Press, Neil, Taylor, Roger, Fullerton, Joe, Tranter, Pamela, Mccarthy, Clive, Keller, Thomas, Arnold, Nicola, Beer, David John, Brown, Lyndon, Cheung, Robert, Christie, Julie, Denholm, Alastair, Haberthuer, Sandra, Hatto, Julia, Keenan, Mark, Mercer, Mark, Oakman, Helen, Sahri, Helene, Tuffnell, Andrew, Tweed, Morris and Trifilieff, Alexandre (2015) The Discovery And Optimisation of 4-(8-(3-Fluorophenyl)-1,7-naphthyridin-6-yl)cyclohexanecarboxylic acid, An Improved PDE4 Inhibitor For The Treatment of COPD. Journal Of Medicinal Chemistry, 58 (17). pp. 6747-6752. ISSN 0022-2623

Abstract

Herein we describe the optimisation 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)cyclohexanecarboxylic acid. Compound 2 was found to have exemplary pharmacokinetics in humans, which enabled a novel dosing regime and the achievement of high plasma drug levels without associated nausea or emesis.

Item Type:	Article
Keywords:	PDE4, phosphodiesterase, therapeutic index, solubility-based optimisation
Date Deposited:	25 Nov 2015 00:45
Last Modified:	25 Nov 2015 00:45
URI:	https://oak.novartis.com/id/eprint/25630