tert-butyl ((R)-1-((2S)-2-((4-cyanobenzyl)carbamoyl)pyrrolidin-1-yl)-1-cyclohexyl-2-oxoethyl)carbamate | 172348-68-4

• 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: tert-butyl ((R)-1-((2S)-2-((4-cyanobenzyl)carbamoyl)pyrrolidin-1-yl)-1-cyclohexyl-2-oxoethyl)carbamate
• 英文别名: Boc-D-Phenylalanylproline (p-cyanobenzyl)amide；tert-butyl N-[(2R)-1-[(2S)-2-[(4-cyanophenyl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 172348-68-4
• 化学式: C₂₇H₃₂N₄O₄
• 分子量: 476.575
• InChiKey: UGQGMWVWVNHXKW-PKTZIBPZSA-N

物化性质

• 沸点：
  756.9±60.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl ((R)-1-((2S)-2-((4-cyanobenzyl)carbamoyl)pyrrolidin-1-yl)-1-cyclohexyl-2-oxoethyl)carbamate 在 盐酸羟胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 C₂₇H₃₅N₅O₅
  参考文献：
  名称：

  Binding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors

  摘要：

  One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong positive cooperativity between an H-bond accepting carbonyl functionality and the adjacent P3 hydrophobic side chain. Adding an H-bond donating amine adjacent to the P3 hydrophobic side chain further increases this positive cooperativity thereby improving the Ki by as much as 546-fold. In contrast, adding an amidine multiple H-bond/salt bridge group in the distal S1 pocket does not affect this cooperativity. An analysis of the crystallographic B-factors of the ligand groups inside the binding site indicates that the strong cooperativity is mainly due to a significant mutual reduction in the residual mobility of the hydrophobic side chain and the H-bonding functionalities that is absent when the separation distance is large. This type of cooperativity is important to encode in binding affinity prediction software, and to consider in SAR studies. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.059
• 作为产物：
  描述：

  4-(氨甲基)苯腈盐酸盐 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 tert-butyl ((R)-1-((2S)-2-((4-cyanobenzyl)carbamoyl)pyrrolidin-1-yl)-1-cyclohexyl-2-oxoethyl)carbamate
  参考文献：
  名称：

  Binding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors

  摘要：

  One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong positive cooperativity between an H-bond accepting carbonyl functionality and the adjacent P3 hydrophobic side chain. Adding an H-bond donating amine adjacent to the P3 hydrophobic side chain further increases this positive cooperativity thereby improving the Ki by as much as 546-fold. In contrast, adding an amidine multiple H-bond/salt bridge group in the distal S1 pocket does not affect this cooperativity. An analysis of the crystallographic B-factors of the ligand groups inside the binding site indicates that the strong cooperativity is mainly due to a significant mutual reduction in the residual mobility of the hydrophobic side chain and the H-bonding functionalities that is absent when the separation distance is large. This type of cooperativity is important to encode in binding affinity prediction software, and to consider in SAR studies. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.059

文献信息

• Dipeptide p-amidinobenzylamides with N-terminal sulfonyl or
  申请人：BASF Aktiengesellschaft

  公开号：US05852051A1

  公开（公告）日：1998-12-22

  Compounds of the formula I ##STR1## in which R.sup.1, A and B have the meanings stated in the description, and the preparation thereof are described. The novel compounds are suitable for controlling diseases.

  本发明涉及公式I的化合物，其中R.sup.1，A和B的含义如描述中所述，并描述了其制备方法。这些新化合物适用于控制疾病。
• [DE] NEUE DIPEPTIDISCHE P-AMIDINOBENZYLAMIDE MIT N-TERMINALEN SULFONYL- BZW. AMINOSULFONYLRESTEN<br/>[EN] NEW DIPEPTIDE P-AMIDINOBENZYLAMIDES WITH N-TERMINAL SULFONYL OR AMINOSULFONYL RADICALS<br/>[FR] NOUVEAUX P-AMIDINOBENZYLAMIDES DIPEPTIDIQUES A RESTES N-TERMINAUX SULFONYLE OU AMINOSULFONYLE
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：WO1996017860A1

  公开（公告）日：1996-06-13

  (DE) Es werden Verbindungen der Formel (I), worin R1, A und B die in der Beschreibung angegebene Bedeutung besitzen, sowie deren Herstellung beschrieben. Die neuen Verbindungen eignen sich zur Bekämpfung von Krankheiten.(EN) The invention pertains to compounds of formula (I), wherein R1, A and B are as indicated in the description, and to their preparation. The new compounds can be used for combatting diseases.(FR) L'invention concerne des composés de formule (I), dans laquelle R1, A et B ont les notations données dans la description, ainsi que leur fabrication. Ces nouveaux composés sont utiles pour combattre des maladies.

  该发明涉及式样为(I)的化合物，其中所述的R1、A和B具有所述的含义，以及它们的制备。这些新化合物可用于对抗疾病。
• D-Phe-Pro-p-Amidinobenzylamine: A potent and highly selective thrombin inhibitor
  作者：Michael R. Wiley、Nickolay Y. Chirgadze、David K. Clawson、Trelia J. Craft、Donetta S. Gifford-Moore、Noel D. Jones、Jennifer L. Olkowski、Leonard C. Weir、Gerald F. Smith

  DOI：10.1016/0960-894x(96)00442-8

  日期：1996.10

  The design, synthesis, and enzyme inhibitory profile of D-Phe-Pro-p-Amidinobenzylamine are presented. This compound has inhibitory activity equivalent to D-Phe-Pro-Arg-H, two orders of magnitude more potent than D-Phe-Pro-Agmatine, The results indicate that binding energy provided by the covalent bond of a transition-state analog can be replaced with noncovalent interactions. Copyright (C) 1996 Elsevier Science Ltd.
• DIPEPTIDISCHE P-AMIDINOBENZYLAMIDE MIT N-TERMINALEN SULFONYL- BZW. AMINOSULFONYLRESTEN
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：EP0796271B1

  公开（公告）日：2000-02-02
• NEUE DIPEPTIDISCHE P-AMIDINOBENZYLAMIDE MIT N-TERMINALEN SULFONYL- BZW. AMINOSULFONYLRESTEN
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：EP0796271A1

  公开（公告）日：1997-09-24