methyl N-benzoyl-N-(piperidin-4-yl)-(S)-methioninate hydrochloride

• 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: methyl N-benzoyl-N-(piperidin-4-yl)-(S)-methioninate hydrochloride
• 英文别名: methyl N-benzoyl-N-(piperidin-4-yl)methioninate hydrochloride；methyl (2S)-2-[benzoyl(piperidin-4-yl)amino]-4-methylsulfanylbutanoate;hydrochloride
• 化学式: C₁₈H₂₆N₂O₃S*ClH
• 分子量: 386.943
• InChiKey: FJRYWVKRHASRBX-NTISSMGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  83.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl N-benzoyl-N-(piperidin-4-yl)-(S)-methioninate hydrochloride 在 sodium hydroxide 、 3 A molecular sieve 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 28.0h， 生成 2-(benzoyl-{1-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethyl]-piperidin-4-yl}-amino)-4-methylsulfanyl-butyric acid
  参考文献：
  名称：

  Potent and Selective Farnesyl Transferase Inhibitors

  摘要：

  We recently described a novel series of CA(1)A(2)X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A(1)A(2) residue. Extensive exploration of structure-activity relationships revealed that replacement of cysteine by substituted benzylimidazoles provided nanomolar FTIs with in vitro activities (18e, IC50 = 4.60 nM on isolated enzyme, EC50 = 20.0 nM for growth inhibition on a tumor cell line). The molecular docking of 18e and 19e in the active site of the enzyme provided details of key interactions with the protein and showed that the methionine or phenylalanine residue fits into the aryl binding site.

  DOI：

  10.1021/jm030502y
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 在 盐酸 、 sodium cyanoborohydride 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 114.0h， 生成 methyl N-benzoyl-N-(piperidin-4-yl)-(S)-methioninate hydrochloride
  参考文献：
  名称：

  Novel N-(4-Piperidinyl)benzamide Antimalarials with Mammalian Protein Farnesyltransferase Inhibitory Activity

  摘要：

  恶性疟原虫的蛋白法尼基转移酶是治疗疟疾的一个潜在靶点，目前已观察到抗药性的增加。本文报告了一系列 N-(4-哌啶基)苯甲酰胺的设计、合成和评估。最有效的化合物在亚摩尔浓度下对寄生虫具有体外活性。

  DOI：

  10.1248/cpb.53.1324

文献信息

• Design, Synthesis, and Pharmacological Evaluation of New Farnesyl Protein Transferase Inhibitors
  作者：Raymond Houssin、Jean Pommery、Marie-Catherine Salaün、Sophie Deweer、Jean-François Goossens、Philippe Chavatte、Jean-Pierre Hénichart

  DOI：10.1021/jm010297r

  日期：2002.1.1

  New CA(1)A(2)X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C-terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heterocycles, taking into account the role of zinc and the metabolic instability of amino acids. The molecular docking of 8 in the active site of the enzyme and the pharmacological

  新的CA（1）A（2）X拟肽被描述为法呢基转移酶抑制剂（FTIs）。它们包括半胱氨酸和蛋氨酸，作为法呢基化蛋白质C端序列的模拟物。此外，考虑到锌的作用和氨基酸的代谢不稳定性，半胱氨酸被杂环取代。8在酶的活性位点上的分子对接以及该化合物的药理学评价说明了一类新的FTI。
• Novel N-(4-Piperidinyl)benzamide Antimalarials with Mammalian Protein Farnesyltransferase Inhibitory Activity
  作者：Adina Ryckebusch、Pauline Gilleron、Régis Millet、Raymond Houssin、Amélie Lemoine、Nicole Pommery、Philippe Grellier、Christian Sergheraert、Jean-Pierre Hénichart

  DOI：10.1248/cpb.53.1324

  日期：——

  Protein farnesyltransferase of Plasmodium falciparum is a potential target in the treatment of malaria for which increased drug resistance is observed. The design, synthesis and evaluation of a series of N-(4-piperidinyl)benzamides is reported. The most potent compounds showed in vitro activity against the parasite at submicromolar concentrations.

  恶性疟原虫的蛋白法尼基转移酶是治疗疟疾的一个潜在靶点，目前已观察到抗药性的增加。本文报告了一系列 N-(4-哌啶基)苯甲酰胺的设计、合成和评估。最有效的化合物在亚摩尔浓度下对寄生虫具有体外活性。
• Potent and Selective Farnesyl Transferase Inhibitors
  作者：Régis Millet、Juozas Domarkas、Raymond Houssin、Pauline Gilleron、Jean-François Goossens、Philippe Chavatte、Cédric Logé,、Nicole Pommery、Jean Pommery、Jean-Pierre Hénichart

  DOI：10.1021/jm030502y

  日期：2004.12.1

  We recently described a novel series of CA(1)A(2)X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A(1)A(2) residue. Extensive exploration of structure-activity relationships revealed that replacement of cysteine by substituted benzylimidazoles provided nanomolar FTIs with in vitro activities (18e, IC50 = 4.60 nM on isolated enzyme, EC50 = 20.0 nM for growth inhibition on a tumor cell line). The molecular docking of 18e and 19e in the active site of the enzyme provided details of key interactions with the protein and showed that the methionine or phenylalanine residue fits into the aryl binding site.