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February 26, 2026RSC Advances0 citationsOpen Access

Positive modulators of N -methyl- d -aspartate receptor: structure–activity relationship study on steroidal C-17 and C-20 oxime ethers

SASantosh Kumar AdlaBKBarbora Hrčka KrausováBKBohdan Kysilov

Key Points

  • To investigate the structure-activity relationships of steroidal C-17 and C-20 oxime ethers as positive modulators of NMDAR.
  • Evaluated the potency and efficacy of pregnenolone C-20 oxime ethers compared to pregnenolone sulfate.
  • Utilized bioisosteric design principles to develop and assess new neurosteroid derivatives.
  • Pregnenolone C-20 oxime ethers demonstrated higher potency and efficacy than pregnenolone sulfate.
  • The study validates the D-ring bioisosteric design strategy in enhancing the neurosteroid properties.

Abstract

Pregnenolone C-20 oxime ethers are highly potent NMDAR PAM neurosteroids, outperforming pregnenolone sulfate in efficacy, potency, and drug-like properties, validating D-ring bioisosteric design as a promising strategy.

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Cite This Study

Adla et al. (2026) studied this question.

synapsesocial.com/papers/699fe34695ddcd3a253e70abhttps://doi.org/10.1039/d5ra07716h
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