5-(2-bromoacetyl)-3H-1,3-benzoxazol-2-one | 58820-00-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 5-(2-bromoacetyl)-3H-1,3-benzoxazol-2-one
• CAS: 58820-00-1
• 化学式: C₉H₆BrNO₃
• 分子量: 256.056
• InChiKey: IZDIYPMQPYXDNU-UHFFFAOYSA-N

物化性质

• 熔点：
  200 °C
• 密度：
  1.744±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 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-(2-bromoacetyl)-3H-1,3-benzoxazol-2-one 、 二苯基亚磷酸甲酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以80%的产率得到
  参考文献：
  名称：

  β-Ketophosphonates as β-lactamase inhibitors: Intramolecular cooperativity between the hydrophobic subsites of a class D β-lactamase

  摘要：

  A series of aryl and arylmethyl beta-aryl-beta-ketophosphonates have been prepared as potential beta-lactamase inhibitors. These compounds, as fast, reversible, competitive inhibitors, were most effective ( micromolar K(i) values) against the class D OXA-1 b-lactamase but had less activity against the OXA-10 enzyme. They were also quite effective against the class C b-lactamase of Enterobacter cloacae P99 but less so against the class A TEM-2 enzyme. Reduction of the keto group to form the corresponding beta-hydroxyphosphonates led to reduced inhibitory activity. Molecular modeling, based on the OXA-1 crystal structure, suggested interaction of the aryl groups with the hydrophobic elements of the enzyme's active site and polar interaction of the keto and phosphonate groups with the active site residues Ser 115, Lys 212 and Thr 213 and with the non-conserved Ser 258. Analysis of binding free energies showed that the beta-aryl and phosphonate ester aryl groups interacted cooperatively within the OXA-1 active site. Overall, the results suggest that quite effective inhibitors of class C and some class D beta-lactamases could be designed, based on the beta-ketophosphonate platform. (c) 2008 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.05.045
• 作为产物：
  描述：

  2-苯并唑啉酮 、 溴乙酰溴 在 三氯化铝 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以82%的产率得到5-(2-bromoacetyl)-3H-1,3-benzoxazol-2-one
  参考文献：
  名称：

  β-Ketophosphonates as β-lactamase inhibitors: Intramolecular cooperativity between the hydrophobic subsites of a class D β-lactamase

  摘要：

  A series of aryl and arylmethyl beta-aryl-beta-ketophosphonates have been prepared as potential beta-lactamase inhibitors. These compounds, as fast, reversible, competitive inhibitors, were most effective ( micromolar K(i) values) against the class D OXA-1 b-lactamase but had less activity against the OXA-10 enzyme. They were also quite effective against the class C b-lactamase of Enterobacter cloacae P99 but less so against the class A TEM-2 enzyme. Reduction of the keto group to form the corresponding beta-hydroxyphosphonates led to reduced inhibitory activity. Molecular modeling, based on the OXA-1 crystal structure, suggested interaction of the aryl groups with the hydrophobic elements of the enzyme's active site and polar interaction of the keto and phosphonate groups with the active site residues Ser 115, Lys 212 and Thr 213 and with the non-conserved Ser 258. Analysis of binding free energies showed that the beta-aryl and phosphonate ester aryl groups interacted cooperatively within the OXA-1 active site. Overall, the results suggest that quite effective inhibitors of class C and some class D beta-lactamases could be designed, based on the beta-ketophosphonate platform. (c) 2008 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.05.045

文献信息

• [EN] SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES BICYCLIQUES SUBSTITUÉS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017184662A1

  公开（公告）日：2017-10-26

  Disclosed are compounds of Formula (I), or a salt thereof, wherein: X is CR4 or N; Y is CR4 or N, provided that Y is N only if X is N; R1 is Formulae (A) or (B); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, R3, R4, L1, R1a, R1b, R1c, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.

  揭示了Formula (I)的化合物或其盐，其中：X为CR4或N；Y为CR4或N，但仅当X为N时，Y才为N；R1为Formulae (A)或(B)；每个W独立地为NR1b或O；Z为键或CHR1d；R1、R2、R3、R4、L1、R1a、R1b、R1c和n在此有定义。还揭示了将这些化合物用作ROMK的抑制剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗心血管疾病方面是有用的。