5-(2-乙氧基苯基)-1,6-二氢-1-甲基-3-丙基-7H-吡唑并[4,3-d]嘧啶-7-硫酮 | 479074-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 5-(2-乙氧基苯基)-1,6-二氢-1-甲基-3-丙基-7H-吡唑并[4,3-d]嘧啶-7-硫酮
• 英文名称: 2-(2-ethoxy)-phenyl-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidine-7-thione
• 英文别名: Thiopyrazolopyrimidine；5-(2-ethoxyphenyl)-1-methyl-3-propyl-4H-pyrazolo[4,3-d]pyrimidine-7-thione
• CAS: 479074-06-1
• 化学式: C₁₇H₂₀N₄OS
• 分子量: 328.438
• InChiKey: TUBOOZSGASWZDM-UHFFFAOYSA-N

物化性质

• 熔点：
  155-157°C
• 溶解度：
  可溶于氯仿（轻微）、甲醇（轻微、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  83.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 5-(2-乙氧基苯基)-1,6-二氢-1-甲基-3-丙基-7H-吡唑并[4,3-d]嘧啶-7-硫酮 在 氯磺酸 、 氯化亚砜 作用下， 以 乙醇 为溶剂， 以90.3%的产率得到硫代西地那非
  参考文献：
  名称：

  The phosphodiesterase 5 inhibitor, KJH-1002, reverses a mouse model of amnesia by activating a cGMP/cAMP response element binding protein pathway and decreasing oxidative damage

  摘要：

  Background and PurposeInhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine‐induced cognitive dysfunction, using memory‐related behavioural tests and biochemical assays.Experimental ApproachIn mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine. The learning and memory abilities of mice were tested using the Morris water maze test, the Y‐maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory‐related bio‐molecules and oxidative stress parameters in brain tissue were measured using Western blot and spectrophotometry respectively.Key ResultsKJH‐1002, a novel and potent inhibitor of PDE5 (IC50 0.059 ± 0.04 nmol·L−1), was synthesized. In the behavioural tests, it markedly improved the memory performance impaired by scopolamine, indicating a restoration of cognitive function in the mice. Moreover, KJH‐1002 increased cGMP levels in the cortex and the scopolamine‐reduced expression of phosphorylated CREB, Levels of ERK 1/2, Akt and brain‐derived neurotrophic factor in the cortex and hippocampus were restored by KJH‐1002 treatment. In addition, KJH‐1002 administration increased the activities of SOD, glutathione peroxidase and glutathione reductase, and decreased the level of malondialdehyde.Conclusion and ImplicationsKJH‐1002 restored cognitive function in scopolamine‐induced amnesia mice by activating the cGMP/CREB signalling pathway and attenuating oxidative stress. The beneficial effects of KJH‐1002 on cognition indicate its potential as a therapeutic candidate for Alzheimer's disease.

  DOI：

  10.1111/bph.14377
• 作为产物：
  描述：

  5-(2-乙氧苯基)-1-甲基-3-丙基-1,6-二氢-7H-吡唑并[4,3-d]嘧啶-7-酮 在 吡啶 、 tetraphosphorus decasulfide 作用下， 反应 6.0h， 以72%的产率得到5-(2-乙氧基苯基)-1,6-二氢-1-甲基-3-丙基-7H-吡唑并[4,3-d]嘧啶-7-硫酮
  参考文献：
  名称：

  Pyrazolopyrimidinone Compound and Imidazo Triazone Compound for Treating Erectile Dysfunction

  摘要：

  公开了用于治疗勃起功能障碍的选择性磷酸二酯酶抑制剂化合物，其化学式为(I)或(II)，以及其药用可接受的盐和构型异构体。在该化学式中，取代基R1、R2、R3、R4和R5的定义如规范中所述。还公开了包含化合物(I)或(II)的医药组合物，以及利用这些化合物制备用于治疗或预防男性勃起功能障碍的药物的用途。

  公开号：

  US20140018351A1

文献信息

• Pyrazolopyrimidinone Compound and Imidazo Triazone Compound for Treating Erectile Dysfunction
  申请人：Wang Jianping

  公开号：US20140018351A1

  公开（公告）日：2014-01-16

  Disclosed are selective phosphodiesterase inhibitor compounds shown in formula (I) or (II) for treating Erectile Dysfunction, the pharmaceutically acceptable salts and configurational isomers thereof. In the formula, the substituents R 1 , R 2 , R 3 , R 4 and R 5 are defined as in the specification. Also disclosed are a medical composition comprising compounds of formula (I) or (II), and the use of these compounds for preparing a drug treating or preventing male Erectile Dysfunction.

  公开了用于治疗勃起功能障碍的选择性磷酸二酯酶抑制剂化合物，其化学式为(I)或(II)，以及其药用可接受的盐和构型异构体。在该化学式中，取代基R1、R2、R3、R4和R5的定义如规范中所述。还公开了包含化合物(I)或(II)的医药组合物，以及利用这些化合物制备用于治疗或预防男性勃起功能障碍的药物的用途。
• Novel pyrazolopyrimidinethione derivatives, preparation methods thereof and their use as therapeutics for erectile dysfunction
  申请人：——

  公开号：US20040176371A1

  公开（公告）日：2004-09-09

  Novel pyrazolopyrimidinethione compounds of formula 1: wherein R 1 and R 2 are independently each hydrogen atom, a C 1 -C 6 alkyl group, or a C 3 -C 6 cycloalkyl group, R 3 is a C 1 -C 6 alkyl group. C 3 -C 6 cycloalkyl group or C 3 -C 6 alkenyl group which is substituted or unsubstituted, X is O or NR 4 , and R 4 is hydrogen atom, or a C 1 -C 6 alkyl group, a C 3 -C 6 cycloalkyl group or a C 3 -C 6 alkenyl group which is unsubstituted or substituted with OH or an alkoxy group, pharmacologically acceptable salts or hydrates thereof, and preparation methods thereof are disclosed. Pharmaceutical compositions comprising the compounds are effectively used for the treatment of erectile dysfunction.

  化合物1的新型吡唑并嘧啶硫酮化合物，其中R1和R2分别独立地为氢原子、C1-C6烷基或C3-C6环烷基，R3为C1-C6烷基、C3-C6环烷基或C3-C6烯基，可以是取代或未取代的，X为O或NR4，而R4为氢原子或C1-C6烷基、C3-C6环烷基或C3-C6烯基，可以是未取代或取代的，其中取代基为OH或烷氧基，其药物学上可接受的盐或水合物以及其制备方法被披露。包含这些化合物的制药组合物可有效用于治疗勃起功能障碍。
• Pyrazolopyrimidinethione Derivatives, Salts and Solvates Thereof, Preparation Methods and Use Thereof
  申请人：Li Shuxin

  公开号：US20070219220A1

  公开（公告）日：2007-09-20

  The present invention disclosed the pyrazolopyrimidinethione derivatives, salts and solvates thereof, preparation methods and use thereof. The pyrazolopyrimidinethione derivatives according to the present invention possess the structure of general formula I, wherein, R 1 , R 2 , R 3 , and R 4 represent alkyl, alkenyl, or aryl; R 5 represents hydrogen, alkyl, alkenyl, alkoxy, cycloalkyloxy, aryl, or alkylacyl; and R 6 represents hydrogen, alkyl, alkenyl, cycloalkyloxy, or alkylacyl. The pharmaceuticals containing the compound of the present invention and used for the treatment of impotence and sexlessness have the advantages of high selectivity over PDE V, long action time, and less side reactions, and the pharmaceuticals will arouse no side reactions of blood pressure decreasing and heart rate increasing, and it has broad market propect.

  本发明揭示了吡唑并嘧啶硫醇衍生物、其盐和溶剂化物、制备方法及其用途。根据本发明，吡唑并嘧啶硫醇衍生物具有一般式I的结构，其中，R1、R2、R3和R4代表烷基、烯基或芳基；R5代表氢、烷基、烯基、烷氧基、环烷氧基、芳基或烷基酰基；R6代表氢、烷基、烯基、环烷氧基或烷基酰基。含有本发明化合物的制药产品用于治疗阳痿和性冷淡具有高选择性PDE V、长效时间和副作用少的优点，并且不会引起血压降低和心率增加的副作用，具有广阔的市场前景。
• Pyrazolopyrimidinone compound and imidazo triazone compound for treating erectile dysfunction
  申请人：Wang Jianping

  公开号：US09221825B2

  公开（公告）日：2015-12-29

  Disclosed are selective phosphodiesterase inhibitor compounds shown in formula (I) or (II) for treating Erectile Dysfunction, the pharmaceutically acceptable salts and configurational isomers thereof. In the formula, the substituents R1, R2, R3, R4 and R5 are defined as in the specification. Also disclosed are methods for preparing same, and a medical composition comprising compounds of formula (I) or (II), and the use of these compounds for preparing a drug treating or preventing male Erectile Dysfunction.

  本发明涉及一种用于治疗勃起功能障碍的选择性磷酸二酯酶抑制剂化合物，其化学式为（I）或（II），以及其药学上可接受的盐和构型异构体。在该式中，取代基R1、R2、R3、R4和R5的定义如规范中所述。本发明还公开了制备这些化合物的方法，以及包含式（I）或（II）化合物的医药组合物，并使用这些化合物制备治疗或预防男性勃起功能障碍的药物。
• PYRAZOLOPYRIMIDINETHIONE DERIVATIVES, SALTS AND SOLVATES THEREOF, PREPARATION METHODS AND USE THEREOF
  申请人：Institute of Radiation Medicine Academy of Military Medical Sciences of the Pla

  公开号：EP1695976A1

  公开（公告）日：2006-08-30

  The present invention disclosed the pyrazolopyrimidinethione derivatives, salts and solvates thereof, preparation methods and use thereof. The pyrazolopyrimidinethione derivatives according to the present invention possess the structure of general formula I , wherein, R1, R2, R3, and R4 represent alkyl, alkenyl, or aryl; R5 represents hydrogen, alkyl, alkenyl, alkoxy, cycloalkyloxy, aryl, or alkylacyl; and R6 represents hydrogen, alkyl, alkenyl, cycloalkyloxy, or alkylacyl. The pharmaceuticals containing the compound of the present invention and used for the treatment of impotence and sexlessness have the advantages of high selectivity over PDEV, long action time, and less side reactions, and the pharmaceuticals will arouse no side reactions of blood pressure decreasing and heart rate increasing, and it has broad market propect.

  本发明公开了吡唑嘧啶硫酮衍生物、其盐和溶剂、制备方法及其用途。根据本发明的吡唑嘧啶硫酮衍生物具有通式I的结构，其中，R1、R2、R3和R4代表烷基、烯基或芳基；R5代表氢、烷基、烯基、烷氧基、环烷氧基、芳基或烷基酰基；R6代表氢、烷基、烯基、环烷氧基或烷基酰基。含有本发明化合物并用于治疗阳痿和无性欲的药物具有对 PDEV 选择性高、作用时间长、副作用小等优点，而且该药物不会引起血压下降和心率加快等副作用，具有广阔的市场前景。