methyl 2,3-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoate | 848846-67-3

• 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 2,3-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoate
• 英文别名: methyl 2,3-dimethyl-4-[[(2S)-4-methyl-2,3-dihydro-1,4-benzoxazin-2-yl]methoxy]benzoate
• CAS: 848846-67-3
• 化学式: C₂₀H₂₃NO₄
• 分子量: 341.407
• InChiKey: QAMMQLJUMXPKQS-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2,3-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoate 在 草酰氯 、 20% palladium hydroxide on carbon 、 四丁基氯化铵 、 氢气 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 6.33h， 生成 [1-(2,3-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoyl)-2-methyl-1H-indol-3-yl]acetic acid
  参考文献：
  名称：

  Discovery of selective indole-based prostaglandin D2 receptor antagonist

  摘要：

  A series of N-benzoyl-2-methylindole-3-acetic acids were synthesized and biologically evaluated as prostaglandin (PG) D-2 receptor antagonists. Some of the selected compounds significantly inhibited OVA-induced vascular permeability in guinea pig conjunctiva after oral dosing. Structure-activity relationship study is presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.014
• 作为产物：
  描述：

  (S)-2-hydroxymethyl-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazine 在 4-二甲氨基吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 methyl 2,3-dimethyl-4-{[(2S)-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methoxy}benzoate
  参考文献：
  名称：

  Discovery of selective indole-based prostaglandin D2 receptor antagonist

  摘要：

  A series of N-benzoyl-2-methylindole-3-acetic acids were synthesized and biologically evaluated as prostaglandin (PG) D-2 receptor antagonists. Some of the selected compounds significantly inhibited OVA-induced vascular permeability in guinea pig conjunctiva after oral dosing. Structure-activity relationship study is presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.014

文献信息

• Carboxylic acid compounds and medicinal compositions containing the same as the active ingredient
  申请人：Naganawa Atsushi

  公开号：US20070004716A1

  公开（公告）日：2007-01-04

  A compound represented by formula (I) wherein the symbols in the formula are the same meanings as those in specification, salts thereof, solvates thereof, or prodrugs thereof binds to DP receptor and shows antagonistic activity for DP receptor. Thus, it is useful for prevention and/or treatment of diseases such as allergic disease (e.g., allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, disorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, urticaria, eczema, diseases accompanied by itch (e.g., atopic dermatitis and urticaria), diseases (e.g., cataract, retinal detachment, inflammation, infection and sleeping disorders) which is generated secondarily as a result of behavior accompanied by itch (e.g., scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis, etc. Since it specifically binds to DP receptor and binds weakly to other prostaglandins receptors, they can be pharmaceuticals having little side effect.

  化合物的化学式为（I），其中公式中的符号与说明书中的含义相同，其盐、溶剂化物或前药具有DP受体结合和DP受体拮抗活性。因此，它可用于预防和/或治疗过敏性疾病（如过敏性鼻炎、过敏性结膜炎、特应性皮炎、支气管哮喘和食物过敏）、全身性肥大细胞病、伴随全身性肥大细胞激活的疾病、过敏性休克、支气管收缩、荨麻疹、湿疹、伴有瘙痒的疾病（如特应性皮炎和荨麻疹）、由于瘙痒行为（如搔抓和敲打）引起的炎症、慢性阻塞性肺疾病、缺血再灌注损伤、脑血管意外、慢性类风湿性关节炎、胸膜炎、溃疡性结肠炎等疾病的治疗。由于它特异性地结合于DP受体，并且弱地结合于其他前列腺素受体，因此可以作为副作用较小的药物。
• CARBOXYLIC ACID COMPOUNDS AND MEDICINAL COMPOSITIONS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1666473B1

  公开（公告）日：2013-01-02
• US7601712B2
  申请人：——

  公开号：US7601712B2

  公开（公告）日：2009-10-13
• US8138335B2
  申请人：——

  公开号：US8138335B2

  公开（公告）日：2012-03-20
• Discovery of selective indole-based prostaglandin D2 receptor antagonist
  作者：Maki Iwahashi、Atsushi Shimabukuro、Takahiro Onoda、Yoko Matsunaga、Yutaka Okada、Ryoji Matsumoto、Fumio Nambu、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2011.06.014

  日期：2011.8

  A series of N-benzoyl-2-methylindole-3-acetic acids were synthesized and biologically evaluated as prostaglandin (PG) D-2 receptor antagonists. Some of the selected compounds significantly inhibited OVA-induced vascular permeability in guinea pig conjunctiva after oral dosing. Structure-activity relationship study is presented. (C) 2011 Elsevier Ltd. All rights reserved.