3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-(6H)-pyridazin-6-one-1-cyclohexan-2-one | 171050-40-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-(6H)-pyridazin-6-one-1-cyclohexan-2-one
• 英文别名: 2-(2-oxocyclohexyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone；3-[2-(2-oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine；2-(2-oxocyclohexyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyridazin-3-one
• CAS: 171050-40-1
• 化学式: C₂₃H₂₀N₄O₂
• 分子量: 384.437
• InChiKey: BBYOAANJEGZXDC-UHFFFAOYSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  67
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-(6H)-pyridazin-6-one-1-cyclohexan-2-one 在 lithium tri(t-butoxy)aluminum hydride 作用下， 以 四氢呋喃 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 2-(2-hydroxycyclohexyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone
  参考文献：
  名称：

  Pyrazolopyridine adenosine antagonists

  摘要：

  本发明涉及一种新型吡唑吡啶化合物，其化学式如下：##STR1##其中R.sup.1为芳基，R.sup.2为环(低)烷基，可能具有一个或多个适当的取代基等；以及其药学上可接受的盐，该盐可用作药物；用于制备所述吡唑吡啶化合物或其盐的过程；包括所述吡唑吡啶化合物或其药学上可接受的盐的药物组合物等。

  公开号：

  US05773530A1
• 作为产物：
  描述：

  2-(2-hydroxycyclohexyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone 在 重铬酸吡啶 、 4 A molecular sieve 作用下， 以 二氯甲烷 为溶剂， 反应 28.5h， 生成 3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-(6H)-pyridazin-6-one-1-cyclohexan-2-one
  参考文献：
  名称：

  Pyrazolopyridine adenosine antagonists

  摘要：

  本发明涉及以下式的新型吡唑吡啶化合物： 其中 R1为芳基，以及 R2为环(较低)烷基，可能具有一个或多个适当的取代基等； 以及其药学上可接受的盐，其作为药物有用；制备所述吡唑吡啶化合物或其盐的方法；包括所述吡唑吡啶化合物或其药学上可接受的盐的药物组合物；等。

  公开号：

  US06355640B1

文献信息

• [EN] PYRAZOLOPYRIDINE ADENOSINE ANTAGONISTS<br/>[FR] COMPOSE PYRAZOLOPYRIDINE ANTAGONISTE DE L'ADENOSINE
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1995018128A1

  公开（公告）日：1995-07-06

  (EN) The present invention relates to a novel pyrazolopyridine compound of formula (I) wherein R1 is aryl, and R2 is cyclo(lower)alkyl which may have one or more suitable substitutent(s), etc; and a pharmaceutically acceptable salt thereof, which is useful as a medicament. The pyrazolopyridine compound or a pharmaceutically acceptable salt thereof is an adenosine antagonist (especially, A1 receptor antagonist) and possesses various pharmacological actions.(FR) L'invention concerne un nouveau composé pyrazolopyridine de formule (I), dans laquelle R1 désigne aryle, et R2 désigne cycloalkyle (inférieur) qui peut avoir un ou plusieurs substituants appropriés, etc.; et un de ses sels acceptable sur le plan pharmaceutique, qui s'utilise comme médicament. Un tel composé pyrazolopyridine ou son sel acceptable sur le plan pharmaceutique est un antagoniste de l'adénosine (notamment un antagoniste du récepteur A1) et présente différents effets pharmacologiques.

  该发明涉及一种新型的吡唑吡啶化合物，其化学式为(I)，其中R1为芳基，R2为环(lower)烷基，可具有一个或多个适当的取代基等；以及其药学上可接受的盐，可用作药物。该吡唑吡啶化合物或其药学上可接受的盐是腺苷拮抗剂（特别是A1受体拮抗剂），并具有各种药理作用。
• Synthesis of the water-soluble adenosine A1 receptor antagonist FR166124 through a novel sequential Horner-Emmons / isomerization reaction
  作者：Satoru Kuroda、Atsushi Akahane、Hiromichi Itani、Shintaro Nishimura、Kieran Durkin、Takayoshi Kinoshita、Isao Nakanishi、Kazuo Sakane

  DOI：10.1016/s0040-4020(99)00590-6

  日期：1999.8

  An efficient synthesis of FR 166124 (1) was achieved through a novel sequential Horner-Emmons - isomerization reaction of cyclohexanone (2) with tert-butyl diethylphosphonoacetate (3) as the key process. Extensive studies of the key reaction indicated that temperature, base and conformation of the Horner-Emmons products were important factors in the isomerization reaction, leading to a proposed mechanism for this unusual Horner-Emmons reaction. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Process Improvements in the Production of a Novel Non-Xanthine Adenosine A₁ Receptor Antagonist. A “One-Pot” Horner-Emmons Isomerization Reaction
  作者：Atsuhiko Zanka、Norihumi Itoh、Satoru Kuroda

  DOI：10.1021/op990066i

  日期：1999.11.1

  Pilot plane scale synthesis of 2-[3-(2-phenylpyrazolo[1,5-a]-pyridin-3-yl-1(6H)-pyridazin-6-one)-1-cyclohexen-1-yl] acetic acid (FR166124) is described. The process involved efficient isomerization of regioisomers produced in a Horner-Emmons reaction and employed ester exchange and hydrolysis with NaOH in MeOH. Challenges encountered in the final purification stage to afford high quality drug substance in pure crystalline form are also described Process improvements and optimization of each step permitted elimination of column chromatography, resulting in a straightforward, practical, and cost-effective synthesis of FR166124. These methods were successfully scaled up in a pilot plant to give bulk drug suitable for pharmacological and toxicological evaluation.
• Discovery of FR166124, a novel water-soluble pyrazolo-[1,5-α]pyridine adenosine A1 receptor antagonist
  作者：Satoru Kuroda、Atsushi Akahane、Hiromichi Itani、Shintaro Nishimura、Kieran Durkin、Takayoshi Kinoshita、Yoshiyuki Tenda、Kazuo Sakane

  DOI：10.1016/s0960-894x(99)00304-2

  日期：1999.7

  Novel 3-(2-cycloalkyl and cycloalkenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]-pyridines were synthesized and evaluated for their adenosine A(1) receptor binding activities. In this series, FR166124 (3) was found to be the most potent and selective: adenosine A(1) receptor antagonist, and the double bond of the cyclohexenyl acetic acid group was essential for selectivity of A(1) receptor binding. Furthermore, the solubility in water of the sodium salt of FR166124 was high. (c) 1999 Elsevier Science Ltd. All rights reserved.
• PYRAZOLOPYRIDINE ADENOSINE ANTAGONISTS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0737193A1

  公开（公告）日：1996-10-16