pyrido[2,3-d]pyridazin-5(6H)-one | 15370-81-7

• 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: pyrido[2,3-d]pyridazin-5(6H)-one
• 英文别名: 6H-pyrido[2,3-d]pyridazin-5-one
• CAS: 15370-81-7
• 化学式: C₇H₅N₃O
• 分子量: 147.136
• InChiKey: DHLCTHXZKHGREA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  pyrido[2,3-d]pyridazin-5(6H)-one 在 platinum(IV) oxide 、 氢气 、 三氟乙酸 、 potassium carbonate 作用下， 以 水 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 48.0h， 以96%的产率得到2,3,4,6-tetrahydropyrido[2,3-d]pyridazin-5(1H)-one
  参考文献：
  名称：

  Tetrahydropyrido[d]pyridazinones—promising scaffolds for drug discovery

  摘要：

  An approach to the synthesis of all possible tetrahydropyrido[d]pyridazinones has been developed. The method relies on the catalytic hydrogenation of the corresponding aromatic counterparts, which were obtained by cyclization of the relevant dibromomethyl-substituted pyridinecarboxylates with hydrazine. The synthetic schemes include 4-5 steps starting from commercially available materials. The tetrahydropyrido[d]pyridazinone scaffolds are combinations of a saturated heterocycle (piperidine) and a privileged aromatic heterocycle (pyridazinone); hence they are promising starting points for the design in medicinal chemistry. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2013.06.029
• 作为产物：
  描述：

  2-甲基烟酸 在 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 一水合肼 作用下， 以 甲醇 、 四氯化碳 为溶剂， 反应 21.0h， 生成 pyrido[2,3-d]pyridazin-5(6H)-one
  参考文献：
  名称：

  Tetrahydropyrido[d]pyridazinones—promising scaffolds for drug discovery

  摘要：

  An approach to the synthesis of all possible tetrahydropyrido[d]pyridazinones has been developed. The method relies on the catalytic hydrogenation of the corresponding aromatic counterparts, which were obtained by cyclization of the relevant dibromomethyl-substituted pyridinecarboxylates with hydrazine. The synthetic schemes include 4-5 steps starting from commercially available materials. The tetrahydropyrido[d]pyridazinone scaffolds are combinations of a saturated heterocycle (piperidine) and a privileged aromatic heterocycle (pyridazinone); hence they are promising starting points for the design in medicinal chemistry. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2013.06.029

文献信息

• [EN] OXADIAZOLE TRANSIENT RECEPTOR POTENTIAL CHANNEL INHIBITORS<br/>[FR] OXADIAZOLE EN TANT QU'INHIBITEURS DE CANAUX POTENTIELS DE RÉCEPTEUR TRANSITOIRE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2018162607A1

  公开（公告）日：2018-09-13

  The invention relates to compounds of formula I: (I) and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

  该发明涉及到式I的化合物：(I)及其药学上可接受的盐。此外，本发明涉及到制造方法和使用式I化合物的方法，以及含有这些化合物的药物组合物。这些化合物可能在治疗由TRPA1介导的疾病和病况，如疼痛方面具有用处。
• Tetrahydrofuran-Based Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonists: Ligand-Based Discovery, Activity in a Rodent Asthma Model, and Mechanism-of-Action via Cryogenic Electron Microscopy
  作者：Jack A. Terrett、Huifen Chen、Daniel G. Shore、Elisia Villemure、Robin Larouche-Gauthier、Martin Déry、Francis Beaumier、Léa Constantineau-Forget、Chantal Grand-Maître、Luce Lépissier、Stéphane Ciblat、Claudio Sturino、Yong Chen、Baihua Hu、Aijun Lu、Yunli Wang、Andrew P. Cridland、Stuart I. Ward、David H. Hackos、Rebecca M. Reese、Shannon D. Shields、Jun Chen、Alessia Balestrini、Lorena Riol-Blanco、Wyne P. Lee、John Liu、Eric Suto、Xiumin Wu、Juan Zhang、Justin Q. Ly、Hank La、Kevin Johnson、Matt Baumgardner、Kang-Jye Chou、Alexis Rohou、Lionel Rougé、Brian S. Safina、Steven Magnuson、Matthew Volgraf

  DOI：10.1021/acs.jmedchem.0c02023

  日期：2021.4.8

  ankyrin 1 (TRPA1) is a nonselective calcium-permeable ion channel highly expressed in the primary sensory neurons functioning as a polymodal sensor for exogenous and endogenous stimuli and has generated widespread interest as a target for inhibition due to its implication in neuropathic pain and respiratory disease. Herein, we describe the optimization of a series of potent, selective, and orally bioavailable

  瞬时受体电位锚蛋白 1 (TRPA1) 是一种非选择性钙渗透性离子通道，在初级感觉神经元中高度表达，充当外源性和内源性刺激的多模式传感器，由于其在神经性疼痛中的作用，作为抑制靶点引起了广泛的兴趣和呼吸道疾病。在此，我们描述了一系列有效的、选择性的、口服生物可利用的 TRPA1 小分子拮抗剂的优化，从而发现了一种新型的基于四氢呋喃的接头。鉴于理化性质的平衡和大鼠 AITC 诱导的疼痛测定中强大的体内靶点参与，化合物20被进展到豚鼠卵清蛋白哮喘模型中，在该模型中它表现出显着的剂量依赖性炎症反应减少。此外，通过低温电子显微镜以3 Å的分辨率确定了与化合物21结合的TRPA1通道的结构，揭示了此类拮抗剂的结合位点和作用机制。
• Herbicides
  申请人：RHONE POULENC AGRICULTURE LTD.

  公开号：EP0634413A1

  公开（公告）日：1995-01-18

  The invention provides compounds of formula:    wherein R and R¹ independently represent hydrogen, optionally halogenated alkyl alkenyl or alkynyl; -(-CR³R⁴)n-(optionally subtituted phenyl); -(-CR³R⁴)nHet; or -(-CR³R⁴)n-Ar, wherein Ar is an optionally substituted bicycle;    wherein at least one of the groups R and R¹ represents -(-CR³R⁴)n-Ar;    R² represents R⁵ or optionally substituted phenyl;    X is oxygen or sulphur; m is 0, 1, 2 or 3;    R³ and R⁴, independently represent hydrogen, alkyl or haloalkyl;    R⁵ is halogen, optionally halogenated alkyl, alkenyl or alkynyl; or a group selected from cyano, nitro, -CO₂R⁶, -S(O)pR⁶, -NR³R⁴, -COR⁶, -S(O)pR⁷, -CO₂R⁷, -OR⁷, -CONR³R⁴, -OSO₂R⁷, -OSO₂R⁸, -OCH₂R⁷, -N(R³)COR⁸, -N(R³)SO₂R⁸, -N(R³)SO₂R⁷, -SO₂NR³R⁴, -Si(R⁸)₃ and -OR⁶;    n is zero, 1 or 2; q is zero or an integer from 1 to 5;    Het represents an optionally substituted heterocycle;    R⁶ represents hydrogen, alkyl or haloalkyl;    p is zero, one or two; r is one or two;    R⁷ represents optionally substituted phenyl;    R⁸ represents alkyl or haloalkyl;    R⁶¹ and R⁶² independently represent hydrogen, halogen, alkyl or haloalkyl;    and agriculturally acceptable salts thereof;    which possess utility as herbicides.

  该发明提供了以下结构的化合物：其中R和R¹分别代表氢、可选择卤代的烷基、烯烃基或炔基；-(-CR³R⁴)n-(可选择取代的苯基)；-(-CR³R⁴)nHet；或-(-CR³R⁴)n-Ar，其中Ar是可选择取代的双环；其中至少一个基团R和R¹代表-(-CR³R⁴)n-Ar；R²代表R⁵或可选择取代的苯基；X为氧或硫；m为0、1、2或3；R³和R⁴独立地代表氢、烷基或卤代烷基；R⁵为卤素、可选择卤代的烷基、烯烃基或炔基；或从氰基、硝基、-CO₂R⁶、-S(O)pR⁶、-NR³R⁴、-COR⁶、-S(O)pR⁷、-CO₂R⁷、-OR⁷、-CONR³R⁴、-OSO₂R⁷、-OSO₂R⁸、-OCH₂R⁷、-N(R³)COR⁸、-N(R³)SO₂R⁸、-N(R³)SO₂R⁷、-SO₂NR³R⁴、-Si(R⁸)₃和-OR⁶中选择的基团；n为零、1或2；q为零或从1到5的整数；Het代表可选择取代的杂环；R⁶代表氢、烷基或卤代烷基；p为零、一或二；r为一或二；R⁷代表可选择取代的苯基；R⁸代表烷基或卤代烷基；R⁶¹和R⁶²独立地代表氢、卤素、烷基或卤代烷基；及其农业可接受的盐；具有除草剂的用途。
• HETEROCYCLIC COMPOUND AND MEDICINAL APPLICATION THEREOF
  申请人：Japan Tobacco, Inc.

  公开号：EP1953147A1

  公开（公告）日：2008-08-06

  The present invention aims at providing a novel heterocyclic compound having HCV entry inhibitory activity and the pharmaceutical use thereof. The present invention provides a therapeutic agent for hepatitis C comprising a heterocyclic compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof as an active ingredient: wherein Q1 is -N=, etc., Q2 is -N-, etc., Q3 is -N=, etc., Q4 is -N-, etc., Q5 is -N-, etc., R1 is a hydrogen atom, etc., R2 is a hydrogen atom, etc., ring A is a monocyclic aryl group optionally having substituent(s), etc., and ring B is a monocyclic aryl group optionally having substituent(s), etc.

  本发明旨在提供一种具有HCV进入抑制活性的新型杂环化合物及其药物用途。本发明提供了一种治疗丙型肝炎的治疗剂，其包括以下式[1]所表示的杂环化合物或其药学上可接受的盐作为活性成分：其中Q1为-N=等，Q2为-N-等，Q3为-N=等，Q4为-N-等，Q5为-N-等，R1为氢原子等，R2为氢原子等，环A为单环芳基，可选地具有取代基等，环B为单环芳基，可选地具有取代基等。
• Parp inhibitors
  申请人：ICOS Corporation

  公开号：US20040087588A1

  公开（公告）日：2004-05-06

  The present invention provides compounds comprising a bicyclic aryl moiety, such as 2H-phthalazin-1-one or derivatives thereof, compositions comprising the same, and methods for producing and using the same. In particular, the present invention provides compounds of the formula: 1 or a pharmaceutically acceptable salt, a hydrate, a solvate, or a prodrug thereof; where Q 1 , Q 2 and Y are those defined herein.

  本发明提供了包含双环芳基基团的化合物，例如2H-萘嗪-1-酮或其衍生物，以及包含这些化合物的组合物，以及制备和使用这些化合物的方法。特别地，本发明提供了式1的化合物：1或其药学上可接受的盐、水合物、溶剂合物或前药；其中Q1、Q2和Y的定义如本文所述。