際際滷shows by User: NathanBrown5 / http://www.slideshare.net/images/logo.gif 際際滷shows by User: NathanBrown5 / Tue, 23 Aug 2016 11:03:08 GMT 際際滷Share feed for 際際滷shows by User: NathanBrown5 On the origins of three-dimensionality in drug-like molecules /slideshow/on-the-origins-of-threedimensionality-in-druglike-molecules/65270783 20160519-ccgugmtalk-160823110308
Many medicinal chemistry relevant structures and core scaffolds tend towards geometric planarity. However, structural planarity may preclude the optimisation of physicochemical properties desirable in drug-like molecules, such as solubility. Furthermore, as new and challenging drug targets, such as protein-protein interactions, become more prevalent in drug design projects, the inherent potential to exploit three-dimensionality of chemical structures in lead optimisation is increasingly important. To this end, there has been recent interest in designing molecular fragments for fragment screening and subsequent derivatisation that exhibit enhanced three-dimensionality [1]. However, it remains unclear the extent to which core scaffolds require enhanced three-dimensionality in order to yield molecular designs with desired three-dimensionality. Here, three computational methods are applied to investigate the emergence of three-dimensionality in drug-like molecules, namely: fragmentation analysis using a recently reported fragmentation algorithm, SynDiR [2]; iterative pruning of pendant substituents using the Scaffold Tree fragmentation rules [3,4]; and the virtual enumeration of drug-like molecules from molecular fragments of varying three-dimensionality. Using the recently published three-dimensionality descriptor Plane of Best Fit (PBF), amongst other descriptors, it is possible to assess the potential three-dimensionality of molecular fragments objectively [5]. The combination of these three approaches to investigate the emergence of three-dimensionality in drug-like molecules informs on the stages at which three-dimensionality should be considered in a drug design project. These methods permit a greater understanding of the properties of the derived functional groups and scaffolds from exemplified medicinal chemistry space and their contributions to three- dimensionality. This study has highlighted key learning that is anticipated to enhance medicinal chemistry design in the future.]]>
Many medicinal chemistry relevant structures and core scaffolds tend towards geometric planarity. However, structural planarity may preclude the optimisation of physicochemical properties desirable in drug-like molecules, such as solubility. Furthermore, as new and challenging drug targets, such as protein-protein interactions, become more prevalent in drug design projects, the inherent potential to exploit three-dimensionality of chemical structures in lead optimisation is increasingly important. To this end, there has been recent interest in designing molecular fragments for fragment screening and subsequent derivatisation that exhibit enhanced three-dimensionality [1]. However, it remains unclear the extent to which core scaffolds require enhanced three-dimensionality in order to yield molecular designs with desired three-dimensionality. Here, three computational methods are applied to investigate the emergence of three-dimensionality in drug-like molecules, namely: fragmentation analysis using a recently reported fragmentation algorithm, SynDiR [2]; iterative pruning of pendant substituents using the Scaffold Tree fragmentation rules [3,4]; and the virtual enumeration of drug-like molecules from molecular fragments of varying three-dimensionality. Using the recently published three-dimensionality descriptor Plane of Best Fit (PBF), amongst other descriptors, it is possible to assess the potential three-dimensionality of molecular fragments objectively [5]. The combination of these three approaches to investigate the emergence of three-dimensionality in drug-like molecules informs on the stages at which three-dimensionality should be considered in a drug design project. These methods permit a greater understanding of the properties of the derived functional groups and scaffolds from exemplified medicinal chemistry space and their contributions to three- dimensionality. This study has highlighted key learning that is anticipated to enhance medicinal chemistry design in the future.]]> Tue, 23 Aug 2016 11:03:08 GMT /slideshow/on-the-origins-of-threedimensionality-in-druglike-molecules/65270783 NathanBrown5@slideshare.net(NathanBrown5) On the origins of three-dimensionality in drug-like molecules NathanBrown5 Many medicinal chemistry relevant structures and core scaffolds tend towards geometric planarity. However, structural planarity may preclude the optimisation of physicochemical properties desirable in drug-like molecules, such as solubility. Furthermore, as new and challenging drug targets, such as protein-protein interactions, become more prevalent in drug design projects, the inherent potential to exploit three-dimensionality of chemical structures in lead optimisation is increasingly important. To this end, there has been recent interest in designing molecular fragments for fragment screening and subsequent derivatisation that exhibit enhanced three-dimensionality [1]. However, it remains unclear the extent to which core scaffolds require enhanced three-dimensionality in order to yield molecular designs with desired three-dimensionality. Here, three computational methods are applied to investigate the emergence of three-dimensionality in drug-like molecules, namely: fragmentation analysis using a recently reported fragmentation algorithm, SynDiR [2]; iterative pruning of pendant substituents using the Scaffold Tree fragmentation rules [3,4]; and the virtual enumeration of drug-like molecules from molecular fragments of varying three-dimensionality. Using the recently published three-dimensionality descriptor Plane of Best Fit (PBF), amongst other descriptors, it is possible to assess the potential three-dimensionality of molecular fragments objectively [5]. The combination of these three approaches to investigate the emergence of three-dimensionality in drug-like molecules informs on the stages at which three-dimensionality should be considered in a drug design project. These methods permit a greater understanding of the properties of the derived functional groups and scaffolds from exemplified medicinal chemistry space and their contributions to three- dimensionality. This study has highlighted key learning that is anticipated to enhance medicinal chemistry design in the future. <img style="border:1px solid #C3E6D8;float:right;" alt="" src="https://cdn.slidesharecdn.com/ss_thumbnails/20160519-ccgugmtalk-160823110308-thumbnail.jpg?width=120&amp;height=120&amp;fit=bounds" /><br> Many medicinal chemistry relevant structures and core scaffolds tend towards geometric planarity. However, structural planarity may preclude the optimisation of physicochemical properties desirable in drug-like molecules, such as solubility. Furthermore, as new and challenging drug targets, such as protein-protein interactions, become more prevalent in drug design projects, the inherent potential to exploit three-dimensionality of chemical structures in lead optimisation is increasingly important. To this end, there has been recent interest in designing molecular fragments for fragment screening and subsequent derivatisation that exhibit enhanced three-dimensionality [1]. However, it remains unclear the extent to which core scaffolds require enhanced three-dimensionality in order to yield molecular designs with desired three-dimensionality. Here, three computational methods are applied to investigate the emergence of three-dimensionality in drug-like molecules, namely: fragmentation analysis using a recently reported fragmentation algorithm, SynDiR [2]; iterative pruning of pendant substituents using the Scaffold Tree fragmentation rules [3,4]; and the virtual enumeration of drug-like molecules from molecular fragments of varying three-dimensionality. Using the recently published three-dimensionality descriptor Plane of Best Fit (PBF), amongst other descriptors, it is possible to assess the potential three-dimensionality of molecular fragments objectively [5]. The combination of these three approaches to investigate the emergence of three-dimensionality in drug-like molecules informs on the stages at which three-dimensionality should be considered in a drug design project. These methods permit a greater understanding of the properties of the derived functional groups and scaffolds from exemplified medicinal chemistry space and their contributions to three- dimensionality. This study has highlighted key learning that is anticipated to enhance medicinal chemistry design in the future.
On the origins of three-dimensionality in drug-like molecules from Nathan Brown
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