methyl 2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-carboxylate | 179950-70-0

• 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: methyl 2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-carboxylate
• 英文别名: 2,2-dimethyl-7-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine；methyl 2,2-dimethyl-3-oxo-4H-1,4-benzoxazine-7-carboxylate
• CAS: 179950-70-0
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: GESDBCNLPUFJMW-UHFFFAOYSA-N

物化性质

• 沸点：
  398.8±42.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-carboxylate 在 二异丁基氢化铝 、 盐酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲苯 、 水 、 乙醚 为溶剂， 反应 4.0h， 生成 7-(hydroxymethyl)-2,2-dimethyl-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  WO2007/89034

  摘要：

  公开号：
• 作为产物：
  描述：

  2-溴-2-甲基丙酰溴 、 4-氨基-3-羟基苯甲酸甲酯 在 碳酸氢钠 、 potassium carbonate 作用下， 以 N-甲基乙酰胺 、 水 、 乙酸乙酯 为溶剂， 生成 methyl 2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-carboxylate
  参考文献：
  名称：

  1, 4-benzoxazine derivative and pharmaceutical compositions containing

  摘要：

  公开了以下式(I)的1,4-苯并噁嗪衍生物：##STR1##或其药学上可接受的盐。本发明的化合物可用作预防或治疗由心肌缺血引起的细胞内酸中毒引起的疾病，如心脏功能障碍、心肌坏死、心律失常、再灌注损伤等，在缺血性心脏病（如心肌梗死、心绞痛等）中观察到这些症状。

  公开号：

  US05597820A1

文献信息

• Design, Synthesis and Quantitative Structure-Activity Relationship Study of N-(3-Oxo-3,4-dihydro-2H-benzo(1,4)oxazine-7-carbonyl)guanidine Derivatives as Potent Na/H Exchange Inhibitors.
  作者：Takeshi YAMAMOTO、Manabu HORI、Ikuo WATANABE、Hisayoshi TSUTSUI、Kengo HARADA、Shoji IKEDA、Joji MARUO、Tominori MORITA、Hiroshi OHTAKE

  DOI：10.1248/cpb.45.1975

  日期：——

  Inhibitiion of the Na/H exchanger is promising approach for treating ischemia-reperfusion injury, but no clinical agent is yet available. Recently, we established the structural requirements for potent inhibitors of the Na/H exchanger. In the present work, we designed N-(3-oxo-3, 4-dihydro-2H-benzo[1, 4]oxazine-7-carbonyl)guanidine 3a as a new lead compound for potent inhibitors with good water-solubility, based on the previous information. During the structural optimization, care was taken to keep the hydrophobicity (clogP) in the range of about 1.5-2.0, which is considered optimum for good bioavailability. Various derivatives of 3a were synthesized and the quantitative structure-activity relationship (QSAR) was studied. The QSAR result indicated that the lengths of the substituents at the 2- and the 4-positions of the 2H-benzo[1, 4]oxazine ring are parabolically related to activity. The most potent compounds were (R) and/or (S)-N-(2-ethyl-4-isopropyl(or ethyl)-3-oxo-3, 4-dihydro-2H-benzo[1, 4]oxazine-7-carbonyl)guanidines 3q-t with IC50 values of 0.036-0.073 μM. The water-solubility of the hydrochlorides and methanesulfonates is 3-5 mg/ml, which is sufficient for therapeutic use.

  抑制 Na/H 交换机是治疗缺血再灌注损伤的一种很有前景的方法，但目前还没有临床药物。最近，我们确定了 Na/H 交换子强效抑制剂的结构要求。在本研究中，我们根据之前的信息设计出了 N-(3-氧代-3, 4-二氢-2H-苯并[1, 4]恶嗪-7-甲酰基)胍 3a 作为一种具有良好水溶性的强效抑制剂的新先导化合物。在结构优化过程中，我们注意将疏水性（clogP）保持在约 1.5-2.0 的范围内，这被认为是具有良好生物利用度的最佳值。合成了 3a 的各种衍生物，并对其进行了定量结构-活性关系（QSAR）研究。QSAR 结果表明，2H-苯并[1, 4]恶嗪环上 2 位和 4 位取代基的长度与活性呈抛物线关系。最有效的化合物是(R)和/或(S)-N-(2-乙基-4-异丙基（或乙基）-3-氧代-3, 4-二氢-2H-苯并[1, 4]恶嗪-7-甲酰基)胍类 3q-t，IC50 值为 0.036-0.073 μM。盐酸盐和甲磺酸盐的水溶性为 3-5 毫克/毫升，足以用于治疗。
• Benzoxazines and Related Nitrogen-Containing Heterobicyclic Compounds Useful as Mineralocorticoid Receptor Modulating Agents
  申请人：Iijima Toru

  公开号：US20090023716A1

  公开（公告）日：2009-01-22

  The present invention relates to a compound, useful as a mineralocorticoid receptor-modulating agent, of the following formula [I]: wherein Ring A is a benzene ring optionally having a substituent(s) other than R 1 etc, R 1 is a group of the formula: R a SO 2 NH— etc, R a is an alkyl group etc, R 2 and R 3 are each a hydrogen atom, a phenyl group, an optionally substituted alkyl group etc, X is an oxygen atom etc, Y is a group of the formula: —C(═O)— etc, Ar is an optionally substituted aryl group or an optionally substituted heteroaryl group, Q is a single bond, an alkylene group etc, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种化合物，可用作矿物质皮质激素受体调节剂，其化学式如下[I]：其中，环A是苯环，可选地具有除R1等之外的取代基；R1是公式RaSO2NH-等的基团；R是烷基等；R2和R3分别是氢原子，苯基，可选地取代的烷基等；X是氧原子等；Y是公式-C（=O）-等的基团；Ar是可选地取代的芳基或可选地取代的杂环基；Q是单键，烷基等，或其药学上可接受的盐。
• MORPHOLINE DERIVATIVE
  申请人：Akatsuka Hidenori

  公开号：US20100240644A1

  公开（公告）日：2010-09-23

  The present invention provides a morpholine derivative of the formula [I]; wherein R 1 is a substituted alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclo group, a cycloalkyl group or an alkyl group; R 2 is a substituted alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclo group, an optionally substituted alkylcarbonyl group, an optionally substituted arylcarbonyl group, an optionally substituted heterocyclo-substituted carbonyl group or a cycloalkylcarbonyl group; T is a methylene group or a carbonyl group; R 3 , R 4 , R 5 and R 6 are the same or different and a hydrogen atom, an optionally substituted carbamoyl group or an optionally substituted alkyl group; or pharmaceutically acceptable salts thereof. These compounds are useful as a renin inhibitor.

  本发明提供了公式[I]的吗啡啶衍生物；其中R1是取代的烷基，可选取代的芳基，可选取代的杂环基，环烷基或烷基；R2是取代的烷基，可选取代的芳基，可选取代的杂环基，可选取代的烷基羰基，可选取代的芳基羰基，可选取代的杂环取代羰基或环烷基羰基；T是亚甲基或羰基；R3，R4，R5和R6相同或不同，是氢原子，可选取代的氨基甲酰基或可选取代的烷基；或其药学上可接受的盐。这些化合物可用作肾素抑制剂。
• Benzoxazines and related nitrogen-containing heterobicyclic compounds useful as mineralocorticoid receptor modulating agents
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：US08188073B2

  公开（公告）日：2012-05-29

  The present invention relates to a compound, useful as a mineralocorticoid receptor-modulating agent, of the following formula [I]: wherein Ring A is a benzene ring optionally having a substituent(s) other than R1 etc, R1 is a group of the formula: RaSO2NH— etc, Ra is an alkyl group etc, R2 and R3 are each a hydrogen atom, a phenyl group, an optionally substituted alkyl group etc, X is an oxygen atom etc, Y is a group of the formula: —C(═O)— etc, Ar is an optionally substituted aryl group or an optionally substituted heteroaryl group, Q is a single bond, an alkylene group etc, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种化合物，可用作矿物质皮质激素受体调节剂，其化学式如下[I]：其中，环A是苯环，可选地具有除R1等以外的取代基；R1是公式RaSO2NH-等的基团，Ra是烷基等；R2和R3分别是氢原子、苯基、可选地取代的烷基等；X是氧原子等；Y是公式-C（═O）-等的基团；Ar是可选地取代的芳基或可选地取代的杂环基团；Q是单键、烷基等，或其药学上可接受的盐。
• BENZOXAZINES AND RELATED NITROGEN-CONTAINING HETEROBICYCLIC COMPOUNDS USEFUL AS MINERALOCORTICOID RECEPTOR MODULATING AGENTS
  申请人：IIJIMA Toru

  公开号：US20110251185A1

  公开（公告）日：2011-10-13

  The present invention relates to a compound, useful as a mineralocorticoid receptor-modulating agent, of the following formula [I]: wherein Ring A is a benzene ring optionally having a substituent(s) other than R 1 etc, R 1 is a group of the formula: R a SO 2 NH— etc, R a is an alkyl group etc, R 2 and R 3 are each a hydrogen atom, a phenyl group, an optionally substituted alkyl group etc, X is an oxygen atom etc, Y is a group of the formula: —C(═O)— etc, Ar is an optionally substituted aryl group or an optionally substituted heteroaryl group, Q is a single bond, an alkylene group etc, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种化合物，其具有以下式[I]，可用作矿物质皮质激素受体调节剂： 其中，环A是苯环，可选择具有取代基(R1等)以外的取代基；R1是公式RaSO2NH-等的基团；R是烷基等；R2和R3分别是氢原子、苯基、可选择取代的烷基等；X是氧原子等；Y是公式-C(═O)-等的基团；Ar是可选择取代的芳基或可选择取代的杂环基；Q是单键、烷基等；或其药学上可接受的盐。