5-(1,3-Benzoxazol-2-yl)-2-fluoroaniline | 1159516-92-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(1,3-Benzoxazol-2-yl)-2-fluoroaniline
• CAS: 1159516-92-3
• 化学式: C₁₃H₉FN₂O
• 分子量: 228.226
• InChiKey: DMUHVOBSPYRTSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氯-5-硝基苯甲酰氯 、 5-(1,3-Benzoxazol-2-yl)-2-fluoroaniline 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以90%的产率得到N-[5-(1,3-benzoxazol-2-yl)-2-fluorophenyl]-2-chloro-5-nitrobenzamide
  参考文献：
  名称：

  Optimization of Chloronitrobenzamides (CNBs) as Therapeutic Leads for Human African Trypanosomiasis (HAT)

  摘要：

  We previously reported the discovery of the activity of chloronitrobenzamides (CNBs) against bloodstream forms of Trypanosoma brucei. Herein we disclose extensive structure activity relationship and structure property relationship studies aimed at identification of tractable early leads for clinical development. These studies revealed a promising lead compound, 17b, that exhibited nanomolar potency against T. brucei (EC50 = 27 nM for T. b. brucei, 7 nM for T. b. rhodesiense, and 2 nM for T. b. gambiense) with excellent selectivity for parasite cells relative to mammalian cell lines (EC50 > 25 mu M). In addition compound 17b displayed suitable physiochemical characteristics and microsomal stability (t(1/2) > 4 h for human and mouse) to justify pursuing in vivo studies.

  DOI：

  10.1021/jm301687p

文献信息

• Optimization of the electrophile of chloronitrobenzamide leads active against Trypanosoma brucei
  作者：Jong Yeon Hwang、David C. Smithson、Gloria Holbrook、Fangyi Zhu、Michele C. Connelly、Marcel Kaiser、Reto Brun、R. Kiplin Guy

  DOI：10.1016/j.bmcl.2013.05.049

  日期：2013.7

  We previously reported the phenylchloronitrobenzamides (PCNBs), a novel class of compounds active against the species of trypanosomes that cause Human African Trypanosomiasis (HAT). Herein, we explored the potential to adjust the reactivity of the electrophilic chloronitrobenzamide core. These studies identified compound 7d that potently inhibited the growth of trypanosomes (EC50 = 120 nM for Trypanosoma b. brucei, 18 nM for Trypanosoma b. rhodesiense, and 38 nM for Trypanosoma b. gambiense) without significant cytotoxicity against mammalian cell lines (EC50 > 25 mu M for HepG2, HEK293, Raji, and BJ cell lines) and also had good stability in microsomal models (t(1/2) > 4 h in both human and mouse). Overall these properties indicate the compound 7d and its analogs are worth further exploration as potential leads for HAT. (C) 2013 Elsevier Ltd. All rights reserved.
• [EN] AGENT FOR TREATMENT OR PREVENTION OF DISEASES ASSOCIATED WITH ACTIVITY OF NEUROTROPHIC FACTORS<br/>[FR] AGENT DE TRAITEMENT OU DE PRÉVENTION DE MALADIES ASSOCIÉES À L'ACTIVITÉ D'AGENTS NEUROTROPHIQUES
  申请人：SUMITOMO CHEMICAL CO

  公开号：WO2010137349A1

  公开（公告）日：2010-12-02

  神経栄養因子の活性を増強し、かつ神経細胞保護作用を有する化合物を提供する。 式（Ｉ）で示される化合物、その薬学的に許容される塩、又はその溶媒和物。 式中、 ＺはＮ、又はＣ－Ｒ２を表し、 Ｘは、 Ｎ－Ｒ３、Ｏ、又はＳを表し、 Ｙは、 Ｃ－Ｒ４、又はＮを表し、 Ｒ１は、 水素原子、置換されていてもよい非環状炭化水素基、または置換されていてもよい環状基を表し、 Ｒ２は、水素原子、置換されていてもよい非環状炭化水素基、又は置換されていてもよい環状基を表し、 Ｒ３は、水素原子、又は置換基を表し、 Ｒ４は、水素原子、又は置換基を表し、 環Ａは、 置換されていてもよいベンゼン環を表し、 環Ｂは、 置換されていてもよいベンゼン環を表す。
• Optimization of Chloronitrobenzamides (CNBs) as Therapeutic Leads for Human African Trypanosomiasis (HAT)
  作者：Jong Yeon Hwang、David Smithson、Fangyi Zhu、Gloria Holbrook、Michele C. Connelly、Marcel Kaiser、Reto Brun、R. Kiplin Guy

  DOI：10.1021/jm301687p

  日期：2013.4.11

  We previously reported the discovery of the activity of chloronitrobenzamides (CNBs) against bloodstream forms of Trypanosoma brucei. Herein we disclose extensive structure activity relationship and structure property relationship studies aimed at identification of tractable early leads for clinical development. These studies revealed a promising lead compound, 17b, that exhibited nanomolar potency against T. brucei (EC50 = 27 nM for T. b. brucei, 7 nM for T. b. rhodesiense, and 2 nM for T. b. gambiense) with excellent selectivity for parasite cells relative to mammalian cell lines (EC50 > 25 mu M). In addition compound 17b displayed suitable physiochemical characteristics and microsomal stability (t(1/2) > 4 h for human and mouse) to justify pursuing in vivo studies.