N-(1(S)-carbomethoxy-3-methylthiopropyl)3-[(4-imidazolylmethyl)-N-methylaminomethyl]benzamide | 180863-39-2

• 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-[(4-imidazolylmethyl)-N-methylaminomethyl]benzamide
• 英文别名: methyl (2S)-2-[[3-[[1H-imidazol-5-ylmethyl(methyl)amino]methyl]benzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 180863-39-2
• 化学式: C₁₉H₂₆N₄O₃S
• 分子量: 390.506
• InChiKey: SIRHFUWRPDBPGY-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(1(S)-carbomethoxy-3-methylthiopropyl)3-[(4-imidazolylmethyl)-N-methylaminomethyl]benzamide 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 N-(1(S)-carboxy-3-methylthiopropyl)3-[(4-imidazolylmethyl)-N-methylaminomethyl]benzamide
  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：

  (S)-4-Methylsulfanyl-2-(3-{[methyl-(1-trityl-1H-imidazol-4-ylmethyl)-amino]-methyl}-benzoylamino)-butyric acid methyl ester 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-(1(S)-carbomethoxy-3-methylthiopropyl)3-[(4-imidazolylmethyl)-N-methylaminomethyl]benzamide
  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

• US5534537A
  申请人：——

  公开号：US5534537A

  公开（公告）日：1996-07-09
• US5578629A
  申请人：——

  公开号：US5578629A

  公开（公告）日：1996-11-26
• [EN] INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE<br/>[FR] INHIBITEURS DE FARNESYL-PROTEINE TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：WO1996030015A1

  公开（公告）日：1996-10-03

  (EN) 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.(FR) L'invention porte sur des composés peptidomimétiques comportant une fraction aminoalkylbenzamide adéquatement substituée. Ces composés instantanés inhibent la farnésyl-protéine transférase et la farnésylation de certaines protéines. De plus, ces inhibiteurs instantanés de farnésyl-protéine transférase différent de ceux préalablement décrits en ce qu'ils ne présentent pas de fraction thiol. Cette absence de thiol offre des avantages uniques en terme de comportement pharacocinétique amélioré chez l'animal, de prévention des réactions chimiques liées au thiol telles que la rapidité d'auto-oxydation ou la formation de disulfures avec des thiols endogènes, et une toxicité systémique réduite. L'invention porte également sur des compositions chimiothérapeutiques contenant lesdits inhibiteurs de farnésyl-protéine transférase et leurs procédés de production.
• Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase
  作者：Terrence M. Ciccarone、Suzanne C. MacTough、Theresa M. Williams、Christopher J. Dinsmore、Timothy J. O'Neill、Daksha Shah、J.Christopher Culberson、Kenneth S. Koblan、Nancy E. Kohl、Jackson B. Gibbs、Allen I. Oliff、Samuel L. Graham、George D. Hartman

  DOI：10.1016/s0960-894x(99)00323-6

  日期：1999.7

  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.