2-(4-氟-2-甲基苯基)-4-哌啶酮樟脑-10-磺酸酯 | 579475-69-7

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 中文名称: 2-(4-氟-2-甲基苯基)-4-哌啶酮樟脑-10-磺酸酯
• 英文名称: 2-(4-fluoro-2-methylphenyl)-4-piperidinone camphor-10-sulfonate
• 英文别名: 2-(4-fluoro-2-methyl-phenyl)-piperidine-4-one 10-camphorsulphonate；(7,7-Dimethyl-2-oxo-1-bicyclo[2.2.1]heptanyl)methanesulfonic acid;2-(4-fluoro-2-methylphenyl)piperidin-4-one
• CAS: 579475-69-7
• 化学式: C₁₀H₁₆O₄S*C₁₂H₁₄FNO
• 分子量: 439.548
• InChiKey: FIFMFFFYARUJID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-氟-2-甲基苯基)-4-哌啶酮樟脑-10-磺酸酯 在 碳酸氢钠 、 sodium carbonate 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 6.25h， 生成 (2R)-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4-oxo-1-piperidinecarboxamide
  参考文献：
  名称：

  Discovery and Biological Characterization of (2R,4S)-1′-Acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4′-bipiperidine-1-carboxamide as a New Potent and Selective Neurokinin 1 (NK₁) Receptor Antagonist Clinical Candidate

  摘要：

  A large body of compelling preclinical evidence supports the clinical use of neurokinin (NK) receptor antagonists in a plethora of CNS and non-CNS therapeutic areas. The significant investment made in this area over the past 2 decades culminated with the observation that NK1 receptor antagonists elicited clinical efficacy in major depression disorders. In addition, aprepitant (Merck) was launched as a new drug able to prevent chemotherapy-induced nausea and vomiting (CINV). After the discovery by GlaxoSmithKline of vestipitant, a wide drug discovery program was launched aimed at identifying additional clinical candidates. New compounds were designed to maximize affinity at the NK1 receptor binding site while retaining suitable physicochemical characteristics to ensure excellent pharmacokinetic and pharmacodynamic properties in vivo. Herein we describe the discovery process of a new NK1 receptor antagonist (casopitant) selected as clinical candidate and progressed into clinical studies to treat major depression disorders.

  DOI：

  10.1021/jm1013264
• 作为产物：
  描述：

  2-(4-fluoro-2-methyl-phenyl)-piperidine-4-one 以74的产率得到2-(4-氟-2-甲基苯基)-4-哌啶酮樟脑-10-磺酸酯
  参考文献：
  名称：

  Org. Process Res. Dev. 2010, 14, 832-839

  摘要：

  DOI：

文献信息

• Chemical compounds
  申请人：——

  公开号：US20040014770A1

  公开（公告）日：2004-01-22

  Formula (1) wherein R represents a halogen atom or a C 1-4 alkyl group; R 1 represents a C 1-4 alkyl group; R 2 represents hydrogen or a C 1-4 alkyl group; R 3 represents hydrogen, or a C 1-4 alkyl group; R 4 represents a trifluorometyl group; R 5 represents hydrogen, a C 1-4 alkyl group or C(0)R 6 ; R 6? represents C 1-4 alkyl, C 3-7 cycloalkyl, NH(C 1-4 alkyl) or N(C1-4alkyl) 2 ; m is zero or an integer from 1 to 3; n is an integer from 1 to 3 and pharmaceutically acceptable salts and solvates thereof; to processes for their preparation and their use in the treatment of conditions mediated bytachykinins.

  公式（1）中，R代表卤原子或C1-4烷基；R1代表C1-4烷基；R2代表氢或C1-4烷基；R3代表氢或C1-4烷基；R4代表三氟甲基基团；R5代表氢、C1-4烷基或C(0)R6；R6代表C1-4烷基、C3-7环烷基、NH(C1-4烷基)或N(C1-4烷基)2；m为零或1至3的整数；n为1至3的整数及其药学上可接受的盐和溶剂化合物；以及它们的制备过程和在通过tachykinins介导的疾病治疗中的用途。