5-Fluoro-2',3',5',6'-tetrahydro-1'H-[2,4']bipyridinyl-4'-ol | 1207865-17-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-Fluoro-2',3',5',6'-tetrahydro-1'H-[2,4']bipyridinyl-4'-ol
• 英文别名: 4-(5-Fluoropyridin-2-yl)piperidin-4-ol
• CAS: 1207865-17-5
• 化学式: C₁₀H₁₃FN₂O
• 分子量: 196.224
• InChiKey: FYUYTAMXNGKVNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-Fluoro-2',3',5',6'-tetrahydro-1'H-[2,4']bipyridinyl-4'-ol 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 N-[2-[4-(5-fluoropyridin-2-yl)-4-hydroxypiperidin-1-yl]-4-methylquinazolin-6-yl]-2-[4-(trifluoromethoxy)phenoxy]acetamide
  参考文献：
  名称：

  黑色素浓缩激素受体 1 (MCHR1) 拮抗剂喹唑啉衍生物的设计和优化

  摘要：

  黑色素浓缩激素（MCH）是能量稳态的重要介质，在代谢和中枢神经系统疾病中发挥作用。描述了作为 MCHR1 拮抗剂的新型喹唑啉衍生物的模型支持设计、合成和多参数优化（生物活性、溶解度、代谢稳定性、hERG）。举例说明了该系列先导化合物减肥原理的体内证明。开发了源自​​ β2-肾上腺素能受体 X 射线结构（包括细胞外环）的精制 hMCHR1 同源模型簇，并用于指导设计。

  DOI：

  10.1016/j.bmcl.2012.03.050

文献信息

• Substituted N-aryl heterocycles, process for their preparation and their use as medicaments
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US20040220191A1

  公开（公告）日：2004-11-04

  The invention relates to substituted N-aryl heterocycles and to the physiologically tolerated salts and physiologically functional derivatives thereof. Compounds of the formula I 1 in which the radicals have the stated meanings, the N-oxides and the physiologically tolerated salts thereof and process for the preparation thereof are described. The compounds are suitable for example as anorectic agents.

  这项发明涉及取代N-芳基杂环化合物及其生理耐受盐和生理功能衍生物。式I的化合物 1 其中基团具有所述含义，其N-氧化物及其生理耐受盐以及其制备方法被描述。这些化合物例如适用作为厌食剂。
• Substituted N-aryl Heterocycles, Process For Their Preparation and Their Use As Medicaments
  申请人：Schwink Lothar

  公开号：US20070207991A1

  公开（公告）日：2007-09-06

  The invention relates to substituted N-aryl heterocycles and to the physiologically tolerated salts and physiologically functional derivatives thereof. Compounds of the formula I in which the radicals have the stated meanings the N-oxides and the physiologically tolerated salts thereof and process for the preparation thereof are described. The compounds are suitable for example as anorectic agents.

  该发明涉及取代的N-芳基杂环化合物及其生理耐受盐和生理功能衍生物。描述了公式I中化合物，其中基团具有所述的含义，以及其N-氧化物和生理耐受盐和其制备方法。这些化合物例如适用于作为抑制食欲的药物。
• Optimizing and characterizing 4-methyl substituted pyrazol-3-carboxamides leading to the peripheral cannabinoid 1 receptor inverse agonist TM38837
  作者：Thomas Högberg、Jean-Marie Receveur、Anthony Murray、Jean-Michel Linget、Pia K. Nørregaard、Paul B. Little、Martin Cooper

  DOI：10.1016/j.bmcl.2023.129572

  日期：2024.1

  with respect to lipophilicity, solubility, CB1 potency, metabolism, distribution to brain and liver, effect on weight loss in diet-induced mice models. A few carboxylic acids and tetrazoles were selected as especially promising with the tetrazole TM38837 subsequently demonstrating impressive efficacy in various animal models of obesity, producing considerable weight loss and improvements on plasma markers

  由相应的 4-氰基甲基吡唑制备了几个系列的用 4-甲基酰胺、4-甲基羧酸和 4-甲基四唑功能化的不同吡唑-3-甲酰胺，并作为大麻素受体 1 (CB1) 拮抗剂和反向激动剂进行了研究，目的是制备化合物与利莫那班相比，CNS（中枢神经系统）介导的副作用更少。对这些化合物的亲脂性、溶解度、CB1 效力、代谢、大脑和肝脏分布以及对饮食诱导小鼠模型体重减轻的影响进行了评估和优化。一些羧酸和四唑被选择为特别有前途的四唑TM38837，随后在各种肥胖动物模型中表现出令人印象深刻的功效，产生显着的体重减轻并改善炎症和葡萄糖稳态的血浆标志物，其剂量显然产生可忽略不计的脑暴露。 TM38837 成为第一个进入临床试验的外周限制性 CB1 拮抗剂或反向激动剂，支持其缺乏 CNS 作用，现在认为非 CNS 介导的功效与高肝脏暴露有关。这为探索非酒精性脂肪肝（NAFLD）和脂肪性肝炎（NASH）等其他适应症提供了机
• Conversion of 4-cyanomethyl-pyrazole-3-carboxamides into CB1 antagonists with lowered propensity to pass the blood–brain-barrier
  作者：Jean-Marie Receveur、Anthony Murray、Jean-Michel Linget、Pia K. Nørregaard、Martin Cooper、Emelie Bjurling、Peter Aadal Nielsen、Thomas Högberg

  DOI：10.1016/j.bmcl.2009.12.003

  日期：2010.1

  A series of amides, amidines and amidoximes have been made from the corresponding nitrile compounds, to provide potent antagonists and inverse agonists for the CB1 receptor with considerably lower lipophiliciy, higher polar surface area and improved plasma/brain ratios compared to the centrally acting rimonabant. Extensive investigations of ADME and in vivo pharmacological properties led to selection of the amide series and specifically the 4-(4-fluorophenyl)piperidin-4-ol derivative D4. A clear improvement in the peripheral pro. le over rimonabant was seen, although some contribution of central effect on the pronounced weight reduction in obese mice cannot be ruled out. (C) 2009 Elsevier Ltd. All rights reserved.
• US7223788B2
  申请人：——

  公开号：US7223788B2

  公开（公告）日：2007-05-29