Haverkate, NA, van Rensburg, M, Kumara, S, Reynisson, J, Leung, E, Pilkington, LI and Barker, D (2021) Improving the solubility of anti-proliferative thieno[2,3-b]quinoline-2-carboxamides. Bioorganic & Medicinal Chemistry, 37 (116092). 1- 10. ISSN 0968-0896

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Thieno[2,3-b]pyridines are a class of compounds known for their potent anti-proliferative activities against a range of human cancer cell lines. In this research, a number of strategies to generate analogues that have improved aqueous solubility whilst retaining the potent anti-proliferative actions, compared to previously-explored compounds in this class, were made. Herein we report the synthesis of 80 novel compounds, comprising two series, all based on the thieno[2,3-b]pyridine core structure. Overall, it was found that introducing alternative heterocycles did not notably improve the solubility or retain anti-proliferative activity seen in previously-reported analogues. However, pleasingly it was discovered, that the best strategy for improving the solubility was the alteration of the appended alkyl ring to introduce polar groups such as alcohols, ketones and substituted amine groups. In addition to this finding, we have discovered a thieno[2,3-b]pyridine, 15e, with greater aqueous solubility that has ever been seen for this class of compounds that is also a potent inhibitor of cancer cell growth, with IC50's in the nanomolar range. This new lead structure will form the basis of future explorations into this class of compounds.

Item Type: Article
Additional Information: © 2021 Published by Elsevier Ltd. The final version of this accepted manuscript and all relevant information related to it can be found online at; https://www.sciencedirect.com/science/article/pii/S0968089621001000?via%3Dihub
Uncontrolled Keywords: Antiproliferative; Solubility; Thieno[2 3-b]pyridines
Subjects: R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Related URLs:
Depositing User: Symplectic
Date Deposited: 05 May 2021 13:41
Last Modified: 10 Mar 2022 01:30
URI: https://eprints.keele.ac.uk/id/eprint/9487

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