：其中R1为取代的卤素原子、氨基、硝基、C1‑6烷基、C1‑6烷氧基，和C1‑6烷基中任意一个或多个取代基所取代，R2分别独立的选自苯基、苄基、取代的苄基、苯乙基、取代的苯乙基、苯丙基、以及取代的苯丙基，R3为取代的H，卤素原子、氨基、硝基、C1‑6烷基、C1‑6烷氧基，和C1‑6烷基中任意一个或多个取代基所取代。本发明还公开了其作为HCN通道抑制剂或TLR4抑制剂的用途，以及制备佐剂、抗炎、镇痛、心力衰竭的药物中的应用。

  公开号：

  CN109867627B

文献信息

• 一种咔唑β-氨基醇类衍生物及其制备方法和 用途
  申请人：南方医科大学

  公开号：CN109867662B

  公开（公告）日：2020-08-14

  本发明涉及一种咔唑β‑氨基醇类衍生物，其药物组合物、制备方法及用途。本发明化合物能够有效的抑制toll样受体4的活性及水平和对HCN通道亚型有抑制作用，其中具体公开了6种化合物，并公开了所述的化合物及其可药用接受的盐在制备TLR4受体抑制剂及应用为佐剂、抗炎、肿瘤免疫等方面的应用。其结构如下式所示：其中R1为取代的卤素原子、氨基、硝基、C1‑6烷基、C1‑6烷氧基，和C1‑6烷基中任意一个或多个取代基所取代，R2为取代的H，卤素原子、氨基、硝基、C1‑6烷基、C1‑6烷氧基，和C1‑6烷基中任意一个或多个取代基所取代。n为1，2，3或4。
• Method for Treating Scleroderma
  申请人：The Regents of the University of Colorado, A body corporate

  公开号：US20150087682A1

  公开（公告）日：2015-03-26

  The present invention provides a method for treating scleroderma by administering a therapeutically effective amount of a toll like receptor 4 inhibitor to a subject in need of such a treatment.

  本发明提供了一种治疗硬皮病的方法，通过向需要此类治疗的受试者施用治疗有效量的Toll样受体4抑制剂。
• TOLL-LIKE RECEPTOR MODULATORS AND USES THEREOF
  申请人：Yin Hang

  公开号：US20120178774A1

  公开（公告）日：2012-07-12

  The present invention provides a compound selected from the group consisting of: where n, m, X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 11 , R 12 , Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 are those defined herein. Some aspects of the invention also provides methods for using these compounds and compositions comprising the same.

  本发明提供了从以下组中选择的化合物：其中n，m，X1，X2，X3，X4，R1，R2，R3，R11，R12，Y1，Y2，Y3，Y4和Y5如本文所定义。本发明的某些方面还提供了使用这些化合物的方法和包含它们的组合物。
• Toll-like receptor modulators and uses thereof
  申请人：Yin Hang

  公开号：US08642614B2

  公开（公告）日：2014-02-04

  The present invention provides a compound of the formula: where n, m, X1, X2, X3, X4, R1, R2 and R3 are those defined herein. Some aspects of the invention also provides methods for using these compounds and compositions comprising the same.

  本发明提供了一个化合物的公式：其中n，m，X1，X2，X3，X4，R1，R2和R3如本文所定义。本发明的某些方面还提供了使用这些化合物的方法和包含相同化合物的组合物。
• Discovery of novel small molecule TLR4 inhibitors as potent anti-inflammatory agents
  作者：Yao Xu、Shujun Chen、Ying Cao、Pingzheng Zhou、Zhipeng Chen、Kui Cheng

  DOI：10.1016/j.ejmech.2018.05.033

  日期：2018.6

  Toll-like receptor 4 (TLR4) initiates innate immune response to release inflammatory cytokines and has been pathologically linked to variety of inflammatory diseases. Recently, we found that Carvedilol, as the classic anti-heart failure and anti-inflammatory clinic drug, could inhibit the TLR4 signaling in the TLR4 overexpressed cells. Herein, we have designed and synthesized a small library of novel Carvedilol derivatives and investigated their potential inhibitory activity. The results indicate that the most potent compound 8a (SMU-XY3) could effectively inhibited TLR4 protein and the LPS triggered alkaline phosphatase signaling in HEK-Blue hTLR4 cells. It down regulated the nitric oxide (NO) in both RAW264.7 cells and BV-2 microglial cells, in addition to blocking the TNF-alpha signaling in ex-vivo human peripheral blood mononuclear cells (PBMC). More interestingly, 8a shows higher affinity to hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) over HCN2, which probably indicates the new application of TLR4 inhibitor 8a in heart failure, coronary heart disease, and other inflammatory diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.