3-methyl-7-methylthio-4-phenylisoxazolo[3,4-d]pyridazine | 475091-37-3

• 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: 3-methyl-7-methylthio-4-phenylisoxazolo[3,4-d]pyridazine
• 英文别名: 3-Methyl-7-methylsulfanyl-4-phenyl-[1,2]oxazolo[3,4-d]pyridazine；3-methyl-7-methylsulfanyl-4-phenyl-[1,2]oxazolo[3,4-d]pyridazine
• CAS: 475091-37-3
• 化学式: C₁₃H₁₁N₃OS
• 分子量: 257.316
• InChiKey: AVKFABDMFPPCRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-methyl-7-methylthio-4-phenylisoxazolo[3,4-d]pyridazine 在 palladium 10% on activated carbon 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 反应 8.0h， 生成 1‐(5‐amino‐6‐methoxy‐3‐phenylpyridazin‐4‐yl)ethan‐1‐one
  参考文献：
  名称：

  Optimization of 4‐amino‐pyridazin‐3(2H)‐one as a valid core scaffold for FABP4 inhibitors

  摘要：

  摘要目前的临床研究表明，脂肪酸结合蛋白 4 抑制剂（FABP4is）具有生物学和治疗学意义，可能在治疗癌症和其他疾病方面显示出潜力。我们试图通过优化以前报道过的基于 4-氨基和 4-脲基哒嗪酮的 FABP4is 系列来发现新的结构，作为创造更有效的 FABP4 抑制剂的更大研究努力的一部分。结果发现 14e 是最有效的类似物，其 IC50 = 1.57 μM，低于阳性对照的 IC50。先进的建模研究和硅学吸收、分布、代谢和排泄-毒性计算表明，14e 是 FABP4i 等体内研究的潜在候选药物。

  DOI：

  10.1002/ardp.202300314
• 作为产物：
  描述：

  3-甲基-4-苯基异恶唑并[3,4-d]哒嗪-7(6H)-酮 在 劳森试剂 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 3-methyl-7-methylthio-4-phenylisoxazolo[3,4-d]pyridazine
  参考文献：
  名称：

  Isoxazolo[3,4-d]pyridazinones and analogues as Leishmania mexicana PDE inhibitors

  摘要：

  A series of isoxazolopyridazinones and analogues has been prepared and evaluated as Leishmania mexicana phosphodiesterase (PDE) inhibitors. Some of the synthesized compounds showed a moderate PDE inhibitory activity at 100 muM and preliminary structure-activity relationships were discussed. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01188-0

文献信息

• 4-Amino-5-vinyl-3(2H)-pyridazinones and analogues as potent antinociceptive agents: Synthesis, SARs, and preliminary studies on the mechanism of action
  作者：Claudia Vergelli、Maria Paola Giovannoni、Stefano Pieretti、Amalia Di Giannuario、Vittorio Dal Piaz、Pierfrancesco Biagini、Claudio Biancalani、Alessia Graziano、Nicoletta Cesari

  DOI：10.1016/j.bmc.2007.05.035

  日期：2007.8

  A series of 4-amino-5-vinyl-3(2H)-pyridazinones and analogues were synthesized and their antinociceptive effect was evaluated in the mouse abdominal constriction model. Several of the novel compounds showed ED(50) values in the range 6-20mg/kg/sc and demonstrated to be able to completely protect all the treated animals from the effect of the noxious stimulus at 30 mg/kg/sc. SAR studies confirmed the

  合成了一系列的4-氨基-5-乙烯基-3（2H）-哒嗪酮及其类似物，并在小鼠腹部收缩模型中评估了它们的抗伤害作用。几种新化合物的ED（50）值在6-20mg / kg / sc范围内，并证明能够完全保护所有处理过的动物免受30 mg / kg / sc的有害刺激的影响。SAR研究证实，二嗪系统第4位的氨基或取代的氨基官能团和第5位的乙烯基具有重要的作用。
• Isoxazolo[3,4-d]pyridazinones and analogues as Leishmania mexicana PDE inhibitors
  作者：Vittorio Dal Piaz、A Rascón、M.E Dubra、M.P Giovannoni、C Vergelli、M.C Castellana

  DOI：10.1016/s0014-827x(01)01188-0

  日期：2002.2

  A series of isoxazolopyridazinones and analogues has been prepared and evaluated as Leishmania mexicana phosphodiesterase (PDE) inhibitors. Some of the synthesized compounds showed a moderate PDE inhibitory activity at 100 muM and preliminary structure-activity relationships were discussed. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
• Optimization of 4‐amino‐pyridazin‐3(2<i>H</i>)‐one as a valid <i>core</i> scaffold for FABP4 inhibitors
  作者：Giuseppe Floresta、Letizia Crocetti、Renan Rodrigues de Oliveira Silva、Vincenzo Patamia、Francesca Mazzacuva、Yu Chee Sonia Chen、Claudia Vergelli、Agostino Cilibrizzi

  DOI：10.1002/ardp.202300314

  日期：2023.10

  Current clinical research suggests that fatty acid‐binding protein 4 inhibitors (FABP4is), which are of biological and therapeutic interest, may show potential in treating cancer and other illnesses. We sought to uncover new structures through the optimization of the previously reported 4‐amino and 4‐ureido pyridazinone‐based series of FABP4is as part of a larger research effort to create more potent FABP4 inhibitors. This led to the identification of 14e as the most potent analog with IC₅₀ = 1.57 μM, which is lower than the IC₅₀ of the positive control. Advanced modeling investigations and in silico absorption, distribution, metabolism, and excretion ‐ toxicity calculations suggested that 14e represents a potential candidate for in vivo studies such as FABP4i.

  摘要目前的临床研究表明，脂肪酸结合蛋白 4 抑制剂（FABP4is）具有生物学和治疗学意义，可能在治疗癌症和其他疾病方面显示出潜力。我们试图通过优化以前报道过的基于 4-氨基和 4-脲基哒嗪酮的 FABP4is 系列来发现新的结构，作为创造更有效的 FABP4 抑制剂的更大研究努力的一部分。结果发现 14e 是最有效的类似物，其 IC50 = 1.57 μM，低于阳性对照的 IC50。先进的建模研究和硅学吸收、分布、代谢和排泄-毒性计算表明，14e 是 FABP4i 等体内研究的潜在候选药物。