4-(吡啶-2-基甲氧基)苯甲酸乙酯 | 50596-38-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(吡啶-2-基甲氧基)苯甲酸乙酯
• 英文名称: ethyl 4-(pyridin-2-ylmethoxy)benzoate
• 英文别名: 4-pyridin-2-ylmethoxy-benzoic acid ethyl ester；Ethyl 4-(pyridin-2-ylmethoxy)benzenecarboxylate；4-Ethoxycarbonylphenoxy-2'-pyridylmethane
• CAS: 50596-38-8
• 化学式: C₁₅H₁₅NO₃
• mdl: MFCD20761695
• 分子量: 257.289
• InChiKey: OJWMBNSRBKSJIK-UHFFFAOYSA-N

物化性质

• 沸点：
  394.3±22.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(吡啶-2-基甲氧基)苯甲酸乙酯 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 methyl 4-methyl-3-(4-(pyridin-2-ylmethoxy)benzamido)benzoate
  参考文献：
  名称：

  Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO

  摘要：

  Cell-based subset screening of compounds using a Gli transcription factor reporter cell assay and shh stimulated cell differentiation assay identified a series of bisamide compounds as hedgehog pathway inhibitors with good potency. Using a ligand-based optimization strategy, heteroaryl groups were utilized as conformationally restricted amide isosteres replacing one of the amides which significantly increased their potency against SMO and the hedgehog pathway while decreasing activity against p38 alpha kinase. We report herein the identification of advanced lead compounds such as imidazole 11c and 11f encompassing good p38 alpha selectivity, low nanomolar potency in both cell assays, excellent physiochemical properties and in vivo pharmacokinetics. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.104
• 作为产物：
  描述：

  2-溴甲基吡啶 、 过氧化氢酶 在 potassium carbonate 作用下， 以 水 、 乙腈 为溶剂， 以80%的产率得到4-(吡啶-2-基甲氧基)苯甲酸乙酯
  参考文献：
  名称：

  Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO

  摘要：

  Cell-based subset screening of compounds using a Gli transcription factor reporter cell assay and shh stimulated cell differentiation assay identified a series of bisamide compounds as hedgehog pathway inhibitors with good potency. Using a ligand-based optimization strategy, heteroaryl groups were utilized as conformationally restricted amide isosteres replacing one of the amides which significantly increased their potency against SMO and the hedgehog pathway while decreasing activity against p38 alpha kinase. We report herein the identification of advanced lead compounds such as imidazole 11c and 11f encompassing good p38 alpha selectivity, low nanomolar potency in both cell assays, excellent physiochemical properties and in vivo pharmacokinetics. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.104

文献信息

• [EN] HETEROCYCLIC AMIDES USEFUL FOR THE TREATMENT OF CANCER AND PSORIASIS<br/>[FR] AMIDES HÉTÉROCYCLIQUES UTILES DANS LE TRAITEMENT DU CANCER ET DU PSORIASIS
  申请人：ASTRAZENECA AB

  公开号：WO2009027746A1

  公开（公告）日：2009-03-05

  The present disclosure relates to heterocyclic amide compounds, which are useful for inhibiting the Hedgehog pathway, and their use in treating a disease or medical condition mediated alone or in part by Hedgehog pathway inhibition. Also disclosed are methods for manufacture of these compounds, pharmaceutical compositions including these compounds, and use of these compounds in the manufacture of medicaments for treating such diseases and medical conditions in a subject. Formula (IA) with the provisio that either R2or R3 is (Z).

  本公开涉及杂环酰胺化合物，这些化合物对抑制Hedgehog途径有用，并且它们在治疗由Hedgehog途径抑制单独或部分介导的疾病或医疗状况中的用途。还公开了这些化合物的制造方法，包括这些化合物的药物组合物，以及利用这些化合物制造用于治疗受试者中的这些疾病和医疗状况的药物的方法。公式（IA），条件是R2或R3中的一个是（Z）。
• Heteroarylamide smoothened inhibitors: Discovery of N-[2,4-dimethyl-5-(1-methylimidazol-4-yl)phenyl]-4-(2-pyridylmethoxy)benzamide (AZD8542) and N-[5-(1H-imidazol-2-yl)-2,4-dimethyl-phenyl]-4-(2- pyridylmethoxy)benzamide (AZD7254)
  作者：Bin Yang、Alexander W. Hird、Michael S. Bodnarchuk、Xiaolan Zheng、Les Dakin、Qibin Su、Kevin Daly、Robert Godin、Maureen M. Hattersley、Patrick Brassil、Sean Redmond、Daniel John Russell、James W. Janetka

  DOI：10.1016/j.bmc.2019.115227

  日期：2020.1

  Aberrant hedgehog (Hh) pathway signaling is implicated in multiple cancer types and targeting the Smoothened (SMO) receptor, a key protein of the Hh pathway, has proven effective in treating metastasized basal cell carcinoma. Our lead optimization effort focused on a series of heteroarylamides. We observed that a methyl substitution ortho to the heteroaryl groups on an aniline core significantly improved

  异常的刺猬（Hh）途径信号传导涉及多种癌症类型，靶向Hh途径的关键蛋白“ Smoothened（SMO）”受体已被证明可有效治疗转移的基底细胞癌。我们的主要优化工作集中在一系列杂芳基酰胺上。我们观察到苯胺核心上杂芳基的邻位甲基取代显着提高了该系列化合物的效价。这些发现早于2013年SMO晶体结构的可用性。在这里，我们回顾性地应用了量子力学计算，以证明o-Me取代通过诱导杂芳基环与核心苯胺之间的二面角扭曲而有利于生物活性构象。o-Me还可以与结合袋中的关键残基侧链形成有利的疏水相互作用。
• Imidazopyridine Compound
  申请人：Sakuraba Shunji

  公开号：US20070249659A1

  公开（公告）日：2007-10-25

  The present invention provides an imidazopyridine compound represented by formula (I), wherein R 1 and R 2 each independently represent a C 1-6 alkyl group et al; R 3 and R 4 each independently represent a hydrogen atom, a methyl et al; Ar 1 is a divalent substituent representing a monocyclic or bicyclic, 3- to 8-membered aromatic or aliphatic heterocyclic group et al; Ar 2 represents an aromatic carbocyclic group, or an aromatic heterocyclic group; W represents —(CH 2 ) m et al, and m indicates an integer of from 0 to 10. This compound acts as a melanin concentrating hormone receptor antagonist, and is useful as treating agents for obesity.

  本发明提供了一种以式（I）表示的咪唑吡啶化合物，其中R1和R2各自独立地表示C1-6烷基等；R3和R4各自独立地表示氢原子、甲基等；Ar1表示一个双价的取代基，该取代基代表一个单环或双环、3-到8-成员的芳香或脂肪族杂环基等；Ar2表示一个芳香碳环基或芳香杂环基；W表示—（CH2）me等，其中m表示从0到10的整数。该化合物作为黑色素浓集激素受体拮抗剂，并且可用作肥胖症的治疗剂。
• Imidazopyridine compound
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US07566781B2

  公开（公告）日：2009-07-28

  The present invention provides an imidazopyridine compound represented by formula (I), wherein R1 and R2 each independently represent a C1-6 alkyl group et al; R3 and R4 each independently represent a hydrogen atom, a methyl et al; Ar1 is a divalent substituent representing a monocyclic or bicyclic, 3- to 8-membered aromatic or aliphatic heterocyclic group et al; Ar2 represents an aromatic carbocyclic group, or an aromatic heterocyclic group; W represents —(CH2)m et al, and m indicates an integer of from 0 to 10. This compound acts as a melanin concentrating hormone receptor antagonist, and is useful as treating agents for obesity.

  本发明提供了一种由式(I)表示的咪唑吡啶化合物，其中R1和R2各自独立地表示C1-6烷基等；R3和R4各自独立地表示氢原子、甲基等；Ar1表示一个双价取代基，代表单环或双环、3-8成员芳香族或脂环异构体基等；Ar2表示一个芳香族碳环基或芳香族异环基；W表示-（CH2）m等，其中m表示0至10的整数。该化合物作为黑色素浓集激素受体拮抗剂，并且可用作治疗肥胖症的药物。
• HETEROCYCLIC AMIDES USEFUL FOR THE TREATMENT OF CANCER AND PSORIASIS
  申请人：Dakin Leslie

  公开号：US20100311748A1

  公开（公告）日：2010-12-09

  The present disclosure relates to heterocyclic amide compounds, which are useful for inhibiting the Hedgehog pathway, and their use in treating a disease or medical condition mediated alone or in part by Hedgehog pathway inhibition. Also disclosed are methods for manufacture of these compounds, pharmaceutical compositions including these compounds, and use of these compounds in the manufacture of medicaments for treating such diseases and medical conditions in a subject. Formula (IA) with the provisio that either R 2 or R 3 is (Z).

  本公开涉及杂环酰胺化合物，其用于抑制Hedgehog途径，并在治疗由Hedgehog途径抑制单独或部分介导的疾病或医疗状况中发挥作用。还公开了这些化合物的制造方法，包括这些化合物的制药组合物以及这些化合物在制造用于治疗主体中的这些疾病和医疗状况的药物中的用途。公式（IA），其中R2或R3为（Z）的情况。