2-fluoro-4-(1H-tetrazol-1-yl)phenol | 1037798-26-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-fluoro-4-(1H-tetrazol-1-yl)phenol
• 英文别名: 1-(3-fluoro-4-hydroxyphenyl)tetrazole；2-fluoro-4-(tetrazol-1-yl)phenol
• CAS: 1037798-26-7
• 化学式: C₇H₅FN₄O
• 分子量: 180.141
• InChiKey: FTESLVUXEDIYKX-UHFFFAOYSA-N

物化性质

• 沸点：
  351.3±52.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 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：
  63.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-fluoro-4-(1H-tetrazol-1-yl)phenol 在 碳酸氢钠 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 Tert-butyl 6-[6-[2-fluoro-4-(tetrazol-1-yl)phenoxy]-5-methylpyrimidin-4-yl]-2,6-diazatricyclo[3.3.1.13,7]decane-2-carboxylate
  参考文献：
  名称：

  Design and Synthesis of Diazatricyclodecane Agonists of the G-Protein-Coupled Receptor 119

  摘要：

  A series of GPR119 agonists based on a 2,6-diazatricyclo[3.3.1.1 similar to 3,7,similar to]decane ring system is described. Also provided is a detailed account of the development of a multigram scale synthesis of the diazatricyclic ring system, which was achieved using a Hofmann-Loffler-Freytag reaction as the key step. The basis for the use of this complex framework lies in an attempt to constrain one end of the molecule in the "agonist conformation" as was previously described for 3-oxa-7-aza-bicyclo[3.3.1]nonanes. Optimization of carbamate analogues of the diazatricylic compounds led to the identification of 32i as a potent agonist of the GPR119 receptor with low unbound human liver microsomal clearance. The use of an agonist response weighted ligand lipophilic efficiency (LLE) termed AgLLE is discussed along with the issues of applying efficiency measures to agonist programs. Ultimately, solubility limited absorption and poor exposure reduced further interest in these molecules.

  DOI：

  10.1021/jm301626p
• 作为产物：
  描述：

  2-氟-4-硝基苯酚 在 palladium 10% on activated carbon sodium azide 、 氢气 作用下， 以 乙醇 、 水 、 溶剂黄146 为溶剂， 100.0 ℃ 、275.8 kPa 条件下， 反应 0.83h， 生成 2-fluoro-4-(1H-tetrazol-1-yl)phenol
  参考文献：
  名称：

  [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO
  [FR] MODULATEURS DU RÉCEPTEUR GPR119 ET TRAITEMENT DE TROUBLES LIÉS À CELUI-CI

  摘要：

  本发明涉及式I的化合物及其药学上可接受的盐、溶剂合物和水合物，这些化合物可作为单一药物代理或与一个或多个额外的药物代理结合使用，例如DPP-IV抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、美格列奈、噻唑烷二酮或抗糖尿病肽类似物，用于治疗例如从以下选择的疾病中选择的疾病：GPR119受体相关疾病；通过增加血液胰高血糖素水平改善的疾病；低骨量症状；神经系统疾病；与代谢相关的疾病；2型糖尿病；肥胖症；以及相关并发症。

  公开号：

  WO2012145361A1

文献信息

• GPR119 AGONIST
  申请人：Nippon Chemiphar Co., Ltd.

  公开号：EP2311822A1

  公开（公告）日：2011-04-20

  A cyclic amine derivative represented by the formula (II) is a GPR119 agonist, and is used as an agent for treating diabetes. wherein Ar0 is phenyl or phenyl having a substituent such as C1-8 alkylsulfonyl or the like, pyridyl, or pyridyl having a substituent such as C1-8 alkylsulfonyl; A0 is (CH2)p, O, or the like; B0 is (CH2)q, or the like, provided that B0 is neither O nor NR25 when A0 is O or NR24; one of U0 and V0 is N, and the other is N or CR26; each of X0\ and Y0 is C1-3 alkylene or C1-3 alkylene having a substituent; R23 is a C1-8 alkyl group or the like; each of R21 and R22 is hydrogen, a halogen atom, or the like.

  公式（II）表示的环胺衍生物是GPR119激动剂，用作治疗糖尿病。其中Ar0是苯或带有取代基如C1-8烷基磺酰基等的苯基，吡啶基，或带有取代基如C1-8烷基磺酰基的吡啶基；A0是（CH2）p，O，或类似物；B0是（CH2）q，或类似物，前提是当A0为O或NR24时，B0既不是O也不是NR25；U0和V0中的一个是N，另一个是N或CR26；X0和Y0中的每一个是C1-3烷基或带有取代基的C1-3烷基；R23是C1-8烷基或类似物；R21和R22中的每一个是氢，卤素原子，或类似物。
• [EN] SUBSTITUTED CYCLOPROPYL COMPOUNDS<br/>[FR] COMPOSÉS DE CYCLOPROPYLE SUBSTITUÉS
  申请人：MERCK SHARP & DOHME

  公开号：WO2014052379A1

  公开（公告）日：2014-04-03

  Substituted cyclopropyl piperidinyl compounds and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-1 19. Pharmaceutical compositions and methods of treatment are also included.

  本文披露了取代环丙基哌啶基化合物及其药用盐，用于治疗或预防2型糖尿病和类似疾病。这些化合物可作为G蛋白偶联受体GPR-119的激动剂。同时还包括药物组合物和治疗方法。
• [EN] L- ( PIPERIDIN-4-YL) -PYRAZOLE DERIVATIVES AS GPR 119 MODULATORS<br/>[FR] DERIVES DE L-(PIPERIDIN-4-YL)-PYRAZOLE UTILISES EN TANT QUE MODULATEURS DU GPR 119
  申请人：PFIZER

  公开号：WO2010140092A1

  公开（公告）日：2010-12-09

  Compounds of Formula I that modulate the activity of the G-protein-coupled receptor GPR119 and their uses in the treatment of diseases linked to the modulation of the G-protein-coupled receptor GPR119 in animals are described herein.

  本文描述了化合物I的化合物，其调节G蛋白偶联受体GPR119的活性，并且它们在治疗与动物中G蛋白偶联受体GPR119调节相关的疾病中的用途。
• [EN] SUBSTITUTED PIPERIDINE DERIVATIVES AND METHODS FOR PREPARING THE SAME<br/>[FR] DÉRIVÉS DE PIPÉRIDINE SUBSTITUÉE ET PROCÉDÉS POUR LES PRÉPARER
  申请人：HYUNDAI PHARM CO LTD

  公开号：WO2013105753A1

  公开（公告）日：2013-07-18

  The present invention relates to a novel compound or a pharmaceutically acceptable salt thereof, a preparation method thereof and a pharmaceutical composition for treating metabolism-related disorder containing the same. Specifically, the present invention relates to a compound of the formula 1, which can activate GPR119 to treat metabolism-related disorders, including diabetes and related diseases, diabetes-related microvascular complications, diabetes-related macrovascular complications, cardiovascular abnormalities, metabolic syndrome and its constituent diseases, and obesity.

  本发明涉及一种新颖化合物或其药用可接受盐，以及其制备方法和含有该化合物的用于治疗与代谢相关疾病的药物组合物。具体而言，本发明涉及一种符合式1的化合物，可以激活GPR119以治疗与代谢相关的疾病，包括糖尿病及相关疾病、糖尿病相关微血管并发症、糖尿病相关大血管并发症、心血管异常、代谢综合征及其组成疾病以及肥胖症。
• [EN] 4- (5-CYANO-PYRAZOL-1-YL) -PIPERIDINE DERIVATIVES AS GPR 119 MODULATORS<br/>[FR] DÉRIVÉS DE 4-(5-CYANOPYRAZOL-1-YL)PIPÉRIDINE EN TANT QUE MODULATEURS DU GPR119
  申请人：PFIZER

  公开号：WO2012069948A1

  公开（公告）日：2012-05-31

  Compounds that modulate the activity of the G-protein-coupled receptor GPR119 and their uses in the treatment of diseases linked to the modulation of the G-protein- coupled receptor GPR119 in animals are described herein.

  本文描述了调节G蛋白偶联受体GPR119活性的化合物及其在治疗与动物中G蛋白偶联受体GPR119调节相关疾病中的用途。