6-溴-4-氧代-3,4-二氢螺[苯并[e][1,3]噁嗪-2,4-哌啶]-1-羧酸叔丁酯 | 690632-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 中文名称: 6-溴-4-氧代-3,4-二氢螺[苯并[e][1,3]噁嗪-2,4-哌啶]-1-羧酸叔丁酯
• 中文别名: 6-溴螺[1,3-苯并恶嗪-2,4'-哌啶]-4（3H）-酮，N-BOCprotected
• 英文名称: 6-bromo-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-1'-carboxylic acid tert-butyl ester
• 英文别名: 6-bromo-1'-(tert-butyloxycarbonyl)spiro[1,3-benzoxazine-2,4'-piperidine]-4(3H)-one；tert-Butyl 6-bromo-4-oxo-3,4-dihydrospiro[benzo[e][1,3]oxazine-2,4'-piperidine]-1'-carboxylate；tert-butyl 6-bromo-4-oxospiro[3H-1,3-benzoxazine-2,4'-piperidine]-1'-carboxylate
• CAS: 690632-05-4
• 化学式: C₁₇H₂₁BrN₂O₄
• 分子量: 397.269
• InChiKey: FKBBJWUNJKLMBK-UHFFFAOYSA-N

物化性质

• 熔点：
  226 °C
• 沸点：
  571.5±50.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 储存条件：
  2-8℃，密封保存，并保持干燥环境。

反应信息

• 作为反应物：
  描述：

  6-溴-4-氧代-3,4-二氢螺[苯并[e][1,3]噁嗪-2,4-哌啶]-1-羧酸叔丁酯 在 盐酸 、 palladium diacetate 、 sodium hydride 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 、 三(邻甲基苯基)磷 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 13.67h， 生成 methyl (E)-3-(1'-benzyl-3-methyl-4-oxospiro[1,3-benzoxazine-2,4'-piperidine]-6-yl)prop-2-enoate
  参考文献：
  名称：

  Synthesis and biological characterization of spiro[2H-(1,3)-benzoxazine-2,4′-piperidine] based histone deacetylase inhibitors

  摘要：

  Histone Deacetylases (HDACs) have become important targets for the treatment of cancer and other diseases. In previous studies we described the development of novel spirocyclic HDAC inhibitors based on the combination of privileged structures with hydroxamic acid moieties as zinc binding group. Herein, we report further explorations, which resulted in the discovery of a new class of spiro[2H-(1,3)-benzoxazine-2,4'-piperidine] derivatives. Several compounds showed good potency of around 100 nM and less in the HDAC inhibition assays, submicromolar IC50 values when tested against tumour cell lines and a remarkable stability in human and mouse microsomes. Two representative examples exhibited a good pharmacokinetic profile with an oral bioavailability equal or higher than 35% and one of them studied in an HCT116 murine xenograft model showing a robust tumour growth inhibition. In addition, the two benzoxazines were found to have a minor affinity for the hERG potassium channel compared to their corresponding ketone analogues. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.061
• 作为产物：
  描述：

  5-溴水杨酰胺 、 N-叔丁氧羰基-4-哌啶酮 在 四氢吡咯 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以40%的产率得到6-溴-4-氧代-3,4-二氢螺[苯并[e][1,3]噁嗪-2,4-哌啶]-1-羧酸叔丁酯
  参考文献：
  名称：

  Spirocyclic derivatives as histone deacetylase inhibitors

  摘要：

  这项发明涉及新的组蛋白去乙酰化酶抑制剂，其一般公式为（I），其中：虚线是可选的附加键；n为零或1至4之间的整数；R1为氢；C1-C6烷基，可选地被芳基或杂环烷基取代；（CO）R3；（SO2）R4；芳基；或杂环烷基；R2为C1-C6烷基，可选地被芳基或杂环烷基取代；芳基；杂环烷基；或（CO）R5；X为CH2，氧或NR6；Y为键，CHR7或NR8；Z为氧，CR9R10或C=R11；而R3、R4、R5、R6、R3、R8、R9、R10和R11如规范中进一步定义；以及其药用可接受的盐。

  公开号：

  EP2110377A1

文献信息

• Modulators of Acetyl-Coenzyme A Carboxylase and Methods of Use Thereof
  申请人：Anderson Richard

  公开号：US20100009982A1

  公开（公告）日：2010-01-14

  The present invention provides compounds of formula I: along with methods of use of these compounds as pharmaceuticals, particularly in the treatment of obesity, metabolic syndrome, atherosclerosis, cardiovascular disease, insulin resistance, diseases associated with reduced neuronal metabolism, and cancer as well as the use of these compounds for treatment of pathogens of humans and animals, and for the control of agricultural pests, particularly fungi, weeds and insects.

  本发明提供了I式化合物，以及这些化合物作为药物的使用方法，特别是在肥胖、代谢综合征、动脉粥样硬化、心血管疾病、胰岛素抵抗、与减少神经代谢有关的疾病和癌症的治疗中的应用，以及这些化合物用于治疗人类和动物的病原体，并用于控制农业害虫，特别是真菌、杂草和昆虫。
• SPIROCYCLIC DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
  申请人：Varasi Mario

  公开号：US20140080823A1

  公开（公告）日：2014-03-20

  This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R 1 is hydrogen; C 1 -C 6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R 3 ; (SO 2 )R 4 ; cycloalkyl; aryl; or heteroaryl; R 2 is C 1 -C 6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R 5 ; X is CH 2 , oxygen or NR 6 ; Y is a bond, CHR 7 or NR 8 ; Z is oxygen, CR 9 R 10 or C═R 11 ; and R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

  本发明涉及新的组蛋白去乙酰化酶抑制剂，其通式为(I)，其中：虚线是可选的额外键；n为零或1至4的整数；R1为氢；C1-C6烷基，可选地被环烷基、芳基或杂芳基取代；(CO)R3；(SO2)R4；环烷基；芳基；或杂芳基；R2为C1-C6烷基，可选地被芳基或杂芳基取代；芳基；杂芳基；或(CO)R5；X为CH2、氧或NR6；Y为键、CHR7或NR8；Z为氧、CR9R10或C═R11；而R3、R4、R5、R6、R7、R8、R9、R10和R11如规范中所进一步定义的；以及其药学上可接受的盐。
• US8110570B2
  申请人：——

  公开号：US8110570B2

  公开（公告）日：2012-02-07
• US8592444B2
  申请人：——

  公开号：US8592444B2

  公开（公告）日：2013-11-26
• US9115148B2
  申请人：——

  公开号：US9115148B2

  公开（公告）日：2015-08-25