Search: onr:"swepub:oai:DiVA.org:uu-136039" >
Synthesis and SAR o...
Synthesis and SAR of potent inhibitors of the Hepatitis C virus NS3/4A protease : Exploration of P2 quinazoline substituents
-
Nilsson, Magnus (author)
-
- Belfrage, Anna Karin (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
-
Lindstrom, Stefan (author)
-
show more...
-
Wahling, Horst (author)
-
Lindquist, Charlotta (author)
-
Ayesa, Susana (author)
-
Kahnberg, Pia (author)
-
Pelcman, Mikael (author)
-
Benkestock, Kurt (author)
-
Agback, Tatiana (author)
-
Vrang, Lotta (author)
-
Terelius, Ylva (author)
-
Wikstrom, Kristina (author)
-
Hamelink, Elizabeth (author)
-
Rydergard, Christina (author)
-
Edlund, Michael (author)
-
Eneroth, Anders (author)
-
Raboisson, Pierre (author)
-
Lin, Tse-I (author)
-
de Kock, Herman (author)
-
Wigerinck, Piet (author)
-
Simmen, Kenneth (author)
-
Samuelsson, Bertil (author)
-
Rosenquist, Asa (author)
-
show less...
-
(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- English.
-
In: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 20:14, s. 4004-4011
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. (C) 2010 Elsevier Ltd. All rights reserved.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- HCV
- NS3/4A protease
- Inhibitors
- P2 substituent
- Quinazoline
- Replicon assay
- In vitro
- DMPK
- In vivo PK
- PHARMACY
- FARMACI
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Nilsson, Magnus
-
Belfrage, Anna K ...
-
Lindstrom, Stefa ...
-
Wahling, Horst
-
Lindquist, Charl ...
-
Ayesa, Susana
-
show more...
-
Kahnberg, Pia
-
Pelcman, Mikael
-
Benkestock, Kurt
-
Agback, Tatiana
-
Vrang, Lotta
-
Terelius, Ylva
-
Wikstrom, Kristi ...
-
Hamelink, Elizab ...
-
Rydergard, Chris ...
-
Edlund, Michael
-
Eneroth, Anders
-
Raboisson, Pierr ...
-
Lin, Tse-I
-
de Kock, Herman
-
Wigerinck, Piet
-
Simmen, Kenneth
-
Samuelsson, Bert ...
-
Rosenquist, Asa
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Pharmaceutical S ...
- Articles in the publication
-
Bioorganic & Med ...
- By the university
-
Uppsala University