Investigating the effects of the core nitrogen atom configuration on the thermodynamic solubility of 6,​5-​bicyclic heterocycles

Cosgrove, Brett and Down, Kenneth and Bertrand, Sophie and Tomkinson, Nicholas C.O. and Barker, Michael D. (2021) Investigating the effects of the core nitrogen atom configuration on the thermodynamic solubility of 6,​5-​bicyclic heterocycles. Bioorganic and Medicinal Chemistry Letters, 33. 127752. ISSN 0960-894X

[thumbnail of Cosgrove-etal-BMCL-2021-Investigating-the-effects-of-the-core-nitrogen-atom-configuration] Text (Cosgrove-etal-BMCL-2021-Investigating-the-effects-of-the-core-nitrogen-atom-configuration)
Cosgrove_etal_BMCL_2021_Investigating_the_effects_of_the_core_nitrogen_atom_configuration.pdf
Accepted Author Manuscript
Restricted to Repository staff only until 13 December 2021.
License: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 logo

Download (471kB) | Request a copy from the Strathclyde author

    Abstract

    Physicochemical properties, such as solubility, are important when prioritising compounds for progression on a drug discovery project. There is limited literature around the systematic effects of core changes on thermodynamic solubility. This work details the synthesis of nitrogen containing 6,5-bicyclic heterocyclic cores which are common scaffolds in medicinal chemistry and the analysis of their physicochemical properties, particularly, thermodynamic solubility. Crystalline solids were obtained where possible to enable a robust comparison of the thermodynamic solubility. Other parameters such as pKa, melting point and lipophilicity were also measured to determine the key factors affecting the observed solubility.

    ORCID iDs

    Cosgrove, Brett, Down, Kenneth, Bertrand, Sophie, Tomkinson, Nicholas C.O. ORCID logoORCID: https://orcid.org/0000-0002-5509-0133 and Barker, Michael D.;