Cyano-(2,2-dimethyl-4-phenyl-tetrahydro-pyran-4-yl)-acetic acid ethyl ester | 109878-42-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Cyano-(2,2-dimethyl-4-phenyl-tetrahydro-pyran-4-yl)-acetic acid ethyl ester
• 英文别名: Ethyl 2-cyano-2-(2,2-dimethyl-4-phenyloxan-4-yl)acetate
• CAS: 109878-42-4
• 化学式: C₁₈H₂₃NO₃
• mdl: MFCD01553245
• 分子量: 301.386
• InChiKey: FDKXEKYTWINJRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Cyano-(2,2-dimethyl-4-phenyl-tetrahydro-pyran-4-yl)-acetic acid ethyl ester 在 盐酸 、 水 、 溶剂黄146 、 potassium hydroxide 作用下， 以 乙二醇 为溶剂， 反应 49.5h， 生成 (2,2-Dimethyl-4-phenyl-tetrahydro-pyran-4-yl)-acetic acid
  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：

  四氢-2 2-二甲基-4H-吡喃-4-酮 在 copper(I) bromide dimethylsulfide complex 、 ammonium acetate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 Cyano-(2,2-dimethyl-4-phenyl-tetrahydro-pyran-4-yl)-acetic acid ethyl ester
  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

• Synthesis and study of the antiinflammatory properties of tetrahydropyran-substituted γ-aminopropanols
  作者：N. S. Arutyunyan、L. A. Akopyan、N. A. Apoyan、A. E. Tumadzhyan、S. A. Vartanyan

  DOI：10.1007/bf00764464

  日期：1989.2
• ARUTYUNYAN, N. S.;AKOPYAN, L. A.;APOYAN, N. A.;TUMADZHYAN, A. E.;VARTANYA+, XIM.-FARMATS. ZH., 23,(1989) N, S. 182-184
  作者：ARUTYUNYAN, N. S.、AKOPYAN, L. A.、APOYAN, N. A.、TUMADZHYAN, A. E.、VARTANYA+

  DOI：——

  日期：——
• ARUTYUNYAN N. S.; GARIBYAN K. M.; AKOPYAN L. A.; TOSUNYAN A. O.; VARTYANY+, ARM. XIM. ZH., 39,(1986) N 7, 438-444
  作者：ARUTYUNYAN N. S.、 GARIBYAN K. M.、 AKOPYAN L. A.、 TOSUNYAN A. O.、 VARTYANY+

  DOI：——

  日期：——