3-fluoro-2-[4-(2-methylpropyloxy)phenyl]-6-(ethyloxycarbonyl)pyrrolo[1,2-a]pyrimid-7-one | 308143-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-fluoro-2-[4-(2-methylpropyloxy)phenyl]-6-(ethyloxycarbonyl)pyrrolo[1,2-a]pyrimid-7-one
• 英文别名: ethyl 8-fluoro-7-[4-(2-methylpropoxy)phenyl]-4-oxo-1H-pyrrolo[1,2-a]pyrimidine-3-carboxylate
• CAS: 308143-23-9
• 化学式: C₂₀H₂₁FN₂O₄
• 分子量: 372.396
• InChiKey: ATZRYJHDWBQPBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-fluoro-2-[4-(2-methylpropyloxy)phenyl]-6-(ethyloxycarbonyl)pyrrolo[1,2-a]pyrimid-7-one 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 17.5h， 生成 1-{N-methyl-N-[2-(2-pyridyl)ethyl]aminomethyl}-3-fluoro-4-(2-fluorobenzyl)-2-[4-(2-methylpropyloxy)phenyl]-6-(ethyloxycarbonyl)pyrrolo[1,2-a]pyrimid-7-one
  参考文献：
  名称：

  A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists

  摘要：

  A new class of small molecule GnRH antagonists, the 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones, was designed and a novel synthesis for these compounds was developed. The synthesis utilizes a base-catalyzed intramolecular cyclization of fluoromethyl pyrimidone 5 to generate the bicyclic core. Amongst the compounds synthesized, we discovered some highly potent GnRH receptor antagonists (e.g., 12. K-i = 9 nM), which showed enhanced stability towards acidic physiological conditions compared to the des-fluoro analogues. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00745-x
• 作为产物：
  描述：

  1-(4-异丁氧基苯基)乙酮 在 四丁基氟化铵 、 sodium ethanolate 、 copper(ll) bromide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 6.5h， 生成 3-fluoro-2-[4-(2-methylpropyloxy)phenyl]-6-(ethyloxycarbonyl)pyrrolo[1,2-a]pyrimid-7-one
  参考文献：
  名称：

  A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists

  摘要：

  A new class of small molecule GnRH antagonists, the 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones, was designed and a novel synthesis for these compounds was developed. The synthesis utilizes a base-catalyzed intramolecular cyclization of fluoromethyl pyrimidone 5 to generate the bicyclic core. Amongst the compounds synthesized, we discovered some highly potent GnRH receptor antagonists (e.g., 12. K-i = 9 nM), which showed enhanced stability towards acidic physiological conditions compared to the des-fluoro analogues. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00745-x

文献信息

• Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
  申请人：Neurocrine Biosciences, Inc.

  公开号：US06346534B1

  公开（公告）日：2002-02-12

  GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein Ar, B, R1, R2, R3a, R3b, R4, R5, R6 and m are as defined herein.

  GnRH受体拮抗剂已被披露，可用于治疗男性和女性的各种与性激素相关的疾病。该发明的化合物具有以下结构：包括立体异构体、前药和其药用盐，其中Ar、B、R1、R2、R3a、R3b、R4、R5、R6和m的定义如本文所述。
• A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists
  作者：Fabio C. Tucci、Yun-Fei Zhu、Zhiqiang Guo、Timothy D. Gross、Patrick J. Connors、R.Scott Struthers、Greg J. Reinhart、Xiaochuan Wang、John Saunders、Chen Chen

  DOI：10.1016/s0960-894x(02)00745-x

  日期：2002.12

  A new class of small molecule GnRH antagonists, the 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones, was designed and a novel synthesis for these compounds was developed. The synthesis utilizes a base-catalyzed intramolecular cyclization of fluoromethyl pyrimidone 5 to generate the bicyclic core. Amongst the compounds synthesized, we discovered some highly potent GnRH receptor antagonists (e.g., 12. K-i = 9 nM), which showed enhanced stability towards acidic physiological conditions compared to the des-fluoro analogues. (C) 2002 Elsevier Science Ltd. All rights reserved.