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Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator
Author(s) -
Nieddu Erika,
Pollarolo Benedetta,
Mazzei Marco T.,
Anzaldi Maria,
Sche Silvia,
Pedemonte Nicoletta,
Galietta Luis J. V.,
Mazzei Mauro
Publication year - 2016
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201500352
Subject(s) - cystic fibrosis transmembrane conductance regulator , chemistry , pyridine , cystic fibrosis , mutant , stereochemistry , combinatorial chemistry , biochemistry , medicinal chemistry , medicine , gene
The phenylhydrazone RDR‐1 is endowed with moderate activity as F508del‐CFTR corrector; nevertheless, its simple structure enables stimulating developments in this class of correctors. Therefore, we synthesized a number of phenylhydrazones 3 by reacting phenylhydrazine derivatives 1 with furfural derivatives 2 . By the same reaction, also the pyridine derivatives 4 , the thiophene derivatives 5 , and the hydrazides 6 and 7 were prepared. All compounds were tested as F508del‐CFTR correctors in the cystic fibrosis (CF) bronchial epithelial cell line CFBE41o‐, using corr‐4a and VX‐809 as controls. Some of the tested compounds emerged as interesting F508del‐CFTR correctors at 20 μM ( 3c ) and 2 μM ( 5d ). 3c and 5d administered together with VX‐809 produced a satisfactory additivity of action. When the structure of 5d was overlapped with RDR‐1 and five other established correctors, a shared central design was clearly visible. This fact may be of interest in the search for new F508del‐CFTR correctors.