5-[(2S,3R)-1-(4-cyano-3-fluorophenyl)-3-hydroxy-2-methylpyrrolidin-3-yl]pyridine-2-carboxylic acid | 1192603-94-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-[(2S,3R)-1-(4-cyano-3-fluorophenyl)-3-hydroxy-2-methylpyrrolidin-3-yl]pyridine-2-carboxylic acid
• CAS: 1192603-94-3
• 化学式: C₁₈H₁₆FN₃O₃
• 分子量: 341.342
• InChiKey: HPUQZUKRASHIMO-VOJFVSQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-[(2S,3R)-1-(4-cyano-3-fluorophenyl)-3-hydroxy-2-methylpyrrolidin-3-yl]pyridine-2-carboxylic acid 、 甲胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以66%的产率得到5-[(2S,3R)-1-(4-cyano-3-fluorophenyl)-3-hydroxy-2-methylpyrrolidin-3-yl]-N-methylpyridine-2-carboxamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives as novel androgen receptor antagonists

  摘要：

  We designed and synthesized a series of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives D and evaluated their potential as novel androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a methyl group at the 2-position (R-2) of the pyrrolidine ring increased the AR binding affinity. The (2S, 3R) configuration of the pyrrolidine ring was favorable for the AR antagonistic activity. It was found that introduction of an amide substituent (R-1) and a pyridin-3-yl group (Q) was effective for reducing the AR agonistic activity which appeared during the optimization of lead compound 6. Compound 54 showed potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft, in which bicalutamide exhibited only partial suppression of tumor growth. Thus, the pyrrolidine derivatives such as 54 are novel AR antagonists, and their properties having efficacy against CRPC are distinct from those of a representative first-generation antagonist, bicalutamide. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.001
• 作为产物：
  描述：

  在 水 、 lithium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 4.0h， 生成 5-[(2S,3R)-1-(4-cyano-3-fluorophenyl)-3-hydroxy-2-methylpyrrolidin-3-yl]pyridine-2-carboxylic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives as novel androgen receptor antagonists

  摘要：

  We designed and synthesized a series of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives D and evaluated their potential as novel androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a methyl group at the 2-position (R-2) of the pyrrolidine ring increased the AR binding affinity. The (2S, 3R) configuration of the pyrrolidine ring was favorable for the AR antagonistic activity. It was found that introduction of an amide substituent (R-1) and a pyridin-3-yl group (Q) was effective for reducing the AR agonistic activity which appeared during the optimization of lead compound 6. Compound 54 showed potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft, in which bicalutamide exhibited only partial suppression of tumor growth. Thus, the pyrrolidine derivatives such as 54 are novel AR antagonists, and their properties having efficacy against CRPC are distinct from those of a representative first-generation antagonist, bicalutamide. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.001