Benzyl-thiazol-5-ylmethyl-amine | 355008-63-8

• 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: Benzyl-thiazol-5-ylmethyl-amine
• 英文别名: Benzyl(1,3-thiazol-5-ylmethyl)amine；1-phenyl-N-(1,3-thiazol-5-ylmethyl)methanamine
• CAS: 355008-63-8
• 化学式: C₁₁H₁₂N₂S
• mdl: MFCD08060603
• 分子量: 204.296
• InChiKey: CLKFVCVNPULACL-UHFFFAOYSA-N

物化性质

• 沸点：
  330.3±22.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Benzyl-thiazol-5-ylmethyl-amine 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Second-Generation Peptidomimetic Inhibitors of Protein Farnesyltransferase Demonstrating Improved Cellular Potency and Significant in Vivo Efficacy

  摘要：

  The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumorderived cell line.

  DOI：

  10.1021/jm9901935
• 作为产物：
  描述：

  N-benzyl-1-(1,3-thiazol-5-yl)methanimine 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 Benzyl-thiazol-5-ylmethyl-amine
  参考文献：
  名称：

  Second-Generation Peptidomimetic Inhibitors of Protein Farnesyltransferase Demonstrating Improved Cellular Potency and Significant in Vivo Efficacy

  摘要：

  The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumorderived cell line.

  DOI：

  10.1021/jm9901935

文献信息

• Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives
  作者：Stephen L. Gwaltney、Stephen J. O'Connor、Lissa T.J. Nelson、Gerard M. Sullivan、Hovis Imade、Weibo Wang、Lisa Hasvold、Qun Li、Jerome Cohen、Wen-Zhen Gu、Stephen K. Tahir、Joy Bauch、Kennan Marsh、Shi-Chung Ng、David J. Frost、Haiying Zhang、Steve Muchmore、Clarissa G. Jakob、Vincent Stoll、Charles Hutchins、Saul H. Rosenberg、Hing L. Sham

  DOI：10.1016/s0960-894x(03)00095-7

  日期：2003.4

  Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered a series of aryl tetrahydropyridines that incorporate substituted glycine, phenylalanine and histidine residues. The design, synthesis, SAR and biological properties of these compounds will be discussed. (C) 2003 Elsevier Science Ltd. All rights reserved.
• US6277871B1
  申请人：——

  公开号：US6277871B1

  公开（公告）日：2001-08-21
• Second-Generation Peptidomimetic Inhibitors of Protein Farnesyltransferase Demonstrating Improved Cellular Potency and Significant in Vivo Efficacy
  作者：Stephen J. O'Connor、Kenneth J. Barr、Le Wang、Bryan K. Sorensen、Andrew S. Tasker、Hing Sham、Shi-Chung Ng、Jerome Cohen、Edward Devine、Sajeev Cherian、Badr Saeed、Haichao Zhang、Jang Yun Lee、Robert Warner、Stephen Tahir、Peter Kovar、Patricia Ewing、Jeffrey Alder、Michael Mitten、Juan Leal、Kennan Marsh、Joy Bauch、Daniel J. Hoffman、Said M. Sebti、Saul H. Rosenberg

  DOI：10.1021/jm9901935

  日期：1999.9.1

  The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumorderived cell line.