N-(2-(1N-tetrazol-5-yl)phenyl)-9-oxo-9H-fluorene-1-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-(1N-tetrazol-5-yl)phenyl)-9-oxo-9H-fluorene-1-carboxamide
• 英文别名: 9-oxo-N-[2-(2H-tetrazol-5-yl)phenyl]fluorene-1-carboxamide
• 化学式: C₂₁H₁₃N₅O₂
• 分子量: 367.367
• InChiKey: BLELSELIFOYDOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  9-芴酮-1-碳酰氯 、 2-(1H-四唑-5-基)苯胺 生成 N-(2-(1N-tetrazol-5-yl)phenyl)-9-oxo-9H-fluorene-1-carboxamide
  参考文献：
  名称：

  使用基于细胞和半胱天冬酶的高通量筛选测定法，发现N-芳基-9-氧代9 H-芴1-羧酰胺作为一系列新的细胞凋亡诱导剂。1.羧酰胺基团的构效关系

  摘要：

  N-（2-甲基苯基）-9-氧代-9 H-芴-1-羧酰胺（2a）通过我们的基于半胱天冬酶和基于细胞的高通量筛选测定被鉴定为新型凋亡诱导剂。发现化合物2a具有亚微摩尔效能，在T47D人乳腺癌，HCT116人结肠癌和SNU398肝细胞癌细胞中对胱天蛋白酶的诱导和生长抑制均具有活性。如通过流式细胞术测定的，其将HCT116细胞阻滞在G 2 / M中，随后凋亡。羧酰胺基团的结构-活性关系（SAR）研究确定了先导化合物N-（2-（1 H-吡唑-1-基）苯基）-9-氧代-9 H-芴-1-羧酰胺（6s）。发现具有增加的水溶性的化合物6s在半胱天冬酶激活测定和在T47D，HCT116和SNU398细胞中分别具有亚微摩尔EC 50和GI 50值的细胞生长抑制测定中保留了广泛的活性。

  DOI：

  10.1016/j.bmcl.2009.04.009

文献信息

• Substituted N-Aryl-9-Oxo-9H-Fluorene-1-Carboxamides and Analogs as Activators of Caspases and Inducers of Apoptosis
  申请人：Kemnitzer E. William

  公开号：US20080096848A1

  公开（公告）日：2008-04-24

  The present invention is directed to substituted N-aryl-9-oxo-9H-fluorene-1-carboxamides and analogs thereof, represented by the general Formula I: (I) wherein R 1 -R 8 , X and Ar are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及取代的N-芳基-9-氧代-9H-芴-1-羧酰胺及其类似物，由通式I表示：（I）其中R1-R8、X和Ar的定义如本文所述。本发明还涉及发现具有I式化合物的化合物是caspase的活化剂和凋亡诱导剂。因此，本发明的caspase活化剂和凋亡诱导剂可用于在发生异常细胞的无控制生长和扩散的各种临床情况下诱导细胞死亡。
• SUBSTITUTED N-ARYL-9-OXO-9H-FLUORENE-1-CARBOXAMIDES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS
  申请人：Cytovia, Inc.

  公开号：EP1804786A2

  公开（公告）日：2007-07-11
• EP1804786A4
  申请人：——

  公开号：EP1804786A4

  公开（公告）日：2008-01-02
• [EN] SUBSTITUTED N-ARYL-9-OXO-9H-FLUORENE-1-CARBOXAMIDES AND ANALOGS AS ACTIVATOR OF CASPASES AND INDUCERS OF APOPTOSIS<br/>[FR] N-ARYL-9-OXO-9H-FLUORENE-1-CARBOXAMIDES SUBSTITUES ET ANALOGUES UTILISES COMME ACTIVATEURS DES CASPASES ET INDUCTEURS DE L'APOPTOSE
  申请人：CYTOVIA INC

  公开号：WO2006039356A2

  公开（公告）日：2006-04-13

  The present invention is directed to substituted N-aryl-9-oxo-9H-fluorene-1-carboxamides and analogs thereof, represented by the general Formula I: (I) wherein R1-R8, X and Ar are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
• Discovery of N-aryl-9-oxo-9H-fluorene-1-carboxamides as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 1. Structure–activity relationships of the carboxamide group
  作者：William Kemnitzer、Nilantha Sirisoma、Bao Nguyen、Songchun Jiang、Shailaja Kasibhatla、Candace Crogan-Grundy、Ben Tseng、John Drewe、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2009.04.009

  日期：2009.6

  cancer, HCT116 human colon cancer, and SNU398 hepatocellular carcinoma cancer cells. It arrested HCT116 cells in G2/M followed by apoptosis as assayed by the flow cytometry. Structure–activity relationship (SAR) studies of the carboxamide group identified the lead compound N-(2-(1H-pyrazol-1-yl)phenyl)-9-oxo-9H-fluorene-1-carboxamide (6s). Compound 6s, with increased aqueous solubility, was found to retain

  N-（2-甲基苯基）-9-氧代-9 H-芴-1-羧酰胺（2a）通过我们的基于半胱天冬酶和基于细胞的高通量筛选测定被鉴定为新型凋亡诱导剂。发现化合物2a具有亚微摩尔效能，在T47D人乳腺癌，HCT116人结肠癌和SNU398肝细胞癌细胞中对胱天蛋白酶的诱导和生长抑制均具有活性。如通过流式细胞术测定的，其将HCT116细胞阻滞在G 2 / M中，随后凋亡。羧酰胺基团的结构-活性关系（SAR）研究确定了先导化合物N-（2-（1 H-吡唑-1-基）苯基）-9-氧代-9 H-芴-1-羧酰胺（6s）。发现具有增加的水溶性的化合物6s在半胱天冬酶激活测定和在T47D，HCT116和SNU398细胞中分别具有亚微摩尔EC 50和GI 50值的细胞生长抑制测定中保留了广泛的活性。