3-Oxo-2-butyl-3,4-dihydro-2H-1,4-benzoxazin | 91640-55-0

• 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: 3-Oxo-2-butyl-3,4-dihydro-2H-1,4-benzoxazin
• 英文别名: 2-butyl-3,4-dihydro-2H-1,4-benzoxazin-3-one；2-butyl-4H-benzo[1,4]oxazin-3-one；2-butyl-4H-1,4-benzoxazin-3-one
• CAS: 91640-55-0
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: SACLVFQTMNPZGV-UHFFFAOYSA-N

物化性质

• 沸点：
  362.0±31.0 °C(predicted)
• 密度：
  1.077±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.58
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-Oxo-2-butyl-3,4-dihydro-2H-1,4-benzoxazin 在 三氟乙酸 、 [双(三氟乙酰氧基)碘]苯 作用下， 反应 0.08h， 以67%的产率得到2-butyl-6-hydroxy-3,4-dihydro-2H-1,4-benzoxazin-3-one
  参考文献：
  名称：

  Bulky 1,4-benzoxazine derivatives with antifungal activity

  摘要：

  For many years the development of new azole antifungals has been quite empirically based. More recently, the publication of the crystal structure of CYP51 of Mycobacterium tuberculosis (MT-CYP51) provided new opportunities to rationalize the knowledge about antifungal action of this class of compounds. Recent studies reported that a 'channel 2 opened' conformation of the enzyme could better explain the interaction with ketoconazole (KTZ)-like drugs. Conformational changes were made on our model of Candida albicans CYP51 (CA-CYP51) previously reported and docking experiments were performed. The results allowed new KTZ analogues to be designed, by predicting that the 1,4-benzoxazine moiety could replace the KTZ aryl-piperazinyl chain. The synthesis of derivatives 12 and 13 was planned.The in vitro antifungal activity was evaluated against different Candida species and low and high capsulated strains of Cryptococcus neoformans. Since the in vitro activity do not necessarily correlate with the in vivo antifungal activity the newly synthesized compounds were also tested in a murine model of systemic C. albicans infection. The therapeutic effect was evaluated in terms of animal survival and of fungal growth in the kidneys, the target organ in systemic candidiasis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.051
• 作为产物：
  描述：

  2-溴己酰氯 在 sodium hydroxide 作用下， 以 乙醚 为溶剂， 生成 3-Oxo-2-butyl-3,4-dihydro-2H-1,4-benzoxazin
  参考文献：
  名称：

  一些 2-取代的 2H-1,4-苯并恶嗪-3(4H)-酮。

  摘要：

  DOI：

  10.1021/jm01241a034

文献信息

• [DE] SUBSTITUIERTE HETEROCYCLEN UND DEREN VERWENDUNG IN ARZNEIMITTELN<br/>[EN] SUBSTITUTED HETEROCYCLES AND THEIR USE IN MEDICAMENTS<br/>[FR] HETEROCYCLIQUES SUBSTITUES ET LEUR UTILISATION DANS DES MEDICAMENTS
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：WO1998050372A1

  公开（公告）日：1998-11-12

  (DE) Es werden Verbindungen der Formel (I) beschrieben, deren Herstellung und Verwendung in Arzneimitteln.(EN) The invention relates to compounds of formula (I), to the production of said compounds and their use in medicaments.(FR) L'invention concerne des composés de la formule (I), leur production et leur utilisation dans des médicaments.

  （德）描述了式 (I) 的化合物，及这些化合物的制备和药用用途。（英）本发明涉及式 (I) 化合物，及其制备及其用于医药品。（法）涉及式 (I) 化合物的发明，这些化合物的制备和药用用途。
• SUBSTITUIERTE HETEROCYCLEN UND DEREN VERWENDUNG IN ARZNEIMITTELN
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP0980362A1

  公开（公告）日：2000-02-23
• US6191127B1
  申请人：——

  公开号：US6191127B1

  公开（公告）日：2001-02-20
• Some 2-Substituted 2H-1,4-Benzoxazin-3(4H)-ones
  作者：Keith W. Wheeler

  DOI：10.1021/jm01241a034

  日期：1962.11.1
• Bulky 1,4-benzoxazine derivatives with antifungal activity
  作者：Renata Fringuelli、Nicola Giacchè、Lara Milanese、Elio Cenci、Antonio Macchiarulo、Anna Vecchiarelli、Gabriele Costantino、Fausto Schiaffella

  DOI：10.1016/j.bmc.2009.04.051

  日期：2009.6

  For many years the development of new azole antifungals has been quite empirically based. More recently, the publication of the crystal structure of CYP51 of Mycobacterium tuberculosis (MT-CYP51) provided new opportunities to rationalize the knowledge about antifungal action of this class of compounds. Recent studies reported that a 'channel 2 opened' conformation of the enzyme could better explain the interaction with ketoconazole (KTZ)-like drugs. Conformational changes were made on our model of Candida albicans CYP51 (CA-CYP51) previously reported and docking experiments were performed. The results allowed new KTZ analogues to be designed, by predicting that the 1,4-benzoxazine moiety could replace the KTZ aryl-piperazinyl chain. The synthesis of derivatives 12 and 13 was planned.The in vitro antifungal activity was evaluated against different Candida species and low and high capsulated strains of Cryptococcus neoformans. Since the in vitro activity do not necessarily correlate with the in vivo antifungal activity the newly synthesized compounds were also tested in a murine model of systemic C. albicans infection. The therapeutic effect was evaluated in terms of animal survival and of fungal growth in the kidneys, the target organ in systemic candidiasis. (C) 2009 Elsevier Ltd. All rights reserved.