(3S,4S)-1-tert-butoxycarbonyl-3,4-diaminopyrrolidine | 1020571-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (3S,4S)-1-tert-butoxycarbonyl-3,4-diaminopyrrolidine
• 英文别名: tert-butyl (3S,4S)-3,4-diaminopyrrolidine-1-carboxylate；(3S,4S)-Tert-butyl 3,4-diaminopyrrolidine-1-carboxylate
• CAS: 1020571-45-2
• 化学式: C₉H₁₉N₃O₂
• 分子量: 201.269
• InChiKey: MOFRNGKMXMQTQR-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  81.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4S)-1-tert-butoxycarbonyl-3,4-diaminopyrrolidine 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 24.0h， 生成 (3S,4S)-3,4-bis-[(4-bromo-benzenesulfonyl)-(3-methyl-but-2-enyl)-amino]pyrrolidine-1-carboxylic acid t-butyl ester
  参考文献：
  名称：

  Two Solutions for the Same Problem: Multiple Binding Modes of Pyrrolidine-Based HIV-1 Protease Inhibitors

  摘要：

  Structure-based drug design is an integral part of industrial and academic drug discovery projects. Initial lead structures are, in general, optimized in terms of affinity using iterative cycles comprising synthesis, biological evaluation, computational methods, and structural analysis. X-ray crystallography commonly suggests the existence of a single well-defined state, termed binding mode, which is generally assumed to be consistent in a series of similar ligands and therefore used for the following optimization process. During the further development of symmetrically disubstituted 3,4-amino-pyrrolidines as human immunodeficiency virus type 1 protease inhibitors, we discovered that, by modification of the P1/P1' moieties of our lead structure, the activity of the inhibitors towards the active-site mutation 1le84Val was altered, however, not being explainable with the initial underlying structure activity relationship. The cocrystallization of the most potent derivative in complex with the human immunodeficiency virus type 1 protease surprisingly led to two different crystal forms (P2(1)2(1)2(1) and P6(1)22). Structural analysis revealed two completely different binding modes; the interaction of the pyrrolidine nitrogen atom with the catalytic aspartates remains as the only similarity. The study presented clearly demonstrates that structural biology has to escort the entire lead optimization process not to fail by an initially observed binding orientation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.jmb.2011.04.052
• 作为产物：
  描述：

  (3S,4S)-N-Boc-3,4-diazidopyrrolidine 在 palladium on activated charcoal 氢气 作用下， 以 正己烷 、 乙酸乙酯 为溶剂， 反应 14.0h， 生成 (3S,4S)-1-tert-butoxycarbonyl-3,4-diaminopyrrolidine
  参考文献：
  名称：

  Structure-Guided Design of C₂-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold

  摘要：

  Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic, HIV protease has proven to be an invaluable drug target because of its essential role in the virus' replication process. By use of pyrrolidine as core structure, symmetric 3,4-bis-N-alkylsulfonamides were designed and synthesized enantioselectively from D-(-)-tartaric acid as a new class of HIV protease inhibitors. Structure-guided design using the cocrystal structure of an initial lead as starting point resulted in a second series of inhibitors with improved affinity. The binding modes of four representatives were determined by X-ray crystallography to elucidate the underlying factors accounting for the SAR. With this information for further rational design, the combination of suitable side chains resulted in a final inhibitor showing a significantly improved affinity of K(i) = 74 nM.

  DOI：

  10.1021/jm701142s

文献信息

• [EN] KINASE INHIBITORS FOR THE TREATMENT OF CENTRAL AND PERIPHERAL NERVOUS SYSTEM DISORDERS<br/>[FR] INHIBITEURS DE KINASE POUR LE TRAITEMENT DE TROUBLES DU SYSTÈME NERVEUX CENTRAL ET PÉRIPHÉRIQUE
  申请人：UNIV MIAMI

  公开号：WO2019089729A1

  公开（公告）日：2019-05-09

  Provided herein are compounds of the general Formula (I) which act as kinase inhibitors, e.g. ROCK, S6K, and/or PKC inhibitors, and are useful in neurite growth and axonal growth.

  本文提供的是一般式(I)的化合物，这些化合物作为激酶抑制剂，例如ROCK、S6K和/或PKC抑制剂，在神经突起生长和轴突生长中具有用处。
• Neuronal Pain Pathway Modulators
  申请人：Ambron Richard

  公开号：US20080176920A1

  公开（公告）日：2008-07-24

  The present invention relates to compounds that may be used to inhibit activation of protein kinase G (“PKG”). It is based, at least in part, on the discovery of the tertiary structure of PKG and the identification of molecules that either bind to the active site of PKG and/or are analogs of balanol.

  本发明涉及可用于抑制蛋白激酶G（PKG）激活的化合物。至少部分基于对PKG的三级结构的发现以及发现绑定于PKG活性位点和/或是巴洛酮类似物的分子的识别。
• [EN] COVALENT INHIBITORS OF PAD4<br/>[FR] INHIBITEURS COVALENTS DE PAD4
  申请人：PADLOCK THERAPEUTICS INC

  公开号：WO2018022897A1

  公开（公告）日：2018-02-01

  The present invention provides compounds of formula I useful as inhibitors of PAD4, compositions thereof, and methods of treating PAD4-related disorders.

  本发明提供了一种公式I的化合物，其可用作PAD4的抑制剂，以及其组合物和治疗PAD4相关疾病的方法。
• Pyrrolidine Derivatives as Plasmepsin Inhibitors: Binding Mode Analysis Assisted by Molecular Dynamics Simulations of a Highly Flexible Protein
  作者：Torsten Luksch、Andreas Blum、Nina Klee、Wibke E. Diederich、Christoph A. Sotriffer、Gerhard Klebe

  DOI：10.1002/cmdc.200900452

  日期：——

  sufficiently opened to accommodate the 3,4‐bis(aminomethylene)pyrrolidines. Molecular dynamics simulations were performed to analyze the flexibility of the protein in greater detail, leading to a binding mode hypothesis for the 3,4‐bis(aminomethylene)pyrrolidines and providing further insight and general implications for the design of Plm II inhibitors.

  纤溶酶II（EC编号：3.4.23.39）和IV（EC编号：3.4.23.B14）是存在于疟原虫恶性疟原虫食物液泡中的天冬氨酸蛋白酶。并参与宿主血红蛋白降解。测试了最初合成为HIV-1蛋白酶抑制剂的一系列吡咯烷衍生物对纤溶酶（Plm）的活性。发现了Plm II和IV同工型的纳摩尔级抑制剂。进行了详细的研究，以鉴定有助于解释潜在的结构-活性关系的推定结合模式。通过使用抑制剂结合的Plm II（PDB ID：1LEE）的晶体结构，生成了吡咯烷3,4-二酯衍生物和取代的3,4-二氨基吡咯烷抑制剂的合理结合模式。建模研究表明，可用的Plm晶体结构的襟翼未充分打开，无法容纳3,4-双（氨基亚甲基）吡咯烷。
• NEURONAL PAIN PATHWAY MODULATORS
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US20150126576A1

  公开（公告）日：2015-05-07

  The present invention relates to compounds that may be used to inhibit activation of protein kinase G (“PKG”). It is based, at least in part, on the discovery of the tertiary structure of PKG and the identification of molecules that either bind to the active site of PKG and/or are analogs of balanol.

  本发明涉及可用于抑制蛋白激酶G（“PKG”）激活的化合物。它至少部分地基于发现PK G的三级结构以及识别既能够与PKG的活性位点结合，又是巴洛诺（balanol）的类似物的分子。