N-methyl-N-(4-nitro-benzoyl)-glycine | 35876-37-0

• 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: N-methyl-N-(4-nitro-benzoyl)-glycine
• 英文别名: N-Methyl-N-(4-nitro-benzoyl)-glycin；(N-Methyl-4-nitrobenzamido)ethanoic acid；2-[methyl-(4-nitrobenzoyl)amino]acetic acid
• CAS: 35876-37-0
• 化学式: C₁₀H₁₀N₂O₅
• mdl: MFCD09741068
• 分子量: 238.2
• InChiKey: UMZUJULAJNWKSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-methyl-N-(4-nitro-benzoyl)-glycine 在 高氯酸 、 乙酸酐 作用下， 生成 3-methyl-2-(4-nitro-phenyl)-5-oxo-4,5-dihydro-oxazolium; perchlorate
  参考文献：
  名称：

  在高氯酸的存在下α酰氨基酸环化，得到5-氧代- Δ 2 -oxazolinium高氯酸盐

  摘要：

  乙酸酐和高氯酸的简单α酰氨基酸的产率-5-氧代Δ动作2个-oxazolinium高氯酸盐，其可以被去质子化，以相应的饱和恶唑啉-5-酮。N-苯甲酰基-L-苯基丙氨酸得到L -4-苄基-2-苯基恶唑啉酮的氢高氯酸盐。由马尿酸制得的盐在用水，甲醇和各种胺处理后会发生开环反应。它与苯甲醛缩合，得到4-亚苄基-2-苯基恶唑啉酮的不稳定几何异构体的氢高氯酸盐。制备了十种N-取代的氧代-恶唑啉鎓高氯酸盐，并报道了它们与苯甲醛和胺的反应。从p获得的双环高氯酸盐-硝基苯甲酰基-L-脯氨酸很容易消旋，可能是通过中性离子的恶唑鎓氧化物消旋；相应的二苯氨基化合物是光学稳定的。

  DOI：

  10.1039/p19720000909
• 作为产物：
  描述：

  肌氨酸 、 4-硝基苯甲酰氯 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 0.5h， 以42%的产率得到N-methyl-N-(4-nitro-benzoyl)-glycine
  参考文献：
  名称：

  Relative structure-inhibition analyses of the N-benzoyl and N-(phenylsulfonyl) amino acid aldose reductase inhibitors

  摘要：

  A number of N-benzoyl amino acids were synthesized and tested to compare structure-inhibition relationships with the isosteric N-(phenylsulfonyl) amino acid (PS-amino acid) aldose reductase inhibitors. Inhibition analyses with these series reveals that their kinetic mechanisms of inhibition are similar, but that significant differences in structure-inhibition relationships exist. For example, while the PS-alanines and PS-2-phenylglycines produce enantioselective inhibition (S > R), no consistent pattern of enantioselectivity is observed with the isosteric N-benzoylalanines and 2-phenylglycines. Also, N-methyl and N-phenyl substitution in the PS-amino acid series does not substantially alter inhibitory activity, while similar substitutions in the N-benzoyl series (particularly N-phenyl) results in a significant increase in inhibitory activity. Proton NMR analysis of the N-benzoylsarcosines reveals that these compounds exist as a mixture of rotamers in solutions including the enzyme assay buffer and that the preferred conformer is one in which the carboxymethyl moiety is trans to the aromatic ring. Similar analyses with the N-benzoyl-N-phenylglycines demonstrate that these derivatives exist exclusively in the trans rotameric conformation in solution. No such N-substituent effects on conformation were observed in the PS-amino acid series. These results suggest that the differences in structure-inhibition trends between these structurally related series may result from the effect of substituents on preferred conformation.

  DOI：

  10.1021/jm00111a030

文献信息

• Analogs of Pteroylglutamic Acid. IV. Replacement of Glutamic Acid by Other Amino Acids
  作者：William B. Wright、Donna B. Cosulich、Marvin J. Fahrenbach、Coy W. Waller、James M. Smith、Martin E. Hultquist

  DOI：10.1021/ja01177a019

  日期：1949.9
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：Merck & Co., Inc.

  公开号：EP0783318A1

  公开（公告）日：1997-07-16
• EP0783318A4
  申请人：——

  公开号：EP0783318A4

  公开（公告）日：1999-10-20
• US5585359A
  申请人：——

  公开号：US5585359A

  公开（公告）日：1996-12-17
• [EN] INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE<br/>[FR] INHIBITEURS DE FARNESYLE-PROTEINE TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：WO1996009836A1

  公开（公告）日：1996-04-04

  (EN) The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation $i(in vivo). These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogs differ from those previously described as inhibitors of Ras farnesyl 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) La présente invention se rapporte à des analogues du motif CAAX de la protéine Ras qui est modifiée par farnésylation $i(in vivo). Ces analogues de CAAX inhibent la farnésylation de Ras. De plus, ils diffèrent des autres analogues précédemment décrits comme étant des inhibiteurs de Ras-farnésyle transférase en ce qu'ils ne possèdent pas une fraction thiol. L'absence de thiol offre des avantages uniques sur le plan du comportement pharmacocinétique amélioré chez les animaux, de la prévention des réactions chimiques dépendant de thiol, telle que l'auto-oxydation rapide et la formation de bisulfure avec des thiols endogènes, et de la toxicité systémique réduite. L'invention se rapporte en outre à des compositions chimiothérapiques contenant ces inhibiteurs de farnésyle transférase et à leurs procédés de production.