2-[1-(Naphth-2-ylmethyl)-1H-imidazol-5-yl]acetic acid methyl ester | 183499-91-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[1-(Naphth-2-ylmethyl)-1H-imidazol-5-yl]acetic acid methyl ester
• 英文别名: methyl 2-[3-(naphthalen-2-ylmethyl)imidazol-4-yl]acetate
• CAS: 183499-91-4
• 化学式: C₁₇H₁₆N₂O₂
• 分子量: 280.326
• InChiKey: FMHZWJPQLDPREU-UHFFFAOYSA-N

物化性质

• 沸点：
  482.8±25.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[1-(Naphth-2-ylmethyl)-1H-imidazol-5-yl]acetic acid methyl ester 以 盐酸 为溶剂， 生成 2-[1-(naphth-2-ylmethyl)-1H-imidazol-5-yl]acetic acid hydrochloride
  参考文献：
  名称：

  Inhibitors of farnesyl-protein transferase

  摘要：

  本发明涉及抑制法尼基-蛋白转移酶（FTase）和致癌基因蛋白Ras法尼酰化的化合物。该发明还涉及含有本发明化合物的化疗组合物以及抑制法尼基-蛋白转移酶和致癌基因蛋白Ras法尼酰化的方法。

  公开号：

  US05891889A1
• 作为产物：
  描述：

  甲基(1-trityl-1H-imidazol-4-yl)乙酸酯 在 甲醇 作用下， 以 乙腈 为溶剂， 生成 2-[1-(Naphth-2-ylmethyl)-1H-imidazol-5-yl]acetic acid methyl ester
  参考文献：
  名称：

  Design and in Vivo Analysis of Potent Non-Thiol Inhibitors of Farnesyl Protein Transferase

  摘要：

  Inhibitors of farnesyl protein transferase (FPTase) based upon a pseudotripeptide template are described that comprise an imidazole group substituted with a hydrophobic substituent. (1,5)-Disubstitution of the imidazole group is shown to be the optimal array that leads to potent and selective inhibitors of FPTase. A variety of aryl and isoprenyl substituents are shown to afford effective inhibitors, and the mechanism by which these compounds inhibit FPTase has been investigated. The biochemical. behavior of these compounds suggests that they bind to FPTase at the site usually occupied by the protein substrate. In experiments in cell culture, the methyl ester prodrugs of these inhibitors are cell permeant and potently inhibit the posttranslational modification of H-Ras protein. Additionally, these molecules revert the phenotype of ras transformed cells as evidenced by their ability to slow the growth of ras transformed cell lines in soft agar. One of the inhibitors, as its methyl prodrug, was evaluated in two in vivo models of tumor growth. The compound selectively inhibited the growth of tumors derived from H-ras transformed cells, in nude mice, and caused the regression of preexisting tumors in an H-ras transgenic animal model.

  DOI：

  10.1021/jm990080l

文献信息

• [EN] INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE<br/>[FR] INHIBITEURS DE FARNESYL-PROTEINE TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：WO1996030343A1

  公开（公告）日：1996-10-03

  (EN) The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.(FR) La présente invention concerne des composés qui inhibent la farnésyl-protéine transférase (FTase) et la farnélysation de l'oncogène Ras protéique. L'invention concerne en outre des compositions chimiothérapeutiques contenant les composés de cette invention, et des procédés servant à inhiber la farnésyl-protéine transférase et la farnélysation de la protéine d'oncogène Ras.

  该发明涉及抑制法尼酰-蛋白转移酶（FTase）和癌基因蛋白Ras的法尼酰化的化合物。该发明进一步涉及含有该发明化合物的化疗组合物和抑制法尼酰-蛋白转移酶和癌基因蛋白Ras的法尼酰化的方法。
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：EP0944388A2

  公开（公告）日：1999-09-29
• EP0944388A4
  申请人：——

  公开号：EP0944388A4

  公开（公告）日：2001-08-16
• US5756528A
  申请人：——

  公开号：US5756528A

  公开（公告）日：1998-05-26
• US5856326A
  申请人：——

  公开号：US5856326A

  公开（公告）日：1999-01-05