Format

Send to

Choose Destination
Bioorg Med Chem. 2011 Dec 1;19(23):6989-99. doi: 10.1016/j.bmc.2011.10.016. Epub 2011 Oct 17.

Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors.

Author information

1
Genkyotex S.A., 16 Chemin des Aulx, CH-1228 Plan-Les-Ouates, Switzerland.

Abstract

Pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives are new chemical entities with good and attractive druglikeness properties. A series of pyrazolo-pyrido-diazepine dione analogs demonstrated to be particularly amenable to lead optimization through a couple of cycles in order to improve specificity for isoforms Nox4 and Nox1 and had excellent pharmacokinetic parameters by oral route. Several molecules such as compound 7c proved to be highly potent in in vitro assays on human lung fibroblasts differentiation as well as in curative murine models of bleomycin-induced pulmonary fibrosis with superior efficiency over Pirfenidone. Pyrazolo-pyrido-diazepine dione derivatives targeting Nox4 and Nox1 isoforms appear highly promising therapeutics for the treatment of idiopathic pulmonary fibrosis.

PMID:
22041175
DOI:
10.1016/j.bmc.2011.10.016
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center