478697-25-5Relevant academic research and scientific papers
A novel dipeptide-based HIV protease inhibitor containing allophenylnorstatine
Abdel-Rahman, Hamdy M.,El-Koussi, Nawal A.,Alkaramany, Gamal S.,Youssef, Adel F.,Kiso, Yoshiaki
, p. 587 - 598 (2007/10/03)
Dipeptide analogues incorporating allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition state mimic at the scissile bond were designed and synthesized in the hope of obtaining a novel KNI series of HIV protease inhibitors. The precursors, N-P2′- 3-(2S,3S)-3-(tert-butyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoyl)-5, 5-dimethylthiazolidine-4-carboxamide (N-Boc-Apns-Dmt-P2′) 4a-p were prepared by deprotection of the synthones N-P2′-(tert- butyloxycarbonyl)-5,5-dimethylthiazolidine-4-carboxamide (Boc-Dmt-P 2′) 2a-p, then coupling with (2S,3S)3-(tert-butyloxycarbonyl) amino-2-hydroxy-4-phenylbutanoic acid (N-Boc-Apns-OH) 3. The deprotected intermediates 4 were coupled with the activated carboxyl groups of the P 2 ligands to afford the target dipeptides. In this work, we fixed at the P2 site either a 2,6-dimethylphenoxyacetyl or a 3-hydroxy-2-methylbenzoyl group. Substitutes at the P2′ site were varied to afford the members of the series 7 and 8. Improved activity of most of the members of series 8 relative to their analogues of series 7 can be partially attributed to the differences in the structures of the P2 moieties. Positional isomerism in the P2′ moieties significantly affected the activity and polarity of the target.
