methanesulfonic acid 2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]ethyl ester | 186202-63-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methanesulfonic acid 2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]ethyl ester
• 英文别名: 2-[3-[(4-Cyanophenyl)methyl]imidazol-4-yl]ethyl methanesulfonate
• CAS: 186202-63-1
• 化学式: C₁₄H₁₅N₃O₃S
• 分子量: 305.357
• InChiKey: QKBGIYRGXZNISV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  93.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methanesulfonic acid 2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]ethyl ester 、 (R)-3-amino-2-oxo-1-phenylpyrrolidine hydrochloride 在 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 4-{5-[2-((R)-2-Oxo-1-phenyl-pyrrolidin-3-ylamino)-ethyl]-imidazol-1-ylmethyl}-benzonitrile
  参考文献：
  名称：

  Design and Biological Activity of (S)-4-(5-{[1-(3-Chlorobenzyl)-2- oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-Aminopyrrolidinone Farnesyltransferase Inhibitor with Excellent Cell Potency

  摘要：

  The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-amino-pyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.

  DOI：

  10.1021/jm010156p
• 作为产物：
  描述：

  [1-(4-Cyanobenzyl)-1H-imidazol-5-yl]acetic acid methyl ester 在 sodium tetrahydroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 methanesulfonic acid 2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]ethyl ester
  参考文献：
  名称：

  Design and Biological Activity of (S)-4-(5-{[1-(3-Chlorobenzyl)-2- oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-Aminopyrrolidinone Farnesyltransferase Inhibitor with Excellent Cell Potency

  摘要：

  The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-amino-pyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.

  DOI：

  10.1021/jm010156p

文献信息

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

  公开号：WO2001017992A1

  公开（公告）日：2001-03-15

  The present invention is directed to compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

  本发明涉及抑制异戊二烯基-蛋白转移酶及癌基因蛋白Ras的异戊二烯基化的化合物。本发明还涉及包含本发明化合物的化疗组合物以及抑制异戊二烯基-蛋白转移酶及癌基因蛋白Ras的异戊二烯基化的方法。
• US5852010A
  申请人：——

  公开号：US5852010A

  公开（公告）日：1998-12-22
• US5998407A
  申请人：——

  公开号：US5998407A

  公开（公告）日：1999-12-07
• Design and Biological Activity of (<i>S</i>)-4-(5-{[1-(3-Chlorobenzyl)-2- oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-Aminopyrrolidinone Farnesyltransferase Inhibitor with Excellent Cell Potency
  作者：Ian M. Bell、Steven N. Gallicchio、Marc Abrams、Douglas C. Beshore、Carolyn A. Buser、J. Christopher Culberson、Joseph Davide、Michelle Ellis-Hutchings、Christine Fernandes、Jackson B. Gibbs、Samuel L. Graham、George D. Hartman、David C. Heimbrook、Carl F. Homnick、Joel R. Huff、Kelem Kassahun、Kenneth S. Koblan、Nancy E. Kohl、Robert B. Lobell、Joseph J. Lynch、Patricia A. Miller、Charles A. Omer、A. David Rodrigues、Eileen S. Walsh、Theresa M. Williams

  DOI：10.1021/jm010156p

  日期：2001.8.1

  The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-amino-pyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.