Reduced cardiac side-effect potential by introduction of polar groups: discovery of NIBR-1282, an orally bioavailable CCR5 antagonist which is active in vivo.
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Thoma, Gebhard, Beerli, Christian, Bigaud, Marc, Bruns, Christian, Cooke, Nigel Graham, Streiff, Markus and Zerwes, Hans-Guenter (2008) Reduced cardiac side-effect potential by introduction of polar groups: discovery of NIBR-1282, an orally bioavailable CCR5 antagonist which is active in vivo. Bioorganic & Medicinal Chemistry letters, 18 (6). pp. 2000-2005. ISSN 1464-3405
Abstract
Introduction of polar groups in a series of potent CCR5 antagonists which are very likely to adversely affect the conduction system in the heart led to the identification of NIBR-1282 which did not show adverse effects when tested in an isolated rabbit heart ex vivo model. Administration of NIBR-1282 in combination with a non-efficacious dose of CsA led to significant prolongation of kidney allograft survival in cynomolgus monkeys.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
| Keywords: | Chemokines; Chemokine receptors; CCR5; Cardiac side-effects; hERG |
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| Date Deposited: | 14 Dec 2009 13:51 |
| Last Modified: | 31 Jan 2013 01:03 |
| URI: | https://oak.novartis.com/id/eprint/911 |