dc.contributor.author | Lazerwith, SE | |
dc.contributor.author | Lew, W | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Morganelli, P | |
dc.contributor.author | Liu, Q | |
dc.contributor.author | Canales, E | |
dc.contributor.author | Clarke, MO | |
dc.contributor.author | Doerffler, E | |
dc.contributor.author | Byun, D | |
dc.contributor.author | Mertzman, M | |
dc.contributor.author | Ye, H | |
dc.contributor.author | Chong, L | |
dc.contributor.author | Xu, L | |
dc.contributor.author | Appleby, T | |
dc.contributor.author | Chen, X | |
dc.contributor.author | Fenaux, M | |
dc.contributor.author | Hashash, A | |
dc.contributor.author | Leavitt, SA | |
dc.contributor.author | Mabery, E | |
dc.contributor.author | Matles, M | |
dc.contributor.author | Mwangi, Julius W. | |
dc.contributor.author | Tian, Y | |
dc.contributor.author | Lee, YJ | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Zhu, C | |
dc.contributor.author | Murray, BP | |
dc.contributor.author | Watkins, WJ | |
dc.date.accessioned | 2013-11-08T06:33:55Z | |
dc.date.available | 2013-11-08T06:33:55Z | |
dc.date.issued | 2013-11-06 | |
dc.identifier.citation | J Med Chem. 2013 Nov 6. [Epub ahead of print] | en |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/pubmed/24144213 | |
dc.identifier.uri | http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/58325 | |
dc.description.abstract | Investigation of thiophene-2-carboxylic acid HCV NS5B site II inhibitors, guided by measurement of cell culture medium binding, revealed the structure-activity relationships for intrinsic cellular potency. The pharmacokinetic profile was enhanced through incorporation of heterocyclic ethers on the N-alkyl substituent. Hydroxyl groups were incorporated to modulate protein binding. Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of the phase 2 clinical candidate GS-9669. The unexpected activity of this compound against the clinically relevant NS5B M423T mutant, relative to the wild type, was shown to arise from both the N-alkyl substituent and the N-acyl group. | en |
dc.language.iso | en | en |
dc.publisher | University of Nairobi | en |
dc.title | The Discovery of GS-9669, a Thumb Site II Non-nucleoside Inhibitor of NS5B for the Treatment of Genotype 1 Chronic Hepatitis C Infection | en |
dc.type | Article | en |
local.publisher | Department of Pharmacology And Pharmacognosy | en |