Format

Send to

Choose Destination
J Med Chem. 2015 Sep 10;58(17):6747-52. doi: 10.1021/acs.jmedchem.5b00902. Epub 2015 Aug 28.

Discovery and Optimization of 4-(8-(3-Fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic Acid, an Improved PDE4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease (COPD).

Author information

1
Novartis Institutes for Biomedical Research , Wimblehurst Road, Horsham, West Sussex RH12 5AB, U.K.

Abstract

Herein we describe the optimization of a series of PDE4 inhibitors, with special focus on solubility and pharamcokinetics, to clinical compound 2, 4-(8-(3-fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic acid. Although compound 2 produces emesis in humans when given as a single dose, its exemplary pharmacokinetic properties enabled a novel dosing regime comprising multiple escalating doses and the resultant achievement of high plasma drug levels without associated nausea or emesis.

PMID:
26288344
DOI:
10.1021/acs.jmedchem.5b00902
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center