Disruption of Crystal Packing in Thieno[2,3-b]pyridines Improves Anti-Proliferative Activity |
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Authors: | Natalie A. Haverkate Euphemia Leung Lisa I. Pilkington David Barker |
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Affiliation: | 1.School of Chemical Sciences, University of Auckland, Auckland 1010, New Zealand; (N.A.H.); (L.I.P.);2.Auckland Cancer Society Research Centre, University of Auckland, Auckland 1023, New Zealand;3.Department of Molecular Medicine and Pathology, University of Auckland, Auckland 1023, New Zealand;4.The MacDiarmid Institute for Advanced Materials and Nanotechnology, Victoria University of Wellington, Wellington 6012, New Zealand |
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Abstract: | 3-Amino-2-arylcarboxamido-thieno[2,3-b]pyridines have been shown to have anti-proliferative activity, but are also known to have poor solubility. This has been previously proposed to be due to their extensive planarity, which allows for intermolecular stacking and crystal packing. We herein report the synthesis of fifteen novel thieno[2,3-b]pyridines that have incorporated bulky, but easily cleavable, ester and carbonate functional groups in an effort to decrease crystal packing. The addition of these ‘prodrug-like’ moieties into the thieno[2,3-b]pyridine resulted in compounds with increased activity against HCT-116 colon cancer cells and the triple-negative breast cancer cell line MDA-MB-231. |
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Keywords: | thieno[2,3-b]pyridines esters anti-proliferative prodrugs |
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