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dc.date.accessioned2018-06-27T09:34:12Z
dc.date.issued2009
dc.identifierhttp://publications.icr.ac.uk/9203/
dc.identifier.citationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (12), pp. 5006 - 5011
dc.identifier.issn0223-5234
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1944
dc.description.abstractIn this work, marketed drug compounds (or known drug space) were used as a metric to test the principles of eliminating parent structures of the nitrenium ion (aryl-amine/nitro compounds) as well as sulphur and halogen containing molecules from screening compound collections. Molecules containing such moieties and/or atoms have biological and physiochemical properties, which possibly make them less attractive as leads in drug development. It was found that precursors to the nitrenium ion were relatively abundant in known drug space at 14%. Thus, their simple elimination from drug-like chemical space is not advisable. Interestingly, the mutagenic potential of the nitrenium ions is linked to their stability and quantum mechanical calculations can be used to estimate it. Furthermore, 24% of drugs investigated contained sulphur atoms and around 28% were halogenated. As some sulphur containing moieties were abundant whilst others were scarce, it was deduced that it would be more effective to eliminate specific molecular scaffolds rather than all sulphur containing molecules. In conclusion, it has been shown that by statistically analysing known drug space a better understanding of the boundaries of drug-like chemical space was established which can help medicinal chemists in finding rewarding regions of chemical space. (C) 2009 Elsevier Masson SAS. All rights reserved.
dc.format.extent5006 - 5011
dc.languageeng
dc.language.isoeng
dc.subjectKnown drug space Marketed drug compounds Drug-like chemical space Aryl-amines Aryl-nitro Carcinogens Nitrenium ions Sulphur atoms Halogen atoms and drug development/discovery HETEROCYCLIC AROMATIC-AMINES BOND-DISSOCIATION ENERGIES PROMISCUOUS INHIBITORS ELECTRON-AFFINITIES COMPOUND LIBRARIES MUTAGENIC POTENCY DISCOVERY DFT PERMEABILITY SOLUBILITY
dc.titleKnown drug space as a metric in exploring the boundaries of drug-like chemical space
dc.typeJournal Article
rioxxterms.licenseref.startdate2009
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
pubs.issue12
pubs.notesnone In this work, marketed drug compounds (or known drug space) were used as a metric to test the principles of eliminating parent structures of the nitrenium ion (aryl-amine/nitro compounds) as well as sulphur and halogen containing molecules from screening compound collections. Molecules containing such moieties and/or atoms have biological and physiochemical properties, which possibly make them less attractive as leads in drug development. It was found that precursors to the nitrenium ion were relatively abundant in known drug space at 14%. Thus, their simple elimination from drug-like chemical space is not advisable. Interestingly, the mutagenic potential of the nitrenium ions is linked to their stability and quantum mechanical calculations can be used to estimate it. Furthermore, 24% of drugs investigated contained sulphur atoms and around 28% were halogenated. As some sulphur containing moieties were abundant whilst others were scarce, it was deduced that it would be more effective to eliminate specific molecular scaffolds rather than all sulphur containing molecules. In conclusion, it has been shown that by statistically analysing known drug space a better understanding of the boundaries of drug-like chemical space was established which can help medicinal chemists in finding rewarding regions of chemical space. (C) 2009 Elsevier Masson SAS. All rights reserved.
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 4 (including Analytical Chemistry)
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 4 (including Analytical Chemistry)
pubs.volume44
pubs.embargo.termsNot known
icr.researchteamMedicinal Chemistry 4 (including Analytical Chemistry)en_US
dc.contributor.icrauthorMirza, Aminen


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