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Structure property relationships of N-acylsulfonamides and related bioisosteres

Francisco, Karol R., Varricchio, Carmine ORCID: https://orcid.org/0000-0002-1673-4768, Paniak, Thomas J., Kozlowski, Marisa C., Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419 and Ballatore, Carlo 2021. Structure property relationships of N-acylsulfonamides and related bioisosteres. European Journal of Medicinal Chemistry 218 , 113399. 10.1016/j.ejmech.2021.113399

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Abstract

The N-acylsulfonamide functional group is a feature of the pharmacophore of several biologically active molecules, including marketed drugs. Although this acidic moiety presents multiple points of attachments that could be exploited to introduce structural diversification, depending on the circumstances, the replacement of the functional group itself with a suitable surrogate, or bioisostere, may be desirable. A number of N-acylsulfonamide bioisosteres have been developed over the years that provide opportunities to modulate both structure and physicochemical properties of this important structural motif. To enable an assessment of the relative impact on physicochemical properties that these replacements may have compared to the N-acylsulfonamide group, we conducted a structure-property relationship study based on matched molecular pairs, in which the N-acylsulfonamide moiety of common template reference structures is replaced with a series of bioisosteres. The data presented, which include an assessment of relative changes in acidity, permeability, lipophilicity and intrinsic solubility, provides a basis for informed decisions when deploying N-acylsulfonamides, or surrogates thereof, in analog design.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Elsevier
ISSN: 0223-5234
Date of First Compliant Deposit: 8 April 2021
Date of Acceptance: 20 March 2021
Last Modified: 07 Jan 2024 18:23
URI: https://orca.cardiff.ac.uk/id/eprint/140374

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