2-[4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]acetonitrile | 337485-98-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]acetonitrile
• CAS: 337485-98-0
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: KFWNOWCMCZOPIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]acetonitrile 在 lithium aluminium tetrahydride 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium t-butanolate 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 2.0h， 生成 3-methoxy-N-{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}aniline
  参考文献：
  名称：

  Discovery and SAR of Methylated Tetrahydropyranyl Derivatives as Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase (ICMT)

  摘要：

  A series of tetrahydropyranyl (THP) derivatives has been developed as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT) for use as anticancer agents. Structural modification of the submicromolar hit compound 3 led to the potent 3-methoxy substituted analogue 27. Further SAR development around the THP ring resulted in an additional 10-fold increase in potency, exemplified by analogue 75 with an IC50 of 1.3 nM. Active and potent compounds demonstrated a dose-dependent increase in Ras cytosolic protein. Potent ICMT inhibitors also reduced cell viability in several cancer cell lines with growth inhibition (GI(50)) values ranging from 0.3 to >100 mu M. However, none of the cellular effects observed using ICMT inhibitors were as pronounced as those resulting from a farnesyltransferase inhibitor.

  DOI：

  10.1021/jm200249a
• 作为产物：
  描述：

  ethyl 2-cyano-2-(2,2-dimethyl-tetrahydropyran-4-ylidene)acetate 在 copper(I) bromide dimethylsulfide complex 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙二醇 为溶剂， 反应 1.5h， 生成 2-[4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]acetonitrile
  参考文献：
  名称：

  Discovery and SAR of Methylated Tetrahydropyranyl Derivatives as Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase (ICMT)

  摘要：

  A series of tetrahydropyranyl (THP) derivatives has been developed as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT) for use as anticancer agents. Structural modification of the submicromolar hit compound 3 led to the potent 3-methoxy substituted analogue 27. Further SAR development around the THP ring resulted in an additional 10-fold increase in potency, exemplified by analogue 75 with an IC50 of 1.3 nM. Active and potent compounds demonstrated a dose-dependent increase in Ras cytosolic protein. Potent ICMT inhibitors also reduced cell viability in several cancer cell lines with growth inhibition (GI(50)) values ranging from 0.3 to >100 mu M. However, none of the cellular effects observed using ICMT inhibitors were as pronounced as those resulting from a farnesyltransferase inhibitor.

  DOI：

  10.1021/jm200249a