4-(2,4-dimethoxyphenyl)-3,5-dimethylpyridazine | 1609581-74-9

• 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: 4-(2,4-dimethoxyphenyl)-3,5-dimethylpyridazine
• 英文别名: 4-(2,4-Dimethoxyphenyl)-3,5-dimethylpyridazine
• CAS: 1609581-74-9
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: GSWJXBKCZVHKBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2,4-dimethoxyphenyl)-3,5-dimethylpyridazine 在 碘代三甲硅烷 、 甲醇 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以26%的产率得到4-(3,5-dimethylpyridazin-4-yl)-3-methoxyphenol
  参考文献：
  名称：

  [EN] HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
  [FR] COMPOSÉS HÉTÉROAROMATIQUES ET LEUR UTILISATION COMME LIGANDS DE LA DOPAMINE D1

  摘要：

  本发明部分提供了化合物I的公式：及其药学上可接受的盐和N-氧化物；制备的过程和中间体；以及其组合物和用途。本发明进一步提供了具有减少D1R耐受性的D1激动剂，相对于多巴胺具有减少β-阿雷斯汀招募活性的D1激动剂，当结合到D1R时与D1R的Ser188显著相互作用但与Ser202的相互作用不显著的D1激动剂，当结合到D1R时与D1R的Asp103相互作用较弱并且与Ser198相互作用较弱的D1激动剂，以及它们的用途。

  公开号：

  WO2014072881A1
• 作为产物：
  描述：

  4-chloro-5-methyl-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium phosphate monohydrate 、 caesium carbonate 、 三氯氧磷 、 三环己基膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.5h， 生成 4-(2,4-dimethoxyphenyl)-3,5-dimethylpyridazine
  参考文献：
  名称：

  [EN] HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
  [FR] COMPOSÉS HÉTÉROAROMATIQUES ET LEUR UTILISATION COMME LIGANDS DE LA DOPAMINE D1

  摘要：

  本发明部分提供了化合物I的公式：及其药学上可接受的盐和N-氧化物；制备的过程和中间体；以及其组合物和用途。本发明进一步提供了具有减少D1R耐受性的D1激动剂，相对于多巴胺具有减少β-阿雷斯汀招募活性的D1激动剂，当结合到D1R时与D1R的Ser188显著相互作用但与Ser202的相互作用不显著的D1激动剂，当结合到D1R时与D1R的Asp103相互作用较弱并且与Ser198相互作用较弱的D1激动剂，以及它们的用途。

  公开号：

  WO2014072881A1

文献信息

• Heteroaromatic Compounds and their Use as Dopamine D1 Ligands
  申请人：PFIZER INC.

  公开号：US20150344490A1

  公开（公告）日：2015-12-03

  The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced β-arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.

  本发明提供了部分式I的化合物及其药学上可接受的盐和N-氧化物；其制备的过程和中间体；以及其组合物和用途。本发明还提供了具有降低D1R失效的D1激动剂，具有相对于多巴胺降低β-阻滞素招募活性的D1激动剂，当结合到D1R时与Ser188显著相互作用但与Ser202显著不相互作用的D1激动剂，当结合到D1R时与Asp103相互作用较弱且与Ser198相互作用较弱的D1激动剂，以及它们的用途。
• HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
  申请人：Pfizer Inc.

  公开号：EP2917219B1

  公开（公告）日：2017-09-27
• COMPOUNDS FOR USE IN STABILIZING P53 MUTANTS
  申请人：Boeckler Frank

  公开号：US20110059953A1

  公开（公告）日：2011-03-10

  Compounds of formula (I): wherein X is selected from CR X and N; R N1 is selected from H and C 1-4 alkyl, which may be substituted by SH or halo; R G1 is selected from H and SH; R C2 is selected from H and optionally substituted C 1-7 alkyl; R C3 is selected from H and optionally substituted C 1-7 alkyl; R x is selected from H, OH and NH 2 ; R C4 is selected from: (i) an optionally substituted C 3-12 N-containing heterocyclyl; (ii) C(═O)NR N5 R N6 , where R N5 and R N6 are independently selected from H, optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl or RN5 and RN6 and the nitrogen atom to which they are attached form an optionally substituted N-containing C 5-7 heterocyclyl group; (iii) C(═O)OR O1 , where R O1 is selected from H, optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl; (iv) C(═O)NHNHSO 2 R S1 , where R S1 is selected from H, optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl; (v) OC(═O)RC8, where RC8 is selected from H, optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl; (vi) OC(═O)NR N7 R N8 , where R N7 and R N8 are independently selected from H, optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl or R N7 and R N8 and the nitrogen atom to which they are attached form an optionally substituted N-containing C 5-7 heterocyclyl group; and (vii) C(═O)CH 2 NH C(═O)NHNH 2 , CHC(CN) 2 , CHC(CN)C(═O)NH 2 , and carboxy; R C5 is selected from H, OH and NH 2 ; or R C4 and R C5 together with the carbon atoms to which they are bound form an optionally substituted aromatic ring containing either 5 or 6 ring atoms, of formula: where Q represents O, N, or CR Q1 ═CR Q2 , where R Q1 and R Q2 are independently selected from H, OH and NH 2 ; R C6 is selected from H, OH and NH 2 ; and R C7 is selected from optionally substituted C3_12 N-containing heterocyclyl, NHC(═O)R C9 , CH 2 NR N2 R N3 and NHC(═S)NHR N4 , where R C9 is selected from optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl, R N2 and R N3 are independently selected from H, optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl or R N2 and R N3 and the nitrogen atom to which they are attached form an optionally substituted N-containing C 5-7 heterocyclyl group, and R N4 is selected from optionally substituted C 1-7 alkyl, optionally substituted C 3-20 heterocyclyl and optionally substituted C 5-20 aryl, and when R C4 and R C5 are not bound together, R C3 may additionally be selected from OR 02 , where R O2 is a C 1-4 alkyl group, and C(═O)OR O3 , where R O3 is a C 1-4 alkyl group and R C2 may additionally be selected from halo, for use in stabilising a p53 protein carrying a Y220C mutation.
• US9617275B2
  申请人：——

  公开号：US9617275B2

  公开（公告）日：2017-04-11
• [EN] HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS<br/>[FR] COMPOSÉS HÉTÉROAROMATIQUES ET LEUR UTILISATION COMME LIGANDS DE LA DOPAMINE D1
  申请人：PFIZER

  公开号：WO2014072881A1

  公开（公告）日：2014-05-15

  The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced β- arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.

  本发明部分提供了化合物I的公式：及其药学上可接受的盐和N-氧化物；制备的过程和中间体；以及其组合物和用途。本发明进一步提供了具有减少D1R耐受性的D1激动剂，相对于多巴胺具有减少β-阿雷斯汀招募活性的D1激动剂，当结合到D1R时与D1R的Ser188显著相互作用但与Ser202的相互作用不显著的D1激动剂，当结合到D1R时与D1R的Asp103相互作用较弱并且与Ser198相互作用较弱的D1激动剂，以及它们的用途。