Herein, we report a new class of amide-based inhibitors (1-4) of N-methyl-d-aspartate receptors (NMDARs) that were prepared as analogues of pregnanolone sulfate (PAS) and pregnanolone glutamate (PAG) - the steroidal neuroprotective NMDAR inhibitors. A series of experiments were conducted to evaluate their physicochemical and biological properties: (i) the inhibitory effect of compounds 3 and 4 on NMDARs was significantly improved (IC50=1.0 and 1.4μM, respectively) as compared with endogenous inhibitor - pregnanolone sulfate (IC50=24.6μM) and pregnanolone glutamate (IC50=51.7μM); (ii) physicochemical properties (logP and logD) were calculated; (iii) Caco-2 assay revealed that the permeability properties of compounds 2 and 4 are comparable with pregnanolone glutamate; (iv) compounds 1-4 have minimal or no adverse hepatic effect; (v) compounds 1-4 cross blood-brain-barrier.
- MeSH
- amidy MeSH
- buňky Hep G2 MeSH
- Caco-2 buňky MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární struktura MeSH
- neurotransmiterové látky chemie farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- receptory N-methyl-D-aspartátu antagonisté a inhibitory metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
