N-(2-hydroxymethylphenyl)-3,3-difluoroazetidin-2-one | 131230-66-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: N-(2-hydroxymethylphenyl)-3,3-difluoroazetidin-2-one
• 英文别名: N-(2-hydroxymethyl phenyl) 3,3-difluoro-2-azetidinone；N-(2-hydroxymethyl phenyl)-3,3-difluoro-2-azetidinone；3,3-difluoro-1-[2-(hydroxymethyl)phenyl]azetidin-2-one
• CAS: 131230-66-5
• 化学式: C₁₀H₉F₂NO₂
• 分子量: 213.184
• InChiKey: WYVNLQCWZMKNBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxymethylphenyl)-3,3-difluoroazetidin-2-one 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 以51%的产率得到1-[2-(氯甲基)苯基]-3,3-二氟氮杂环丁-2-酮
  参考文献：
  名称：

  Inhibition of human leukocyte elastase by functionalized N-aryl azetidin-2-ones: substituent effects at C-3 and benzylic positions

  摘要：

  A series of functionalized N-aryl azetidin-2-ones with a latent alkylating group was prepared by a flexible four-step synthesis. They met criteria expected for a suicide-type inactivation of human leukocyte elastase (HLE) and porcine pancreatic elastase (PPE), with no inactivation of trypsin- and chymotrypsin-like proteases. The inhibition potency was dependent on the halogen substituents at C-3 (F, F; Cl, Cl; Br, Br) and the nature and the position relative to nitrogen of the latent benzylic leaving group (F, Cl, Br). Better inactivations of HLE compared with PPE were observed with azetidinones gem-disubstituted by Cl and Br rather than by F. Their protio analogs, which are devoid of the latent quinoniminium methide electrophile, behave as simple substrates of elastases.

  DOI：

  10.1016/0223-5234(96)88226-2
• 作为产物：
  描述：

  N-(2-tert-butyldimethylsilyloxymethylphenyl)-3,3-difluoroazetidin-2-one 在 氢氟酸 作用下， 以 乙腈 为溶剂， 反应 0.08h， 以59%的产率得到N-(2-hydroxymethylphenyl)-3,3-difluoroazetidin-2-one
  参考文献：
  名称：

  Inhibition of human leukocyte elastase by functionalized N-aryl azetidin-2-ones: substituent effects at C-3 and benzylic positions

  摘要：

  A series of functionalized N-aryl azetidin-2-ones with a latent alkylating group was prepared by a flexible four-step synthesis. They met criteria expected for a suicide-type inactivation of human leukocyte elastase (HLE) and porcine pancreatic elastase (PPE), with no inactivation of trypsin- and chymotrypsin-like proteases. The inhibition potency was dependent on the halogen substituents at C-3 (F, F; Cl, Cl; Br, Br) and the nature and the position relative to nitrogen of the latent benzylic leaving group (F, Cl, Br). Better inactivations of HLE compared with PPE were observed with azetidinones gem-disubstituted by Cl and Br rather than by F. Their protio analogs, which are devoid of the latent quinoniminium methide electrophile, behave as simple substrates of elastases.

  DOI：

  10.1016/0223-5234(96)88226-2

文献信息

• N-aryl-azetidinones, their preparation process and their use as elastase
  申请人：Scientifique

  公开号：US05030628A1

  公开（公告）日：1991-07-09

  The invention relates to N-aryl-azetidinones, their preparation process and their use as active serine elastase inhibitors. The N-aryl-azetidinones are in accordance with formula: ##STR1## in which R.sup.1 and R.sup.2 can be a halogen atom or an organic radical, R.sup.3 represents a halogen atom or another good starting group and R.sup.4 represents H or an organic radical. The compounds with R.sup.3 .dbd.Cl or OSO.sub.2 CH.sub.3, R.sup.4 .dbd.H and R.sup.1 .dbd.R.sup.2 .dbd.F or R.sup.1 .dbd.F and R.sup.2 .dbd.Br are irreversible and selective elastase inhibitors.

  该发明涉及N-芳基-氮杂环丙酮酸酯，其制备过程以及它们作为活性丝氨酸弹性蛋白酶抑制剂的用途。N-芳基-氮杂环丙酮酸酯符合以下结构式：##STR1## 其中R.sup.1和R.sup.2可以是卤素原子或有机基团，R.sup.3代表卤素原子或另一个良好的起始基团，R.sup.4代表H或有机基团。具有R.sup.3 .dbd.Cl或OSO.sub.2 CH.sub.3，R.sup.4 .dbd.H和R.sup.1 .dbd.R.sup.2 .dbd.F或R.sup.1 .dbd.F和R.sup.2 .dbd.Br的化合物是不可逆和选择性的弹性蛋白酶抑制剂。
• JOYEAU, ROGER;KOBAITER, RANDA;WAKSELMAN, MICHEL;REBOUD, MICHELE
  作者：JOYEAU, ROGER、KOBAITER, RANDA、WAKSELMAN, MICHEL、REBOUD, MICHELE

  DOI：——

  日期：——
• US5030628A
  申请人：——

  公开号：US5030628A

  公开（公告）日：1991-07-09
• Inhibition of human leukocyte elastase by functionalized N-aryl azetidin-2-ones: substituent effects at C-3 and benzylic positions
  作者：I Vergely、N Boggetto、V Okochi、S Golpayegani、M Reboud-Ravaux、R Kobaiter、R Joyeau、M Wakselman

  DOI：10.1016/0223-5234(96)88226-2

  日期：1995.1

  A series of functionalized N-aryl azetidin-2-ones with a latent alkylating group was prepared by a flexible four-step synthesis. They met criteria expected for a suicide-type inactivation of human leukocyte elastase (HLE) and porcine pancreatic elastase (PPE), with no inactivation of trypsin- and chymotrypsin-like proteases. The inhibition potency was dependent on the halogen substituents at C-3 (F, F; Cl, Cl; Br, Br) and the nature and the position relative to nitrogen of the latent benzylic leaving group (F, Cl, Br). Better inactivations of HLE compared with PPE were observed with azetidinones gem-disubstituted by Cl and Br rather than by F. Their protio analogs, which are devoid of the latent quinoniminium methide electrophile, behave as simple substrates of elastases.