3-oxo-2,3,4,5,6,8-hexahydro-isoxazolo[5,4-c]azepine-7-carboxylic acid methyl ester | 65202-65-5

• 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: 3-oxo-2,3,4,5,6,8-hexahydro-isoxazolo[5,4-c]azepine-7-carboxylic acid methyl ester
• 英文别名: methyl 3-oxo-4,5,6,8-tetrahydro-[1,2]oxazolo[5,4-c]azepine-7-carboxylate
• CAS: 65202-65-5
• 化学式: C₉H₁₂N₂O₄
• 分子量: 212.205
• InChiKey: PWXMCQIMRBKLRU-UHFFFAOYSA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.89
• 重原子数：
  15.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  75.8
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-oxo-2,3,4,5,6,8-hexahydro-isoxazolo[5,4-c]azepine-7-carboxylic acid methyl ester 、 氢溴酸 以83%的产率得到
  参考文献：
  名称：

  KROGSGAARD-LARSEN P., ACTA CHEM. SCAND., 1977, B31, NO

  摘要：

  DOI：
• 作为产物：
  描述：

  1,4-dioxa-7-aza-spiro[4.6]undecane-7,11-dicarboxylic acid 11-ethyl ester 7-methyl ester 、 羟胺 、 盐酸 以24%的产率得到
  参考文献：
  名称：

  KROGSGAARD-LARSEN P., ACTA CHEM. SCAND., 1977, B31, NO

  摘要：

  DOI：

文献信息

• Annulated Heterocyclic Bioisosteres of Norarecoline. Synthesis and Molecular Pharmacology at Five Recombinant Human Muscarinic Acetylcholine Receptors
  作者：Hans Braeuner-Osborne、Bjarke Ebert、Mark R. Brann、Erik Falch、Povl Krogsgaard-Larsen

  DOI：10.1021/jm00012a019

  日期：1995.6

  A series of O-alkylated analogs of 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO) were synthesized and characterized as ligands for muscarinic acetylcholine receptors (mAChRs). O-Methyl-THAO (4a), O-ethyl-THAO (4b), O-isopropyl-THAO (4c), and O-propargyl-THAO (4d) were shown to be potent inhibitors of the binding of tritiated quinuclidinyl benzilate (QNB), pirenzepine (PZ), and oxotremorine-M (Oxo-M) to tissue membrane preparations. In the [3H]-Oxo-M binding assay, receptor affinities in the low nanomolar range were measured for 4a (IC50 = 0.010 microM), 4b (IC50 = 0.003 microM), 4c (IC50 = 0.011 microM), and 4d (IC50 = 0.0008 microM). Pharmacological effects (EC50 or Ki values) and intrinsic activities (per cent of maximal carbachol responses) were determined using five recombinant human mAChRs (m1-m5) and the functional assay, receptor selection and amplification technology (R-SAT). Compound 4c antagonized carbachol-induced responses at m1, m3, and m5. With the exception of 4b, which was an antagonist at m5, 4a,b,d showed partial agonism at m1-m5 with very similar subtype selectivity (m2 > m4 > m1 > or = m3 > m5). Agonist index values for 4a-d, which were calculated from [3H]QNB (brain) and [3H]Oxo-M (brain) binding data, were shown to be predictive of pharmacologically determined intrinsic activities at m1-m5, the same rank order of intrinsic activity being observed at all five mAChRs (4a > 4d > 4b > 4c). It is concluded that within this class of high-affinity mAChR (m1-m5) ligands, containing secondary amino groups, minor changes of the bioisosteric ester alkyl groups have marked effects on potency and, in particular, intrinsic activity.