Synthesis of metabolically stable and biologically active modulators of NMDA receptors

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00645835" target="_blank" >RIV/61388963:_____/25:00645835 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/25:00645835
Result on the web
<a href="https://hdl.handle.net/11104/0375621" target="_blank" >https://hdl.handle.net/11104/0375621</a>
DOI - Digital Object Identifier
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Result language
angličtina
Original language name
Synthesis of metabolically stable and biologically active modulators of NMDA receptors
Original language description
The poster presents the design, synthesis and pharmacological characterization of metabolically stable steroidal modulators of N methyl D aspartate receptors (NMDARs) based on a pregnenolone scaffold functionalized as C 20 oxime ethers. A modular synthetic route was optimized so that the oxime derivatization is introduced in the final step, enabling rapid preparation of focused libraries with systematically varied carboxylic acid chain length and terminal functionalities. Whole cell patch clamp recordings at GluN1/GluN2B receptors revealed that many oxime analogues act as positive allosteric modulators, with selected C 20 derivatives displaying higher efficacy and potency than the parent hit and the endogenous neurosteroid pregnenolone sulfate. The study further demonstrates high stability of these oximes in rat plasma, reduced stability for long chain ketone analogues in microsomes, and documents that several compounds combine NMDAR potentiation with favorable kinetic and thermodynamic solubility profiles, nominating lead structures for in vivo evaluation in models of glutamatergic dysfunction.
Czech name
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Czech description
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Project
<a href="/en/project/TN02000109" target="_blank" >TN02000109: Personalised Medicine: From Translational Research into Biomedical Applications</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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