N-(4-methoxy-2-nitrophenyl)-4-pyridinecarboxamide | 68279-97-0

• 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-(4-methoxy-2-nitrophenyl)-4-pyridinecarboxamide
• 英文别名: N-(4-methoxy-2-nitrophenyl)pyridine-4-carboxamide
• CAS: 68279-97-0
• 化学式: C₁₃H₁₁N₃O₄
• 分子量: 273.248
• InChiKey: JOVGZSBPOPXXFG-UHFFFAOYSA-N

物化性质

• 沸点：
  383.0±37.0 °C(Predicted)
• 密度：
  1.384±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  异烟酸酰氯 、 2-硝基-4-甲氧基苯胺 生成 N-(4-methoxy-2-nitrophenyl)-4-pyridinecarboxamide
  参考文献：
  名称：

  Substituted nicotinamides and analogs as activators of caspases and inducers of apoptosis and the use thereof

  摘要：

  本发明涉及代替烟酰胺和其类似物，由公式V:1表示或其药学上可接受的盐或前药，其中：Ar'和Ar分别是可选取代的芳基或可选取代的杂芳基，但是所述可选取代的杂芳基的环结构不包括超过两个氮原子；R11是氢；或烷基，环烷基，芳基或杂芳基，每个都是可选取代的。本发明还涉及发现公式V化合物是caspase的激活剂和凋亡诱导剂。因此，本发明的化合物可用于在各种临床情况下诱导细胞死亡，其中发生异常细胞的不受控制的生长和扩散。

  公开号：

  US20020010185A1

文献信息

• Substituted nicotinamides and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cytovia, Inc.

  公开号：US20020010185A1

  公开（公告）日：2002-01-24

  The present invention is directed to substituted nicotinamides and analogs thereof, represented by Formula V: 1 or a pharmaceutically acceptable salt or prodrug thereof, wherein: Ar′ and Ar are independently optionally substituted aryl or optionally substituted heteroaryl, provided that the ring structure of said optionally substituted heteroaryl comprises not more than two nitrogen atoms; and R 11 is hydrogen; or alkyl, cycloalkyl, aryl or heteroaryl, each of which is optionally substituted. The present invention also relates to the discovery that compounds having Formula V are activators of caspases and inducers of apoptosis. Therefore, the compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及被代换的烟酰胺和其类似物，由化学式V:1或其药学上可接受的盐或前药所代表，其中：Ar′和Ar分别是可选择代替的芳基或可选择代替的杂芳基，前提是所述可选择代替的杂芳基的环结构不超过两个氮原子；以及R11为氢；或烷基，环烷基，芳基或杂芳基，每种都可选择代替。本发明还涉及发现具有化学式V的化合物是caspases的激活剂和凋亡诱导剂。因此，本发明的化合物可用于诱导在各种临床病况中发生未受控制的异常细胞生长和扩散的细胞死亡。
• [EN] SUBSTITUTED NICOTINAMIDES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF<br/>[FR] NICOTINAMIDES SUBSTITUEES, LEURS ANALOGUES, ACTIVATEURS DES CASPASES ET INDUCTEURS DE L'APOPTOSE ET LEUR EMPLOI
  申请人：CYTOVIA INC

  公开号：WO2001055115A1

  公开（公告）日：2001-08-02

  The present invention is directed to substituted nicotinamides and analogs thereof, represented by Formula (V) or a pharmaceutically acceptable salt or prodrug thereof, wherein: Ar' and Ar are independently optionally substituted aryl or optionally substituted heteroaryl, provided that the ring structure of said optionally substituted heteroaryl comprises not more than two nitrogen atoms; and R11 is hydrogen; or alkyl, cycloalkyl, aryl or heteroaryl, each of which is optionally substituted. The present invention also relates to the discovery that compounds having Formula (V) are activators of caspases and inducers of apoptosis. Therefore, the compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及代替烟酰胺和其类似物，由式（V）或其药学上可接受的盐或前药所表示，其中：Ar'和Ar分别是可选取的取代芳基或可选取的取代杂环芳基，但所述可选取的杂环芳基的环结构不包括超过两个氮原子；R11是氢；或是可选取的烷基、环烷基、芳基或杂环芳基，每个都可以被取代。本发明还涉及到发现具有式（V）的化合物是caspase的激活剂和凋亡诱导剂。因此，本发明的化合物可用于在各种临床情况下诱导细胞死亡，其中发生异常细胞的无控制生长和扩散。
• SUBSTITUTED NICOTINAMIDES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1257536A1

  公开（公告）日：2002-11-20
• US6794397B2
  申请人：——

  公开号：US6794397B2

  公开（公告）日：2004-09-21
• Discovery of Substituted <i>N</i>-Phenyl Nicotinamides as Potent Inducers of Apoptosis Using a Cell- and Caspase-Based High Throughput Screening Assay
  作者：Sui Xiong Cai、Bao Nguyen、Shaojuan Jia、John Herich、John Guastella、Sanjeeva Reddy、Ben Tseng、John Drewe、Shailaja Kasibhatla

  DOI：10.1021/jm0205200

  日期：2003.6.1

  By applying a novel cell- and caspase-based HTS assay, a series of N-phenyl nicotinamides has been identified as a new class of potent inducers of apoptosis. Through SAR studies, a 20-fold increase in potency was achieved from a screening hit N-(4-methoxy-2-nitrophenyl)-pyridine-3-carboxamide (1) to lead compound 6-methyl-N-(4-ethoxy-2-nitrophenyl)pyridine-3-carboxamide (10), with an EC50 of 0.082 muM in the caspase activation assay in T47D breast cancer cells. The N-phenyl nicotinamides also were found to be active in the growth inhibition assay where compound 10 had a GI(50) value of 0.21 muM in T47D cells. More importantly, compound 10 was found to be equipotent in MES-SA cells and paclitaxel-resistant, p-glycoprotein overexpressed MES-SA/DX5 cells. Compounds 1 and 6-chloro-N-(4-ethoxy-2-nitrophenyl)pyridine-3-carboxamide (8), a more potent analogue, were found to arrest T47D cells in G(2)/M phase of the cell cycle followed by induction of apoptosis as measured by flow cytometry. Compound 8, which was more potent than 1 in the caspase activation assay, also was found to be more potent in G(2)/M arrest and apoptosis assay. These data confirm that the cell-based caspase activation assay is useful for screening for inducers of apoptosis, as well as for SAR studies and lead optimization. Upon further characterization, N-phenyl nicotinamides were found to be inhibitors of microtubule polymerization in vitro. The identification of N-phenyl nicotinamides as a novel series of inducers of apoptosis demonstrates that our cell- and caspase-based FITS assay is useful for the discovery and optimization of potentially novel anticancer agents.