5-benzoyl-3H-1,3-benzoxazol-2-one | 132709-79-6

• 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: 5-benzoyl-3H-1,3-benzoxazol-2-one
• 英文别名: 5-Benzoyl-2(3H)-benzoxazolone；5-benzoylbenzoxazolone
• CAS: 132709-79-6
• 化学式: C₁₄H₉NO₃
• 分子量: 239.23
• InChiKey: UGXLBVHPHKIKLK-UHFFFAOYSA-N

物化性质

• 熔点：
  169-170 °C(Solv: ethanol (64-17-5))
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-benzoyl-3H-1,3-benzoxazol-2-one 、 (4-异氰酸丁基)苯 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 15.5h， 以73%的产率得到5-benzoyl-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide
  参考文献：
  名称：

  Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure–Activity Relationship (SAR) Studies

  摘要：

  Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads.

  DOI：

  10.1021/acs.jmedchem.5b01188
• 作为产物：
  描述：

  苯甲酰氯 在 盐酸 、 aluminum (III) chloride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 5-benzoyl-3H-1,3-benzoxazol-2-one
  参考文献：
  名称：

  Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure–Activity Relationship (SAR) Studies

  摘要：

  Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads.

  DOI：

  10.1021/acs.jmedchem.5b01188

文献信息

• Cyclization-Activated Prodrugs: N-(Substituted 2-hydroxyphenyl and 2-hydroxypropyl)carbamates Based on Ring-Opened Derivatives of Active Benzoxazolones and Oxazolidinones as Mutual Prodrugs of Acetaminophen
  作者：Alain Vigroux、Michel Bergon、Chantal Zedde

  DOI：10.1021/jm00020a012

  日期：1995.9

  intermediates which cyclize at any pH to the corresponding oxazolidinone drugs. As opposed to model A, the rates of hydrolysis of mutual prodrugs of model B clearly exhibit a catalytic role of the plasma. It is concluded from the plasma studies that the carbamate substrates can be enzymatically transformed into potent electrophiles, i.e., isocyanates. In the case of the present study, the prodrugs are

  分别合成了基于掩蔽的活性苯并恶唑酮（A型）和恶唑烷酮（B型）的N-（取代的2-羟苯基）-和N-（取代的2-羟丙基）氨基甲酸酯，并将其评估为潜在的药物递送系统。制备了一系列与模型A有关的烷基和芳基N-（5-氯-2-羟基苯基）氨基甲酸酯1。这些是骨骼肌松弛药氯唑沙宗的开放药物。相应的4-乙酰氨基苯甲酸酯，名为chlorzacetamol，是氯唑沙宗和对乙酰氨基酚的共同前药。通过将4-乙酰氨基苯基1,2,2,2-四氯乙基碳酸酯与适当的苯胺缩合，可在两步过程中获得氯苯乙胺和其他两种活性苯并恶唑酮和对乙酰氨基酚的互用前药。根据模型B，使用适当的胺类似地获得了对乙酰氨基酚和活性恶唑烷酮的两种互用前药（美他沙酮和美芬沙酮）。发现所有制备的氨基甲酸酯前药在水性（pH 6-11）和血浆（pH 7.4）介质中释放母体药物。在37度水介质中对前药1进行的详细机理研究表明，离去基团ROH的布朗斯台德型关系log t1
• Aromatase inhibitor compounds and uses thereof
  申请人：Park Chang-Ha

  公开号：US20070054899A1

  公开（公告）日：2007-03-08

  The invention concerns the use of a compound of formula (I) inhibitor of aromatase for the preparation of a pharmaceutical formulation intended for treatment of cancer or psoriasis. It equally relates to compounds of formula (I), notably for their use as active ingredients of a medication.

  该发明涉及使用式(I)的化合物作为芳香化酶抑制剂，用于制备用于治疗癌症或牛皮癣的药物配方。同时，它还涉及到式(I)的化合物，特别是它们作为药物的活性成分的用途。
• Regioselectivity in the c-acylation of 2(3H)-benzoxazolones
  作者：Hocine Aichaoui、Jacques H. Poupaert、Daniel Lesieur、Jean-Pierre Hénichart

  DOI：10.1016/s0040-4020(01)82317-6

  日期：1991.8

  Unequivocal synthetic routes towards 5- and 6-acyl-2(3H)-benzoxazolones are described. Comparison of the physicochemical properties of the compounds obtained by direct acylation under various Friedel-Crafts reaction conditions always leads to the conclusion that 6-acyl derivatives are the only isolated products. This observation contradicts previously published results.
• LESIEUR, DAHIEL;AISHAOUI, HOCINE;LESPAGNOL, CHARLES;BONNET, JACQUELINE
  作者：LESIEUR, DAHIEL、AISHAOUI, HOCINE、LESPAGNOL, CHARLES、BONNET, JACQUELINE

  DOI：——

  日期：——
• JPH02289557A
  申请人：——

  公开号：JPH02289557A

  公开（公告）日：1990-11-29