ABSTRACT
To explore novel monoamine reuptake inhibitor with antidepressant activity, a series of substituted aryl alkanol piperidine derivatives were designed and synthesized. All of them were new compounds, and their structures were confirmed with 1H NMR and HR-MS. The results showed that compounds 4, 5 and 8 displayed strong 5-HT, NA and DA reuptake inhibiting activities in vitro. Among the tested compounds, 4, 5 and 13 exhibited potent antidepressant activities in the mice forced swimming test. Compounds 4 and 5 have potent antidepressant activities and are worth further development.
Subject(s)
Animals , Male , Mice , Rats , Antidepressive Agents , Chemistry , Pharmacology , Dopamine , Metabolism , Molecular Structure , Motor Activity , Neurotransmitter Uptake Inhibitors , Chemistry , Pharmacology , Norepinephrine , Metabolism , Piperidines , Chemistry , Pharmacology , Random Allocation , Rats, Sprague-Dawley , Serotonin , Metabolism , Structure-Activity Relationship , Swimming , Synaptosomes , MetabolismABSTRACT
To explore novel histone deacetylase (HDACs) inhibitors with anti-tumor activity, MS-275, a HDACs inhibitor, was prepared and used as a lead compound to design new N-substituted benzamide derivatives. MS-275 and eleven target compounds were obtained, and their structures were confirmed by 1H NMR and HR-MS individually. The results showed that the activity of compound 9d was equal to MS-275 in HDACs inhibition tests in vitro and worthy of further investigation. Compound 5c, 5d and 9c displayed obvious dose-effect relationship, which possessed moderate HDACs inhibitory activities. Ten compounds except 9e had selective inhibitory activities on Hut78.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , Pharmacology , Benzamides , Chemistry , Pharmacology , Cell Line, TumorABSTRACT
Compound SIPI5047 was synthesize by using piperazine as starting material in five reaction steps, and its central none-opioid analgesic activity was studied. Its analgesic activity, pharmacological mechanism, action type and drug dependence were well studied in vivo and in vitro. The results show that SIPI5047 has potent analgesic activities in vivo, which is quite similar to morphine and also much more powerful than paracetamol. SIPI5047 has no efficacy to reduce fever or inflammation, but has an obvious action on central nervous system. SIPI5057 has no apparent affinity with the mu-receptor and it is an antagonist that acts on the polyamine site of the NMDA receptor. SIPI5057 appears no drug dependence. SIPI5047 is a novel central none-opioid analgesic agent and more worthy of further research as a new drug candidate.
Subject(s)
Animals , Female , Male , Mice , Rats , Analgesics , Pharmacology , Toxicity , Motor Activity , Pain Measurement , Methods , Piperazines , Pharmacology , Toxicity , Random Allocation , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate , Receptors, Opioid, mu , Metabolism , Substance-Related DisordersABSTRACT
To synthesize aralkyl-ketone piperazine derivatives as analgesic agents, the N atom of the one side of piperazine ring is protected by formyl group firstly, then the unprotected N atom is alkylated to prepare aralkyl-ketone piperazine derivatives. Their analgesic biological activities were well studied by mice writhing model, rat hot plate model and rat tail flick model. Sixty four compounds were synthesized and pharmacological tests in vivo revealed these compounds have potent analgesic activities, especially compound I12, I14, I14 I21 and I37. These four compounds are more worthy for further research.