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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.

Press, Neil and Taylor, Roger and Fullerton, Joe and Tranter, Pamela and Mccarthy, Clive and Keller, Thomas and Arnold, Nicola and Beer, David John and Brown, Lyndon and Cheung, Robert and Christie, Julie and Denholm, Alastair and Haberthuer, Sandra and Hatto, Julia and Keenan, Mark and Mercer, Mark and Oakman, Helen and Sahri, Helene and Tuffnell, Andrew and 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

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