(1H)-Imidazo<4,5-d>pyriddazine-4(5H)-one | 28682-94-2

• 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: (1H)-Imidazo<4,5-d>pyriddazine-4(5H)-one
• 英文别名: 2-aza-3-deazahypoxanthine；imidazo<4,5-d>pyridazine-4-one；imidazo[4,5-d]pyridazin-4-one；imidazo[4,5-d]pyridazine；1H-4,5-Dihydro-imidazo<4,5-d>pyridazon-(4)；1,5-dihydro-imidazo[4,5-d]pyridazin-4-one；1,5-Dihydro-imidazo[4,5-d]pyridazin-4-on；1H-Imidazo[4,5-d]pyridazin-7-ol；3,6-dihydroimidazo[4,5-d]pyridazin-7-one
• CAS: 28682-94-2
• 化学式: C₅H₄N₄O
• mdl: MFCD11557171
• 分子量: 136.113
• InChiKey: DSZCQHJBMSIMNX-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 密度：
  1.89±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  10
• 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：
  70.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1H)-Imidazo<4,5-d>pyriddazine-4(5H)-one 在 三氟甲磺酸三甲基硅酯 、 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 27.0h， 生成 4-amino-1-(2-C-methyl-β-D-ribofuranosyl)imidazo[4,5-d]pyridazine
  参考文献：
  名称：

  2'-C-甲基-β-D-呋喃基咪唑[4,5-D]哒嗪衍生物（2-AZA-3-脱氮杂嘌呤核苷类似物）的合成

  摘要：

  为了评价它们的抗病毒特性，已经合成了两种咪唑并[4,5-d]哒嗪2-C-甲基-β-D-呋喃核苷衍生物。

  DOI：

  10.1081/ncn-200060225
• 作为产物：
  描述：

  Methyl 1-<(benzyloxy)methyl>-5-(1,3-dioxolan-2-yl)-2-(phenylthio)imidazole-4-carboxylate 在 盐酸 、 aluminum amalgam 、 肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 24.5h， 生成 (1H)-Imidazo<4,5-d>pyriddazine-4(5H)-one
  参考文献：
  名称：

  Multifunctionalization of imidazole via sequential halogen-metal exchange: a new route to purine-ring analogs

  摘要：

  A new method for the synthesis of purine-ring analogs based upon the sequential halogen-metal exchange functionalization of 1-[(benzyloxy)methyl]-2,4,5-triiodoimidazole (1) has been developed and is illustrated by the synthesis of (1H)-imidazo[4,5-d]pyridazin-4(5H)-one (2-aza-3-deazahypoxanthine, 8). Treatment of 1 with BuLi followed by quench with PhSSPh afforded the 2-(phenylthio) derivative, which upon treatment with BuLi followed by quench with DMF gave the 5-carboxaldehyde. This aldehyde was converted into its ethylene acetal, which was treated with BuLi followed by quench with ClCO2CH3 to afford a 4-(methoxycarbonyl)imidazole. Removal of the phenylthio group with Al(Hg) and the (benzyloxy)methyl and ethylene acetal protecting groups concomitantly with 3 M HCl afforded methyl 5(4)-formylimidazole-4(5)-carboxylate, which underwent cyclo-condensation with ethanolic NH2NH2 to give target 8. This synthetic approach was found amenable to modification by efficient ''one-pot'' multistep transformations. Thus, treatment of 1 with (a) BuLi, (b) (CH3)3SiCl, (c) BuLi, (d) (CH3)2NN(CH3)CHO, (e) BuLi, and (f) (CH3OCO)2O afforded the N-protected 4-(methoxycarbonyl)-imidazole-5-carboxaldehyde (13) in 25% yield directly from 1. Imidazole 13 was then elaborated to 8 in two steps. 1-Formyl-1,2,2-trimethylhydrazine is a recommended replacement for DMF as a tandem formylating/ortho-metalation directing agent.

  DOI：

  10.1021/jo00040a011

文献信息

• Purine nucleoside analogues for treating flaviviridae including hepatitis C
  申请人：Idenix Pharmaceuticals, Inc.

  公开号：US09186369B2

  公开（公告）日：2015-11-17

  This invention is directed to a method for treating a host, especially a human, infected with hepatitis C, flavivirus and/or pestivirus, comprising administering to that host an effective amount of an anti-HCV biologically active pentofuranonucleoside where the pentofuranonucleoside base is an optionally substituted 2-azapurine. The optionally substituted pentofuranonucleoside, or a salt or prodrug thereof, may be administered alone or in combination with one or more optionally substituted pentofuranonucleosides or other anti-viral agents.

  这项发明涉及一种治疗宿主，特别是感染丙型肝炎、黄病毒和/或猪瘟病毒的方法，包括向该宿主施用一种抗HCV生物活性的戊呋喃核苷的有效量，其中戊呋喃核苷的碱基是一种可选择取代的2-氮杂嘌呤。可选择取代的戊呋喃核苷，或其盐或前药，可以单独或与一个或多个可选择取代的戊呋喃核苷或其他抗病毒药剂联合使用。
• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE GAMMA SÉCRÉTASE
  申请人：SCHERING CORP

  公开号：WO2009076352A1

  公开（公告）日：2009-06-18

  This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula [Chemical formula should be inserted here as it appears on abstract in electronic form.] Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's disease using the compounds of formula (I).

  这项发明提供了一种新型的化合物，它们是γ-分泌酶的调节剂。这些化合物的化学式为[在电子形式的摘要中插入化学式]。还披露了调节γ-分泌酶活性的方法以及使用化合物(I)治疗阿尔兹海默病的方法。
• The Preparation of Several 4-Substituted Imidazo[4,5-d]pyridazines as Possible Purine Antimetabolites
  作者：John A. Carbon

  DOI：10.1021/ja01555a047

  日期：1958.11
• Multifunctionalization of imidazole via sequential halogen-metal exchange: a new route to purine-ring analogs
  作者：Michael P. Groziak、Lulin Wei

  DOI：10.1021/jo00040a011

  日期：1992.7

  A new method for the synthesis of purine-ring analogs based upon the sequential halogen-metal exchange functionalization of 1-[(benzyloxy)methyl]-2,4,5-triiodoimidazole (1) has been developed and is illustrated by the synthesis of (1H)-imidazo[4,5-d]pyridazin-4(5H)-one (2-aza-3-deazahypoxanthine, 8). Treatment of 1 with BuLi followed by quench with PhSSPh afforded the 2-(phenylthio) derivative, which upon treatment with BuLi followed by quench with DMF gave the 5-carboxaldehyde. This aldehyde was converted into its ethylene acetal, which was treated with BuLi followed by quench with ClCO2CH3 to afford a 4-(methoxycarbonyl)imidazole. Removal of the phenylthio group with Al(Hg) and the (benzyloxy)methyl and ethylene acetal protecting groups concomitantly with 3 M HCl afforded methyl 5(4)-formylimidazole-4(5)-carboxylate, which underwent cyclo-condensation with ethanolic NH2NH2 to give target 8. This synthetic approach was found amenable to modification by efficient ''one-pot'' multistep transformations. Thus, treatment of 1 with (a) BuLi, (b) (CH3)3SiCl, (c) BuLi, (d) (CH3)2NN(CH3)CHO, (e) BuLi, and (f) (CH3OCO)2O afforded the N-protected 4-(methoxycarbonyl)-imidazole-5-carboxaldehyde (13) in 25% yield directly from 1. Imidazole 13 was then elaborated to 8 in two steps. 1-Formyl-1,2,2-trimethylhydrazine is a recommended replacement for DMF as a tandem formylating/ortho-metalation directing agent.
• 10.1081/ncn-200060225
  作者：Leroy、Dukhan、Durka、Chaves、Bragnier、Storer、Gosselin

  DOI：10.1081/ncn-200060225

  日期：——

  In order to evaluate their antiviral properties, two imidazo[4,5-d]pyridazine 2-C-methyl-β-D-ribofuranonucleoside derivatives have been synthesized.

  为了评价它们的抗病毒特性，已经合成了两种咪唑并[4,5-d]哒嗪2-C-甲基-β-D-呋喃核苷衍生物。

表征谱图