Title
Selection of a respiratory syncytial virus fusion inhibitor clinical candidate: 2: discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121) Selection of a respiratory syncytial virus fusion inhibitor clinical candidate: 2: discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121)
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Washington, D.C. ,
Subject
Pharmacology. Therapy
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Volume/pages
51(2008) :4 , p. 875-896
ISSN
0022-2623
ISI
000253353800019
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572−4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.
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