N2-(5-(2,3-bis(tert-butoxycarbonyl)guanidino)pentanoyl)-Nw'-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-arginyl-L-leucine | 882297-58-7

• 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: N2-(5-(2,3-bis(tert-butoxycarbonyl)guanidino)pentanoyl)-Nw'-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-arginyl-L-leucine
• CAS: 882297-58-7
• 化学式: C₄₁H₆₈N₈O₁₁S
• 分子量: 881.104
• InChiKey: YIBLZUWIWACWKI-VMPREFPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.37
• 重原子数：
  61.0
• 可旋转键数：
  17.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  278.3
• 氢给体数：
  7.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N2-(5-(2,3-bis(tert-butoxycarbonyl)guanidino)pentanoyl)-Nw'-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-arginyl-L-leucine 在 polystyrene-carbodiimide 、 HOBt-6-carboxamidomethyl polystyrene 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (2S)-N-[(1R,2S)-2-(3-chlorophenyl)cyclohexyl]-2-[[(2S)-5-(diaminomethylideneamino)-2-[5-(diaminomethylideneamino)pentanoylamino]pentanoyl]amino]-4-methylpentanamide
  参考文献：
  名称：

  CDK2/cyclinA inhibitors: Targeting the cyclinA recruitment site with small molecules derived from peptide leads

  摘要：

  The syntheses of potent small molecule inhibitors of the CDK2/cyclinA recruitment site are described. Structure-activity trends of nanomolar octapeptides were examined through amino-acid substitution and truncation of the sequence resulting in the identification of a smaller, albeit significantly less potent, tetrapeptide lead. These losses in affinity were recovered by side-chain optimization and by rigidification of the peptide backbone using a combination of solid-phase parallel synthesis and structure-based design. Finally, two guanidine functionalities were replaced to improve drug-like properties, resulting in neutral small molecules equal in activity to that of the peptide lead. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.004
• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 N,N'-bis( tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine 、 5-[[芴甲氧羰基]氨基]戊酸 、 Fmoc-Pbf-L-精氨酸 生成 N2-(5-(2,3-bis(tert-butoxycarbonyl)guanidino)pentanoyl)-Nw'-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-arginyl-L-leucine
  参考文献：
  名称：

  CDK2/cyclinA inhibitors: Targeting the cyclinA recruitment site with small molecules derived from peptide leads

  摘要：

  The syntheses of potent small molecule inhibitors of the CDK2/cyclinA recruitment site are described. Structure-activity trends of nanomolar octapeptides were examined through amino-acid substitution and truncation of the sequence resulting in the identification of a smaller, albeit significantly less potent, tetrapeptide lead. These losses in affinity were recovered by side-chain optimization and by rigidification of the peptide backbone using a combination of solid-phase parallel synthesis and structure-based design. Finally, two guanidine functionalities were replaced to improve drug-like properties, resulting in neutral small molecules equal in activity to that of the peptide lead. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.004