7-tert-butyl-1-chloro-4-nitro-9(10H)-acridinone | 166756-49-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-tert-butyl-1-chloro-4-nitro-9(10H)-acridinone
• 英文别名: 7-tert-butyl-1-chloro-4-nitro-10H-acridin-9-one
• CAS: 166756-49-6
• 化学式: C₁₇H₁₅ClN₂O₃
• 分子量: 330.771
• InChiKey: OUXIMFYALBWIOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-tert-butyl-1-chloro-4-nitro-9(10H)-acridinone 在 镍 一水合肼 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 4-Amino-7-tert-butyl-1-(2-diethylamino-ethylamino)-10H-acridin-9-one
  参考文献：
  名称：

  抗肿瘤咪唑并rid啶酮的结构-活性关系：体内合成和抗白血病活性。

  摘要：

  几种新的5-氨基-6H-咪唑并[4,5,1-de] -ac啶-6-一个在苯环上带有OH，OCH3，CH3，叔丁基或OCH2O的5-氨基取代衍生物的合成组进行了描述。8-OH取代的化合物或双取代的7-OH-10-OCH3化合物具有抗鼠P388白血病的有效体内活性。5-[[2-[[2-[[（（二乙基氨基）乙基]氨基]乙基]氨基] -8-羟基-6H-咪唑并[4,5,1-de] -rid啶-6-one显示最高的活性（4c）。

  DOI：

  10.1021/jm950564r
• 作为产物：
  描述：

  2-<(tert-butylphenyl)amino>-6-chloro-3-nitrobenzoic acid 在 三氯氧磷 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.5h， 以94%的产率得到7-tert-butyl-1-chloro-4-nitro-9(10H)-acridinone
  参考文献：
  名称：

  Bisimidazoacridones and Related Compounds: New Antineoplastic Agents with High Selectivity against Colon Tumors

  摘要：

  A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N-2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[4,5,1-de]acridim-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen. This antitumor effect was also apparent in colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo assays involving xenografts of tumor derived from HCT-116 in nude mice. The tested compounds exhibited relatively low acute toxicity and were well tolerated by the treated animals. The bisimidazoacridones interact with nucleic acids in vitro but preliminary experimental and modeling data indicate that in spite of their structure, they may not be bis-intercalators. While the precise mode of action of these compounds is not yet understood, they appear to be excellent candidates for clinical development.

  DOI：

  10.1021/jm00016a007

文献信息

• ACRIDONE-DERIVED BISINTERCALATORS AS CHEMOTHERAPEUTIC AGENTS
  申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP0750612A1

  公开（公告）日：1997-01-02
• [EN] ACRIDONE-DERIVED BISINTERCALATORS AS CHEMOTHERAPEUTIC AGENTS<br/>[FR] COMPOSES INTERCALAIRES BIFONCTIONNELS DERIVES D'ACRIDONE UTILISES EN TANT QU'AGENTS CHIMIOTHERAPEUTIQUES
  申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：WO1995025093A1

  公开（公告）日：1995-09-21

  (EN) The present invention provides a compound having structure (I), wherein R is -H, -CH3, or -C2H5; R1 and R2 are independently -H, -OH, -NH2, -OCH3, -C(CH3)3, or a halogen atom; n is 2 to 6; X and X' are independently -N or -NO2; Y and Y' are independently -N, -CH, or -H; and the double-slash represents a double bond or no bond; such that when X or X' is -N, Y or Y' is -CH or -N, and the double-slash is a double bond, and when X or X' is -NO2, Y or Y' is -H, and the double-slash is no bond. The present invention also provides a pharmaceutical composition comprising the compound above and a pharmaceutically acceptable carrier. The present invention further provides a method for treating a neoplastic cell growth in a subject in need of such treatment which comprises administering to the subject an amount of the pharmaceutical composition above effective to treat the neoplastic cell growth. Lastly, the present invention provides nucleic acid labeled with the compound above, as well as a method for detecting nucleic acid in a sample.(FR) L'invention concerne un composé possédant la structure (I) dans laquelle R représente -H, -CH3 ou -C2H5; R1 et R2 représentent indépendamment -H, -OH, -NH2, -OCH3, -C(CH3)3 ou un atome d'halogène; n représente 2 à 6; X et X' représentent indépendamment -N ou -NO2; Y et Y' représentent indépendamment -N, -CH ou -H et la double barre oblique représente une liaison double ou l'absence de liaison, de telle manière que, quand X ou X' représente -N, Y ou Y' représente -CH ou -N et la double barre oblique représente une liaison double, et quand X ou X' représente -NO2, Y ou Y' représente -H et la double barre oblique représente l'absence de liaison. L'invention concerne également une composition pharmaceutique comprenant ledit composé et un excipient pharmaceutiquement acceptable. Elle concerne encore un procédé de traitement d'une croissance cellulaire néoplasique chez un patient qui consiste à administrer une dose efficace de ladite composition audit patient, afin de traiter ladite croissance cellulaire. Elle concerne enfin un acide nucléique marqué au moyen dudit composé, ainsi qu'un procédé de détection d'acide nucléique dans un échantillon.
• Structure−Activity Relationship for Antineoplastic Imidazoacridinones: Synthesis and Antileukemic Activity <i>in Vivo</i>
  作者：Wieslaw M. Cholody、Barbara Horowska、Jolanta Paradziej-Lukowicz、Sante Martelli、Jerzy Konopa

  DOI：10.1021/jm950564r

  日期：1996.1.1

  Synthesis of several new 5-amino-substituted derivatives of 5-amino-6H-imidazo[4,5,1-de]-acridin-6-one bearing in the benzene ring OH, OCH3, CH3, tert-butyl, or OCH2O groups is described. 8-OH-substituted compounds or double-substituted 7-OH-10-OCH3 compounds demonstrated potent in vivo activity against murine P388 leukemia. The highest activity was exhibited by 5-[[2-[[2-(diethylamino)ethyl]amino

  几种新的5-氨基-6H-咪唑并[4,5,1-de] -ac啶-6-一个在苯环上带有OH，OCH3，CH3，叔丁基或OCH2O的5-氨基取代衍生物的合成组进行了描述。8-OH取代的化合物或双取代的7-OH-10-OCH3化合物具有抗鼠P388白血病的有效体内活性。5-[[2-[[2-[[（（二乙基氨基）乙基]氨基]乙基]氨基] -8-羟基-6H-咪唑并[4,5,1-de] -rid啶-6-one显示最高的活性（4c）。
• Bisimidazoacridones and Related Compounds: New Antineoplastic Agents with High Selectivity against Colon Tumors
  作者：Wieslaw M. Cholody、Lidia Hernandez、Lawrence Hassner、Dominic A. Scudiero、Draginja B. Djurickovic、Christopher J. Michejda

  DOI：10.1021/jm00016a007

  日期：1995.8

  A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N-2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[4,5,1-de]acridim-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen. This antitumor effect was also apparent in colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo assays involving xenografts of tumor derived from HCT-116 in nude mice. The tested compounds exhibited relatively low acute toxicity and were well tolerated by the treated animals. The bisimidazoacridones interact with nucleic acids in vitro but preliminary experimental and modeling data indicate that in spite of their structure, they may not be bis-intercalators. While the precise mode of action of these compounds is not yet understood, they appear to be excellent candidates for clinical development.