4-[3-(2,4-dichlorophenyl)-1H-pyrazol-5-yl]piperidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[3-(2,4-dichlorophenyl)-1H-pyrazol-5-yl]piperidine
• 英文别名: 4-[5-(2,4-dichlorophenyl)-2H-pyrazol-3-yl]piperidine
• 化学式: C₁₄H₁₅Cl₂N₃
• 分子量: 296.199
• InChiKey: FKEBRCPVZPTAMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-[3-(2,4-dichlorophenyl)-1H-pyrazol-5-yl]piperidine 、 (R)-(2-tert-butoxycarbonylamino-2-cyclohexyl-acetylamino)acetic acid pentafluorophenyl ester 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 [(R)-Cyclohexyl-(2-{4-[5-(2,4-dichloro-phenyl)-2H-pyrazol-3-yl]-piperidin-1-yl}-2-oxo-ethylcarbamoyl)-methyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Integrating Fragment Assembly and Biophysical Methods in the Chemical Advancement of Small-Molecule Antagonists of IL-2:  An Approach for Inhibiting Protein−Protein Interactions

  摘要：

  Fragment assembly has shown promise for discovering small-molecule antagonists for difficult targets, including protein-protein interactions. Here, we describe a process for identifying a 60 nM inhibitor of the interleukin-2 (IL-2)/IL-2 receptor (IL-2Ralpha) interaction. By use of fragment-based approaches, a compound with millimolar affinity was evolved to a hit series with low micromolar activity, and these compounds were optimized into a lead series with nanomolar affinity. Fragment assembly was useful not only for hit identification, but also for lead optimization. Throughout the discovery process, biophysical methods and structural biology demonstrated that compounds bound reversibly to IL-2 at the IL-2 receptor binding site.

  DOI：

  10.1021/jm049967u

文献信息

• Electrochemical Aminoxyl-Mediated α-Cyanation of Secondary Piperidines for Pharmaceutical Building Block Diversification
  作者：Alastair J. J. Lennox、Shannon L. Goes、Matthew P. Webster、Hannes F. Koolman、Stevan W. Djuric、Shannon S. Stahl

  DOI：10.1021/jacs.8b08145

  日期：2018.9.12

  Secondary piperidines are ideal pharmaceutical building blocks owing to the prevalence of piperidines in commercial drugs. Here, we report an electrochemical method for cyanation of the heterocycle adjacent to nitrogen without requiring protection or substitution of the N-H bond. The reaction utilizes ABNO (9-azabicyclononane N-oxyl) as a catalytic mediator. Electrochemical oxidation of ABNO generates

  由于哌啶在商业药物中的普遍存在，二级哌啶是理想的药物成分。在这里，我们报告了一种无需保护或取代 NH 键即可使与氮相邻的杂环氰化的电化学方法。该反应使用 ABNO（9-氮杂双环壬烷 N-氧基）作为催化介质。ABNO 的电化学氧化产生相应的氧代铵物质，促进 2°哌啶脱氢为环亚胺，然后加入氰化物。低电位介导的电解过程与哌啶环上的各种杂环和氧化敏感取代基相容，并能够合成非天然氨基酸。
• From Hit to Lead. Combining Two Complementary Methods for Focused Library Design. Application to μ Opiate Ligands
  作者：Rébecca Poulain、Dragos Horvath、Béatrice Bonnet、Christian Eckhoff、Béatrice Chapelain、Marie-Christine Bodinier、Benoît Déprez

  DOI：10.1021/jm010877o

  日期：2001.10.1

  Compound 1 obtained by random screening and displaying a micromolar activity on the mu opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.