{"id":"W2413557253","doi":"10.1016/j.bmcl.2016.06.021","title":"Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK","year":2016,"lang":"en","type":"article","venue":"Bioorganic & Medicinal Chemistry Letters","topic":"Quinazolinone synthesis and applications","field":"Chemistry","cited_by":20,"is_retracted":false,"has_abstract":false,"ca_institutions":"University Health Network; Princess Margaret Cancer Centre","funders":"Canadian Institutes of Health Research","keywords":"Chemistry; Potency; Bioavailability; Kinase; Tyrosine kinase; Moiety; Selectivity; Pharmacokinetics; Pharmacology; Stereochemistry; Structure–activity relationship; Threonine; Tyrosine-kinase inhibitor; Cancer; Biochemistry; Enzyme; In vitro; Signal transduction; Serine; Internal medicine; Medicine","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0002422945,0.0004380517,0.0006786053,0.00008913768,0.00009751519,0.00002474592,0.0004238847,0.0002329824,0.0004458086],"category_scores_gemma":[0.0002979133,0.0003232913,0.000151389,0.00034572,0.0007474154,0.0001824646,0.000166941,0.0002204189,0.00001458662],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001587282,"about_ca_system_score_gemma":0.0001979308,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001561043,"about_ca_topic_score_gemma":0.000005198346,"domain_scores_codex":[0.9973972,0.00001394855,0.0008564781,0.0006891605,0.0005605316,0.0004826243],"domain_scores_gemma":[0.9981028,0.0002655759,0.0006132516,0.0006578111,0.0001710682,0.0001895083],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.0001465879,0.0002687747,0.002435955,0.0004714216,0.0001379921,0.000009200028,0.00006788645,4.348863e-7,0.9931532,0.0001016727,0.001564089,0.001642757],"study_design_scores_gemma":[0.001603516,0.0000581439,0.001465449,0.0006804725,0.000173388,0.00006185674,0.0001669274,0.000005272243,0.9942369,0.0000510142,0.001126205,0.0003708771],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9921325,0.0008610198,0.0002853043,0.004712606,0.0000613535,0.0001382507,0.0002005785,0.00006944363,0.001538985],"genre_scores_gemma":[0.9976479,0.0002694461,0.0003425259,0.0001765578,0.0003990141,0.00002644793,0.00003503823,0.00006049253,0.001042516],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.005515503,"threshold_uncertainty_score":0.9999219,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.00882445863781131,"score_gpt":0.2103943622607764,"score_spread":0.2015699036229651,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}