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• W3048006799 abstract "Cystic fibrosis is a genetic disease caused by loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator gene, encoding for CFTR protein. The most frequent mutation is the deletion of phenylalanine at position 508 (F508del), which leads to distinct defects in channel gating and cellular processing. In last years, several thiazole containing small molecules, endowed with dual F508del-CFTR modulator activity, proved to be able to target these defects. In search of new chemical entities able to restore CFTR function, we designed and synthesized a small series of sixteen thiazole derivatives. The designed compounds were studied as correctors and potentiators of F508del-CFTR. Although none of the molecules showed significant corrector activity, compounds 10 and 11 exhibited potentiator effects, thus allowing to determine some basic structural features which enable to obtain F508del-CFTR potentiator activity. In silico ADME studies showed that these derivatives obey Lipinski’s rule of five and are expected to be orally bioavailable. Therefore, these molecules may represent a good starting point for the design of analogues endowed with improved CFTR potentiator activity and a good pharmacokinetic profile." @default.
• W3048006799 created "2020-08-13" @default.
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• W3048006799 date "2020-11-01" @default.
• W3048006799 modified "2023-10-13" @default.
• W3048006799 title "Synthesis and biological evaluation of thiazole derivatives on basic defects underlying cystic fibrosis" @default.
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• W3048006799 doi "https://doi.org/10.1016/j.bmcl.2020.127473" @default.
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