2-iodo-6-oxo-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepine-9-carbonitrile | 1003869-21-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-iodo-6-oxo-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepine-9-carbonitrile
• 英文别名: 2-iodo-6-oxo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepine-9-carbonitrile
• CAS: 1003869-21-3
• 化学式: C₁₇H₁₀IN₃O
• 分子量: 399.19
• InChiKey: GOLUZFQVAFLMJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  68.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-iodo-6-oxo-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepine-9-carbonitrile 、 丁烯酮 在 palladium diacetate 三乙胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 以40%的产率得到6-oxo-2-[(E)-3-oxobut-1-enyl]-7,12-dihydro-5H-indolo[3,2-d][1]benzazepine-9-carbonitrile
  参考文献：
  名称：

  2-(3-Aryl-3-oxopropen-1-yl)-9-tert-butyl-paullones: A New Antileishmanial Chemotype

  摘要：

  A screening program directed to find new agents against Leishmania donovani, the parasite causing visceral leishmaniasis, revealed that paullones attenuate the proliferation of axenic amastigotes. Because these structures were not active in a test system involving infected macrophages, a structure optimization campaign was carried out. Concomitant introduction of an unsaturated side chain into the 2-position and a tert-butyl substituent into the 9-position of the parent scaffold led to compounds inhibiting also parasites dwelling in macrophages. By inclusion of the so elaborated scaffold into a chalcone substructure, the toxicity against uninfected host cells was significantly reduced. For the synthesis of this new compound class, a novel modification of the Heck-type palladium-catalyzed C,C-cross coupling strategy was used, employing a ketone Mannich base as precursor for the alkene reactant. The so-prepared compounds exhibited improved antileishmanial activity both on axenic amastigotes (GI(50) < 1 mu M) as well as on parasites in infected macrophages.

  DOI：

  10.1021/jm7012166
• 作为产物：
  描述：

  4-氰基苯肼盐酸盐 、 7-iodo-3,4-dihydro-1H-1-benzazepine-2,5-dione 在 sodium acetate 、 硫酸 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 以31%的产率得到2-iodo-6-oxo-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepine-9-carbonitrile
  参考文献：
  名称：

  2-(3-Aryl-3-oxopropen-1-yl)-9-tert-butyl-paullones: A New Antileishmanial Chemotype

  摘要：

  A screening program directed to find new agents against Leishmania donovani, the parasite causing visceral leishmaniasis, revealed that paullones attenuate the proliferation of axenic amastigotes. Because these structures were not active in a test system involving infected macrophages, a structure optimization campaign was carried out. Concomitant introduction of an unsaturated side chain into the 2-position and a tert-butyl substituent into the 9-position of the parent scaffold led to compounds inhibiting also parasites dwelling in macrophages. By inclusion of the so elaborated scaffold into a chalcone substructure, the toxicity against uninfected host cells was significantly reduced. For the synthesis of this new compound class, a novel modification of the Heck-type palladium-catalyzed C,C-cross coupling strategy was used, employing a ketone Mannich base as precursor for the alkene reactant. The so-prepared compounds exhibited improved antileishmanial activity both on axenic amastigotes (GI(50) < 1 mu M) as well as on parasites in infected macrophages.

  DOI：

  10.1021/jm7012166

文献信息

• METHODS AND COMPOSITIONS OF P27KIP1 TRANSCRIPTIONAL MODULATORS
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL

  公开号：US20160030445A1

  公开（公告）日：2016-02-04

  In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof; and agents that inhibit the expression of p27 Kip1 , or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising β-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Methods and Compositions of P27KIP1 Transcriptional Modulators
  申请人：St. Jude Children's Research Hospital

  公开号：US20170189477A1

  公开（公告）日：2017-07-06

  In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof and agents that inhibit the expression of p27 Kip1 , or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising β-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• US9572815B2
  申请人：——

  公开号：US9572815B2

  公开（公告）日：2017-02-21
• [EN] PAULLONE DERIVATIVES AND ITS USE<br/>[FR] DÉRIVÉS DE PAULLONE ET LEURS UTILISATION
  申请人：UNIV BRAUNSCHWEIG TECH CAROLO WILHELMINA

  公开号：WO2009010298A2

  公开（公告）日：2009-01-22

  The present invention relates to new paullone derivatives. In particular, the present invention relates to new paullone derivatives having anti-protozoan activity, in particular, anti-leishmanial activity. In a further aspect, the present invention relates to pharmaceutical compositions containing said paullones.
• [EN] METHODS AND COMPOSITIONS OF P27KIP1 TRANSCRIPTION MODULATORS<br/>[FR] PROCÉDÉS ET COMPOSITIONS DE MODULATEURS DE LA TRANSCRIPTION DE P27KIP1
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2014145205A2

  公开（公告）日：2014-09-18

  In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof; and agents that inhibit the expression of p27Kipl, or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising β-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.