Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
ACS Med Chem Lett ; 5(3): 264-9, 2014 Mar 13.
Article in English | MEDLINE | ID: mdl-24900818

ABSTRACT

We have previously reported the discovery of our P2-P4 macrocyclic HCV NS3/4a protease inhibitor MK-5172, which in combination with the NS5a inhibitor MK-8742 recently received a breakthrough therapy designation from the US FDA for treatment of chronic HCV infection. Our goal for the next generation NS3/4a inhibitor was to achieve pan-genotypic activity while retaining the pharmacokinetic profile of MK-5172. One of the areas for follow-up investigation involved replacement of the quinoxaline moiety in MK-5172 with a quinoline and studying the effect of substitution at 4-position of the quinoline. The rationale for this effort was based on molecular modeling, which indicated that such modifications would improve interactions with the S2 subsite, in particular with D79. We wish to report herein the discovery of highly potent inhibitors with pan-genotypic activity and an improved profile over MK-5172, especially against gt-3a and A156 mutants.

3.
Chem Soc Rev ; 38(11): 3092-101, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19847344

ABSTRACT

This tutorial review highlights new research in the area of pericyclic domino reactions. It is directed towards chemists interested in cascading reactions and the total synthesis of natural products. Concise approaches to natural frameworks are described, as well as the application of domino reactions in the context of target-oriented synthesis and total synthesis.


Subject(s)
Biological Products/chemical synthesis , Catalysis , Cyclization
SELECTION OF CITATIONS
SEARCH DETAIL
...