Subnanomolar indazole-5-carboxamide inhibitors of monoamine oxidase B (MAO-B) continued: indications of iron binding, experimental evidence for optimised solubility and brain penetration

References

• Santos MA, Chand K, Chaves S. Recent progress in multifunctional metal chelators as potential drugs for Alzheimer´s disease. Coord Chem Rev 2016;327–328:287–303.
   Web of Science ®Google Scholar
• Meredith GE, Totterdell S, Beales M, et al. Impaired glutamate homeostasis and programmed cell death in a chronic MPTP mouse model of Parkinson’s disease. Exp Neurol 2009;219:334–40.
   PubMed Web of Science ®Google Scholar
• Belaidi AA, Bush AI. Iron neurochemistry in Alzheimer’s disease and Parkinson’s disease: targets for therapeutics. J Neurochem 2016;139(Suppl I):179–97.
   Web of Science ®Google Scholar
• Dunkel P, Chai CL, Sperlágh B, et al. Clinical utility of neuroprotective agents in neurodegenerative disease: current status of drug development for Alzhemer’s, Parkinson’s and Huntington´s diseases, and amyotrophic lateral sclerosis. Exp Opin Investig Drugs 2012;21:1267–308.
   PubMed Web of Science ®Google Scholar
• Jankovic J, Poewe W. Therapies in Parkinson’s disease. Curr Opin Neurol 2012;25:433–47.
   PubMed Web of Science ®Google Scholar
• Tong J, Meyer JH, Furukawa Y, et al. Distribution of monoamine oxidase proteins in human brain: implication for brain imaging studies. J Cereb Blood Flow Metab 2013;33:863–71.
   PubMed Web of Science ®Google Scholar
• Shih JC, Chen K, Ridd MJ. Monoamine oxidase: from genes to behavior. Annu Rev Neurosci 1999;22:197–217.
   PubMed Web of Science ®Google Scholar
• Nicotra A, Pierucci F, Parvez H, et al. Monoamine oxidase expression during development and aging. NeuroToxicol 2004;25:155–65.
   PubMed Web of Science ®Google Scholar
• Youdim MBH, Lavie I. Selective MAO-A and MAO-B inhibitors, radical scavengers and nitric oxide synthase inhibitors in Parkinson’s disease. Life Sci 1994;55:2077–82.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wang H, Chen H-Z. AChE inhibition-based multi-target-directed ligands, a novel pharmacological approach for the symptomatic and disease-modifying therapy of Alzheimer’s disease. Curr Neuropharmacol 2016;14:364–75.
   PubMed Web of Science ®Google Scholar
• Fowler JS, Logan J, Volkow ND, et al. Evidence that formulations of the selective MAO-B inhibitor selegiline, which bypass first-pass metabolism, also inhibit MAO-A in the human brain. Neuropsychopharmacology 2015;40:650–7.
   PubMed Web of Science ®Google Scholar
• Kumar B, Sheetal Mantha AK, et al. Recent developments on the structure-activity relationship studies of MAO inhibitors and their role in different neurological disorders. RSC Adv 2016;6:42660–83.
   Web of Science ®Google Scholar
• Fabbri M, Rosa MM, Abreu D, et al. Clinical pharmacology review of safinamide for the treatment of Parkinson’s disease. Neurodegener Dis Manag 2015;5:481–96.
   PubMed Web of Science ®Google Scholar
• Tzvetkov NT. Substituted indazole or indole derivatives as in vitro MAO-B inhibitors. Patent WO2014/107771, 2014.
   Google Scholar
• Tzvetkov NT, Hinz S, Gastreich M, et al. Indazole- and indole-5-carboxamides: selective and reversible monoamine oxidase B inhibitors with subnanomolar potency. J Med Chem 2014;57:6679–703.
   PubMed Web of Science ®Google Scholar
• Tzvetkov NT, Stammler H-G, Neumann B, et al. Crystal structures, binding interactions, and ADME evaluation of brain penetrant N-substituted indazole-5-carboxamides as subnanomolar, selective monoamine oxidase B and dual MAO-A/B inhibitors. Eur J Med Chem 2017;127:470–92.
   PubMed Web of Science ®Google Scholar
• Carradori S, Silvestri R. New frontiers in selective human MAO-B inhibitors. J Med Chem 2015;58:6717–32.
   PubMed Web of Science ®Google Scholar
• SeeSAR v.5.5, BioSolveIT GmbH, Sankt Augustin, Germany 2017. Available from: http://www.biosolveit.de/SeeSAR.
   Google Scholar
• LeadIT v.2.1.9, BiosolveIT GmbH, Sankt Augustin, Germany 2016. Available from: http://www.biosolveit.de/LeadIT.
   Google Scholar
• Binda C, Wang J, Pisani I, et al. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem 2007;50:5848–52.
   PubMed Web of Science ®Google Scholar
• Schneider N, Hindle S, Lange G, et al. Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function. J Comput Aided Mol Des 2012;26:701–23.
   PubMed Web of Science ®Google Scholar
• Schärfer C, Schulz-Gasch T, Ehrlich HC, et al. Torsion angle preferences in druglike chemical space: a comprehensive guide . J Med Chem 2013;56:2016–28.
   PubMed Web of Science ®Google Scholar
• Di L, Kerns EH, Fan K, et al. High throughput artificial membrane permeability assay for blood-brain barrier. Eur J Med Chem 2003;38:223–32.
   PubMed Web of Science ®Google Scholar
• Cheng YC, Prusoff WH. Relationships between the inhibition constant (Ki) and the concentration of inhibitor which causes 50% inhibition (IC50) of an enzymatic reaction. Biochem Pharmacol 1973;22:3099–108.
   PubMed Web of Science ®Google Scholar
• Clark DE. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J Pharm Sci 1999;88:807–14.
   PubMed Web of Science ®Google Scholar
• Wager TT, Hou X, Verhoest PR, Villalobos A. Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enhance alignment of drug-like properties. ACS Chem Neurosci 2010;1:435–49.
   PubMed Web of Science ®Google Scholar
• Hitchcock SA, Pennington LD. Structure-brain exposure relationships. J Med Chem 2006;49:7559–83.
   PubMed Web of Science ®Google Scholar
• Ahsan MJ, Samy JG, Khalilullah H, et al. Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents. Bioorg Med Chem Lett 2011;21:7246–50.
   PubMed Web of Science ®Google Scholar
• Abad-Zapatero C. Ligand efficiency indices for effective drug discovery. Expert Opin Drug Discov 2007;2:469–88.
   PubMed Web of Science ®Google Scholar
• Vilar S, Chakrabarti M, Costanzi S. Prediction of passive blood-brain partitioning: straightforward and effective classification models based on in silico derived physicochemical descriptors. J Mol Graph Model 2010;28:899–903.
   PubMed Web of Science ®Google Scholar
• Johnson TW, Dress KR, Edwards M. Using the Golden Triangle to optimize clearance and oral absorption. Bioorg Med Chem Lett 2009;19:5560–4.
   PubMed Web of Science ®Google Scholar