5-[5-[4-(3-chlorophenyl)piperazin-1-yl]sulfonyl-2-ethoxyphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one | 1007310-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-[5-[4-(3-chlorophenyl)piperazin-1-yl]sulfonyl-2-ethoxyphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one
• CAS: 1007310-76-0
• 化学式: C₂₇H₃₁ClN₆O₄S
• 分子量: 571.1
• InChiKey: DIVIXKVYEIPDME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-乙氧基-3-(1-甲基-7-氧代-3-丙基-6,7-二氢-1H-吡唑并[4,3-d]嘧啶-5-基)苯磺酰氯 、 1-(3-氯苯基)哌嗪 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 0.08h， 以77%的产率得到5-[5-[4-(3-chlorophenyl)piperazin-1-yl]sulfonyl-2-ethoxyphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluations of Sildenafil Analogues for Treatment of Erectile Dysfunction

  摘要：

  The 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyll-l-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, sildenafil, is a cGMP-specific phosphodiesterase-5 (PDE5) inhibitor used for penile erectile dysfunction. In the search for more potent and selective PDE5 inhibitors, new sildenafil analogues (6a-v), characterized by the presence on the sulfonyl group in the 5' position of novel N-4-substituted piperazines or ethylenediamine moiety, were prepared by traditional and micro wave-assisted synthesis and tested in rabbit isolated aorta and corpus cavernosum. Similarly to sildenafil, several analogues showed IC50 values in the nanomolar range. In the in vitro studies, all the tested compounds caused concentration-dependent relaxations in both rabbit isolated aorta and corpus cavernosum. All sildenafil analogues potentiated the nitric oxide-dependent vasodilation in endothelium-intact rabbit aorta. Compound 6f exhibited great pEC(50) value in corpus cavernosum, and compounds 6r and 6u in isolated aorta were found as potent as sildenafil for inhibiting PDE5. Because several analogues were significantly more lipophilic than sildenafil, these compounds may offer a new lead for development of new sildenafil analogues.

  DOI：

  10.1021/jm701400r

文献信息

• Synthesis and Pharmacological Evaluations of Sildenafil Analogues for Treatment of Erectile Dysfunction
  作者：Haroldo A. Flores Toque、Fernanda B. M. Priviero、Cleber E. Teixeira、Elisa Perissutti、Ferdinando Fiorino、Beatrice Severino、Francesco Frecentese、Raquel Lorenzetti、Juliana S. Baracat、Vincenzo Santagada、Giuseppe Caliendo、Edson Antunes、Gilberto De Nucci

  DOI：10.1021/jm701400r

  日期：2008.5.1

  The 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyll-l-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, sildenafil, is a cGMP-specific phosphodiesterase-5 (PDE5) inhibitor used for penile erectile dysfunction. In the search for more potent and selective PDE5 inhibitors, new sildenafil analogues (6a-v), characterized by the presence on the sulfonyl group in the 5' position of novel N-4-substituted piperazines or ethylenediamine moiety, were prepared by traditional and micro wave-assisted synthesis and tested in rabbit isolated aorta and corpus cavernosum. Similarly to sildenafil, several analogues showed IC50 values in the nanomolar range. In the in vitro studies, all the tested compounds caused concentration-dependent relaxations in both rabbit isolated aorta and corpus cavernosum. All sildenafil analogues potentiated the nitric oxide-dependent vasodilation in endothelium-intact rabbit aorta. Compound 6f exhibited great pEC(50) value in corpus cavernosum, and compounds 6r and 6u in isolated aorta were found as potent as sildenafil for inhibiting PDE5. Because several analogues were significantly more lipophilic than sildenafil, these compounds may offer a new lead for development of new sildenafil analogues.