ALLOPHENYLNORSTATINE-CONTAINING HIV-1 PROTEASE INHIBITORS: DESIGN, SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS FOR SELECTED P2 LIGANDS

Abdel-Rahman, Hamdy M.; El-Koussi, Nawal A.; Alkaramany, Gamal S.; Youssef, Adel F.; Kiso, Yoshiaki

doi:10.21608/bfsa.2005.65236

ALLOPHENYLNORSTATINE-CONTAINING HIV-1 PROTEASE INHIBITORS: DESIGN, SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS FOR SELECTED P2 LIGANDS

Document Type : Original Article

Authors

¹ Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

² Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto, 607-8412 Japan

10.21608/bfsa.2005.65236

Abstract

The design and development of potent HIV protease inhibitors remain an attractive target for antiviral therapy. A novel class of HIV protease inhibitors containing allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition state mimic have been reported. In this work we fixed P2` (as tert-butylamino or 2-methylbenzylamino) and changed P2 moiety to provide two series of dipeptide analogs. Preliminary evaluation of the activity of the synthesized derivatives were determined as percentage of enzyme inhibition at 5  M level. The results showed that the introduction of 2-methylbenzylamino moiety as P2` ligand 6a-e considerably improved HIV inhibitory activity in comparison with the tert-butyl amino analogs 5a-e. It was found that compounds in both series retained activity still less than the lead compounds KNI-577 and KNI-727.