The use of structural alerts to avoid the toxicity of pharmaceuticals

Claesson, 2018, Systematic approach to organizing structural alerts for reactive metabolite formation from potential drugs, Chem. Res. Toxicol., 10.1021/acs.chemrestox.8b00046 Stepan, 2011, Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States, Chem. Res. Toxicol., 24, 1345, 10.1021/tx200168d Uetrecht, 2009, Immune-mediated adverse drug reactions, Chem. Res. Toxicol., 22, 24, 10.1021/tx800389u Tafazoli, 2005, Peroxidases: a role in the metabolism and side effects of drugs, Drug Discov. Today, 10, 617, 10.1016/S1359-6446(05)03394-5 EMEA, 2008 Alves, 2016, Alarms about structural alerts, Green Chem., 18, 4348, 10.1039/C6GC01492E Corrigendum to Regulation (EC) No 1907/2006 Corrigendum to Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 Concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), Establishing a European Chemicals Agency, Amending Directive 1999/45/EC and Repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 As Well As Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC (OJ L 396, 30.12.2006) http://data.europa.eu/eli/reg/2006/1907/corrigendum/2007-05-29/oj. Uetrecht, 2003, Screening for the potential of a drug candidate to cause idiosyncratic drug reactions, Drug Discov. Today, 8, 832, 10.1016/S1359-6446(03)02816-2 Gardner, 1998, A comparison of the covalent binding of clozapine and olanzapine to human neutrophils in vitro and in vivo, Mol. Pharmacol., 53, 999 Chen, 2002, Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation, Chem. Res. Toxicol., 15, 907, 10.1021/tx0200109 Kemp, 2002, Characterization of raloxifene glucuronidation in vitro: contribution of intestinal metabolism to presystemic clearance, Drug Metab. Dispos., 30, 694, 10.1124/dmd.30.6.694 Siraki, 2008, Procainamide, but not N-acetylprocainamide, induces protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis, Chem. Res. Toxicol., 21, 1143, 10.1021/tx700415b Uetrecht, 1985, Reactivity and possible significance of hydroxylamine and nitroso metabolites of procainamide, J. Pharmacol. Exp. Ther., 232, 420 Smith, 2001, 10.1002/3527600213 Fischer, 1991, Possible role of free radical formation in clozapine (clozaril)-induced agranulocytosis, Mol. Pharmacol., 40, 846 Kalgutkar, 2005, Minimising the potential for metabolic activation in drug discovery, Expert Opin. Drug Metab. Toxicol., 1, 91, 10.1517/17425255.1.1.91 Liu, 1995, Clozapine is oxidized by activated human neutrophils to a reactive nitrenium ion that irreversibly binds to the cells, J. Pharmacol. Exp. Ther., 275, 1476 Maggs, 1995, The metabolic formation of reactive intermediates from clozapine, a drug associated with agranulocytosis in man, J. Pharmacol. Exp. Ther., 275, 1463 Uetrecht, 1999, New concepts in immunology relevant to idiosyncratic drug reactions: the "danger hypothesis" and innate immune system, Chem. Res. Toxicol., 12, 387, 10.1021/tx980249i Naisbitt, 1998, Metabolism-dependent neutrophil cytotoxicity of amodiaquine: a comparison with pyronaridine and related antimalarial drugs, Chem. Res. Toxicol., 11, 1586, 10.1021/tx980148k Tingle, 1995, The bioactivation of amodiaquine by human polymorphonuclear leucocytes in vitro: chemical mechanisms and the effects of fluorine substitution, Biochem. Pharmacol., 50, 1113, 10.1016/0006-2952(95)00236-S Kalgutkar, 2005, Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4, Drug Metab. Dispos., 33, 243, 10.1124/dmd.104.001735 Sim, 1988, Metabolites of procainamide and practolol inhibit complement components C3 and C4, Biochem. J., 251, 323, 10.1042/bj2510323 Kilicarslan, 2001, Flunitrazepam metabolism by cytochrome P450S 2C19 and 3A4, Drug Metab. Dispos., 29, 460 Zhou, 2014, Part 2. Compound articles Peterson, 2013, Reactive metabolites in the biotransformation of molecules containing a furan ring, Chem. Res. Toxicol., 26, 6, 10.1021/tx3003824 Njoku, 1997, Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury, Anesth. Analg., 84, 173, 10.1213/00000539-199701000-00031 Bolze, 2002, Development of an in vitro screening model for the biosynthesis of acyl glucuronide metabolites and the assessment of their reactivity toward human serum albumin, Drug Metab. Dispos., 30, 404, 10.1124/dmd.30.4.404 Castillo, 1995, Disposition and reactivity of ibuprofen and ibufenac acyl glucuronides in vivo in the rhesus monkey and in vitro with human serum albumin, Drug Metab. Dispos., 23, 566 Wang, 2004, A novel approach for predicting acyl glucuronide reactivity via Schiff base formation: development of rapidly formed peptide adducts for LC/MS/MS measurements, Chem. Res. Toxicol., 17, 1206, 10.1021/tx049900+ Bocker, 1986, Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450, J. Med. Chem., 29, 1596, 10.1021/jm00159a007 Guengerich, 1988, Cytochrome P-450-catalyzed hydroxylation and carboxylic acid ester cleavage of Hantzsch pyridine esters, J. Biol. Chem., 263, 8176, 10.1016/S0021-9258(18)68458-3 Mason, 1991, Reevaluating equilibrium and kinetic binding parameters for lipophilic drugs based on a structural model for drug interaction with biological membranes, J. Med. Chem., 34, 869, 10.1021/jm00107a001 Smith, 1996, Design of drugs involving the concepts and theories of drug metabolism and pharmacokinetics, Med. Res. Rev., 16, 243, 10.1002/(SICI)1098-1128(199605)16:3<243::AID-MED2>3.0.CO;2-Z Jorga, 1999, Metabolism and excretion of tolcapone, a novel inhibitor of catechol-O-methyltransferase, Br. J. Clin. Pharmacol., 48, 513, 10.1046/j.1365-2125.1999.00036.x Smith, 2003, In vitro metabolism of tolcapone to reactive intermediates: relevance to tolcapone liver toxicity, Chem. Res. Toxicol., 16, 123, 10.1021/tx025569n Wikberg, 1993, Identification of major metabolites of the catechol-O-methyltransferase inhibitor entacapone in rats and humans, Drug Metab. Dispos., 21, 81 Liu, 2000, Metabolism of ticlopidine by activated neutrophils: implications for ticlopidine-induced agranulocytosis, Drug Metab. Dispos., 28, 726 Reist, 2000, Very slow chiral inversion of clopidogrel in rats: a pharmacokinetic and mechanistic investigation, Drug Metab. Dispos., 28, 1405 Pereillo, 2002, Structure and stereochemistry of the active metabolite of clopidogrel, Drug Metab. Dispos., 30, 1288, 10.1124/dmd.30.11.1288 Kalgutkar, 2005, A comprehensive listing of bioactivation pathways of organic functional groups, Curr. Drug Metab., 6, 161, 10.2174/1389200054021799 Durant, 1977, Cyanoguanidine-thiourea equivalence in the development of the histamine H2-receptor antagonist, cimetidine, J. Med. Chem., 20, 901, 10.1021/jm00217a007