5-(3-chlorophenyl)spiro[cyclobutane-1,3-[3H]indole]-2'(1'H)-one | 304875-76-1

• 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-(3-chlorophenyl)spiro[cyclobutane-1,3-[3H]indole]-2'(1'H)-one
• 英文别名: 5-(3-chlorophenyl)spiro[1H-indole-3,1'-cyclobutane]-2-one
• CAS: 304875-76-1
• 化学式: C₁₇H₁₄ClNO
• 分子量: 283.757
• InChiKey: GYSRYBPJNDBMKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-(3-chlorophenyl)spiro[cyclobutane-1,3-[3H]indole]-2'(1'H)-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 生成 5''-(3-Chlorophenyl)spiro[cyclobutane-1,3''-[3H]indole]-2''(1''H)-thione
  参考文献：
  名称：

  新型的5-芳基-1,3-二氢吲哚-2-硫酮。口服有效的孕激素受体激动剂。

  摘要：

  在我们对3,3-二取代-5-芳基氧吲哚衍生的孕酮受体（PR）拮抗剂的研究过程中，我们发现将酰胺官能团改变为硫代酰胺会导致化合物显示出强大的PR激动剂活性。在这种交流中，将讨论各种5-芳硫基-羟吲哚的合成，结构活性关系（SAR）和体内活性。

  DOI：

  10.1016/s0960-894x(03)00129-x
• 作为产物：
  描述：

  spiroindol>-2'(1'H)-one 在 四(三苯基膦)钯 、 溴 、 sodium acetate 、 sodium carbonate 、 溶剂黄146 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 生成 5-(3-chlorophenyl)spiro[cyclobutane-1,3-[3H]indole]-2'(1'H)-one
  参考文献：
  名称：

  New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles

  摘要：

  A neck series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structurc-activiy relationships (SARs) of various 3,3-substituents are discussed where it is clear that small alkyl and spiroalkyl groups are required to achieve better PR antagonist activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00746-1

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。
• New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles
  作者：Andrew Fensome、Reinhold Bender、Jeffrey Cohen、Mark A. Collins、Valerie A. Mackner、Lori L. Miller、John W. Ullrich、Richard Winneker、Jay Wrobel、Puwen Zhang、Zhiming Zhang、Yuan Zhu

  DOI：10.1016/s0960-894x(02)00746-1

  日期：2002.12

  A neck series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structurc-activiy relationships (SARs) of various 3,3-substituents are discussed where it is clear that small alkyl and spiroalkyl groups are required to achieve better PR antagonist activity. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Novel 5-aryl-1,3-dihydro-indole-2-thiones
  作者：Andrew Fensome、Marci Koko、Jay Wrobel、Puwen Zhang、Zhiming Zhang、Jeffrey Cohen、Scott Lundeen、Kelly Rudnick、Yuan Zhu、Richard Winneker

  DOI：10.1016/s0960-894x(03)00129-x

  日期：2003.4

  studies on 3,3-disubstituted-5-aryloxindoles derived progesterone receptor (PR) antagonists we discovered that changing the amide funtionality to a thio-amide resulted in compounds displaying potent PR agonist activity. In this communication, the synthesis, structure activity relationships (SAR) and in vivo activity of various 5-arylthio-oxindoles will be discussed.

  在我们对3,3-二取代-5-芳基氧吲哚衍生的孕酮受体（PR）拮抗剂的研究过程中，我们发现将酰胺官能团改变为硫代酰胺会导致化合物显示出强大的PR激动剂活性。在这种交流中，将讨论各种5-芳硫基-羟吲哚的合成，结构活性关系（SAR）和体内活性。