{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chayka A"],"funding":["?stav organick? chemie a biochemie Akademie ved Cesk? republiky"],"pagination":["10135-10151"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11215778"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(12)"],"pubmed_abstract":["Yohimbine, a natural indole alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis. Nevertheless, its broader clinical use faces challenges due to its low receptor selectivity. A structure-activity relationship study of novel yohimbine analogues identified amino esters of yohimbic acid as potent and selective ADRA2A antagonists. Specifically, amino ester <b>4n</b>, in comparison to yohimbine, showed a 6-fold higher ADRA1A/ADRA2A selectivity index (SI > 556 for <b>4n</b>) and a 25-fold higher ADRA2B/ADRA2A selectivity index. Compound <b>4n</b> also demonstrated high plasma and microsomal stability, moderate-to-low membrane permeability determining its limited ability to cross the blood-brain barrier, and negligible tox"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Structure-Based Drug Design of ADRA2A Antagonists Derived from Yohimbine."],"pmcid":["PMC11215778"],"funding_grant_id":["RVO 61388963"],"pubmed_authors":["Janeba Z","Kuzmova E","Strmen T","Osifova Z","Broz B","Kozak J","Tloust'ova E","Dracinsky M","Chayka A","Mertlikova-Kaiserova H","Dvorakova A","Cesnek M"],"additional_accession":[]},"is_claimable":false,"name":"Structure-Based Drug Design of ADRA2A Antagonists Derived from Yohimbine.","description":"Yohimbine, a natural indole alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis. Nevertheless, its broader clinical use faces challenges due to its low receptor selectivity. A structure-activity relationship study of novel yohimbine analogues identified amino esters of yohimbic acid as potent and selective ADRA2A antagonists. Specifically, amino ester <b>4n</b>, in comparison to yohimbine, showed a 6-fold higher ADRA1A/ADRA2A selectivity index (SI > 556 for <b>4n</b>) and a 25-fold higher ADRA2B/ADRA2A selectivity index. Compound <b>4n</b> also demonstrated high plasma and microsomal stability, moderate-to-low membrane permeability determining its limited ability to cross the blood-brain barrier, and negligible tox","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-05-29T10:04:43.579Z","creation":"2025-04-07T02:11:49.74Z"},"accession":"S-EPMC11215778","cross_references":{"pubmed":["38857067"],"doi":["10.1021/acs.jmedchem.4c00323"]}}