3-methyl-5-trifluoromethyl-3,4-dihydro-2H-pyrazole-3-carboxylic acid (4-cyano-2-ethyl-5-trifluoromethyl-phenyl)-amide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-methyl-5-trifluoromethyl-3,4-dihydro-2H-pyrazole-3-carboxylic acid (4-cyano-2-ethyl-5-trifluoromethyl-phenyl)-amide
• 英文别名: N-[4-cyano-2-ethyl-5-(trifluoromethyl)phenyl]-5-methyl-3-(trifluoromethyl)-1,4-dihydropyrazole-5-carboxamide
• 化学式: C₁₆H₁₄F₆N₄O
• 分子量: 392.304
• InChiKey: BOVHHDLOWQJHGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  77.3
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-氨基-5-碘-2-(三氟甲基)苯甲腈 在 palladium on activated charcoal 、 copper(l) iodide 、 bis(triphenylphosphine)palladium(II) dichloride 四丁基氟化铵 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 55.0 ℃ 、275.8 kPa 条件下， 反应 0.33h， 生成 3-methyl-5-trifluoromethyl-3,4-dihydro-2H-pyrazole-3-carboxylic acid (4-cyano-2-ethyl-5-trifluoromethyl-phenyl)-amide
  参考文献：
  名称：

  Design, Synthesis, and in Vivo SAR of a Novel Series of Pyrazolines as Potent Selective Androgen Receptor Modulators

  摘要：

  A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure- activity relationships (SAR) were investigated at the R-1 to R-6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the RI and 2 positions and a small group at the R1 and RI position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.

  DOI：

  10.1021/jm0613976

文献信息

• NOVEL HETEROCYCLE DERIVATIVES USEFUL AS SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARMS)
  申请人：Zhang Xuqing

  公开号：US20090131365A1

  公开（公告）日：2009-05-21

  The present invention is directed to novel heterocycle derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the androgen receptor.

  本发明涉及新型杂环衍生物，包含它们的制药组合物以及它们在治疗受雄激素受体调节的疾病和病状中的应用。
• US7465809B2
  申请人：——

  公开号：US7465809B2

  公开（公告）日：2008-12-16
• US7781473B2
  申请人：——

  公开号：US7781473B2

  公开（公告）日：2010-08-24
• US8088811B2
  申请人：——

  公开号：US8088811B2

  公开（公告）日：2012-01-03
• Design, Synthesis, and in Vivo SAR of a Novel Series of Pyrazolines as Potent Selective Androgen Receptor Modulators
  作者：Xuqing Zhang、Xiaojie Li、George F. Allan、Tifanie Sbriscia、Olivia Linton、Scott G. Lundeen、Zhihua Sui

  DOI：10.1021/jm0613976

  日期：2007.8.1

  A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure- activity relationships (SAR) were investigated at the R-1 to R-6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the RI and 2 positions and a small group at the R1 and RI position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.