硫代西地那非 | 479073-79-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 硫代西地那非
• 中文别名: 巯基西地那非
• 英文名称: 5-[2-ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidine-7-thione
• 英文别名: thiosildenafil；thiodenafil；5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-4H-pyrazolo[4,3-d]pyrimidine-7-thione
• CAS: 479073-79-5
• 化学式: C₂₂H₃₀N₆O₃S₂
• 分子量: 490.651
• InChiKey: LJUBVCQVNMLSTQ-UHFFFAOYSA-N

物化性质

• 熔点：
  172-174?C
• 沸点：
  676.1±65.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（轻微）、乙酸乙酯（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  硫代西地那非 、 柠檬酸 在 氯化亚砜 作用下， 以 水 、 丙酮 为溶剂， 反应 1.5h， 以97%的产率得到KJH-1002
  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 劳森试剂 、 氯磺酸 、 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 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

文献信息

• 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。
• Structure elucidation of phototransformation products of unapproved analogs of the erectile dysfunction drug sildenafil in artificial freshwater with UPLC-Q Exactive-MS
  作者：Jaume Aceña、Sandra Pérez、Piero Gardinali、José Luis Abad、Peter Eichhorn、Nubia Heuett、Damià Barceló

  DOI：10.1002/jms.3461

  日期：2014.12

  product ion spectra. Mass spectral analysis of deuterated H‐SDF, labeled on the N‐ethyl group, allowed to gain mechanistic insight into the fragmentation pathway of the substituted piperazine ring and to support the postulated photoproduct structures. The mass spectral fragmentation confirmed the stepwise destruction of the piperazine ring eventually producing a sulfonic acid derivative (C17H20N4O5S: 392

  在这项研究中，西得那非（SDF）的四种未经批准的类似物在人造淡水中在合成阳光下被光降解。选择高纯西地那非（H-SDF），羟基高纯-西地那非（HH-SDF），去甲新西地那非（NR-SDF）和硫代西地那非（T-SDF）是因为它们在天然草药产品中经常被检测为掺假品。使用UPLC-Orbitrap（Q Exactive）-MS，基于高分辨率（+）ESI产物离子谱，鉴定了H-SDF，HH-SDF和T-SDF共有的六种光产物以及九种不同分子量的独特转化产物。氘代H-SDF的质谱分析（标记在N-乙基上）允许对取代的哌嗪环的断裂路径进行机械分析，并支持假定的光产物结构。17 H 20 N 4 O 5 S：392.1151 Da）。相比之下，NR-SDF的光降解结构中没有哌嗪环，仅形成两个突出的光产物，这些产物是由磺酰胺的N，N-脱烷基化然后水解而产生的。目前的工作是对勃起功能障碍药物类似物的光降解的首次研究，并且是对环境样品中两种转化产物（m
• 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
  作者：Lijun Zhang、Jae Hong Seo、Huan Li、Ghilsoo Nam、Hyun Ok Yang

  DOI：10.1111/bph.14377

  日期：2018.8

  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.