N-[2-(2,2-dimethyl-4-phenyltetrahydro-2H-pyran-4-yl)ethyl]-3-methoxyaniline | 1313603-42-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[2-(2,2-dimethyl-4-phenyltetrahydro-2H-pyran-4-yl)ethyl]-3-methoxyaniline
• 英文别名: N-[2-[(4S)-2,2-dimethyl-4-phenyloxan-4-yl]ethyl]-3-methoxyaniline
• CAS: 1313603-42-7
• 化学式: C₂₂H₂₉NO₂
• 分子量: 339.478
• InChiKey: DMMQLOOWARMXLU-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl 2-cyano-2-(2,2-dimethyl-tetrahydropyran-4-ylidene)acetate 在 lithium aluminium tetrahydride 、 copper(I) bromide dimethylsulfide complex 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 potassium hydroxide 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 乙二醇 、 异丙醇 、 甲苯 、 乙腈 为溶剂， 反应 3.5h， 生成 N-[2-(2,2-dimethyl-4-phenyltetrahydro-2H-pyran-4-yl)ethyl]-3-methoxyaniline 、 N-[2-(2,2-dimethyl-4-phenyltetrahydro-2H-pyran-4-yl)ethyl]-3-methoxyaniline
  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

文献信息

• Discovery and SAR of Methylated Tetrahydropyranyl Derivatives as Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase (ICMT)
  作者：Weston R. Judd、Paul M. Slattum、Khanh C. Hoang、Leena Bhoite、Liisa Valppu、Glen Alberts、Brita Brown、Bruce Roth、Kirill Ostanin、Liwen Huang、Daniel Wettstein、Burt Richards、J. Adam Willardsen

  DOI：10.1021/jm200249a

  日期：2011.7.28

  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.