4-(4-fluoropiperidin-1-yl)benzoic acid | 718632-63-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-fluoropiperidin-1-yl)benzoic acid
• CAS: 718632-63-4
• 化学式: C₁₂H₁₄FNO₂
• 分子量: 223.247
• InChiKey: JCJLEYBMOBJUSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-fluoropiperidin-1-yl)benzoic acid 在 草酰氯 、 sode de l'acide trichloroisocyanurique 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3-chloro-2-(4-(4-fluoropiperidin-1-yl)phenyl)-7-methoxyquinolin-4(1H)-one
  参考文献：
  名称：

  Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis

  摘要：

  A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified similar to 100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further similar to 90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.

  DOI：

  10.1021/acs.jmedchem.6b01718
• 作为产物：
  描述：

  4-氟哌啶 在 水 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 4-(4-fluoropiperidin-1-yl)benzoic acid
  参考文献：
  名称：

  Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis

  摘要：

  A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified similar to 100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further similar to 90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.

  DOI：

  10.1021/acs.jmedchem.6b01718

文献信息

• Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton
  作者：Zhen Chen、Wakana Mori、Xiaoyun Deng、Ran Cheng、Daisuke Ogasawara、Genwei Zhang、Michael A. Schafroth、Kenneth Dahl、Hualong Fu、Akiko Hatori、Tuo Shao、Yiding Zhang、Tomoteru Yamasaki、Xiaofei Zhang、Jian Rong、Qingzhen Yu、Kuan Hu、Masayuki Fujinaga、Lin Xie、Katsushi Kumata、Yuancheng Gou、Jingjin Chen、Shuyin Gu、Liang Bao、Lu Wang、Thomas Lee Collier、Neil Vasdev、Yihan Shao、Jun-An Ma、Benjamin F. Cravatt、Christopher Fowler、Lee Josephson、Ming-Rong Zhang、Steven H. Liang

  DOI：10.1021/acs.jmedchem.8b01778

  日期：2019.4.11

  and [18F]37 ([18F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms.

  单酰基甘油脂酶（MAGL）是丝氨酸水解酶，可降解内源性大麻素系统（eCB）中的2-花生四烯酸甘油酯（2-AG）。MAGL的选择性抑制已成为治疗多种病理状况（包括慢性疼痛，炎症，癌症和神经变性）的潜在治疗方法。本文中，我们通过在哌嗪基氮杂环丁烷支架上的“尾部转换”公开了可逆和不可逆的MAGL抑制剂的新型阵列。我们开发了一种不可逆结合的先导MAGL抑制剂8和可逆结合的化合物17和37，它们适用于用11C或18F进行放射性标记。[11C] 8（[11C] MAGL-2-11）在大脑中对MAGL表现出高脑摄取和极好的结合特异性。可逆放射性配体[11C] 17（[11C] PAD）和[18F] 37（[18F] MAGL-4-11）也表现出对外周器官MAGL的出色体内结合特异性。这项工作可能为以可逆和不可逆结合机制的可调性为目标的以MAGL为目标的正电子发射断层显像示踪剂的开发铺平道路。
• Substituted pyrrolo-pyrazole derivatives as kinase inhibitors
  申请人：Brasca Gabriella Maria

  公开号：US20070004705A1

  公开（公告）日：2007-01-04

  Compounds represented by formula (Ia) or (Ib) and wherein R and R 1 are as defined in the description, and pharmaceutically acceptable salts thereof, are disclosed; the said compounds are useful in the treatment of cell cycle proliferative disorders, e.g. cancer, associated with an altered cell cycle dependent kinase activity.

  本发明公开了由式(Ia)或(Ib)所代表的化合物，其中R和R1如说明书所定义，并且其药学上可接受的盐。所述化合物可用于治疗与细胞周期依赖性激酶活性改变相关的细胞周期增殖性疾病，例如癌症。
• Substituted Pyrrolo-Pyrazole Derivatives as Kinase Inhibitors
  申请人：Brasca Maria Gabriella

  公开号：US20090082346A1

  公开（公告）日：2009-03-26

  Compounds represented by formula (Ia) or (Ib) and wherein R and R 1 are as defined in the description, and pharmaceutically acceptable salts thereof, are disclosed; the said compounds are useful in the treatment of cell cycle proliferative disorders, e.g. cancer, associated with an altered cell cycle dependent kinase activity.

  公式（Ia）或（Ib）所代表的化合物，其中R和R1如描述中所定义，并且其药学上可接受的盐被揭示出来；这些化合物在治疗细胞周期增殖性疾病，例如与改变的细胞周期依赖性激酶活性相关的癌症中有用。
• SUBSTITUTED PYRROLO-PYRAZOLE DERIVATIVES AS KINASE INHIBITORS
  申请人：Brasca Maria Gabriella

  公开号：US20130017170A1

  公开（公告）日：2013-01-17

  Compounds represented by formula (Ia) or (Ib) and wherein R and R 1 are as defined in the description, and pharmaceutically acceptable salts thereof, are disclosed; the said compounds are useful in the treatment of cell cycle proliferative disorders, e.g. cancer, associated with an altered cell cycle dependent kinase activity.

  公式(Ia)或(Ib)代表的化合物，其中R和R1如描述中定义的那样，并且其药学上可接受的盐被揭示；这些化合物在治疗细胞周期增殖性疾病，例如与改变的细胞周期依赖性激酶活性相关的癌症中有用。
• [EN] SUBSTITUTED PYRROLO-PYRAZOLE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DERIVES DE PYRROLO-PYRAZOLES SUBSTITUES CONSTITUANT DES INHIBITEURS DE KINASES
  申请人：PHARMACIA ITALIA SPA

  公开号：WO2004056827A3

  公开（公告）日：2004-10-28