TPA123 | 202930-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: TPA123
• 英文别名: 7-cyclobutyl-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine；Dkp4ygh6WN；7-cyclobutyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine
• CAS: 202930-12-9
• 化学式: C₁₉H₁₉N₇O
• 分子量: 361.406
• InChiKey: VACJUKKURQMWHE-UHFFFAOYSA-N

物化性质

• 熔点：
  228 °C
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  83
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,2,4-噻唑[4,3-b]吡嗪e, 6-氯-3-苯基- 在 ammonium persulfate 、 硫酸 、 sodium hydride 、 silver nitrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 TPA123
  参考文献：
  名称：

  7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4- triazol-3-ylmethoxy)-3-(2-fluorophenyl)- 1,2,4-triazolo[4,3-b]pyridazine:  A Functionally Selective γ-Aminobutyric Acid_A (GABA_A) α2/α3-Subtype Selective Agonist That Exhibits Potent Anxiolytic Activity but Is Not Sedating in Animal Models

  摘要：

  There is increasing evidence that compounds with selectivity for gamma-aminobutyric acid(A) (GABA(A)) alpha 2- and/or alpha 3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABA(A) alpha 2/alpha 3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclinical animal assays.

  DOI：

  10.1021/jm058034a

文献信息

• [EN] PREPARATION AND USE OF CRYSTALLINE BETA-D-NICOTINAMIDE RIBOSIDE<br/>[FR] PRÉPARATION ET UTILISATION DE BÊTA-D-NICOTINAMIDE RIBOSIDE CRISTALLIN
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2015186068A1

  公开（公告）日：2015-12-10

  Provided herein are crystalline beta-D-nicotinamide riboside chloride compositions and methods of preparation and use thereof. Also provided are related pharmaceutical compositions and methods of use thereof. The crystalline beta-D-nicotinamide riboside chloride compositions may be used to treat a disease or disorder that would benefit from increased NAD levels including a mitochondrial disease or disorder, insulin resistance, a metabolic syndrome, diabetes, obesity, or for increasing insulin sensitivity in a subject.

  本文提供晶体质的β-D-烟酰胺核苷酸氯化物组合物的制备和使用方法。还提供相关的药物组合物及其使用方法。晶体质的β-D-烟酰胺核苷酸氯化物组合物可用于治疗需要提高NAD水平的疾病或疾病，包括线粒体疾病或疾病，胰岛素抵抗，代谢综合征，糖尿病，肥胖症或用于增加受试者胰岛素敏感性。
• Combination treatment for anxiety and depression
  申请人：Pfizer Inc.

  公开号：US20020165217A1

  公开（公告）日：2002-11-07

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a GABA-A alpha ⅔ agonist in combination with an SRI antidepressant agent with improvement in efficacy. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a GABA-A alpha ⅔ agonist, and an SRI antidepressant agent.

  本发明涉及一种治疗哺乳动物（包括人类）抑郁症或焦虑症的方法，通过给哺乳动物（包括人类）以GABA-A alpha ⅔ 激动剂和SRI抗抑郁剂的联合使用以提高疗效。同时，本发明还涉及含有药学上可接受载体、GABA-A alpha ⅔ 激动剂和SRI抗抑郁剂的制药组合物。
• [EN] SUBSTITUTED TRIAZOLO-PYRIDAZINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS<br/>[FR] DERIVES DE TRIAZOLO-PYRIDAZINE SUBSTITUES SERVANT DE LIGANDS POUR RECEPTEURS DE GABA
  申请人：MERCK SHARP & DOHME LIMITED

  公开号：WO1998004559A2

  公开（公告）日：1998-02-05

  (EN) A class of substituted or 7,8-ring fused 1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position and a substituted alkoxy moiety at the 6-position, are selective ligands for GABAA receptors, in particular having high affinity for the $g(a)2 and/or $g(a)3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.(FR) L"invention porte sur une catégorie de dérivés de 1,2,4-triazolo[4,3-b]pyridazine substitués ou fusionnés à 7,8 anneaux, possédant à la position (3) un substituant cycloalkyle, phényle ou hétéroaryle éventuellement substitué et, à la position (6), une fraction d"alkoxy substitué, ces dérivés étant des ligands sélectifs pour récepteurs de GABAA présentant en particulier une grande affinité pour les sous-unités $g(a)2 et/ou $g(a)3 de ceux-ci, ce qui les rend utiles pour le traitement et/ou la prévention des troubles du système nerveux central, notamment l"anxiété et les convulsions.

  一类取代的或7,8-环融合的1,2,4-三唑并[4,3-b]吡啶嘧啶衍生物，在3位具有可选取代的环烷基、苯基或杂环芳基取代基，在6位具有取代的烷氧基官能团，是GABAA受体的选择性配体，特别是具有高亲和力的$g(a)2和/或$g(a)3亚单位，因此对于治疗和/或预防中枢神经系统疾病，包括焦虑和惊厥，具有益处。
• Modulators of CDC2-like kinases (CLKS) and methods of use thereof
  申请人：Milne Jill

  公开号：US20070248590A1

  公开（公告）日：2007-10-25

  Provided herein are methods for using Cdc2-like kinase (Clk) modulators for treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, ocular disorders, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a Clk modulating compound in combination with another therapeutic agent.

  本文提供了使用Cdc2-like kinase (Clk)调节剂治疗和/或预防各种疾病和障碍的方法，包括与衰老或压力有关的疾病或障碍、糖尿病、肥胖症、神经退行性疾病、心血管疾病、血液凝结障碍、炎症、癌症、眼部疾病和/或潮红，以及需要增加线粒体活动的疾病或障碍。此外，提供了包含Clk调节化合物与另一种治疗剂联合使用的组合物。
• Novel compositions for preventing and treating neurodegenerative and blood coagulation disorders
  申请人：Milburn Michael

  公开号：US20060276393A1

  公开（公告）日：2006-12-07

  Provided herein are methods and compositions for treating or preventing neurodegenerative disorders or blood coagulation disorders. Methods may comprise modulating the activity or level of a sirtuin, such as SIRT1 or Sir2. Exemplary methods comprise contacting a cell with a sirtuin activating compound, such as a flavone, stilbene, flavanone, isoflavone, catechin, chalcone, tannin or anthocyanidin; or an inhibitory compound, such as nicotinamide.

  本文提供了治疗或预防神经退行性疾病或血液凝固疾病的方法和组合物。方法可以包括调节sirtuin的活性或水平，例如SIRT1或Sir2。示例方法包括使用sirtuin激活化合物（例如黄酮，苯乙烯，黄烷酮，异黄酮，儿茶素，查尔酮，单宁或花青素）或抑制化合物（例如烟酰胺）与细胞接触。