6-chloro-3-methyl-2-phenylquinoline-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-chloro-3-methyl-2-phenylquinoline-4-carboxylic acid
• 化学式: C₁₇H₁₂ClNO₂
• mdl: MFCD03419305
• 分子量: 297.741
• InChiKey: CDZCTMBUDWLODM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-3-methyl-2-phenylquinoline-4-carboxylic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-{[(6-chloro-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid
  参考文献：
  名称：

  Potent and Selective Human Prostaglandin F (FP) Receptor Antagonist (BAY-6672) for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

  摘要：

  Idiopathic pulmonary fibrosis (IPF) is a rare and devastating chronic lung disease of unknown etiology. Despite the approved treatment options nintedanib and pirfenidone, the medical need for a safe and well-tolerated antifibrotic treatment of IPF remains high. The human prostaglandin F receptor (hFP-R) is widely expressed in the lung tissue and constitutes an attractive target for the treatment of fibrotic lung diseases. Herein, we present our research toward novel quinoline-based hFP-R antagonists, including synthesis and detailed structure-activity relationship (SAR). Starting from a high-throughput screening (HTS) hit of our corporate compound library, multiple parameter improvements-including increase of the relative oral bioavailability F_rel from 3 to ≥100%-led to a highly potent and selective hFP-R antagonist with complete oral absorption from suspension. BAY-6672 (46) represents-to the best of our knowledge-the first reported FP-R antagonist to demonstrate in vivo efficacy in a preclinical animal model of lung fibrosis, thus paving the way for a new treatment option in IPF.

  DOI：

  10.1021/acs.jmedchem.0c00834
• 作为产物：
  描述：

  5-氯靛红 、 苯丙酮 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 16.0h， 以92%的产率得到6-chloro-3-methyl-2-phenylquinoline-4-carboxylic acid
  参考文献：
  名称：

  Synthesis of Substituted Quinoline-4-carboxylic Acids

  摘要：

  利用改良的Pfitzinger方法，在水酸性条件下，通过酮与靛红衍生物的缩合，成功实现了一系列喹啉-4-羧酸的高产率合成。此外，还描述了便捷合成替代靛红前体的方法。

  DOI：

  10.1055/s-1993-25987

文献信息

• SUBSTITUTED N-BICYCLO-2-ARYL-QUINOLIN-4-CARBOXAMIDES AND USE THEREOF
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20180036300A1

  公开（公告）日：2018-02-08

  The present application relates to novel substituted N-bicyclo-2-arylquinoline-4-carboxamide derivatives, to processes for preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases, and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of fibrotic and inflammatory disorders.

  本申请涉及新型的取代N-双环[2.arylquinoline-4-carboxamide]衍生物，涉及其制备过程，涉及单独或联合使用该化合物治疗和/或预防疾病，以及涉及使用该化合物生产用于治疗和/或预防疾病的药物，特别用于治疗和/或预防纤维化和炎症性疾病。
• SUBSTITUTED N,2-DIARYLQUINOLINE-4-CARBOXAMIDES AND THE USE THEREOF AS ANTI-INFLAMMATORY AGENTS
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20170260140A1

  公开（公告）日：2017-09-14

  The present application relates to novel substituted N,2-diarylquinoline-4-carboxamide derivatives, to processes for preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases, and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of fibrotic and/or inflammatory disorders.

  本申请涉及新颖的取代N,2-二芳基喹啉-4-甲酰胺衍生物，其制备方法，单独或组合使用以治疗和/或预防疾病，以及用于生产治疗和/或预防疾病的药物，特别是用于治疗和/或预防纤维化和/或炎症性疾病。
• Synthesis of Substituted Quinoline-4-carboxylic Acids
  作者：Karen Lackey、Daniel D. Sternbach

  DOI：10.1055/s-1993-25987

  日期：——

  A high yielding synthesis of a variety of quinoline-4-carboxylic acids has been accomplished using a modified Pfitzinger approach involving the condensation of a ketone with an isatin derivative employing aqueous acid conditions. A convenient synthesis of the substituted isatin precursor is also described.

  利用改良的Pfitzinger方法，在水酸性条件下，通过酮与靛红衍生物的缩合，成功实现了一系列喹啉-4-羧酸的高产率合成。此外，还描述了便捷合成替代靛红前体的方法。
• Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US10117864B2

  公开（公告）日：2018-11-06

  The present application relates to novel substituted N-bicyclo-2-arylquinoline-4-carboxamide derivatives, to processes for preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases, and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of fibrotic and inflammatory disorders.

  本申请涉及新型取代的 N-双环-2-芳基喹啉-4-甲酰胺衍生物、其制备工艺、其单独使用或组合使用以治疗和/或预防疾病，以及其用于生产治疗和/或预防疾病的药物，特别是用于治疗和/或预防纤维化和炎症性疾病。
• Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US10189788B2

  公开（公告）日：2019-01-29

  The present application relates to novel substituted N,2-diarylquinoline-4-carboxamide derivatives, to processes for preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases, and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of fibrotic and/or inflammatory disorders.

  本申请涉及新型取代的 N,2-二基喹啉-4-甲酰胺衍生物、其制备工艺、其单独使用或组合使用以治疗和/或预防疾病，以及其用于生产治疗和/或预防疾病的药物，特别是治疗和/或预防纤维化和/或炎症性疾病。