N-(1(S)-carbomethoxy-3-methylthiopropyl)3-aminomethylbenzamide | 160813-66-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(1(S)-carbomethoxy-3-methylthiopropyl)3-aminomethylbenzamide
• 英文别名: methyl (2S)-2-[[3-(aminomethyl)benzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 160813-66-1
• 化学式: C₁₄H₂₀N₂O₃S
• 分子量: 296.39
• InChiKey: LFBNSZVCUGKPPV-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(1(S)-carbomethoxy-3-methylthiopropyl)3-aminomethylbenzamide 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 (S)-4-Methylsulfanyl-2-(3-{[methyl-(1-trityl-1H-imidazol-4-ylmethyl)-amino]-methyl}-benzoylamino)-butyric acid methyl ester
  参考文献：
  名称：

  Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase

  摘要：

  The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Substitutions on an imidazolylmethyl-AMBA-methionine template gave a highly potent and cell active inhibitor. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00323-6
• 作为产物：
  描述：

  N-(1(S)-carbomethoxy-3-methylthiopropyl)3-chloromethylbenzamide 在 palladium on activated charcoal 叠氮化锂 、 氢气 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 生成 N-(1(S)-carbomethoxy-3-methylthiopropyl)3-aminomethylbenzamide
  参考文献：
  名称：

  Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase

  摘要：

  The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Substitutions on an imidazolylmethyl-AMBA-methionine template gave a highly potent and cell active inhibitor. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00323-6

文献信息

• Prodrugs of inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05534537A1

  公开（公告）日：1996-07-09

  The present invention comprises peptidomimetic compounds which comprise a suitably substituted aminoalkylbenzamide moiety. The instant compounds inhibit the farnesyl protein transferase enzyme and the farnesylation of certain proteins. Furthermore, the instant farnesyl protein transferase inhibitors differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

  本发明涵盖了包含适当取代的氨基烷基苯甲酰基团的肽类似化合物。这些化合物抑制了法尼基蛋白转移酶酶和某些蛋白质的法尼醇化。此外，这些法尼基蛋白转移酶抑制剂与先前描述的抑制法尼基蛋白转移酶的抑制剂不同，因为它们没有硫醇基团。缺乏硫醇基团在改善动物的药代动力学行为、预防硫醇依赖性化学反应（如快速自氧化和与内源硫醇形成二硫键）以及减少全身毒性方面提供了独特的优势。本发明还包括含有这些法尼醇转移酶抑制剂的化疗组合物和其生产方法。
• Benzamide-containing inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05578629A1

  公开（公告）日：1996-11-26

  The present invention comprises peptidomimetic compounds which comprise a suitably substituted aminoalkylbenzamide moiety. The instant compounds inhibit the farnesyl protein transferase enzyme and the farnesylation of certain proteins. Furthermore, the instant farnesyl protein transferase inhibitors differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

  本发明涉及一种包含适当取代的氨基烷基苯甲酰胺基团的肽类似物化合物。这些化合物能够抑制法尼酰基蛋白转移酶和某些蛋白质的法尼酰化。此外，这些法尼酰基蛋白转移酶抑制剂与以前描述的法尼酰基蛋白转移酶抑制剂不同，因为它们不具有巯基。缺乏巯基提供了独特的优势，可以改善动物的药代动力学行为，防止巯基依赖性化学反应，如快速自氧化和与内源性巯基形成二硫键，以及减少系统毒性。此外，本发明还包括含有这些法尼酰转移酶抑制剂的化疗组合物和其生产方法。
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：EP0817630A1

  公开（公告）日：1998-01-14
• EP0817630A4
  申请人：——

  公开号：EP0817630A4

  公开（公告）日：1999-01-27
• US5534537A
  申请人：——

  公开号：US5534537A

  公开（公告）日：1996-07-09