Use of phosphodiesterase 9A inhibitor for preventing and treating vascular dementia

A technology of phosphodiesterase and vascular dementia, applied in the field of medicine, can solve problems such as LW33 vascular dementia that have not yet been seen

Inactive Publication Date: 2019-10-18
SUN YAT SEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, up to now, there is no application of LW33 as a treatment for vascular dementia

Method used

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  • Use of phosphodiesterase 9A inhibitor for preventing and treating vascular dementia
  • Use of phosphodiesterase 9A inhibitor for preventing and treating vascular dementia
  • Use of phosphodiesterase 9A inhibitor for preventing and treating vascular dementia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1, the impact of LW33 on the viability of BV2 cells

[0034](1) Experimental materials: BV2 (mouse microglia), purchased from the Cell Bank of the Chinese Academy of Sciences; DMEM medium (Gibco, USA); fetal bovine serum (Gibco, USA); CCK8 (Dojin Institute of Chemistry, Japan); Bay73- 6691(1-(2-chlorophenyl)-6-[(2R)-3,3,3-trifluoro-2-methylpropyl]-1,5-dihydro-4H-pyrazolo[3 ,4-d]pyrimidin-4-one, Bayer); PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl] -1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, MCE, USA).

[0035] (2) Experiment method: 5.0×10 3 The BV2 cells were added to the wells of a 96-well plate and cultured for 24 hours. The original culture solution was aspirated, and the complete culture solution containing LW33 at different concentrations (0.1 μM, 0.3 μM, 1 μM) was added, and the complete culture solution without LW33 was added as a normal control. Continue culturing for 24 hours, add 10 μ...

Embodiment 2

[0037] Example 2, the effect of LW33 on the proliferation of BV2 cells induced by LPS

[0038] (1) Experimental materials

[0039] Mouse microglia BV2 (Cell Bank, Chinese Academy of Sciences), DMEM medium (Gibco, USA), fetal bovine serum (Gibco, USA), CCK8 (Japanese colleagues), LPS (Sigma)

[0040] (2) Experimental method

[0041] 5.0×10 3 The BV2 cells were added to the wells of the 96-well plate and cultured for 24 hours. Divide BV2 cells into:

[0042] Control group: LPS treatment group (1μg / mL action time 24h);

[0043] LPS treatment group (1μg / mL action time 24h)+LW33 0.1μM;

[0044] LPS treatment group (1μg / mL action time 24h)+LW33 0.3μM;

[0045] LPS treatment group (1μg / mL action time 24h)+LW33 1μM;

[0046] LPS treatment group (1μg / mL action time 24h)+Bay73-6691 3μM;

[0047] LPS treatment group (1μg / mL action time 24h)+PF-04447943 3μM;

[0048] After 24h, CCK8 detected cell proliferation. The LPS unstimulated group was used as the control, and the differen...

Embodiment 3

[0050] Example 3. Effect of LW33 on LPS-induced BV2 inflammatory factor mRNA level

[0051] (1) Materials and methods: HLF cells were purchased from the Experimental Animal Center of Sun Yat-sen University;

[0052] BV2 was purchased from the Cell Bank of the Chinese Academy of Sciences, DMEM medium (Gibco, USA), fetal bovine serum (Gibco, USA), 0.25% trypsin (Gibco, USA), double antibody (Gibco, USA), LPS (Sigma), DMSO (MPBIO), IL-1, IL-1β, TNF-α primers (Shanghai Sangong), Thermo Revert Aid Kit kit (Thermo Fisher Scientific)

[0053] (2) Test method

[0054] The cells were seeded in 60mm dishes and cultured in a cell culture incubator. When the cells grew to 50-60% confluent, BV2 cells were pretreated with 0.1, 0.3, 1 μM LW33 and 3 μM Bay73-6691, PF-04447943 for 1 hour, then added 1 μg / mL LPS for stimulation, and extracted after 24 hours The total cellular RNA was subjected to real-time fluorescence quantitative PCR test. After measuring the concentration, take 1 μg of t...

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PUM

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Abstract

The present invention belongs to the technical field of a medicine, and more specifically relates to the use of a phosphodiesterase 9A (PDE9A) inhibitor LW33 shown as a formula I, a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising one of the inhibitor and the salt. The compound of the invention can be applied to the preparation of a drug for preventing or / and treating vascular dementia, and can also be used for preparing the drug for improving learning and memory dysfunction of a mice unilateral common carotid artery ligation (UCCAo) model and a rat arterial ischemia model, can also be used to prepare the drug for lowering IL-1beta, IL-6, MDA in serum and increasing the SOD content in serum and preparing the drug for influencing the pathological structure of vascular dementia in mice and rats.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to the use of a phosphodiesterase 9A inhibitor for preventing and treating vascular dementia. Background technique [0002] Vascular dementia (Vascular Dementia, VaD) is a progressive disease that affects cognitive ability caused by reduced blood flow to the brain, accounting for about 17-20% of all dementia patients (AD) is the second leading form of dementia and is prevalent in the elderly population. Clinical manifestations include cognitive impairment and neurological deficits. [0003] The heterogeneity of cerebrovascular disease makes it challenging to elucidate the mechanisms of neuropathology and mechanisms of vascular dementia. Sufficient supply of cerebral blood flow is of great significance to maintain the integrity of brain structure and function, and subtle lesions of cerebral blood vessels may cause long-term irreversible damage to cognitive function. It is curren...

Claims

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Application Information

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IPC IPC(8): A61K31/522A61P25/28A61P9/10
CPCA61K31/522A61P25/28A61P9/10
Inventor 刘培庆罗海彬陈健文谌正楠李民
Owner SUN YAT SEN UNIV
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