methyl (2S)-2-[benzoyl-[1-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperidin-4-yl]amino]-3-phenylpropanoate | 833490-43-0

• 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 (2S)-2-[benzoyl-[1-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperidin-4-yl]amino]-3-phenylpropanoate
• CAS: 833490-43-0
• 化学式: C₃₄H₃₅N₅O₃
• 分子量: 561.684
• InChiKey: XSJWOMAHMIQEAO-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  91.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[benzoyl-[1-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperidin-4-yl]amino]-3-phenylpropanoate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以90%的产率得到2-(benzoyl-{1-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethyl]-piperidin-4-yl}-amino)-3-phenyl-propionic 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 132.0h， 生成 methyl (2S)-2-[benzoyl-[1-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperidin-4-yl]amino]-3-phenylpropanoate
  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

• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT NEUROINFLAMMATORY DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160303146A1

  公开（公告）日：2016-10-20

  This invention provides methods and pharmaceutical compositions that can treat neuroinflammatory disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT AUTOIMMUNE DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160375041A1

  公开（公告）日：2016-12-29

  The invention provides methods and pharmaceutical compositions that can treat autoimmune disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• 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.