AI Article Synopsis
- A series of σ2R compounds with benzimidazolone and diazacycloalkane cores were synthesized and tested for their binding affinity in radioligand assays.
- Modifying a lead compound by substituting the piperazine with diazaspiroalkanes and fused systems decreased its binding affinity to σ2R, while specific bridged and amino analogs showed strong nanomolar affinity.
- Computational studies indicated that high binding affinity of these compounds is mainly due to hydrogen bond interactions with ASP29 and π-stacking with TYR150 in the σ2R/TMEM97 structure.
Article Abstract
A series of σ2R compounds containing benzimidazolone and diazacycloalkane cores was synthesized and evaluated in radioligand binding assays. Replacing the piperazine moiety in a lead compound with diazaspiroalkanes and the fused octahydropyrrolo[3,4-b] pyrrole ring system resulted in a loss in affinity for the σ2R. On the other hand, the bridged 2,5-diazabicyclo[2.2.1]heptane, 1,4-diazepine, and a 3-aminoazetidine analog possessed nanomolar affinities for the σ2R. Computational chemistry studies were also conducted with the recently published crystal structure of the σ2R/TMEM97 and revealed that hydrogen bond interactions with ASP29 and π-stacking interactions with TYR150 were largely responsible for the high binding affinity of small molecules to this protein.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332756 | PMC |
| http://dx.doi.org/10.3390/ijms23158259 | DOI Listing |
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Article Synopsis
- A series of σ2R compounds with benzimidazolone and diazacycloalkane cores were synthesized and tested for their binding affinity in radioligand assays.
- Modifying a lead compound by substituting the piperazine with diazaspiroalkanes and fused systems decreased its binding affinity to σ2R, while specific bridged and amino analogs showed strong nanomolar affinity.
- Computational studies indicated that high binding affinity of these compounds is mainly due to hydrogen bond interactions with ASP29 and π-stacking with TYR150 in the σ2R/TMEM97 structure.
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