6-(2-bromopropanoyl)-2H-1,4-benzoxazin-3(4H)-one | 58819-99-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-(2-bromopropanoyl)-2H-1,4-benzoxazin-3(4H)-one
• 英文别名: 6-(2-bromopropionyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazine；6-(2-bromopropanoyl)-4H-1,4-benzoxazin-3-one
• CAS: 58819-99-1
• 化学式: C₁₁H₁₀BrNO₃
• 分子量: 284.109
• InChiKey: XLDRTZBXAQUHCB-UHFFFAOYSA-N

物化性质

• 沸点：
  465.1±45.0 °C(Predicted)
• 密度：
  1.565±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  6-(2-bromopropanoyl)-2H-1,4-benzoxazin-3(4H)-one 在 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 2.0h， 生成 6-[4-(4-fluorophenyl)-1-(4-methoxybenzyl)-2-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists

  摘要：

  Dihydrofuran-2-one and dihydropyrrol-2-one derivatives were identified as novel, potent and selective mineralocorticoid receptor (MR) antagonists by the structure-based drug design approach utilizing the crystal structure of MR/compound complex. Introduction of lipophilic substituents directed toward the unfilled spaces of the MR and identification of a new scaffold, dihydropyrrol-2-one ring, led to potent in vitro activity. Among the synthesized compounds, dihydropyrrol-2-one 11i showed an excellent in vitro activity (MR binding IC50 = 43 nM) and high selectivity over closely related steroid receptors such as the androgen receptor (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) (>200-fold for AR and PR, 100-fold for GR). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.043
• 作为产物：
  描述：

  2H-1,4-苯并噁嗪-3(4H)-酮 、 2-溴丙酰氯 在 aluminum (III) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 12.0h， 以89%的产率得到6-(2-bromopropanoyl)-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists

  摘要：

  Dihydrofuran-2-one and dihydropyrrol-2-one derivatives were identified as novel, potent and selective mineralocorticoid receptor (MR) antagonists by the structure-based drug design approach utilizing the crystal structure of MR/compound complex. Introduction of lipophilic substituents directed toward the unfilled spaces of the MR and identification of a new scaffold, dihydropyrrol-2-one ring, led to potent in vitro activity. Among the synthesized compounds, dihydropyrrol-2-one 11i showed an excellent in vitro activity (MR binding IC50 = 43 nM) and high selectivity over closely related steroid receptors such as the androgen receptor (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) (>200-fold for AR and PR, 100-fold for GR). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.043

文献信息

• Imidazo-heterocyclic compounds and pharmaceutical composition comprising
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04621084A1

  公开（公告）日：1986-11-04

  New imidazo-heterocyclic compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen, lower alkyl or halogen, R.sup.2 is hydrogen, lower alkyl, halogen, aminomethyl optionally substituted with lower alkyl, or piperazin-1-yl-methyl optionally substituted with lower alkyl, R.sup.3 is a partially suturated heterocyclic group selected from benzothiazolinyl, benzoxazolinyl, benzimidazolinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 3,4-dihydro-2H-1,4-benzoxazinyl and 1,2,3,4-tetrahydroquinoxalinyl, which is substituted with oxo, thioxo, imino or lower alkylimino, and which may be substituted with lower alkyl optionally substituted with lower alkanoyloxy, lower alkoxycarbonyl, pyridyl or lower alkylamino; or an unsaturated heterocyclic group selected from benzoxazolyl and benzimidazolyl, which may be substituted with lower alkyl or pyridyl(lower)alkylthio, and Y is .dbd.N-- or a group of the formula: ##STR2## in which R.sup.4 is hydrogen, hydroxy, lower alkyl, lower alkoxy or ar(lower)alkoxy, and pharmaceutically acceptable salts thereof, and processes for preparation thereof and pharmaceutical composition comprising the same. These derivatives and pharmaceutically acceptable salts thereof are useful as cardiotonic agents and untiulcer agents.

  新的咪唑-杂环化合物的化学式翻译如下：其中R.sup.1为氢、较低的烷基或卤素，R.sup.2为氢、较低的烷基、卤素、氨甲基（可选择性地取代为较低的烷基）或哌嗪-1-基甲基（可选择性地取代为较低的烷基），R.sup.3为从苯并噻唑基、苯并噁唑基、苯并咪唑基、3,4-二氢-2H-1,4-苯并噻唑基、3,4-二氢-2H-1,4-苯并噁唑基和1,2,3,4-四氢喹喔啉基中选择的部分饱和杂环基，该基取代为氧代、硫代、亚胺或较低的烷基亚胺，并且可以取代为可选择性地取代为较低的烷基、可选择性地取代为较低的烷酰氧基、较低的烷氧羰基、吡啶基或较低的烷基氨基；或从苯并噁唑基和苯并咪唑基中选择的不饱和杂环基，该基可以取代为较低的烷基或吡啶基（较低）烷基硫基，Y为.dbd.N--或化学式的一个基团：其中R.sup.4为氢、羟基、较低的烷基、较低的烷氧基或芳基（较低）烷氧基，以及其药学上可接受的盐，以及其制备方法和包含它们的药物组合物。这些衍生物及其药学上可接受的盐可用作心力衰竭药物和抗溃疡药物。
• Studies on Antiulcer Drugs. I. Synthesis and Antiulcer Activities of Imidazo(1,2-a)pyridinyl-2-oxobenzoxazolidines-3-oxo-2H-1,4-benzoxazines and Related Compounds.
  作者：Yousuke KATSURA、Shigetaka NISHINO、Hisashi TAKASUGI

  DOI：10.1248/cpb.39.2937

  日期：——

  A series of imidazo[1, 2-α]pyridinyl-2-oxobenzoxazolidines (4a-i), -3-oxo-2H-1, 4-benzoxazines (5a-q), their thio-analogues (4j-p and 5r-t) and 5, 6, 7, 8-tetrahydroimidazo[1, 2-α]pyridinyl derivatives (8 and 9) were synthesized and tested for anti-stress ulcer activity in rats. Several compounds were found to be more active than the reference compounds, zolimidine, cimetidine and sucralfate. Among them, compound 4e, 5i and 5l also exhibited potent protective activity against ethanol-induced gastric lesion. The synthesis and structure-activity relationships of these compounds are discussed.

  合成了一系列咪唑[1, 2-α]吡啶基-2-氧苯并噁唑烷（4a-i）、-3-氧-2H-1, 4-苯并噁唑（5a-q）、它们的硫类类似物（4j-p 和 5r-t）以及5, 6, 7, 8-四氢咪唑[1, 2-α]吡啶衍生物（8和9），并对其在大鼠中进行抗应激溃疡活性测试。研究发现几个化合物的活性超过了参考化合物唑咪丁、西咪替丁和硫糖铝。其中，化合物4e、5i和5l对乙醇诱导的胃损伤表现出强大的保护活性。讨论了这些化合物的合成及结构-活性关系。
• Imidazo-heterocyclic compounds, processes for preparation thereof and pharmaceutical composition comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0120589B1

  公开（公告）日：1988-06-08
• US4621084A
  申请人：——

  公开号：US4621084A

  公开（公告）日：1986-11-04
• Design, synthesis, and structure–activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists
  作者：Tomoaki Hasui、Taiichi Ohra、Norio Ohyabu、Kouhei Asano、Hideki Matsui、Atsushi Mizukami、Noriyuki Habuka、Satoshi Sogabe、Satoshi Endo、Christopher S. Siedem、Tony P. Tang、Cassandra Gauthier、Lisa A. De Meese、Steven A. Boyd、Shoji Fukumoto

  DOI：10.1016/j.bmc.2013.07.043

  日期：2013.10

  Dihydrofuran-2-one and dihydropyrrol-2-one derivatives were identified as novel, potent and selective mineralocorticoid receptor (MR) antagonists by the structure-based drug design approach utilizing the crystal structure of MR/compound complex. Introduction of lipophilic substituents directed toward the unfilled spaces of the MR and identification of a new scaffold, dihydropyrrol-2-one ring, led to potent in vitro activity. Among the synthesized compounds, dihydropyrrol-2-one 11i showed an excellent in vitro activity (MR binding IC50 = 43 nM) and high selectivity over closely related steroid receptors such as the androgen receptor (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) (>200-fold for AR and PR, 100-fold for GR). (C) 2013 Elsevier Ltd. All rights reserved.