{"doi":"10.1111/cbdd.13691","title":"Synthesis, pharmacological evaluations, and molecular docking studies on a new 1,3,4,11b‐tetrahydro‐1<i>H</i>‐fluoreno[9,1‐<i>cd</i>]azepine framework: Rigidification of D<sub>1</sub> receptor selective 1‐phenylbenzazepines and discovery of a new 5‐HT<sub>6</sub> receptor scaffold","abstract":"Abstract The novel 1,3,4,11b‐tetrahydro‐1 H ‐fluoreno[9,1‐ cd ]azepine framework, a structurally rigidified variant of the 1‐phenylbenzazepine template, was synthesized via direct arylation as a key reaction. Evaluation of the binding affinities of the rigidified compounds across a battery of serotonin, dopamine, and adrenergic receptors indicates that this scaffold unexpectedly has minimal affinity for D 1 and other dopamine receptors and is selective for the 5‐HT 6 receptor. The affinity of these systems at the 5‐HT 6 receptor is significantly influenced by electronic and hydrophobic interactions as well as the enhanced rigidity of the ligands. Molecular docking studies indicate that the reduced D 1 receptor affinity of the rigidified compounds may be due in part to weaker H‐bonding interactions between the oxygenated moieties on the compounds and specific receptor residues. Key receptor–ligand H‐bonding interactions, salt bridges, and π–π interactions appear to be responsible for the 5‐HT 6 receptor affinity of the compounds. Compounds 10 (6,7‐dimethoxy‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) and 12 (6,7‐dimethoxy‐2‐methyl‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) have been identified as structurally novel, high affinity (K i = 5 nM), selective 5‐HT 6 receptor ligands.","journal":"Chemical Biology & Drug Design","year":2020,"id":109208,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":513403,"name":"Ian L. Alberts","orcid":"0000-0002-8992-4407","position":1,"is_corresponding":false},{"id":89574,"name":"Wayne W. Harding","orcid":"0000-0002-1866-3553","position":2,"is_corresponding":false},{"id":516952,"name":"Rajan Giri","orcid":null,"position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-18T23:12:50.712357Z","pmid":"32279445","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}