L-leucinyl-L-norvaline methyl ester hydrochloride | 1426227-63-5

• 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: L-leucinyl-L-norvaline methyl ester hydrochloride
• 英文别名: L-leucinyl-norvaline methyl ester hydrochloride
• CAS: 1426227-63-5
• 化学式: C₁₂H₂₄N₂O₃*ClH
• 分子量: 280.795
• InChiKey: AXCVISVSPYGKHU-IYPAPVHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.24
• 重原子数：
  18.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  L-leucinyl-L-norvaline methyl ester hydrochloride 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 24.0h， 生成 N-(N-(N-(benzyloxycarbonyl)aminomethylphosphonyl)-L-leucinyl)norvalinate dilithium
  参考文献：
  名称：

  剖析对分子水平的疏水作用：水，焓和熵在配体与嗜热菌素结合中的作用

  摘要：

  疏水作用与配体的疏水基团连续替换蛋白质结合位点中的水分子有关。尽管疏水作用被认为是由熵驱动的，但是在模型系统Thermosin中，可以观察到焓和熵的大变化。水分子结合特征的结构变化最终决定了疏水作用的热力学。

  DOI：

  10.1002/anie.201208561
• 作为产物：
  描述：

  (N-(tert-butoxycarbonyl)-L-leucinyl)-L-norvaline methyl ester 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以483 mg的产率得到L-leucinyl-L-norvaline methyl ester hydrochloride
  参考文献：
  名称：

  相邻基团对疏水结合热力学的影响：疏水效应增加了复杂的方面

  摘要：

  使用等温滴定量热法（ITC）对在浅疏水口袋中结合的配体侧链进行系统修饰的热力学后果进行了评估，无论是否存在相邻的配体羧酸酯基团。数据显示，羧酸盐可能会通过改变未结合状态和结合状态下水合水的H键/组织状态来显着改变这些修饰的相对热力学特征。发现该羧酸酯基团在某些情况下是前焓的，对熵的，而在另一些情况下是反焓的，对熵的。还观察到了显着的焓-熵补偿关系，这反映了疏水作用受相关水环境的热力学状态支配的事实。

  DOI：

  10.1021/jm401609a

文献信息

• Additivity or cooperativity: Which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?
  作者：Nader N. Nasief、David Hangauer

  DOI：10.1016/j.ejmech.2014.11.056

  日期：2015.1

  Predicting how binding affinity responds to ligand structural modifications in structure-activity relationship studies (SAR) is a major challenge in medicinal chemistry. This is particularly true when two or more of these modifications are carried out simultaneously. In this study, we present binding affinity data from several series of thermolysin inhibitors in which simultaneous structural modifications were investigated to determine whether they are cooperative or additive. Data revealed that, while additivity is at work in some cases, cooperativity is more commonly demonstrated. Cooperativity and additivity were then correlated with ligand descriptors, such as the spacing and the topological features of the modified groups, in a manner that may provide guidance as to when each model should be utilized. Cooperativity was particularly associated with contiguous groups and small unbranched hydrophobic side chain. Additivity, on the other hand, was associated with moderately distant hydrophobic group combinations and side chain branching. Such correlations can improve the predictability of SAR studies and can provide a starting point for additional investigations that may lead to further significant enhancements in the current scoring functions. (C) 2014 Elsevier Masson SAS. All rights reserved.