tert-butyl 3-(2-propynyloxy)-5,6,7,8-tetrahydro-4H-isoxazolo<4,5-c>azepine-5-carboxylate | 123732-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 3-(2-propynyloxy)-5,6,7,8-tetrahydro-4H-isoxazolo<4,5-c>azepine-5-carboxylate
• 英文别名: tert-Butyl 3-(2-Propynyloxy)-5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-5-carboxylate；tert-butyl 3-(2-propynyloxy)-5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepine-5-carboxylate；tert-butyl 3-prop-2-ynoxy-4,6,7,8-tetrahydro-[1,2]oxazolo[4,5-c]azepine-5-carboxylate
• CAS: 123732-48-9
• 化学式: C₁₅H₂₀N₂O₄
• 分子量: 292.335
• InChiKey: ABKVHQLJONTLNC-UHFFFAOYSA-N

物化性质

• 沸点：
  449.4±45.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  64.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(2-propynyloxy)-5,6,7,8-tetrahydro-4H-isoxazolo<4,5-c>azepine-5-carboxylate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以267 mg (64%)的产率得到3-(2-propynyloxy)-5,6,7,8-tetrahydro-4H-isoxazolo<4,5-c>azepinium chloride
  参考文献：
  名称：

  5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]-azepine derivatives

  摘要：

  本发明涉及以下式的新化合物：##STR1## 其中R.sup.1是烷基，烯基，炔基，支链或直链，具有1-6个碳原子，可以未取代或可选地取代为氟，羟基或苯基，其中苯基可以用卤素，三氟甲基，较低的烷基，羟基或较低的烷氧基取代; R.sup.2是氢或较低的烷基（1-6个C原子）; R.sup.3和R.sup.4相同或不同，每个代表氢，烷基（1-6个C原子）或环烷基（3-6个C原子），或苯基，可选地用卤素，三氟甲基，较低的烷基（1-6个C原子），羟基或较低的烷氧基（1-6个C原子）或苯基-较低的烷基（7-10个C原子）取代，其中苯基可以用卤素，三氟甲基，较低的烷基（1-6个C原子），羟基或较低的烷氧基（1-6个C原子）取代;以及其各个异构体和药学上可接受的酸加盐。此外，本发明还涉及制备式I化合物的方法，新的中间体，含有该化合物的制药组合物，以及通过给予式I化合物的非毒性有效量治疗由乙酰胆碱（AcCh）或肌动系统功能障碍引起的疾病的方法。

  公开号：

  US04960769A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 20.0h， 生成 tert-butyl 3-(2-propynyloxy)-5,6,7,8-tetrahydro-4H-isoxazolo<4,5-c>azepine-5-carboxylate
  参考文献：
  名称：

  Annulated Heterocyclic Bioisosteres of Norarecoline. Synthesis and Molecular Pharmacology at Five Recombinant Human Muscarinic Acetylcholine Receptors

  摘要：

  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.

  DOI：

  10.1021/jm00012a019

文献信息

• US4960769A
  申请人：——

  公开号：US4960769A

  公开（公告）日：1990-10-02