5-(2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-1-methyl-pyrrole-2-carbonitrile | 305832-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-(2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-1-methyl-pyrrole-2-carbonitrile
• 英文别名: 5-(spiro[cyclohexane-1,3'-[3H]indole]-2'-oxo-5'-yl)-1H-pyrrole-1-methyl-2-carbonitrile；5-(2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-1-methylpyrrole-2-carbonitrile；1-methyl-5-(2-oxospiro[1H-indole-3,1'-cyclohexane]-5-yl)pyrrole-2-carbonitrile
• CAS: 305832-82-0
• 化学式: C₁₉H₁₉N₃O
• 分子量: 305.379
• InChiKey: WMIPEGGWIZEEMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  57.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-1-methyl-pyrrole-2-carbonitrile 在 劳森试剂 、 乙腈 作用下， 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 以95%的产率得到5-(1',2'-dihydro-2'-thioxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-1-methylpyrrole-2-carbonitrile
  参考文献：
  名称：

  Methods for minimizing thioamide impurities

  摘要：

  使用诱饵剂来减少在反应过程中形成硫代酰胺化合物的方法，例如在含有亚硝基团的羰基化合物的硫代化反应中。

  公开号：

  US20050228179A1
• 作为产物：
  描述：

  5-溴螺环[环己烷-1,3-吲哚]-2(1H)-酮 在 四(三苯基膦)钯 、 sodium ethanolate 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.17h， 生成 5-(2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-1-methyl-pyrrole-2-carbonitrile
  参考文献：
  名称：

  Novel pyrrole-containing progesterone receptor modulators

  摘要：

  A series of 1,4-dihydro-2H-[d][3,1]-benzoxazin-2-one and 1,3-dihydro-[3H]-indol-2-one containing 6- or 5-, respectively, appended substituted pyrrole moieties were synthesized and evaluated for their ability to modulate the activity of the progesterone receptor (PR). Key structural changes to the pyrrole moieties of these molecules were shown to have a predictive influence as to whether the compounds behaved as PR agonists or antagonists. Compounds with the 5'-cyano-2'-pyrrole moiety (e.g.,.32, 33, and 38) were shown to be potent PR agonists (EC50'S Of 1.1, 1.8, and 2.8 nM, respectively). Compounds with the 5'-nitro-2'-pyrrole moiety (e.g., 34 and 36) were shown to be PR antagonists IC50'S Of 180 and 36nM, respectively). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.054

文献信息

• Thio-oxindole derivatives
  申请人：American Home Products Corporation

  公开号：US06355648B1

  公开（公告）日：2002-03-12

  This invention relates to compounds which are agonists of the progesterone receptor which have the general structures: wherein: R1 and R2 are H, alkyl, substituted alkyl; OH; O(alkyl); O(substituted alkyl); OAc; aryl; substituted aryl; heteroaryl; substituted heteroaryl; alkylaryl; alkylheteroaryl; 1-propynyl; or 3-propynyl; or R1 and R2 are joined to form an alkyl, alkenyl or heterocyclic ring; or R1 and R2 together comprise a double bond to CMe2; C(cycloalkyl), O, or C(cycloether); R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, alkynyl, substituted alkynyl, or CORA; RA is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; R4 is H, halogen, CN, NH2, NO2, C1 to C6 alkyl, or substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; R5 is optionally substituted and selected from a benzene ring, a five or six membered heterocyclic ring with 1, 2, or 3 heteroatoms selected from O, S, SO, SO2 or NR6; or an indol-4-yl, indol-7-yl or benzo-2-thiophene moiety; Q1 is S, NR7, CR8R9; or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.

  这项发明涉及激素受体的激动剂化合物，其具有以下一般结构： 其中： R1和R2为H、烷基、取代烷基；OH；O(烷基)；O(取代烷基)；OAc；芳基；取代芳基；杂环芳基；取代杂环芳基；烷基芳基；烷基杂环芳基；1-丙炔基；或3-丙炔基；或R1和R2连接形成烷基、烯基或杂环环；或R1和R2共同包括与CMe2形成双键的C(环烷基)、O或C(环醚)；R3为H、OH、NH2、C1至C6烷基、取代C1至C6烷基、C3至C6烯基、炔基、取代炔基，或CORA；RA为H、C1至C3烷基、取代C1至C3烷基、C1至C3烷氧基、取代C1至C3烷氧基、C1至C3氨基烷基，或取代C1至C3氨基烷基；R4为H、卤素、CN、NH2、NO2、C1至C6烷基，或取代C1至C6烷基、C1至C6烷氧基，取代C1至C6烷氧基、C1至C6氨基烷基，或取代C1至C6氨基烷基；R5为可选择取代并选自苯环、具有1、2或3个来自O、S、SO、SO2或NR6的杂原子的五元或六元杂环环；或吲哚-4-基、吲哚-7-基或苯并-2-噻吩基团；Q1为S、NR7、CR8R9；或其药学上可接受的盐，以及使用这些化合物诱导避孕或治疗与孕激素相关的癌症和腺癌的方法。
• Design, Synthesis, and SAR of New Pyrrole-Oxindole Progesterone Receptor Modulators Leading to 5-(7-Fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1<i>H</i>-indol-5-yl)-1-methyl-1<i>H</i>-pyrrole-2-carbonitrile (WAY-255348)
  作者：Andrew Fensome、William R. Adams、Andrea L. Adams、Tom J. Berrodin、Jeff Cohen、Christine Huselton、Arthur Illenberger、Jeffrey C. Kern、Valerie A. Hudak、Michael A. Marella、Edward G. Melenski、Casey C. McComas、Cheryl A. Mugford、Ov D. Slayden、Matthew Yudt、Zhiming Zhang、Puwen Zhang、Yuan Zhu、Richard C. Winneker、Jay E. Wrobel

  DOI：10.1021/jm701080t

  日期：2008.3.1

  We have continued to explore the 3,3-dialkyl-5-aryloxindole series of progesterone receptor (PR) modulators looking for new agents to be used in female healthcare: contraception, fibroids, endometriosis, and certain breast cancers. Previously we reported that subtle structural changes with this and related templates produced functional switches between agonist and antagonist properties ( Fensome et

  我们继续探索3,3-二烷基-5-芳基吲哚系列孕酮受体（PR）调节剂，以寻找用于女性保健的新药物：避孕，肌瘤，子宫内膜异位症和某些乳腺癌。先前，我们报道了该模板和相关模板的微妙结构变化在激动剂和拮抗剂特性之间产生了功能转换（Fensome等，Biorg。Med。Chem。Lett。2002，12，3487; 2003，13，1317）。我们在本文中报道了5-（2-氧代吲哚-5-基）-1 H-吡咯-2-腈类化合物中的新功能开关。我们发现3，3-二烷基取代基的大小对于控制功能响应很重要。因此，小的基团（二甲基）提供有效的PR拮抗剂，而较大的基团（螺环己基）是PR激动剂。
• [EN] THIO-OXINDOLE DERIVATIVES<br/>[FR] DERIVES DE THIO-OXINDOLE
  申请人：AMERICAN HOME PROD

  公开号：WO2000066555A1

  公开（公告）日：2000-11-09

  This invention relates to compounds which are agonists of the progesterone receptor which have general structures (1) or (2) wherein the substituents are as defined; or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.

  本发明涉及一类通式（1）或（2）的孕激素受体激动剂化合物及其药学上可接受的盐，其中取代基如所定义；以及使用这些化合物诱导避孕或治疗孕激素相关的癌症和腺癌的方法。
• COUPLING PROCESS FOR GENERATING REACTIVE BORON-CONTAINING DERIVATIVES OF N-SUBSTITUTED PYRROLE-2-CARBONITRILES TO PRODUCE BIARYLS
  申请人：Wilk Bogdan Kazimierz

  公开号：US20090054663A1

  公开（公告）日：2009-02-26

  A convenient preparation of boron-containing compounds, borate salts, pyrrolecarbonitrile boron-containing compounds, N-substituted-pyrrole-2-carbonitrile boron-containing compounds, and derivatives thereof is provided. The present invention also provides for the use of these boron-containing compounds and derivatives thereof in coupling reactions to provide bi-aryl compounds.

  本发明提供了含硼化合物、硼酸盐、吡咯碳腈硼含物、N-取代吡咯-2-碳腈硼含物及其衍生物的便捷制备方法。本发明还提供了使用这些含硼化合物及其衍生物进行偶联反应以提供双芳基化合物的方法。
• THIO-OXINDOLE DERIVATIVES
  申请人：American Home Products Corporation

  公开号：EP1181275A1

  公开（公告）日：2002-02-27