{"doi":"10.1016/j.bmcl.2018.12.041","title":"Lead generation and optimization of novel GPR119 agonists with a spirocyclic cyclohexane structure","abstract":null,"journal":"Bioorganic & Medicinal Chemistry Letters","year":2019,"id":656229,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1713040,"name":"Jun Mizukami","orcid":null,"position":1,"is_corresponding":false},{"id":471663,"name":"Takashi Watanabe","orcid":"0000-0002-9015-5246","position":2,"is_corresponding":false},{"id":1713041,"name":"Genki Mori","orcid":null,"position":3,"is_corresponding":false},{"id":1713043,"name":"Minoru Ubukata","orcid":null,"position":4,"is_corresponding":false},{"id":1713045,"name":"Katsunori Suwa","orcid":null,"position":5,"is_corresponding":false},{"id":1713047,"name":"Sumiaki Fukuda","orcid":null,"position":6,"is_corresponding":false},{"id":1713048,"name":"Tamotsu Negoro","orcid":null,"position":7,"is_corresponding":false},{"id":1713049,"name":"Motohide Sato","orcid":null,"position":8,"is_corresponding":false},{"id":1713050,"name":"Takashi Inaba","orcid":null,"position":9,"is_corresponding":false},{"id":1713039,"name":"Kazuhito Harada","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Lead generation and optimization of novel GPR119 agonists with a spirocyclic cyclohexane structure","abstract":"We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which linked potency and lipophilicity. Subsequent optimization studies of 8 for improvement of solubility afforded representative 21. Compound 21 had no inhibitory activity against six CYP isoforms and showed favorable pharmacokinetic properties and hypoglycemic activity in rats.","is_dataset_classified":null,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30587450","pmcid":null,"openalex_id":"https://openalex.org/W2903879755","authors":[],"funders":[],"total_grants":0,"fwci":0.2472,"citation_percentile":0.53635861,"influential_citations":0,"citation_trend":[{"year":2019,"count":2},{"year":2021,"count":1},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"green","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://doi.org/10.7270/q29w0js9","host_type":"repository"},{"url":"https://doi.org/10.7270/q29w0js9","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S0960894X18309880?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0960894X18309880?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bmcl.2018.12.041","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30587450","host_type":"repository"}],"fields_of_study":["Receptor Mechanisms and Signaling","Drug Transport and Resistance Mechanisms","Neuropeptides and Animal Physiology","Animals","Cyclohexanes","Cytochrome P-450 Enzyme Inhibitors","Cytochrome P-450 Enzyme System","Dose-Response Relationship, Drug","Humans","Hypoglycemic Agents","Ligands","Microsomes, Liver","Molecular Structure","Rats","Rats, Sprague-Dawley","Receptors, G-Protein-Coupled","Spiro Compounds","Structure-Activity Relationship"],"mesh_terms":["Animals","Cyclohexanes","Cytochrome P-450 Enzyme System","Dose-Response Relationship, Drug","Humans","Hypoglycemic Agents","Ligands","Microsomes, Liver","Spiro Compounds","Structure-Activity Relationship","Molecular Structure","Rats, Sprague-Dawley","Receptors, G-Protein-Coupled","Rats","Cytochrome P-450 Enzyme Inhibitors"],"keywords":["Lipophilicity","Chemistry","Lead compound","Cyclohexane","Ligand efficiency","Solubility","Agonist","Structure–activity relationship","Potency","Ligand (biochemistry)","Stereochemistry","Combinatorial chemistry","In vitro","Receptor","Biochemistry","Organic chemistry","Gpr119 Agonist","Spirocyclic Structure"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T20:13:25.201576Z","pmid":null,"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":[]}