3-(1,3-苯并恶唑-2-基)-4-氟苯胺 | 220705-28-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-(1,3-苯并恶唑-2-基)-4-氟苯胺
• 英文名称: 3-benzoxazol-2-yl-4-fluorophenylamine
• 英文别名: 3-(1,3-Benzoxazol-2-yl)-4-fluoroaniline
• CAS: 220705-28-2
• 化学式: C₁₃H₉FN₂O
• mdl: MFCD03425815
• 分子量: 228.226
• InChiKey: GSPQMNYKHHIKRO-UHFFFAOYSA-N

物化性质

• 熔点：
  153-156
• 沸点：
  380.6±32.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

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

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  3-(1,3-苯并恶唑-2-基)-4-氟苯胺 以 二苯醚 、 乙醇 为溶剂， 反应 2.5h， 生成 ethyl 7-benzoxazol-2-yl-6-fluoro-4-hydroxyquinoline-3-carboxylate
  参考文献：
  名称：

  7-苯并恶唑-2-基和7-苯并噻唑-2-基-6-氟喹诺酮类化合物的合成

  摘要：

  氟喹诺酮类，7-苯并恶唑-2-基-1-乙基-6-氟-1,4-二氢-4-氧喹啉-3-羧酸和7-苯并噻唑-2-基-1-乙基-6-氟-合成了1，4-二氢-4-氧代喹啉-3-羧酸。这些化合物是通过使用Gould-Jacobs途径制得的喹啉环系统获得的。通过5-氨基-2-氟苯甲酸与2-氨基苯酚或2-氨基硫代苯酚的环化脱水反应，可得到所需的苯胺，3-苯并恶唑-2-基-4-氟苯胺和3-苯并噻唑-2-基-4-氟苯胺。分别使用多磷酸。

  DOI：

  10.1002/jhet.5570350610
• 作为产物：
  描述：

  邻氟苯甲酸 在 palladium on activated charcoal 硫酸 、 硝酸 、 环己烯 作用下， 以 乙醇 为溶剂， 反应 10.75h， 生成 3-(1,3-苯并恶唑-2-基)-4-氟苯胺
  参考文献：
  名称：

  7-苯并恶唑-2-基和7-苯并噻唑-2-基-6-氟喹诺酮类化合物的合成

  摘要：

  氟喹诺酮类，7-苯并恶唑-2-基-1-乙基-6-氟-1,4-二氢-4-氧喹啉-3-羧酸和7-苯并噻唑-2-基-1-乙基-6-氟-合成了1，4-二氢-4-氧代喹啉-3-羧酸。这些化合物是通过使用Gould-Jacobs途径制得的喹啉环系统获得的。通过5-氨基-2-氟苯甲酸与2-氨基苯酚或2-氨基硫代苯酚的环化脱水反应，可得到所需的苯胺，3-苯并恶唑-2-基-4-氟苯胺和3-苯并噻唑-2-基-4-氟苯胺。分别使用多磷酸。

  DOI：

  10.1002/jhet.5570350610

文献信息

• Discovery of an Orally Bioavailable Inhibitor of Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation
  作者：Jared T. Hammill、Deepak Bhasin、Daniel C. Scott、Jaeki Min、Yizhe Chen、Yan Lu、Lei Yang、Ho Shin Kim、Michele C. Connelly、Courtney Hammill、Gloria Holbrook、Cynthia Jeffries、Bhuvanesh Singh、Brenda A. Schulman、R. Kiplin Guy

  DOI：10.1021/acs.jmedchem.7b01282

  日期：2018.4.12

  We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1- UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg). This work lays out the discovery of an orally bioavailable analogue, NAcM-OPT (67). Compound 67 retains the favorable biochemical and cellular activity of compound 7 but is significantly more stable both in vitro and in vivo. Compound 67 is orally bioavailable, well tolerated in mice, and currently used to study the effects of acute pharmacologic inhibition of the DCN1-UBE2M interaction on the NEDD8/CUL pathway.
• 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.
• 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.
• Synthesis of 7-benzoxazol-2-yl and 7-benzothiazol-2-yl-6-fluoroquinolones
  作者：Thomas O. Richardson、Vinayak P. Shanbhag、Kimberly Adair、Shantel Smith

  DOI：10.1002/jhet.5570350610

  日期：1998.11

  4-dihydro-4-oxoquinoline-3-carboxylic acid, were synthesized. The compounds were obtained by use of the Gould-Jacobs route to the quinoline ring system. The required anilines, 3-benzoxazol-2-yl-4-fluorophenylamine and 3-benzothiazol-2-yl-4-fluorophenylamine were obtained by the cyclodehydration reaction of 5-amino-2-fluorobenzoic acid with 2-aminophenol or 2-aminothiophenol respectively using polyphosphoric

  氟喹诺酮类，7-苯并恶唑-2-基-1-乙基-6-氟-1,4-二氢-4-氧喹啉-3-羧酸和7-苯并噻唑-2-基-1-乙基-6-氟-合成了1，4-二氢-4-氧代喹啉-3-羧酸。这些化合物是通过使用Gould-Jacobs途径制得的喹啉环系统获得的。通过5-氨基-2-氟苯甲酸与2-氨基苯酚或2-氨基硫代苯酚的环化脱水反应，可得到所需的苯胺，3-苯并恶唑-2-基-4-氟苯胺和3-苯并噻唑-2-基-4-氟苯胺。分别使用多磷酸。