Abstract
Utilising ‘beyond rule of five’ chemical space is becoming increasingly important in drug design, but is usually at odds with good oral absorption. The formation of intramolecular hydrogen bonds in drug molecules is hypothesised to shield polarity facilitating improved membrane permeability and intestinal absorption. NMR based evidence for intramolecular hydrogen bonding in several ‘beyond rule of five’ oral drugs is described. Furthermore, the propensity for these drugs to form intramolecular hydrogen bonds could be predicted for through modelling the lowest energy conformation in the gas phase. The modulation of apparent lipophilicity through intramolecular hydrogen bonding in these molecules is supported by intrinsic cell permeability and intestinal absorption data in rat and human.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
