5-(3'-methoxybiphenyl-3-yl)-5-methylthiomorpholin-3-one | 1436711-63-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(3'-methoxybiphenyl-3-yl)-5-methylthiomorpholin-3-one
• 英文别名: 5-[3-(3-Methoxyphenyl)phenyl]-5-methylthiomorpholin-3-one；5-[3-(3-methoxyphenyl)phenyl]-5-methylthiomorpholin-3-one
• CAS: 1436711-63-5
• 化学式: C₁₈H₁₉NO₂S
• 分子量: 313.42
• InChiKey: NDEJGBYIYWAKHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(3'-methoxybiphenyl-3-yl)-5-methylthiomorpholin-3-one 在 tetraphosphorus decasulfide 、 六甲基二硅氧烷 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 1.0h， 以170 mg的产率得到
  参考文献：
  名称：

  Core Refinement toward Permeable β-Secretase (BACE-1) Inhibitors with Low hERG Activity

  摘要：

  By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 mu M to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds.

  DOI：

  10.1021/jm3011349
• 作为产物：
  描述：

  5-[3-(3-Methoxyphenyl)phenyl]-5-methylimidazolidine-2,4-dione 在 氯磺酸 、 sodium tetrahydroborate 、 barium hydroxide octahydrate 、 碘 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 72.0h， 生成 5-(3'-methoxybiphenyl-3-yl)-5-methylthiomorpholin-3-one
  参考文献：
  名称：

  Core Refinement toward Permeable β-Secretase (BACE-1) Inhibitors with Low hERG Activity

  摘要：

  By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 mu M to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds.

  DOI：

  10.1021/jm3011349

文献信息

• Core Refinement toward Permeable β-Secretase (BACE-1) Inhibitors with Low hERG Activity
  作者：Tobias Ginman、Jenny Viklund、Jonas Malmström、Jan Blid、Rikard Emond、Rickard Forsblom、Anh Johansson、Annika Kers、Fredrik Lake、Fernando Sehgelmeble、Karin J. Sterky、Margareta Bergh、Anders Lindgren、Patrik Johansson、Fredrik Jeppsson、Johanna Fälting、Ylva Gravenfors、Fredrik Rahm

  DOI：10.1021/jm3011349

  日期：2013.6.13

  By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 mu M to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds.