tert-butyl {3-[(3-{3-cyano-6-[4-fluoro-2-(methoxymethoxy)-phenyl]-2-[(furan-2-ylcarbonyl)amino]pyridin-4-yl}phenyl)-amino]-3-oxopropyl}carbamate | 925923-00-8

• 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: tert-butyl {3-[(3-{3-cyano-6-[4-fluoro-2-(methoxymethoxy)-phenyl]-2-[(furan-2-ylcarbonyl)amino]pyridin-4-yl}phenyl)-amino]-3-oxopropyl}carbamate
• 英文别名: tert-butyl N-[3-[3-[3-cyano-6-[4-fluoro-2-(methoxymethoxy)phenyl]-2-(furan-2-carbonylamino)pyridin-4-yl]anilino]-3-oxopropyl]carbamate
• CAS: 925923-00-8
• 化学式: C₃₃H₃₂FN₅O₇
• 分子量: 629.645
• InChiKey: YRHDYCZJZSLGAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  165
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl {3-[(3-{3-cyano-6-[4-fluoro-2-(methoxymethoxy)-phenyl]-2-[(furan-2-ylcarbonyl)amino]pyridin-4-yl}phenyl)-amino]-3-oxopropyl}carbamate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 3.5h， 以32%的产率得到N-{4-[3-(β-alanylamino)phenyl]-3-cyano-6-(4-fluoro-2-hydroxyphenyl)pyridin-2-yl}furan-2-carboxamide hydrochloride
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 2-acylamino-4,6-diphenylpyridine derivatives as novel antagonists of GPR54

  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 has an essential role to modulate sex-hormones including GnRH. Though antagonists of GPR54 are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis, small molecule GPR54 antagonists have not been reported. We have synthesized a series of 2-acylamino-4,6-diphenylpyridines to identify potent GPR54 antagonists. Detailed structure-activity relationship studies led to compound 9l with an IC50 value of 3.7 nM in a GPR54 binding assay, and apparent antagonistic activity in a cellular functional assay. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.036
• 作为产物：
  描述：

  Boc-beta-丙氨酸 、 N-{4-(3-aminophenyl)-3-cyano-6-[4-fluoro-2-(methoxymethoxy)phenyl]pyridin-2-yl}furan-2-carboxamide 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 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl {3-[(3-{3-cyano-6-[4-fluoro-2-(methoxymethoxy)-phenyl]-2-[(furan-2-ylcarbonyl)amino]pyridin-4-yl}phenyl)-amino]-3-oxopropyl}carbamate
  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

文献信息

• 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
  作者：Toshitake Kobayashi、Satoshi Sasaki、Naoki Tomita、Seiji Fukui、Masaharu Nakayama、Atsushi Kiba、Masami Kusaka、Shin-ichi Matsumoto、Masashi Yamaguchi、Fumio Itoh、Atsuo Baba

  DOI：10.1016/j.bmc.2010.05.061

  日期：2010.7

  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.
• Synthesis and structure–activity relationships of 2-acylamino-4,6-diphenylpyridine derivatives as novel antagonists of GPR54
  作者：Toshitake Kobayashi、Satoshi Sasaki、Naoki Tomita、Seiji Fukui、Noritaka Kuroda、Masaharu Nakayama、Atsushi Kiba、Yoshihiro Takatsu、Tetsuya Ohtaki、Fumio Itoh

  DOI：10.1016/j.bmc.2010.04.036

  日期：2010.6.1

  GPR54 is a G protein-coupled receptor (GPCR) which was formerly an orphan receptor. Recent functional study of GPR54 revealed that the receptor has an essential role to modulate sex-hormones including GnRH. Though antagonists of GPR54 are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis, small molecule GPR54 antagonists have not been reported. We have synthesized a series of 2-acylamino-4,6-diphenylpyridines to identify potent GPR54 antagonists. Detailed structure-activity relationship studies led to compound 9l with an IC50 value of 3.7 nM in a GPR54 binding assay, and apparent antagonistic activity in a cellular functional assay. (C) 2010 Elsevier Ltd. All rights reserved.