{"doi":"10.1101/2023.12.04.569845","title":"Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3","abstract":"Abstract We report the synthesis of 2,6-disubstituted pyrazines as potent cell active CSNK2A inhibitors. 4’-Carboxyphenyl was found to be the optimal 2-pyrazine substituent for CSNK2A activity, with little tolerance for additional modification. At the 6-position, modifications of the 6-isopropylaminoindazole substituent were explored to improve selectivity over PIM3 while maintaining potent CSNK2A inhibition. The 6-isopropoxyindole analogue 6c was identified as a nanomolar CSNK2A inhibitor with 30-fold selectivity over PIM3 in cells. Replacement of the 6-isopropoxyindole by isosteric ortho-methoxy anilines, such as 7c , generated analogues with selectivity for CSNK2A over PIM3 and improved the kinome-wide selectivity. The optimized 2,6-disubstituted pyrazines showed inhibition of viral replication consistent with their CSNK2A activity. Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":397845,"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":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":634299,"name":"Andreas Krämer","orcid":"0000-0003-3294-2660","position":1,"is_corresponding":false},{"id":1174022,"name":"Benjamin G. Strickland","orcid":"0009-0007-4241-2045","position":2,"is_corresponding":false},{"id":891302,"name":"Jeffery L. Smith","orcid":"0000-0003-2189-0420","position":3,"is_corresponding":false},{"id":891300,"name":"Rebekah J. Dickmander","orcid":"0000-0002-5367-6587","position":4,"is_corresponding":false},{"id":392102,"name":"Nathaniel J. Moorman","orcid":"0000-0003-4952-6858","position":5,"is_corresponding":false},{"id":273796,"name":"Timothy M. Willson","orcid":"0000-0003-4181-8223","position":6,"is_corresponding":false},{"id":912101,"name":"Kareem A. Galal","orcid":"0000-0002-1768-8003","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T01:19:43.776284Z","pmid":"38106118","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":[]}