| This paper is divided into two parts:The first part is the synthesis of a series of 3-aryl succinimides using Michael addition reaction catalyzed by 1,1,1,3,3,3-hexafluoro-2-propanol(HFIP).3-Aryl succinimide and its derivatives are key structural scalfolds often found in natural products and biologically active synthetic small molecules,and useful synthetic intermediates for the construction of advanced materials and polymers.The Michael addition reaction is generally widely used for C-C carbon-carbon coupling of electron-poor olefins and C(sp3)-H type nucleophiles.However,here we propose a Michael addition reaction with the use of a maleimide derivative as an electron-poor olefin and an electron-rich aromatic hydrocarbon as a C(sp2)-H type nucleophiles in 1,1,1,3,3,3-hexafluoro-2-propanol(HFIP).This reaction does not add any metal catalyst or reagent,and directly constructs 3-aryl succieimide by N,iV?disubstituted aniline and maleimide.It provides a concise and environmentally friendly strategy with high selectivity and wide application.The second part is the design,synthesis and biological evaluation of small molecular ligands of sigma-l receptors.Sigma-1 receptor is a receptor-type molecular chaperone that is involved in the regulation of central nervous system(CNS),thereby exerting analgesic,memory impairment,anti-epilepsy,anti-depression and neuroprotection.It represents an important target for the development of CNS drugs.To date,although multi-targeted drugs offtargeting the sigma-1 receptor have been marketed,there is no drug that selectively acts on the sigma-1 receptor on the market.Therefore,it is extremely urgent to develop novel and effective sigma-1 receptor ligands.Herein,we begin from Fluvoxamine,a serotonin reuptake inhibitor well binds to sigma-1 receptors,,and finallyprovide a series of sigma-1 receptor ligand with high affinity and selectivity by the aid of sigma-1 receptor pharmacophore. |
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