(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[[methylamino(methylazaniumylidene)methyl]amino]pentanoate

• 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: (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[[methylamino(methylazaniumylidene)methyl]amino]pentanoate
• 化学式: C₂₃H₂₈N₄O₄
• 分子量: 424.5
• InChiKey: DQWCPMLQUQTZMJ-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  112
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[[methylamino(methylazaniumylidene)methyl]amino]pentanoate 、 1-(3,5-二氯苯基)-5-甲基-1,2,4-三唑-3-羧酸 、 芴甲氧羰基-L-β-高亮氨酸 、 (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(3-thienyl)propanoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成
  参考文献：
  名称：

  Iterative Conversion of Cyclin Binding Groove Peptides into Druglike CDK Inhibitors with Antitumor Activity

  摘要：

  The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structureactivity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites of the cyclin binding groove provide for the replacement of binding determinants with more druglike functionality through REPLACE, a strategy for the iterative conversion of peptidic blockers of proteinprotein interactions into pharmaceutically relevant compounds. As a result, REPLACE is further exemplified in combining optimized peptidic sequences with effective N-terminal capping groups to generate more stable compounds possessing antitumor activity consistent with on-target inhibition of cell cycle CDKs. The compounds described here represent prototypes for a next generation of kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with first generation CDK inhibitors.

  DOI：

  10.1021/jm5015023

文献信息

• PEPTIDE-COMPOUND CYCLIZATION METHOD
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP2813512A1

  公开（公告）日：2014-12-17

  An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.

  本发明的目的是提供发现对韧性靶标有效的药物的方法，这些靶标在传统上很难被发现。本发明涉及环化多肽化合物的新方法，以及实现上述目的的新的多肽化合物和由其组成的化合物库。
• EP2813512B1
  申请人：——

  公开号：EP2813512B1

  公开（公告）日：2021-03-31
• US9409952B2
  申请人：——

  公开号：US9409952B2

  公开（公告）日：2016-08-09
• Iterative Conversion of Cyclin Binding Groove Peptides into Druglike CDK Inhibitors with Antitumor Activity
  作者：Padmavathy Nandha Premnath、Sandra N. Craig、Shu Liu、Erin L. Anderson、Asterios I. Grigoroudis、George Kontopidis、Tracy L. Perkins、Michael D. Wyatt、Douglas L. Pittman、Campbell McInnes

  DOI：10.1021/jm5015023

  日期：2015.1.8

  The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structureactivity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites of the cyclin binding groove provide for the replacement of binding determinants with more druglike functionality through REPLACE, a strategy for the iterative conversion of peptidic blockers of proteinprotein interactions into pharmaceutically relevant compounds. As a result, REPLACE is further exemplified in combining optimized peptidic sequences with effective N-terminal capping groups to generate more stable compounds possessing antitumor activity consistent with on-target inhibition of cell cycle CDKs. The compounds described here represent prototypes for a next generation of kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with first generation CDK inhibitors.