A class of 2-hydroxychalcone compounds, their preparation methods and uses

Abstract

The invention discloses a novel 2-hydroxyl chalcone compound (I), as well as pharmacy acceptable salt, preparation method, medical composition, and purpose thereof in preparing medicines for treating and / or preventing neurodegenerative diseases including but not limited to vascular dementia, Alzheimer's diseases, Parkinson's diseases, Huntington's diseases, dementia relevant to HIV, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, glaucoma and the like (As shown in the description.).

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to a new class of 2-hydroxychalcone compounds (I) and pharmaceutically acceptable salts thereof, their preparation methods, pharmaceutical compositions and preparations for the treatment and / or prevention of neurodegeneration Use in medicines for related diseases, including but not limited to vascular dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, progressive lateral sclerosis, neuropathic pain , glaucoma and other neurodegenerative diseases. Background technique [0002] Alzheimer's disease (Alzheimer's disease, AD, senile dementia) is a degenerative disease of the central nervous system mainly characterized by progressive cognitive impairment and memory impairment. Vascular diseases and cancers are high-incidence diseases, which have risen to the fourth cause of death in developed countries such as Europe and th...

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Problems solved by technology

In previous studies, we designed and synthesized scutellarin aglycon carbamate derivatives (CN101337956A, CN102603698A), stilbene or ethane carbamate for the acetylcholinesterase and oxidative stress factors in the pathogenesis of AD Ester compounds (CN102816090A), isoflavone carbamate compounds (CN102827131A), flavonoid alkylamine compounds (CN103087024A), genistein alkylamine compounds (CN103113340A), stilbene oxyalkylamine compounds (CN103073440A), although these compounds have good acetylcholinesterase inhibitory and antioxidant activities, but for Aβ 1-42 Inhibition of self-aggregation was weak (its IC 50 greater than 20.0 µM), for Cu 2+ induced Aβ 1-42 Inhibition of aggregation (inhibition rates of less than 65.0% at a concentration of 25.0 µM) and 2+ induced Aβ 1-42 The aggregation disaggregation activity (the disaggregation rate is less than 60.0% at the concentration of 25.0 µM) is not satisfactory, resulting in the suboptimal efficacy of these compounds against AD in transgenic animal models

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