N-(4-carboxybenzyl)-2,5-dimethylpyrrole | 313701-95-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-carboxybenzyl)-2,5-dimethylpyrrole
• 英文别名: 4-[(2,5-dimethyl-1H-pyrrol-1-yl)methyl]benzoic acid；4-[(2,5-dimethylpyrrol-1-yl)methyl]benzoic acid
• CAS: 313701-95-0
• 化学式: C₁₄H₁₅NO₂
• mdl: MFCD01860277
• 分子量: 229.279
• InChiKey: DKSYSLOSBLCHEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.214
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  N-(4-carboxybenzyl)-2,5-dimethylpyrrole 、 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain

  摘要：

  Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active against rhodesain and T. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary SAR studies. We envision that in vitro enzymatic assays will further expand the use of the covalent tethering method, a simple fragment-based drug discovery technique to discover covalent drug leads. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.08.074
• 作为产物：
  描述：

  4-氨甲基苯甲酸 、 2,5-己二酮 在 溶剂黄146 作用下， 反应 0.17h， 以77%的产率得到N-(4-carboxybenzyl)-2,5-dimethylpyrrole
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of N-Carboxyphenylpyrrole Derivatives as Potent HIV Fusion Inhibitors Targeting gp41

  摘要：

  On the basis of the structures of small-molecule hits targeting the HIV-1 gp41, N-(4-carboxy-3-hydi-oxy)plieiiyl-2,5-dimethylpyl-role (2, NB-2), and N-(3-carboxy-4-chloro)phenylpyrrole (A(1), NB-64), 42 N-carboxyphenylpyrrole derivatives in two categories (A and B series) were designed and synthesized. We found that I I compounds exhibited promising anti-HIV-1 activity at micromolar level and their antiviral activity was correlated with their inhibitory activity on gp41 six-helix bundle formation, suggesting that these compounds block HIV fusion and entry by disrupting gp41 core formation. The structure-activity relationship and molecular docking analysis revealed that the carboxyl group Could interact with either Arg579 or Lys574 to form salt bridges and two methyl groups on the pyrrole ring were favorable for interaction with the residues in gp41 pocket. The most active compound, N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole (A(12)), partially occupied the deep hydrophobic pocket, suggesting that enlarging the molecular size of A(12) could improve its binding affinity and anti-HIV-1 activity for further development as a small-molecule HIV fusion and entry inhibitor.

  DOI：

  10.1021/jm800869t

文献信息

• A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases
  作者：Stefan G. Kathman、Ziyang Xu、Alexander V. Statsyuk

  DOI：10.1021/jm500345q

  日期：2014.6.12

  reported which irreversibly tethers drug-like fragments to catalytic cysteines. We attached an electrophile to 100 fragments without significant alterations in the reactivity of the electrophile. A mass spectrometry assay discovered three nonpeptidic inhibitors of the cysteine protease papain. The identified compounds display the characteristics of irreversible inhibitors. The irreversible tethering system

  报道了一种新的基于片段的药物发现方法，该方法不可逆地将类药物片段束缚在催化半胱氨酸上。我们将亲电试剂连接到 100 个片段上，而亲电试剂的反应性没有显着改变。质谱分析发现了半胱氨酸蛋白酶木瓜蛋白酶的三种非肽抑制剂。鉴定出的化合物显示出不可逆抑制剂的特征。不可逆的束缚系统也显示出特异性：三种鉴定出的木瓜蛋白酶抑制剂不与 UbcH7、USP08 或带有 GST 标签的人类鼻病毒 3C 蛋白酶共价反应。
• Small molecules for the modulation of MCL-1 and methods of modulating cell death, cell division, cell differentiation and methods of treating disorders
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10000511B2

  公开（公告）日：2018-06-19

  This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.

  本发明涉及以高亲和力和选择性与存活蛋白 MCL-1 选择性结合的化合物、含有此类化合物的药物组合物，以及使用这些化合物或组合物调节 MCL-1 活性和治疗过度增殖性疾病、血管生成疾病、细胞周期调节疾病、自噬调节疾病、炎症性疾病和/或感染性疾病和/或增强细胞移植和/或伤口修复，可作为单独制剂或与其他活性成分组合使用。
• Chemical entities that kill senescent cells for use in treating age-related disease
  申请人：Unity Biotechnology, Inc.

  公开号：US10195213B2

  公开（公告）日：2019-02-05

  Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.

  本文公开的化合物可有效治疗与衰老有关的各种疾病状态。所公开的化合物可用于消除衰老细胞以治疗疾病。化合物的给药方式包括单次给药和循环给药。
• METHODS AND COMPOUNDS FOR REGULATING APOPTOSIS
  申请人：Reed John C.

  公开号：US20090118135A1

  公开（公告）日：2009-05-07

  An assay for determining compounds that inhibit activity of a BCl-2 protein, or affect conversion of Bcl-2 from an antiapoptotic to a proapoptotic form are described. In addition, compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified.
• SMALL MOLECULES FOR THE MODULATION OF MCL-1 AND METHODS OF MODULATING CELL DEATH, CELL DIVISION, CELL DIFFERENTIATION AND METHODS OF TREATING DISORDERS
  申请人：Walensky Loren D.

  公开号：US20130035304A1

  公开（公告）日：2013-02-07

  This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.