2-[1,1-dimethyl-2-oxo-2-(7-azabicyclo[2.2.1]heptan-7-yl)ethyl]-4-[2-(4-{morpholinocarbonyl}piperidin-1-yl)ethyl]-5-(3,5-dimethylphenyl)-6H-thieno[2,3-b]pyrrole | 666850-79-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-[1,1-dimethyl-2-oxo-2-(7-azabicyclo[2.2.1]heptan-7-yl)ethyl]-4-[2-(4-{morpholinocarbonyl}piperidin-1-yl)ethyl]-5-(3,5-dimethylphenyl)-6H-thieno[2,3-b]pyrrole
• 英文别名: 2-[1,1-dimethyl-2-oxo-2-azabicyclo[2.2.1]heptan-7-ylethyl]-4-[2-(4-{morpholinocarbonyl}piperidin-1-yl)ethyl]-5-(3,5-dimethylphenyl)-6H-thieno[2,3-b]pyrrole；1-(7-aza-bicyclo[2.2.1]heptan-7-yl)-2-(5-(3,5-dimethylphenyl)-4-(2-(4-(morpholine-4-carbonyl)piperidin-1-yl)ethyl)-6H-thieno[2,3-b]pyrrol-2-yl)-2-methylpropan-1-one；1-(7-azabicyclo[2.2.1]heptan-7-yl)-2-[5-(3,5-dimethylphenyl)-4-[2-[4-(morpholine-4-carbonyl)piperidin-1-yl]ethyl]-6H-thieno[2,3-b]pyrrol-2-yl]-2-methylpropan-1-one
• CAS: 666850-79-9
• 化学式: C₃₆H₄₈N₄O₃S
• 分子量: 616.868
• InChiKey: NDUYMDVQDJTRFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[1,1-dimethyl-2-oxo-2-(7-azabicyclo[2.2.1]heptan-7-yl)ethyl]-4-[2-(4-{morpholinocarbonyl}piperidin-1-yl)ethyl]-5-(3,5-dimethylphenyl)-6H-thieno[2,3-b]pyrrole 在 镍 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、172.26 kPa 条件下， 反应 16.0h， 以52%的产率得到3-[3,3-dimethyl-4-oxo-4-(7-azabicyclo[2.2.1]heptan-7-yl)butyl]-4-[2-{4-(morpholin-4-ylcarbonyl)piperidin-1-yl}ethyl]-5-(3,5-dimethylphenyl)-1H-pyrrole
  参考文献：
  名称：

  [EN] PYRROLE DERIVATIVES AS GONADOTROPIN RELEASING HORMONE (GNRH) ANTAGONISTS
  [FR] DERIVES DE PYRROLE UTILISES EN TANT QU'ANTAGONISTES DE L'HORMONE LIBERANT DE LA GONADOTROPHINE (GNRH)

  摘要：

  这项发明涉及一组新型噻吩-吡咯烯化合物，其化学式为（I），其中：R1、R2、R3、R4、M 和 R5 如规范中所定义，作为促性腺激素释放激素拮抗剂。化学式（I）的新型化合物也被要求。该发明还涉及所述化合物的药物配方、使用所述化合物的治疗方法以及所述化合物的制备方法。

  公开号：

  WO2005079805A1
• 作为产物：
  描述：

  trans-4-aminocyclohexanol hydrochloride 在 lithium aluminium tetrahydride 、 氯化亚砜 、 偶氮二甲酸二叔丁酯 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丁酰胺 、 异丙醇 为溶剂， 反应 113.75h， 生成 2-[1,1-dimethyl-2-oxo-2-(7-azabicyclo[2.2.1]heptan-7-yl)ethyl]-4-[2-(4-{morpholinocarbonyl}piperidin-1-yl)ethyl]-5-(3,5-dimethylphenyl)-6H-thieno[2,3-b]pyrrole
  参考文献：
  名称：

  [EN] PYRROLE DERIVATIVES AS GONADOTROPIN RELEASING HORMONE (GNRH) ANTAGONISTS
  [FR] DERIVES DE PYRROLE UTILISES EN TANT QU'ANTAGONISTES DE L'HORMONE LIBERANT DE LA GONADOTROPHINE (GNRH)

  摘要：

  这项发明涉及一组新型噻吩-吡咯烯化合物，其化学式为（I），其中：R1、R2、R3、R4、M 和 R5 如规范中所定义，作为促性腺激素释放激素拮抗剂。化学式（I）的新型化合物也被要求。该发明还涉及所述化合物的药物配方、使用所述化合物的治疗方法以及所述化合物的制备方法。

  公开号：

  WO2005079805A1

文献信息

• [EN] 6H-THIENO`2, 3-B!PYRROLE DERIVATIVES AS ANTAGONISTS OF GONADOTROPIN RELEASING HORMONE (GNRH)<br/>[FR] DERIVES DE 6H-THIENO`2,3-B!PYRROLE EN TANT QU'ANTAGONISTES DE LA GONADOLIBERINE (GNRH)
  申请人：ASTRAZENECA AB

  公开号：WO2004018480A1

  公开（公告）日：2004-03-04

  The invention relates to a group of novel thieno-pyrrole compounds of Formula (I): wherein: R1, R2, R3, R4 and R5 are as defined in the specification, which are useful as gonadotrophin releasing hormone antagonists. The invention also relates to pharmaceutical formulations of said compounds, methods of treatment using said compounds and to processes for the preparation of said compounds.

  这项发明涉及一组新型噻吩-吡咯烷化合物的化学式（I）：其中：R1、R2、R3、R4和R5如规范中定义，这些化合物可用作促性腺激素释放激素拮抗剂。该发明还涉及所述化合物的药物配方、使用所述化合物的治疗方法以及所述化合物的制备方法。
• 6H-THIENO[2,3-b]PYRROLE DERIVATIVES AS ANTAGONISTS OF GONADOTROPIN RELEASING HORMONE (GNRH)
  申请人：Foote Michael Kevin

  公开号：US20080045517A1

  公开（公告）日：2008-02-21

  The invention relates to a group of novel thieno-pyrrole compounds of Formula (I): wherein: R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the specification, which are useful as gonadotrophin releasing hormone antagonists. The invention also relates to pharmaceutical formulations of said compounds, methods of treatment using said compounds and to processes for the preparation of said compounds.

  该发明涉及一组新型噻吩-吡咯化合物，其化学式为(I)：其中：R1、R2、R3、R4和R5如规范中所定义，这些化合物可用作促性腺激素释放激素拮抗剂。该发明还涉及该化合物的制药配方、使用该化合物的治疗方法以及制备该化合物的过程。
• Synthesis and structure–activity relationships of thieno[2,3-b]pyrroles as antagonists of the GnRH receptor
  作者：Jean Claude Arnould、Bénédicte Delouvrié、Pascal Boutron、Al G. Dossetter、Kevin M. Foote、Annie Hamon、Urs Hancox、Craig S. Harris、Mike Hutton、Maryannick Lamorlette、Zbigniew Matusiak

  DOI：10.1016/j.bmcl.2007.09.099

  日期：2007.12

  A new class of small-molecule GnRH antagonists, the thieno[2,3-b]pyrroles, was designed. Herein, the synthesis and structure-activity relationships are described. Substitution at the C4 position was investigated; during this study, it was observed that introducing piperazines and piperidines improved the physical properties of the compounds while retaining good in vitro potency. This exploration led to the discovery of amidopiperidines with improved pharmacokinetic properties. (c) 2007 Elsevier Ltd. All rights reserved.
• 6H-THIEN 2, 3-B]PYRROLE DERIVATIVES AS ANTAGONISTS OF GONADOTROPIN RELEASING HORMONE (GNRH)
  申请人：AstraZeneca AB

  公开号：EP1543012B1

  公开（公告）日：2008-07-16
• Pyrrole derivatives as gonadotropin releasing hormone (gnrh) antagonists
  申请人：Harris Steven Craig

  公开号：US20070185106A1

  公开（公告）日：2007-08-09

  The invention relates to a group of novel thieno-pyrrole compounds of formula (I) wherein: R 1 , R 2 , R 3 , R 4 M, and R 5 are as defined in the specification, as inter alia, gonadotrophin releasing hormone antagonists. Novel compounds of formula (I) are also claimed. The invention also relates to pharmaceutical formulations of said compounds, methods of treatment using said compounds and to processes for the preparation of said compounds.