{"id":"W2287304059","doi":"10.1021/acs.jmedchem.5b01296","title":"3-Oxo-hexahydro-1<i>H</i>-isoindole-4-carboxylic Acid as a Drug Chiral Bicyclic Scaffold: Structure-Based Design and Preparation of Conformationally Constrained Covalent and Noncovalent Prolyl Oligopeptidase Inhibitors","year":2015,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Peptidase Inhibition and Analysis","field":"Medicine","cited_by":25,"is_retracted":false,"has_abstract":true,"ca_institutions":"McGill University","funders":"Canadian Institutes of Health Research; Fonds Québécois de la Recherche sur la Nature et les Technologies","keywords":"Bicyclic molecule; Chemistry; Oligopeptidase; Docking (animal); Stereochemistry; Covalent bond; Isoindole; Chemical synthesis; Combinatorial chemistry; Enzyme; In vitro; Biochemistry; Organic chemistry","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":[],"consensus_categories":[],"category_scores_codex":[0.0009694643,0.0002815969,0.000703692,0.0002278344,0.00005968998,0.00003140523,0.00009795383,0.0001513018,0.0001246993],"category_scores_gemma":[0.0004504839,0.0002188209,0.0001615053,0.0002341523,0.0004024672,0.0001958593,0.0000311326,0.0003794173,0.000001366382],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001301722,"about_ca_system_score_gemma":0.001146106,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00001047637,"about_ca_topic_score_gemma":0.000001441377,"domain_scores_codex":[0.9972742,0.00008816151,0.001102721,0.0002204001,0.001086001,0.0002284869],"domain_scores_gemma":[0.9974008,0.0001096212,0.001002857,0.0001829555,0.0006229545,0.000680818],"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":[0.003764933,0.0003300062,0.001918372,0.001181544,0.0003976297,0.0002671476,0.001429679,0.0006008081,0.9858512,0.00001778119,0.002007158,0.002233716],"study_design_scores_gemma":[0.01424014,0.001357107,0.0005827099,0.003068127,0.0006852606,0.004176014,0.001259659,0.007900238,0.9658328,0.0002781569,0.0003174417,0.0003023942],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9950141,0.0007739438,0.001140257,0.001841037,0.0000441666,0.0003129191,0.00002067438,0.00001762725,0.0008353253],"genre_scores_gemma":[0.9961331,0.00004790941,0.002645943,0.0006121924,0.0003626996,0.000004087447,0.00004324403,0.00001728127,0.000133493],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.02001848,"threshold_uncertainty_score":0.8923257,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01457629796192505,"score_gpt":0.2803241580751664,"score_spread":0.2657478601132414,"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."}}