(S)-2-((S)-2-Amino-butyrylamino)-4-methyl-pentanoic acid [(1R,2S)-2-(3-chloro-phenyl)-cyclohexyl]-amide | 911141-80-5

• 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: (S)-2-((S)-2-Amino-butyrylamino)-4-methyl-pentanoic acid [(1R,2S)-2-(3-chloro-phenyl)-cyclohexyl]-amide
• 英文别名: (2S)-2-[[(2S)-2-aminobutanoyl]amino]-N-[(1R,2S)-2-(3-chlorophenyl)cyclohexyl]-4-methylpentanamide
• CAS: 911141-80-5
• 化学式: C₂₂H₃₄ClN₃O₂
• 分子量: 407.984
• InChiKey: BWDDAOVUMDKTJX-HAGHYFMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-((S)-2-Amino-butyrylamino)-4-methyl-pentanoic acid [(1R,2S)-2-(3-chloro-phenyl)-cyclohexyl]-amide 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 0.08h， 生成 N-((S)-1-{(S)-1-[(1R,2S)-2-(3-Chloro-phenyl)-cyclohexylcarbamoyl]-3-methyl-butylcarbamoyl}-propyl)-4-(thiazol-2-ylaminomethyl)-benzamide
  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：

  ((S)-1-{(S)-1-[(1R,2S)-2-(3-Chloro-phenyl)-cyclohexylcarbamoyl]-3-methyl-butylcarbamoyl}-propyl)-carbamic acid tert-butyl ester 在 盐酸 作用下， 生成 (S)-2-((S)-2-Amino-butyrylamino)-4-methyl-pentanoic acid [(1R,2S)-2-(3-chloro-phenyl)-cyclohexyl]-amide
  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

文献信息

• CDK2/cyclinA inhibitors: Targeting the cyclinA recruitment site with small molecules derived from peptide leads
  作者：Georgette Castanedo、Kevin Clark、Shumei Wang、Vickie Tsui、Mengling Wong、John Nicholas、Dineli Wickramasinghe、James C. Marsters、Daniel Sutherlin

  DOI：10.1016/j.bmcl.2005.12.004

  日期：2006.3

  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.