N-(4-aminobenzoyl)-L-methionine methyl ester | 154383-61-6

• 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-(4-aminobenzoyl)-L-methionine methyl ester
• 英文别名: 4-aminobenzoylmethionine methyl ester；N-[(4-amino)benzoyl]methionine methyl ester；N-(1(S)-carbomethoxy-3-methylthiopropyl)4-aminobenzamide；methyl (2S)-2-[(4-aminobenzoyl)amino]-4-methylsulfanylbutanoate
• CAS: 154383-61-6
• 化学式: C₁₃H₁₈N₂O₃S
• 分子量: 282.364
• InChiKey: JRSYHWOXHJZPDZ-NSHDSACASA-N

物化性质

• 沸点：
  525.6±50.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 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-(4-aminobenzoyl)-L-methionine methyl ester 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 3.0h， 生成 (S)-2-[4-(3-Hexadecylcarbamoyl-propionylamino)-benzoylamino]-4-methylsulfanyl-butyric acid methyl ester
  参考文献：
  名称：

  非肽，非烯丙基双底物法呢基转移酶抑制剂。第3部分：法呢基转移酶抑制活性中心部分的结构要求。

  摘要：

  最近，我们已经描述了非肽类，非异戊二烯双底物类似物是一种新型的法呢基转移酶抑制剂，其由法呢基模拟物，接头和AAX-拟肽亚结构组成。通过这项研究，我们证明了连接法呢基模拟物和我们抑制剂的连接亚结构的酰胺功能对其活性至关重要。我们建议酰胺与法呢基转移酶活性中心的必需锌离子结合。除了最初使用的1-丙氨酰基部分作为合适的连接结构之外，我们分别鉴定了琥珀酸和戊二酸。甘氨酸也可用于此功能，前提是通过向拟肽亚结构中引入额外的亚甲基单元来扩大α-酰胺基团与拟肽亚结构中心之间的距离。

  DOI：

  10.1016/s0968-0896(00)00173-5
• 作为产物：
  描述：

  L-蛋氨酸甲酯盐酸盐 在 N-甲基吗啉 、 tin(ll) chloride 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 16.0h， 生成 N-(4-aminobenzoyl)-L-methionine methyl ester
  参考文献：
  名称：

  法呢基转移酶新型模块化双底物类似物抑制剂的设计、合成和评价。

  摘要：

  可以从法呢基转移酶抑制剂开发用于治疗癌症的有前景的潜在化学疗法。提出了一类新的模块化双底物法呢基转移酶抑制剂，可以直接合成。这种抑制剂的一个例子是化合物 1，其 IC50 值为 3.7 μM。

  DOI：

  10.1002/(sici)1521-3773(19990712)38:13/14<2032::aid-anie2032>3.0.co;2-d

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。
• [EN] INHIBITORS OF PRENYL TRANSFERASES<br/>[FR] INHIBITEURS DES PRENYLE TRANSFERASES
  申请人：UNIVERSITY OF PITTSBURGH

  公开号：WO1996021456A1

  公开（公告）日：1996-07-18

  (EN) Compounds which inhibit prenyl transferases, particularly farnysyltransferase and geranylgeranyl transferase I, processes for preparing the compounds, pharmaceutical compositions containing the compounds, and methods of use.(FR) L'invention a pour objet des composés inhibiteurs des prényle transférases, particulièrement, des farnysyltransférases et des géranylgéranyle transférases I. L'invention traite également de procédés de préparations de ces composés, de compositions pharmaceutiques contenant ces composés et de leurs procédés d'utilisation.

  (EN) 抑制戊二烯转移酶，尤其是戊二烯基转移酶和戊二烯基转移酶I的化合物，制备这些化合物的方法，包含这些化合物的制药组合物以及使用方法。 (FR) 本发明涉及抑制戊二烯转移酶的化合物，尤其是戊二烯基转移酶和戊二烯基转移酶I的化合物，制备这些化合物的方法，包含这些化合物的制药组合物以及使用方法。
• New agents for cutaneous photoprotection: derivatives of α-amino acids, 4-aminobenzoic and 4-methoxycinnamic acids
  作者：MJ Zhao、D Robert、L Jung

  DOI：10.1016/0223-5234(93)90050-o

  日期：1993.1

  Derivatives of sulfur-containing or sulfur-free alpha-amino acids, 4-aminobenzoic and 4-methoxycinnamic acids, which are potential sun screens, have been synthesized. The effects on melanin formation of 2 compounds (2 and 12) were studied via enzymatic reactions and cell culture. It was shown that these 2 compounds can enhance pigmentation.
• Design, synthesis and early structure–activity relationship of farnesyltransferase inhibitors which mimic both the peptidic and the prenylic substrate
  作者：Martin Schlitzer、Markus Böhm、Isabel Sattler、Hans-Martin Dahse

  DOI：10.1016/s0968-0896(00)00138-3

  日期：2000.8

  Inhibition of the farnesylation of ras proteins has been identified as a promising target in tumor therapy. Only a few farnesyltransferase inhibitors are bisubstrate analogues displaying features of both substrates, the farnesylpyrophosphate and the C-terminal CAAX-tetrapeptide sequence of the res protein. These known bisubstrate analogues consist of an AAX-tripeptide and a farnesyl residue connected through various linkers. We have developed a class of novel compounds that mimic a bisubstrate inhibitor structure and that differ from the known ones by lacking peptidic or farnesylic substructures. Long chain fatty acids and aryl-substituted carboxylic acids were used as farnesyl surrogates. These structures were linked to isoleucine amide, benzoic acid amide, N-substituted aminobenzenesulfonamides and N-alpha-aryl-substituted methionine derivatives, respectively, which function as AA- or AAX-mimetics. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Non-Thiol Farnesyltransferase Inhibitors: Evaluation of Different AA(X)-Peptidomimetic Substructures in Combination with Arylic Cysteine Replacements
  作者：Jacek Sakowski、Markus Böhm、Isabel Sattler、Martin Schlitzer

  DOI：10.1002/1521-4184(200204)335:4<135::aid-ardp135>3.0.co;2-7

  日期：2002.4

  In the course of our studies on non-thiol farnesyltransferase inhibitors based on the 2,5-diaminobenzophenone AAX-peptidomimetic substructure, we have developed the (4-nitrophenyl)butyryl (R-1), the (2-naphthyl)acryloyl (R-2), the 4-nitrocinnamoyl (R-3), and the 5-(4-nitrophenyl)furylacryloyl (R-4) groups as useful cysteine replacements. In this study, we combined these four groups with other AA(X)-peptidomimetic substructures (5-10: R = H) reported in the literature. The 5-(4-nitrophenyl)furylacryloyl moiety (R-4) turned out to be the most useful non-thiol cysteine replacement yielding in all cases the most active inhibitors. By combination of this 5-(4-nitrophenyl)furylacryloyl moiety (R 4) with the structurally simple AAX-peptidomimetics 4-aminobenzophenone (5) and 4-aminodiphenylsulfone (6) potent, readily accessible non-thiol farnesyltransferase inhibitors were obtained (IC50 = 12 nM and 10 nM).