1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate | 884487-29-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: 1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate
• 英文别名: 1-tert-butyl 4-ethyl 6-methyl-5-oxoazepane-1,4-dicarboxylate；6-methyl-5-oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester；1-O-tert-butyl 4-O-ethyl 6-methyl-5-oxoazepane-1,4-dicarboxylate
• CAS: 884487-29-0
• 化学式: C₁₅H₂₅NO₅
• 分子量: 299.367
• InChiKey: WBFLXEMIJBGVTA-UHFFFAOYSA-N

物化性质

• 沸点：
  388.6±42.0 °C(Predicted)
• 密度：
  1.096±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate 、 环丙甲脒盐酸盐 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以64%的产率得到tert-butyl 2-cyclopropyl-4-hydroxy-9-methyl-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate
  参考文献：
  名称：

  WO2006/44762

  摘要：

  公开号：
• 作为产物：
  描述：

  1-BOC-5-氧代氮杂环庚烷-甲酸乙酯 、 碘甲烷 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 为溶剂， 反应 2.0h， 以60%的产率得到1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate
  参考文献：
  名称：

  [EN] 6,7,8,9-TETRAHYDRO-5H-1,4,7,10A-TETRAAZA-CYCLOHEPT[F]INDENE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS, THEIR USE AND PROCESSES FOR PREPARING THEM
  [FR] DÉRIVÉS DE 6,7,8,9-TÉTRAHYDRO-5H-1,4,7,10A-TÉTRAAZA-CYCLOHEPT[F]INDÈNE, COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSÉS, LEUR UTILISATION ET PROCÉDÉS POUR PRÉPARER CEUX-CI

  摘要：

  本发明涉及由式（I）定义的化合物，其中基团X、Y、W和R1至R4如权利要求1中所定义，具有有价值的药理活性。特别是这些化合物是5-HT2C受体的激动剂，因此适用于治疗和预防可以受到该受体抑制影响的疾病，如代谢和中枢神经系统相关疾病。

  公开号：

  WO2010060952A1
• 作为试剂：
  描述：

  1-BOC-5-氧代氮杂环庚烷-甲酸乙酯 、 3-甲基-4-氧代哌啶-1-羧酸叔丁酯 在 1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate 作用下， 以yielding 100% of title compound which的产率得到1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate
  参考文献：
  名称：

  Pyrimido [4,5-D] azepine derivatives as 5-HT2c agonists

  摘要：

  本发明提供一种式子(I)的化合物或其药学上可接受的盐，其中变量R1、R2、R3a、R3b、R3b、R3d和R100的定义如本文所述。本发明还涉及包含式子(I)化合物的药物组合物以及使用式子(I)化合物或包含式子(I)化合物的药物组合物治疗5-HT2c受体介导的疾病的方法。

  公开号：

  US07928099B2

文献信息

• Pyrimido [4,5-D] Azepine Derivatives As 5-HT2C Agonists
  申请人：Andrews Mark

  公开号：US20100113422A1

  公开（公告）日：2010-05-06

  The present invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof wherein the variables R 1 , R 2 , R 3a , R 3b , R 3b , R 3d , and R 100 are as defined herein. The invention is also directed to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a 5-HT 2c receptor-mediated disorders with a compound of formula (I) or a pharmaceutical composition comprising a compound of formula (I).

  本发明提供了式（I）的化合物：或其药学上可接受的盐，其中变量R1、R2、R3a、R3b、R3b、R3d和R100如本文所定义。本发明还涉及包括式（I）化合物的制药组合物，以及使用式（I）的化合物或包括式（I）的制药组合物治疗5-HT2c受体介导的疾病的方法。
• 6,7,8,9-Tetrahydro-5H-1,4,7,10a-tetraaza-cyclohept[f]indene derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them
  申请人：Mueller Stephan-Georg

  公开号：US20120165304A1

  公开（公告）日：2012-06-28

  The present invention relates to compounds defined by formula (I), wherein the groups X, Y, W and R 1 to R 4 are defined as in claim 1 , possessing valuable pharmacological activity. Particularly the compounds are agonists of the 5-HT2C receptor, and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this receptor, such as metabolic and CNS-related disorders.

  本发明涉及由式(I)定义的化合物，其中X、Y、W和R1至R4基团如权利要求1中所定义，具有有价值的药理活性。特别地，这些化合物是5-HT2C受体激动剂，因此适用于治疗和预防可以受到该受体抑制影响的疾病，例如代谢和中枢神经系统相关疾病。
• 6,7,8,9-tetrahydro-5H-1,4,7,10a-tetraaza-cyclohept[f]indene derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them
  申请人：Mueller Stephan-Georg

  公开号：US09346816B2

  公开（公告）日：2016-05-24

  The present invention relates to compounds defined by formula I wherein the groups X, Y, W and R1 to R4 are defined as in claim 1, possessing valuable pharmacological activity. Particularly the compounds are agonists of the 5-HT2C receptor, and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this receptor, such as metabolic and CNS-related disorders.

  本发明涉及一种由式I定义的化合物，其中X、Y、W和R1至R4基团如权利要求1所定义，具有有价值的药理活性。特别地，这些化合物是5-HT2C受体激动剂，因此适用于治疗和预防可以通过抑制该受体受影响的代谢和中枢神经系统相关疾病。
• Multiparameter Optimization in CNS Drug Discovery: Design of Pyrimido[4,5-<i>d</i>]azepines as Potent 5-Hydroxytryptamine 2C (5-HT_2C) Receptor Agonists with Exquisite Functional Selectivity over 5-HT_2A and 5-HT_2B Receptors
  作者：R. Ian Storer、Paul E. Brennan、Alan D. Brown、Peter J. Bungay、Kelly M. Conlon、Matthew S. Corbett、Robert P. DePianta、Paul V. Fish、Alexander Heifetz、Danny K. H. Ho、Alan S. Jessiman、Gordon McMurray、Cesar Augusto F. de Oliveira、Lee R. Roberts、James A. Root、Veerabahu Shanmugasundaram、Michael J. Shapiro、Melanie Skerten、Dominique Westbrook、Simon Wheeler、Gavin A. Whitlock、John Wright

  DOI：10.1021/jm5003292

  日期：2014.6.26

  A series of 4-substituted pyrimido[4,5-d]azepines that are potent, selective 5-HT2C receptor partial agonists is described. A rational medicinal chemistry design strategy to deliver CNS penetration coupled with SAR-based optimization of selectivity and agonist potency provided compounds with the desired balance of preclinical properties. Lead compounds 17 (PF-4479745) and 18 (PF-4522654) displayed robust pharmacology in a preclinical canine model of stress urinary incontinence (SUI) and no measurable functional agonism at the key selectivity targets 5-HT2A and 5-HT2B in relevant tissue-based assay systems. Utilizing recent advances in the structural biology of GPCRs, homology modeling has been carried out to rationalize binding and agonist efficacy of these compounds.
• 6,7,8,9-TETRAHYDRO-5H-1,4,7,10A-TETRAAZA-CYCLOHEPT[F]INDENE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS, THEIR USE AND PROCESS FOR PREPARING THEM
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2384328B1

  公开（公告）日：2013-02-13