N-[3-cyano-6-(4-fluoro-2-hydroxyphenyl)-4-{3-[(piperidin-2-ylacetyl)amino]phenyl}pyridin-2-yl]furan-2-carboxamide hydrochloride | 925929-56-2

• 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: N-[3-cyano-6-(4-fluoro-2-hydroxyphenyl)-4-{3-[(piperidin-2-ylacetyl)amino]phenyl}pyridin-2-yl]furan-2-carboxamide hydrochloride
• 英文别名: n-(3-Cyano-6-(4-fluoro-2-hydroxyphenyl)-4-{3-[(piperidin-2-ylacetyl)amino]phenyl}pyridin-2-yl)-2-furamide hydrochloride；N-[3-cyano-6-(4-fluoro-2-hydroxyphenyl)-4-[3-[(2-piperidin-2-ylacetyl)amino]phenyl]pyridin-2-yl]furan-2-carboxamide;hydrochloride
• CAS: 925929-56-2
• 化学式: C₃₀H₂₆FN₅O₄*ClH
• 分子量: 576.027
• InChiKey: RLQUZZUGAYUYRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.87
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  140
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[3-cyano-6-(4-fluoro-2-hydroxyphenyl)-4-{3-[(piperidin-2-ylacetyl)amino]phenyl}pyridin-2-yl]furan-2-carboxamide hydrochloride 、 碘乙烷 、 N,N-二异丙基乙胺 在 乙酸乙酯 、 Brine 、 magnesium sulfate 作用下， 以 叔丁醇 、 碳酸氢钠 为溶剂， 反应 16.0h， 以to give N-[3-cyano-4-[3-({[(2S)-1-ethylpyrrolidin-2-yl]acetyl}amino)phenyl]-6-(4-fluoro-2-hydroxyphenyl)pyridin-2-yl]-2-furamide的产率得到N-[3-cyano-4-[3-({[(2S)-1-ethylpyrrolidine-2-yl]acetyl}amino)phenyl]-6-(4-fluoro-2-hydroxyphenyl)pyridin-2-yl]-2-furamide
  参考文献：
  名称：

  PYRIDYLPHENOL COMPOUND AND USE THEREOF

  摘要：

  本发明提供了一种具有转移素受体拮抗活性的化合物，可用于预防和治疗激素依赖性癌症、良性前列腺增生、子宫内膜异位症、早熟、子宫肌瘤等。更具体地，本发明提供了一种化合物，其表示为以下公式：或其盐、前药及含有该化合物的药物制剂；其中环A表示一个5-至8-成员的同环或异环族群，可选地具有除公式—X-R1以外的取代基，其中X表示键或空间组分，而R1表示可选地取代的氨基或可选地取代的含氮杂环族群；环B表示可选地取代的苯环；R2表示可选地取代的同环或异环族群；而R3和R4独立地表示氢原子、氰基、酰基或可选地取代的碳氢基团。

  公开号：

  US20090156646A1
• 作为产物：
  描述：

  tert-butyl 2-{2-[(3-{3-cyano-6-[4-fluoro-2-(methoxymethoxy)phenyl]-2-[(furan-2-ylcarbonyl)amino]pyridin-4-yl}phenyl)amino]-2-oxoethyl}piperidine-1-carboxylate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 40.0h， 以77%的产率得到N-[3-cyano-6-(4-fluoro-2-hydroxyphenyl)-4-{3-[(piperidin-2-ylacetyl)amino]phenyl}pyridin-2-yl]furan-2-carboxamide hydrochloride
  参考文献：
  名称：

  2-Acylamino-4,6-diphenylpyridine derivatives as novel GPR54 antagonists with good brain exposure and in vivo efficacy for plasma LH level in male rats

  摘要：

  GPR54 is a G protein-coupled receptor (GPCR) which was formerly an orphan receptor. Recent functional study of GPR54 revealed that the receptor plays an essential role to modulate sex-hormones including GnRH. Thus, antagonists of GPR54 are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis. We recently reported 2-acylamino-4,6-diphenylpyridines as the first small molecule GPR54 antagonists with high potency. However, the representative compound 1 showed low brain exposure, where GPR54 acts as a modulator of gonadotropins by binding with its endogenous ligand, metastin. In order to discover compounds that have not only potent GPR54 antagonistic activity but also good brain permeability, we focused on converting the primary amine on the side chain to a secondary or tertiary amine, and finally we identified 15a containing a piperazine group. This compound exhibited high affinity to human and rat GPR54, apparent antagonistic activity, and high brain exposure. In addition, intravenous administration of 15a to castrated male rat suppressed plasma LH level, which indicates the possibility of a small molecule GPR54 antagonist as a novel drug for sex-hormone dependent diseases. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.061