ethyl 1-(4-chlorophenyl)-5-cyano-4-methyl-6-oxo-1,6-dihydrodihydropyridazine-3-carboxylate | 115592-30-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 1-(4-chlorophenyl)-5-cyano-4-methyl-6-oxo-1,6-dihydrodihydropyridazine-3-carboxylate
• 英文别名: ethyl 1-(4-chlorophenyl)-5-cyano-1,6-dihydro-4-methyl-6-oxo-3-pyridazinecarboxylate；ethyl 1-(4-chlorophenyl)-5-cyano-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate；ethyl-1-(4-chlorophenyl)-5-cyano-1,6-dihydro-4-methyl-6-oxopyridazine-3-carboxylate；ethyl 1-(4-chlorophenyl)-5-cyano-4-methyl-6-oxopyridazine-3-carboxylate
• CAS: 115592-30-8
• 化学式: C₁₅H₁₂ClN₃O₃
• mdl: MFCD01105233
• 分子量: 317.732
• InChiKey: GQSXRXPDXGQJJN-UHFFFAOYSA-N

物化性质

• 溶解度：
  7.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  82.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4-chlorophenyl)-5-cyano-4-methyl-6-oxo-1,6-dihydrodihydropyridazine-3-carboxylate 在 吗啉 、 sulfur 作用下， 反应 0.92h， 生成 ethyl 5-amino-3-(4-bromophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate
  参考文献：
  名称：

  [EN] AMINOTHIENOPYRIDAZINE INHIBITORS OF TAU ASSEMBLY
  [FR] INHIBITEURS AMINOTHIÉNOPYRIDAZINIQUES DE L'ASSEMBLAGE DES MICROTUBULES SOUS L'EFFET DE LA PROTÉINE TAU

  摘要：

  公开号：

  WO2011037985A8
• 作为产物：
  描述：

  对氯苯胺 在 盐酸 、 sodium acetate 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 4.07h， 生成 ethyl 1-(4-chlorophenyl)-5-cyano-4-methyl-6-oxo-1,6-dihydrodihydropyridazine-3-carboxylate
  参考文献：
  名称：

  Aminothienopyridazine inhibitors of tau aggregation: Evaluation of structure–activity relationship leads to selection of candidates with desirable in vivo properties

  摘要：

  Previous studies demonstrated that members of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors exhibit a promising combination of in vitro activity as well as favorable pharmacokinetic properties (i.e., brain-penetration and oral bioavailability). Here we report the synthesis and evaluation of several new analogues. These studies indicate that the thienopyridazine core is essential for inhibition of tau fibrillization in vitro, while the choice of the appropriate scaffold decoration is critical to impart desirable ADME-PK properties. Among the active, brain-penetrant ATPZ inhibitors evaluated, 5-amino-N-cyclopropyl-3-(4-fluorophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide (43) was selected to undergo maximum tolerated dose and one-month tolerability testing in mice. The latter studies revealed that this compound is well-tolerated with no notable side-effects at an oral dose of 50 mg/kg/day. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.027

文献信息

• α, β-Unsaturated Nitriles in Heterocyclic Synthesis: Synthesis of Several Arylpyridine and Arylpyridazine Derivatives
  作者：Galal Hamza Elgemeie、Hassan Attia Elfahham、Yusria Rizk Ibrahiem、Mohamed Hilmy Elnagdi

  DOI：10.1002/ardp.19893220905

  日期：——

  Several new azabiaryls and diazabiaryls were synthesized utilizing readily obtainable α, β‐unsaturated nitriles.

  利用容易获得的α，β-不饱和腈合成了几种新的氮杂二芳基和二氮杂二芳基。
• Synthesis of Polyfunctional Pyridazine Derivatives Using a Solvent-Free Microwave Assisted Method
  作者：Eddy Sotelo、Raúl Mocelo、Margarita Suárez、André Loupy

  DOI：10.1080/00397919708004105

  日期：1997.7

  Abstract The synthesis of several polyfunctional pyridazine derivatives has been carried out very efficiently under microwave irradiation and solvent-free conditions allowing short reaction times and high yields. Non thermal effects induced by microwave were observed.

  摘要 几种多功能哒嗪衍生物的合成在微波辐射和无溶剂条件下进行，反应时间短，收率高。观察到由微波引起的非热效应。
• AMINOTHIENOPYRIDAZINE INHIBITORS OF TAU ASSEMBLY
  申请人：Ballatore Carlo

  公开号：US20130029983A1

  公开（公告）日：2013-01-31

  The present invention is directed to methods of inhibiting a tauopathy in a patient by administration of a compound of formula I: Novel aminothienopyridazine compounds are also described.

  本发明涉及通过给予I型化合物来抑制患者的tau病变的方法：还描述了新的氨基噻吩吡嗪化合物。
• Discovery of Brain-Penetrant, Orally Bioavailable Aminothienopyridazine Inhibitors of Tau Aggregation
  作者：Carlo Ballatore、Kurt R. Brunden、Francesco Piscitelli、Michael J. James、Alex Crowe、Yuemang Yao、Edward Hyde、John Q. Trojanowski、Virginia M.-Y. Lee、Amos B. Smith

  DOI：10.1021/jm100138f

  日期：2010.5.13

  Agents capable of preventing the misfolding and sequestration of the microtubule-stabilizing protein tau into insoluble fibrillar aggregates hold considerable promise for the prevention and/or treatment of neurodegenerative tauopathies such as Alzheimer's disease. Because tauopathies are characterized by amyloidosis that is restricted to the central nervous system (CNS), plausible candidate compounds for in vivo evaluation must both prevent tau fibrillization and achieve significant brain levels. Recently, we reported the discovery of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors and now describe a series of new analogues that are both effective inhibitors of tau fibrillization and display significant brain-to-plasma exposure ratios after administration to mice. Further, two of the most promising examples, 15 and 16, were found to reach significant brain exposure levels following oral administration. Taken together, these results suggest that examples from the ATPZ class hold promise as candidates for in vivo efficacy studies in animal models of neurodegenerative tauopathies.
• Abu-Shanab, Fathi A.; Wakefield, Basil; Al-Omran, Fatima, Journal of Chemical Research, Miniprint, 1995, # 12, p. 2924 - 2946
  作者：Abu-Shanab, Fathi A.、Wakefield, Basil、Al-Omran, Fatima、Khalek, Mervat M. Abdel、Elnagdi, Mohamed Hilmy

  DOI：——

  日期：——