4-(4-methoxybenzoyl)pyridine-3-carboxylic acid | 482641-83-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-methoxybenzoyl)pyridine-3-carboxylic acid
• 英文别名: 4-(4-Methoxybenzoyl)pyridine-3-carboxylic acid
• CAS: 482641-83-8
• 化学式: C₁₄H₁₁NO₄
• 分子量: 257.246
• InChiKey: RRXGYRXXFWFRSK-UHFFFAOYSA-N

物化性质

• 沸点：
  506.4±45.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.49
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(4-methoxybenzoyl)pyridine-3-carboxylic acid 在 氯化亚砜 、 magnesium 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 生成 6-ethoxycarbonyl-7-hydroxy-5-(4-methoxyphenyl)-7-(3,4-methylenedioxyphenyl)-7H-cyclopenta[c]pyridine
  参考文献：
  名称：

  6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives

  摘要：

  Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC50 value of 2.4 nM against I-125-labeled ET-1 binding to human ETA receptors and a 170-fold selectivity for ETA over ETB receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound I in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization Oil Substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ETA selective antagonist 2p with an IC50 Value of 0.87 nM for ETA receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00122-0
• 作为产物：
  描述：

  4-溴苯甲醚 、 吡啶-3,4-二甲酸酐 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 生成 4-(4-methoxybenzoyl)pyridine-3-carboxylic acid
  参考文献：
  名称：

  6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives

  摘要：

  Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC50 value of 2.4 nM against I-125-labeled ET-1 binding to human ETA receptors and a 170-fold selectivity for ETA over ETB receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound I in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization Oil Substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ETA selective antagonist 2p with an IC50 Value of 0.87 nM for ETA receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00122-0

文献信息

• [EN] FUSED PYRIDAZINE DERIVATIVES AS NLRP3 INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDAZINE FUSIONNÉS UTILISÉS COMME INHIBITEURS DE NLRP3
  申请人：[en]TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：WO2023194964A1

  公开（公告）日：2023-10-12

  Disclosed are compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein α, β, m, R5, R6, R7, R9, R10, R11, Ra, Rb, X1, X2, X3, X4and X8are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula (I), to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with NLRP3.