1-(3,5-二氯苯基)-5-甲基-1,2,4-三唑-3-羧酸 | 338408-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(3,5-二氯苯基)-5-甲基-1,2,4-三唑-3-羧酸
• 英文名称: 1-(3,5-dichlorophenyl)-5-methyl-1H-1,2,4-triazole-3-carboxylic acid
• 英文别名: 35DCPT；1-(3,5-dichlorophenyl)-5-methyl-1,2,4-triazole-3-carboxylic acid
• CAS: 338408-13-2
• 化学式: C₁₀H₇Cl₂N₃O₂
• mdl: MFCD00173546
• 分子量: 272.09
• InChiKey: CZTNDZALWLHXBA-UHFFFAOYSA-N

物化性质

• 熔点：
  202-204°C
• 沸点：
  521.5±60.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-(3,5-二氯苯基)-5-甲基-1,2,4-三唑-3-羧酸 、 FMOC-L-精氨酸 、 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 1-(3,5-dichlorophenyl)-5-methyl-1H-1,2,4-triazole-3-carboxamide-R-beta-homoleucine-3-thienylalanine-NH2
  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
• 作为产物：
  描述：

  ethyl 1-(3,5-dichlorophenyl)-5-methyl-1H-1,2,4-triazole-3-carboxylate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 1-(3,5-二氯苯基)-5-甲基-1,2,4-三唑-3-羧酸
  参考文献：
  名称：

  通过 REPLACE 介导的片段组装优化非 ATP 竞争性 CDK/细胞周期蛋白凹槽抑制剂

  摘要：

  药物发现的一个主要挑战是开发和改进靶向蛋白质-蛋白质相互作用的方法。用于生成蛋白质-蛋白质相互作用抑制剂的 REPLACE（通过计算富集替代部分配体替代物）策略的进一步示例表明，它可用于优化关键决定因素的片段替代物，以有效的方式将它们组合起来，并已实现用于靶向细胞周期蛋白调节亚基上的细胞周期蛋白依赖性激酶 2 (CDK2) 底物募集位点的化合物。取代关键电荷-电荷相互作用的苯基杂环等排体为结合细胞周期蛋白凹槽提供了新的结构见解。特别是，这些结果揭示了在 N 端加帽肽的晶体结构中观察到的 H 键的关键贡献。此外，通过环取代探测了模拟二肽相互作用的双（芳基）醚 C 端封端基团的构效关系，从而增加了与主要疏水口袋的互补性。该研究进一步验证了 REPLACE 作为将肽类化合物转化为药学相关性更强的化合物的有效策略。

  DOI：

  10.1021/jm3013882

文献信息

• Cyclin Based Inhibitors of CDK2 and CDK4
  申请人：McInnes Campbell

  公开号：US20130289240A1

  公开（公告）日：2013-10-31

  Structural and functional analysis of peptide inhibitor binding to the cyclin D and cyclin A groove has been investigated and used to design peptides that provide the basis for structure-activity relationships, have improved binding and have potential for development as chemical biology probes, as potential diagnostics and as therapeutics in the treatment of proliferative diseases including cancer and inflammation.

  研究了肽抑制剂与环D和环A凹槽的结构和功能分析，并用于设计肽，为结构活性关系提供基础，改善结合并具有作为化学生物学探针、潜在诊断和治疗增殖性疾病（包括癌症和炎症）的潜力。
• 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.
• LOW AFFINITY SCREENING METHOD
  申请人：Graffinity Pharmaceuticals Aktiengesellschaft

  公开号：EP1360489A1

  公开（公告）日：2003-11-12
• Low affinity screening method
  申请人：——

  公开号：US20040082079A1

  公开（公告）日：2004-04-29

  A parallel high throughput screening method on a solid support is disclosed that allows the detection of low affinity binding partners, comprising the steps of:(a) providing a library of different ligands;(b) forming a binding matrix comprising the ligands on a solid support by immobilising said ligands on the support; (c) contacting a target of interest with said binding matrix; (d) parallely determining a binding value of the ligand/target interaction for each type of ligand comprised in the binding matrix; (e) selecting those ligands the binding value of which in an immobilised state towards the target exceeds a predetermined threshold; (f) evaluating the affinity of each of the ligands selected in step (e) in a non-immobilised state towards the target; (g) identifying at least one ligand of step (f) as low affinity binding ligand.
• CYCLIN BASED INHIBITORS OF CDK2 AND CDK4
  申请人：McInnes Campbell

  公开号：US20140316107A1

  公开（公告）日：2014-10-23

  Structural and functional analysis of peptide inhibitor binding to the cyclin D1 groove has been investigated and used to design peptides that provide the basis for structure-activity relationships, have improved binding and have potential for development as chemical biology probes, as potential diagnostics and as therapeutics in the treatment of proliferative diseases including cancer and inflammation.