5-(4-hydroxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 5-(4-hydroxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one
• 英文别名: 5-(4-hydroxyphenyl)-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one
• 化学式: C₁₅H₁₆N₄O₂
• 分子量: 284.318
• InChiKey: SGGADBIIZSNUOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-甲基-3-丙基-1H-吡唑-5-甲酸 在 氯化亚砜 、 硫酸 、 硝酸 、 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 21.0h， 生成 5-(4-hydroxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one
  参考文献：
  名称：

  [EN] PYRAZOLOPYRIMIDINONES FOR THE TREATMENT OF IMPOTENCE AND PROCESS FOR THE PREPARATION THEREOF
  [FR] PYRAZOLOPYRIMIDINONES POUR LE TRAITEMENT DE L'IMPUISSANCE ET PROCÉDÉ DE PRÉPARATION CORRESPONDANT

  摘要：

  本发明涉及作为PDE5抑制剂的吡唑嘧啶酮化合物，具有更好的IC50值、良好的体内有效性和PK特性，以及其制备方法。本发明涵盖基于吡唑嘧啶酮的化合物，这些化合物已经被设计、合成和筛选用于PDE5抑制活性，其PDE5抑制潜力在本发明中提供。这些设计的化合物在筛选PDE5抑制活性时表现出纳摩尔级的效力，并且在体内表现出更好的有效性。这些化合物可以用于治疗男性勃起功能障碍或阳痿的治疗。

  公开号：

  WO2015114647A1

文献信息

• A modified, economical and efficient synthesis of variably substituted pyrazolo[4,3-<i>d</i>]pyrimidin-7-ones
  作者：Khalid Mohammed Khan、Ghulam Murtaza Maharvi、Muhammad Iqbal Choudhary、Atta-ur- Rahman、Shahnaz Perveen

  DOI：10.1002/jhet.5570420608

  日期：2005.9

  treated with various aroyl amides under microwave (MW) irradiation to afford 4-aroylamino-1-methyl-3-propyl-1H-pyrazole-5-carboxamides 10-22 and 5-aryl-1-methyl-3-propyl-1,6-dihydro-1H-pyrazolo[4,3-d]pyrimidin-7-ones 23-35. The 1H-pyrazole-5-carboxamides 10-22 were also converted to pyrimidinones 23-35 either by conventional heating or by MW irradiation. However, MW irradiation method gives excellent yields

  1-甲基-3-丙基-1 H-吡唑-5-羧酸（3）在黑暗中仅在4位被溴溴化。然后通过依次用亚硫酰氯和氢氧化铵处理，将溴化产物8转化为1-甲基-3-丙基-1 H-吡唑-5-羧酰胺9。在微波（MW）照射下，用各种芳基酰胺处理羧酰胺9，得到4-芳酰基氨基-1-甲基-3-丙基-1 H-吡唑-5-羧酰胺10-22和5-芳基-1-甲基-3-丙基-1,6-二氢-1 H-吡唑并[4,3 - d ]嘧啶-7-酮23-35。1小时通过常规加热或通过MW辐射，也将-吡唑-5-羧酰胺10-22转化为嘧啶酮23-35。但是，MW辐照法可在很短的时间内提供极好的收率。
• Pyrazolopyrimidinones for the treatment of impotence and process for the preparation thereof
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

  公开号：US10017511B2

  公开（公告）日：2018-07-10

  The present invention relates to Pyrazolopyrimidinone compounds as PDE5 inhibitors with better IC50 value, good in vivo efficacy and PK profile and a process for the preparation thereof. The present invention covers the pyrazolo pyrimidinone based compounds that have been designed, synthesized and screened for PDE5 inhibitory activity and its PDE5 inhibitory potential is provided in this invention. These designer compounds have shown nanomolar potency when screened for PDE5 inhibitory activity and also shown better in vivo efficacy. These compounds can be used in the treatment of male erectile dysfunction or in the treatment of impotence.

  本发明涉及吡唑嘧啶酮类化合物作为PDE5抑制剂，具有较好的IC50值、良好的体内疗效和PK谱及其制备工艺。本发明涵盖了经过设计、合成和筛选的具有 PDE5 抑制活性的吡唑并嘧啶酮类化合物，本发明提供了其 PDE5 抑制潜力。这些设计化合物在进行 PDE5 抑制活性筛选时显示出纳摩尔效力，并显示出较好的体内疗效。这些化合物可用于治疗男性勃起功能障碍或阳痿。
• Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs
  作者：Cuihua Wang、Trent D. Ashton、Alden Gustafson、Nicholas D. Bland、Stefan O. Ochiana、Robert K. Campbell、Michael P. Pollastri

  DOI：10.1016/j.bmcl.2012.01.119

  日期：2012.4

  Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and wellbeing in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis of 5-substituted-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one analogs and their biological evaluation as anticancer agents: mTOR inhibitors
  作者：G. Lakshma Reddy、Santosh Kumar Guru、M. Srinivas、Anup Singh Pathania、Priya Mahajan、Amit Nargotra、Shashi Bhushan、Ram A. Vishwakarma、Sanghapal D. Sawant

  DOI：10.1016/j.ejmech.2014.04.051

  日期：2014.6

  A microwave assisted strategy for synthesis of series of 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones has been developed and their biological evaluation as anticancer agents is described. The synthetic protocol involves simple procedure by oxidative coupling of 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide with different aldehydes in presence of K2S2O8 offering 5-substituted-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one compounds in excellent yields. The in vitro anticancer activity screening against human cancer cell lines HeLa, CAKI-I, PC-3, MiaPaca-2, A549 gave good results. The in detailed mechanistic correlation studies of compound 3m revealed that the compound shows anticancer activity through apoptosis mechanism and also inhibits mTOR with nonomolar potency. The design was based on docking with mTOR protein. The concentration dependent cell cycle analysis, western blotting experiment and nuclear cell morphology studies have been described.
• PYRAZOLOPYRIMIDINONES FOR THE TREATMENT OF IMPOTENCE AND PROCESS FOR THE PREPARATION THEREOF
  申请人：Council of Scientific and Industrial Research

  公开号：EP3099689A1

  公开（公告）日：2016-12-07