3-(5-(4-chlorophenyl)-1-(3-chloropyridazin-6-yl)-3-pyrazolyl]propionic acid | 153708-81-7

• 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-(5-(4-chlorophenyl)-1-(3-chloropyridazin-6-yl)-3-pyrazolyl]propionic acid
• 英文别名: 3-[5-(4-Chlorophenyl)-1-(6-chloropyridazin-3-yl)pyrazol-3-yl]propanoic acid
• CAS: 153708-81-7
• 化学式: C₁₆H₁₂Cl₂N₄O₂
• 分子量: 363.203
• InChiKey: UEVIRFIONYRFDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(5-(4-chlorophenyl)-1-(3-chloropyridazin-6-yl)-3-pyrazolyl]propionic acid 在 4-二甲氨基吡啶 、 sodium methylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-(5-(4-chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1Hpyrazol-3-yl)-1-(piperidin-1-yl)propan-1-one
  参考文献：
  名称：

  Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation

  摘要：

  Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke. Here, we describe the synthesis and structure activity relationships of potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold. Analogs from this series demonstrated potent anti-aggregatmy activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born. 1,5-Diarylpyrazole-3-carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5.7-83 nM). On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.048
• 作为产物：
  描述：

  对氯苯乙酮 在 potassium tert-butylate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(5-(4-chlorophenyl)-1-(3-chloropyridazin-6-yl)-3-pyrazolyl]propionic acid
  参考文献：
  名称：

  Erguen, Burcu Caliskan; Nunez, Maria Teresa; Labeaga, Luis, Arzneimittel-Forschung/Drug Research, 2010, vol. 60, # 8, p. 497 - 505

  摘要：

  DOI：

文献信息

• Screening and evaluation of rat kidney aldose reductase inhibitory activity of some pyridazine derivatives
  作者：Murat Şüküroğlu、Burcu Çalişkan-Ergün、Net Das-Evcimen、Mutlu Sarikaya、Erden Banoğlu、Sibel Suzen

  DOI：10.1007/s00044-006-0021-1

  日期：2007.8

  treat diabetic complications. AR inhibitors belong to different chemical classes, one of which comprises pyridazinone analogues. At present, however, side effects and/or insufficient pharmacokinetic profiles have made most of the drug candidates undesirable. We evaluated a series of 2 H -pyridazine-3-one and 6-chloropyridazine analogues via an in vitro spectrophotometric assay for their ability to inhibit

  醛糖还原酶（AR）是一种催化葡萄糖转化为山梨糖醇的酶，山梨糖醇又通过山梨糖醇脱氢酶转化为果糖。通过该代谢途径增加的葡萄糖通量与糖尿病并发症如神经病，肾病，视网膜病和白内障的发展有关。因此，AR抑制剂似乎具有预防或治疗糖尿病并发症的潜力。AR抑制剂属于不同的化学类别，其中一种包含哒嗪酮类似物。然而，目前，副作用和/或不足的药代动力学特征使大多数候选药物不合需要。我们通过 体外 评估了一系列2 H- 哒嗪-3-一和6-氯哒嗪类似物 分光光度法测定其抑制大鼠肾脏AR的能力。研究表明，在哒嗪酮上引入吡唑环导致AR抑制能力显着降低。此外，在2 H- 哒嗪-3-一和6-氯哒嗪上引入乙酸侧链 并没有改善AR抑制活性，这是出乎意料的结果。基于对2 H- 哒嗪-3-一和6-氯哒嗪衍生物的初步AR抑制筛选结果 ，我们着手合成更多的衍生物以发现更多的活性分子。
• US5242940A
  申请人：——

  公开号：US5242940A

  公开（公告）日：1993-09-07
• Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation
  作者：Serkan Levent、Burcu Çalışkan、Murat Çiftçi、Yeşim Özkan、İdil Yenicesu、Hüseyin Ünver、Erden Banoglu

  DOI：10.1016/j.ejmech.2013.03.048

  日期：2013.6

  Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke. Here, we describe the synthesis and structure activity relationships of potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold. Analogs from this series demonstrated potent anti-aggregatmy activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born. 1,5-Diarylpyrazole-3-carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5.7-83 nM). On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Erguen, Burcu Caliskan; Nunez, Maria Teresa; Labeaga, Luis, Arzneimittel-Forschung/Drug Research, 2010, vol. 60, # 8, p. 497 - 505
  作者：Erguen, Burcu Caliskan、Nunez, Maria Teresa、Labeaga, Luis、Ledo, Francisco、Darlington, Janice、Bain, Gretchen、Cakir, Bilge、Banoglu, Erden

  DOI：——

  日期：——