5-bromo-6-(3-fluorophenyl)pyridin-2-amine | 868360-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-bromo-6-(3-fluorophenyl)pyridin-2-amine
• CAS: 868360-25-2
• 化学式: C₁₁H₈BrFN₂
• 分子量: 267.1
• InChiKey: BBYMNFIUXZMNRJ-UHFFFAOYSA-N

物化性质

• 沸点：
  351.2±42.0 °C(Predicted)
• 密度：
  1.565±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-6-(3-fluorophenyl)pyridin-2-amine 在 四(三苯基膦)钯 、 硫酸 、 氢溴酸 、 caesium carbonate 、 溶剂黄146 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 78.17h， 生成 6-(3-fluorophenyl)-5-[4-(quinolin-2-ylmethoxy)phenyl]pyridin-2(1H)-one
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of 5,6-Disubstituted Pyridin-2(1H)-one Derivatives as Phosphodiesterase 10A (PDE10A) Antagonists

  摘要：

  We report the design and synthesis of novel 5,6-diarylated pyridin-2(1H)-one derivatives as pharmacophoric PDE10A inhibitors. This highly potent molecular scaffold was developed from an inactive diarylpyridine-2-amine derivative 3b by extensive and systematic analogue synthesis and SAR analysis. Further optimization of the scaffold resulted in identification of pyridin-2(1H)-one 18b as a lead compound with good potency (IC50 = 1.6 nM) and selectivity (>6000-fold) over other related PDEs but with a poor pharmacokinetic profile. Careful metabolite profiling of 18b revealed that poor systemic exposure in rats (C-max = 44 ng/mL; AUC(0-t), = 359 ng.h/mL) at 10 mg/kg was due to the formation of O-glucuronide conjugate by phase 2 metabolism. The structure of the glucuronide metabolite was confirmed by retention time and LC-MS/MS fragmentation matching with the synthetic glucuronide 26. The problem of low exposure of 18b was effectively addressed by its conversion to an acetate prodrug 25b, which upon oral dosing resulted in an improved pharmacokinetic profile (C-max = 359 ng.h/mL; AUC(0-t), = 2436 ng.h/mL) and a desirable brain to plasma ratio of 1.2. The prodrug 25b showed good efficacy in selected rodent models of psychosis.

  DOI：

  10.1021/acs.jmedchem.5b01240
• 作为产物：
  描述：

  6-氨基-2,3-二溴吡啶 、 3-氟苯基硼酸 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 生成 5-bromo-6-(3-fluorophenyl)pyridin-2-amine
  参考文献：
  名称：

  [EN] CONDENSED PYRIDINE DERIVATIVES USEFUL AS A28 ADENOSINE RECEPTOR ANTAGONISTS
  [FR] DERIVES DE PYRIDINE CONDENSES UTILES COMME ANTAGONISTES DU RECEPTEUR DE L'ADENOSINE A28

  摘要：

  本发明涉及由式(I)表示的A2B腺苷受体的新拮抗剂。这些化合物对于治疗患有病理状况或疾病，可通过拮抗A2B腺苷受体来改善的主体是有用的，例如哮喘、支气管痉挛、过敏性疾病、高血压、动脉粥样硬化、再灌注损伤、心肌缺血、视网膜病变、炎症、胃肠道疾病、细胞增殖障碍、糖尿病和/或自身免疫疾病。

  公开号：

  WO2005100353A1

文献信息

• [EN] CONDENSED PYRIDINE DERIVATIVES USEFUL AS A28 ADENOSINE RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PYRIDINE CONDENSES UTILES COMME ANTAGONISTES DU RECEPTEUR DE L'ADENOSINE A28
  申请人：ALMIRALL PRODESFARMA SA

  公开号：WO2005100353A1

  公开（公告）日：2005-10-27

  The present invention relates to new antagonists of the A2B adenosine receptor represented by formula (I). Those compounds are useful for treating a subject afflicted with a pathological condition or disease susceptible to amelioration by antagonism of the A2B adenosine receptor such as asthma, bronchoconstriction, allergic diseases, hypertension, atherosclerosis, reperfusion injury, myocardial ischemia, retinopathy, inflammation, gastrointestinal tract disorders, cell proliferation disorders, diabetes mellitus, and/or autoimmune diseases.

  本发明涉及由式(I)表示的A2B腺苷受体的新拮抗剂。这些化合物对于治疗患有病理状况或疾病，可通过拮抗A2B腺苷受体来改善的主体是有用的，例如哮喘、支气管痉挛、过敏性疾病、高血压、动脉粥样硬化、再灌注损伤、心肌缺血、视网膜病变、炎症、胃肠道疾病、细胞增殖障碍、糖尿病和/或自身免疫疾病。
• Condensed Pyridine Derivatives Useful as A2B Adenosine Receptor Antagonists
  申请人：Vidal Juan Bernat

  公开号：US20090023763A1

  公开（公告）日：2009-01-22

  New antagonists of the A 2B adenosine receptor represented by formula (I) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as antagonists of the A 2B adenosine receptor.

  本文披露了由公式（I）表示的A2B腺苷受体的新拮抗剂，以及它们的制备过程，包含它们的制药组合物和用作A2B腺苷受体拮抗剂的治疗用途。
• AMINOPYRIDINE COMPOUND, PREPARATION METHOD THEREFOR AND USE THEREOF
  申请人：Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

  公开号：EP3904348A1

  公开（公告）日：2021-11-03

  The present invention discloses an aminopyridine compounds, a preparation method and use thereof, particularly the aminopyridine compounds of formula (I), pharmaceutical compositions containing the same, the method for preparing the same and the use thereof in the prophylaxis or treatment of an adenosine A2a receptor related disease.

  本发明公开了一种氨基吡啶化合物及其制备方法和用途，特别是式(I)的氨基吡啶化合物、含有该化合物的药物组合物、制备方法及其在预防或治疗腺苷A2a受体相关疾病中的用途。
• [EN] AMINOPYRIDINE COMPOUND, PREPARATION METHOD THEREFOR AND USE THEREOF<br/>[FR] COMPOSÉ AMINOPYRIDINE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 氨基吡啶类化合物及其制备方法和用途
  申请人：SICHUAN KELUN BIOTECH BIOPHARMACEUTICAL CO LTD

  公开号：WO2020135195A1

  公开（公告）日：2020-07-02

  （I）本发明公开了氨基吡啶类化合物及其制备方法和用途，具体为式(I)的氨基吡啶类化合物、包含其的药物组合物、其制备方法及其用于预防或治疗腺苷A2a受体相关疾病的用途。
• CONDENSED PYRIDINE DERIVATIVES USEFUL AS A28 ADENOSINE RECEPTOR ANTAGONISTS
  申请人：Almirall Prodesfarma, S.A.

  公开号：EP1735310A1

  公开（公告）日：2006-12-27