((S)-2-(tert-butoxycarbonylamino)pentanoyl)-L-leucine methyl ester | 78664-45-6

• 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-(tert-butoxycarbonylamino)pentanoyl)-L-leucine methyl ester
• 英文别名: tert.-Butoxycarbonyl-L-norvalyl-L-leucine methyl ester；BOC-Nva-Leu-OMe；methyl (2S)-4-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]pentanoate
• CAS: 78664-45-6
• 化学式: C₁₇H₃₂N₂O₅
• 分子量: 344.451
• InChiKey: BFEIQTWZUFRSRC-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ((S)-2-(tert-butoxycarbonylamino)pentanoyl)-L-leucine methyl ester 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Additivity or cooperativity: Which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2014.11.056
• 作为产物：
  描述：

  L-亮氨酸甲酯盐酸盐 、 N-tert-butoxycarbonyl-L-norvaline 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到((S)-2-(tert-butoxycarbonylamino)pentanoyl)-L-leucine methyl ester
  参考文献：
  名称：

  Additivity or cooperativity: Which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2014.11.056

文献信息

• Tripeptides acting on the central nervous system and a process for the
  申请人：Patentbureau DANUBIA

  公开号：US04386073A1

  公开（公告）日：1983-05-31

  The invention relates to new peptide derivatives which act on the central nervous system and correspond to the general formula (I), X--Y--W--NH.sub.2 (I) wherein X is L-pyroglutamyl, D-pyroglutamyl, L-2-keto-imidazolidine-4-carbonyl, L-6-keto-pipecolyl, L-thiazolidine-4-carbonyl, L-prolyl or orotyl group, Y is L-leucyl, L-norvalyl or L-histidyl group, and W is L-prolyl, D-prolyl, L-thiazolidine-4-carbonyl, L-pipecolyl, L-homoprolyl, L-leucyl, L-isoleucyl, L-methionyl or D-pipecolyl group, or the W-NH.sub.2 group stands for pyrrolidyl or piperidyl group, with the proviso that if X is L-pyroglutamyl and Y is L-histidyl group, W is other than L-prolyl group, and pharmaceutically acceptable complexes thereof. These compounds are prepared by methods commonly applied in the peptide chemistry.

  本发明涉及一种新的肽衍生物，其作用于中枢神经系统，符合通式（I），X-Y-W-NH.sub.2（I），其中X为L-吡咯糜酰基，D-吡咯糜酰基，L-2-酮咪唑啉-4-羧酰基，L-6-酮-哌嗪基，L-噻唑啉-4-羧酰基，L-脯氨酰基或乌洛替基，Y为L-亮氨酰基，L-异戊氨酰基或L-组氨酰基，W为L-脯氨酰基，D-脯氨酰基，L-噻唑啉-4-羧酰基，L-哌嗪基，L-同型脯氨酰基，L-亮氨酰基，L-异亮氨酰基，L-甲硫氨酰基或D-哌嗪基，或W-NH.sub.2基团代表吡咯烷基或哌啶基，但如果X为L-吡咯糜酰基且Y为L-组氨酰基，则W为除L-脯氨酰基以外的其他基团，以及其药学上可接受的复合物。这些化合物是通过肽化学中常用的方法制备的。
• US4386073A
  申请人：——

  公开号：US4386073A

  公开（公告）日：1983-05-31
• 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.