2-hydroxy-4-pyrrol-1-yl-benzoic acid methyl ester | 454473-64-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-hydroxy-4-pyrrol-1-yl-benzoic acid methyl ester
• 英文别名: N-(3-hydroxy-4-methoxycarbonylphenyl)pyrrole；methyl 2-hydroxy-4-(1H-pyrrol-1-yl)benzenecarboxylate；methyl 2-hydroxy-4-(1H-pyrrol-1-yl)benzoate；methyl 2-hydroxy-4-pyrrol-1-ylbenzoate
• CAS: 454473-64-4
• 化学式: C₁₂H₁₁NO₃
• mdl: MFCD02083001
• 分子量: 217.224
• InChiKey: FOBLNLGBEWRJLG-UHFFFAOYSA-N

物化性质

• 熔点：
  121-124 °C
• 沸点：
  351.6±32.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-hydroxy-4-pyrrol-1-yl-benzoic acid methyl ester 在 sodium hexamethyldisilazane 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,3-dimethyl-2-imidazolinone 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 (3-amino-6-(pyrrol-1-yl)-benzofuran-2-yl)-(2,4-dichlorophenyl)-methanone
  参考文献：
  名称：

  WO2008/25509

  摘要：

  公开号：
• 作为产物：
  描述：

  2,5-二甲氧基四氢呋喃 、 2-羟基-4-氨基苯甲酸甲酯 在 溶剂黄146 作用下， 反应 0.17h， 以71%的产率得到2-hydroxy-4-pyrrol-1-yl-benzoic acid methyl ester
  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

• [EN] BENZOFURAN AND BENZOTHIOPHENE DERIVATIVES USEFUL IN THE TREATMENT OF HYPER-PROLIFERATIVE DISORDERS<br/>[FR] DERIVES DE BENZOFURANE ET DE BENZOTHIOPHENE UTILISES DANS LE TRAITEMENT DE TROUBLES HYPERPROLIFERATIFS
  申请人：BAYER PHARMACEUTICALS CORP

  公开号：WO2003072561A1

  公开（公告）日：2003-09-04

  This invention relates to novel benzofuran and benzothiophene derivatives of the general formula and their use for the treatment of hyper-proliferative disorders.

  这项发明涉及一般式的新型苯并呋喃和苯并噻吩衍生物及其用于治疗高增殖性疾病的用途。
• [EN] PYRROL-1 -YL BENZOIC ACID DERIVATES USEFUL AS MYC INHIBITORS<br/>[FR] DÉRIVÉS D'ACIDE PYRROL-1-YL-BENZOÏQUE UTILES EN TANT QU'INHIBITEURS DE MYC
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2014071247A1

  公开（公告）日：2014-05-08

  The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.

  本发明提供了式(I-A)、(I-B)和(I-C)的化合物、药用可接受的盐及其药用组合物。本发明的化合物可用于抑制Myc（例如，c-Myc）活性。本发明进一步提供了使用所述化合物治疗Myc介导的疾病（例如，癌症和其他增殖性疾病）的方法。本发明还提供了用于识别Myc抑制剂的检测方法。
• [EN] BENZO[1,3]DIOXINE DERIVATIVES AND THEIR USE AS LPAR5 ANTAGONISTS<br/>[FR] DÉRIVÉS DE BENZO[1,3]DIOXINE ET LEUR UTILISATION COMME ANTAGONISTES DE LPAR5
  申请人：SANOFI SA

  公开号：WO2013171318A1

  公开（公告）日：2013-11-21

  The present invention relates to compounds of the formula (I), wherein the residues A, R1 to R5, Z1 and Z2 have the meanings indicated in the claims. The compounds of the formula (I) are valuable pharmacologically active compounds for use in the treatment of diverse disorders, for example cardiovascular disorders like thromboembolic diseases or restenoses. The compounds of the invention are effective antagonists of the platelet LPA receptor LPAR5 (GPR92) and can in general be applied in conditions in which an undesired activation of the platelet LPA receptor LPAR5, the mast cell LPA receptor LPAR5 or the microglia cell LPA receptor LPAR5 is present or for the cure or prevention of which an inhibition of the platelet, mast cell or microglia cell LPA receptor LPAR5 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula (I), their use, in particular as active ingredients in medicaments, and pharmaceutical compositions comprising them.

  本发明涉及式(I)的化合物，其中残基A，R1到R5，Z1和Z2具有所述索引中指示的含义。式(I)的化合物是用于治疗不同疾病的有价值的药理活性化合物，例如心血管疾病，如血栓栓塞性疾病或再狭窄。本发明的化合物是血小板LPA受体LPAR5（GPR92）的有效拮抗剂，通常可应用于存在不希望的血小板LPA受体LPAR5，肥大细胞LPA受体LPAR5或微胶质细胞LPA受体LPAR5的情况，或者用于治疗或预防需要抑制血小板，肥大细胞或微胶质细胞LPA受体LPAR5的情况。本发明还涉及制备式(I)的化合物的过程，它们的用途，特别是作为药物活性成分，并包括它们的制药组合物。
• METHODS OF INHIBITING THE FORMATION OF AMYLOID-BETA DIFFUSABLE LIGANDS USING ACYLHYDRAZIDE COMPOUNDS
  申请人：Look Gary Charles

  公开号：US20110098309A1

  公开（公告）日：2011-04-28

  Disclosed are methods of inhibiting, regulating, and/or modulating the formation of soluble, globular, non-fibrillar, neurotoxic amyloid β1-42 oligomers from amyloid β1-42 monomers using acylhydrazide compounds. Also disclosed are methods of treating a patient suffering from diseases associated with the formation of soluble, globular, non-fibrillar, neurotoxic amyloid β1-42 oligomers using acylhydrazide compounds.

  本发明涉及使用酰肼化合物抑制、调节和/或调节可溶性、球形、非纤维化、神经毒性淀粉样β1-42寡聚体从淀粉样β1-42单体形成的方法。本发明还涉及使用酰肼化合物治疗患有与可溶性、球形、非纤维化、神经毒性淀粉样β1-42寡聚体形成有关的疾病的患者的方法。
• Benzo[1,3]Dioxine Derivatives And Their Use As LPAR5 Antagonists
  申请人：SANOFI

  公开号：US20150111889A1

  公开（公告）日：2015-04-23

  The present invention relates to compounds of the formula (I), wherein the residues A, R 1 to R 5 , Z 1 and Z 2 have the meanings indicated in the claims. The compounds of the formula (I) are valuable pharmacologically active compounds for use in the treatment of diverse disorders, for example cardiovascular disorders like thromboembolic diseases or restenoses. The compounds of the invention are effective antagonists of the platelet LPA receptor LPAR5 (GPR92) and can in general be applied in conditions in which an undesired activation of the platelet LPA receptor LPAR5, the mast cell LPA receptor LPAR5 or the microglia cell LPA receptor LPAR5 is present or for the cure or prevention of which an inhibition of the platelet, mast cell or microglia cell LPA receptor LPAR5 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula (I), their use, in particular as active ingredients in medicaments, and pharmaceutical compositions comprising them.

  本发明涉及式（I）的化合物，其中残基A，R1至R5，Z1和Z2具有权利要求书中所示的含义。式（I）的化合物是有价值的药理活性化合物，可用于治疗多种疾病，例如心血管疾病如血栓栓塞病或再狭窄。本发明的化合物是血小板LPA受体LPAR5（GPR92）的有效拮抗剂，通常可用于存在血小板LPA受体LPAR5、肥大细胞LPA受体LPAR5或微胶质细胞LPA受体LPAR5的不良活化条件，或预防或治疗需要抑制血小板、肥大细胞或微胶质细胞LPA受体LPAR5的情况。本发明还涉及制备式（I）化合物的方法，它们的用途，特别是作为药物中的活性成分，以及包含它们的制药组合物。