{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0002326504,0.0003401263,0.0002505878,0.0002217432,0.0001082266,0.0003986997,0.0003271003,0.000245127,0.001122507],"category_scores_gemma":[0.0001557789,0.0001610819,0.0001709701,0.0001107069,0.0001874918,0.0002303551,0.0001851843,0.000376996,0.0003684902],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002927729,"about_ca_system_score_gemma":0.0002310031,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0004409224,"about_ca_topic_score_gemma":0.001756295,"domain_scores_codex":[0.9999263,0.00001559707,0.000004184345,0.00001181511,0.00001762583,0.00002447001],"domain_scores_gemma":[0.9999579,0.000006463177,0.00001240732,0.000003352652,0.000009638401,0.00001026231],"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":[0.0003777237,0.0001631667,0.000337024,0.0002326886,0.00002203609,0.0003068158,0.00007183371,0.0009670911,0.9713423,0.001399406,0.0007484867,0.02403153],"study_design_scores_gemma":[0.0006141593,0.003510758,0.004093105,0.00003762271,0.00009104318,0.001105668,0.00004632485,0.004025148,0.9542447,0.0004047562,0.03179548,0.00003127706],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9479908,0.02271091,0.01662469,0.0008237169,0.0001901538,0.0002912694,0.0007226294,0.0003005723,0.01034533],"genre_scores_gemma":[0.9813671,0.007884989,0.004609564,0.0001303616,0.00005491504,0.00006939587,0.000441228,0.00001535375,0.005427061],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001122507,"threshold_uncertainty_score":0.003755152,"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."}}