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：——
• 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.