189205-48-9Relevant academic research and scientific papers
2',6'-Dimethylphenoxyacetyl: A new achiral high affinity P3-P2 ligand for peptidomimetic-based HIV protease inhibitors
Beaulieu, Pierre L.,Anderson, Paul C.,Cameron, Dale R.,Croteau, Gilbert,Gorys, Vida,Grand-Ma?tre, Chantal,Lamarre, Daniel,Liard, Francine,Paris, William,Plamondon, Louis,Soucy, Fran?ois,Thibeault, Diane,Wernic, Dominik,Yoakim, Christiane,Pav, Susan,Tong, Liang
, p. 1094 - 1108 (2007/10/03)
Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P3-P2 quinaldic-valine portion of 1 was replaced by 2',6'-dimethylphenoxyacetyl. With EC50's in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P3-P2 position of hydroxyethylamine-based HIV protease inhibitors.
