Discovery of N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a Potent and Orally Bioavailable CFTR Potentiator | Zendy

Sabine Hadidaꝉ | Zendy; Fredrick Van Goor | Zendy; Jinglan Zhou | Zendy; Vijayalaksmi Arumugam | Zendy; Jason McCartney | Zendy; Anna Hazlewood | Zendy; Caroline J. Decker | Zendy; Paul A. Negulescu | Zendy; Peter D. J. Grootenhuis | Zendy

Open Access

Discovery of N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a Potent and Orally Bioavailable CFTR Potentiator

Author(s) -

Sabine Hadidaꝉ,

Fredrick Van Goor,

Jinglan Zhou,

Vijayalaksmi Arumugam,

Jason McCartney,

Anna Hazlewood,

Caroline J. Decker,

Paul A. Negulescu,

Peter D. J. Grootenhuis

Publication year - 2014

Publication title -

journal of medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.01

H-Index - 261

eISSN - 1520-4804

pISSN - 0022-2623

DOI - 10.1021/jm5012808

Subject(s) - ivacaftor , chemistry , potentiator , carboxamide , pharmacology , bioavailability , benzazepines , stereochemistry , cystic fibrosis transmembrane conductance regulator , biochemistry , medicine , gene

Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screening in NIH-3T3 cells expressing the F508del-CFTR mutation. Extensive medicinal chemistry and iterative structure-activity relationship (SAR) studies to evaluate potency, selectivity, and pharmacokinetic properties resulted in the identification of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, 48, ivacaftor), an investigational drug candidate approved by the FDA for the treatment of CF patients 6 years of age and older carrying the G551D mutation.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research