tert-butyl 6-methyl-4-oxo-3,4-dihydrospiro[benzo[e][1,3]oxazine-2,4'-piperidine]-1'-carboxylate | 1204345-63-0

• 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: tert-butyl 6-methyl-4-oxo-3,4-dihydrospiro[benzo[e][1,3]oxazine-2,4'-piperidine]-1'-carboxylate
• 英文别名: tert-butyl 6-methyl-4-oxospiro[3H-1,3-benzoxazine-2,4'-piperidine]-1'-carboxylate
• CAS: 1204345-63-0
• 化学式: C₁₈H₂₄N₂O₄
• 分子量: 332.4
• InChiKey: AMGWICZGXNGBHG-UHFFFAOYSA-N

物化性质

• 沸点：
  548.3±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 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

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-methyl-4-oxo-3,4-dihydrospiro[benzo[e][1,3]oxazine-2,4'-piperidine]-1'-carboxylate 在 盐酸 、 1-丙基磷酸酐 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 1'-(1H-indazole-5-carbonyl)-6-methylspiro[benzo[e][1,3]oxazine-2,4'-piperidin]-4(3H)-one
  参考文献：
  名称：

  Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

  摘要：

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.

  DOI：

  10.1021/jm401033t
• 作为产物：
  描述：

  5-甲基水杨酰胺 、 N-叔丁氧羰基-4-哌啶酮 在 吗啉 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以19%的产率得到tert-butyl 6-methyl-4-oxo-3,4-dihydrospiro[benzo[e][1,3]oxazine-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

  摘要：

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.

  DOI：

  10.1021/jm401033t

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。
• MODULATORS OF ACETYL-COENZYME A CARBOXYLASE AND METHODS OF USE THEREOF
  申请人：Cropsolution, Inc.

  公开号：EP2310015A1

  公开（公告）日：2011-04-20
• US8110570B2
  申请人：——

  公开号：US8110570B2

  公开（公告）日：2012-02-07
• [EN] MODULATORS OF ACETYL-COENZYME A CARBOXYLASE AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE L'ACÉTYL-COENZYME A CARBOXYLASE ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：CROPSOLUTION INC

  公开号：WO2010008521A1

  公开（公告）日：2010-01-21

  The present invention provides compounds of formula I [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.
• Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure
  作者：David A. Griffith、Robert L. Dow、Kim Huard、David J. Edmonds、Scott W. Bagley、Jana Polivkova、Dongxiang Zeng、Carmen N. Garcia-Irizarry、James A. Southers、William Esler、Paul Amor、Kathrine Loomis、Kirk McPherson、Kevin B. Bahnck、Cathy Préville、Tereece Banks、Dianna E. Moore、Alan M. Mathiowetz、Elnaz Menhaji-Klotz、Aaron C. Smith、Shawn D. Doran、David A. Beebe、Matthew F. Dunn

  DOI：10.1021/jm401033t

  日期：2013.9.12

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.