Bold, Guido; Faessler, Alexander; Capraro, Hans-Georg; Cozens, Robert; Klimkait, Thomas; Lazdins, Janis; Mestan, Juergen; Poncioni, Bernard; Roesel, Johannes; Stover, David; Tintelnot-Blomley, Marina; Acemoglu, Figan; Beck, Werner; Boss, Eugen; Eschbach, Martin; Huerlimann, Thomas; Masso, Elvira; Roussel, Serge; Ucci-Stoll, Katharina; Wyss, Dominique; Lang, Marc published the artcile< New Aza-Dipeptide Analogs as Potent and Orally Absorbed HIV-1 Protease Inhibitors: Candidates for Clinical Development>, Formula: C10H7NOS, the main research area is human immunodeficiency virus protease inhibitor azapeptide; azadipeptide analog preparation HIV protease inhibitor; azapeptide analog preparation antiviral.
On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex, aza-dipeptide analogs, e.g. I (R1 = Ph, pyrid-2-yl, thiazol-2-yl, thiazol-5-yl, diethylamino, 2-methyl-2H-tetrazol-5-yl, 2-tert-butyl-2H-tetrazole-5-yl; R2, R3 = iso-Pr, sec-Bu, tert-Bu; R4 = MeO, EtO) carrying N-(bis-aryl-methyl) substituents on the (hydroxyethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally or orthogonally protected dipeptide isosteres, sym. and asym. acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxyethyl)hydrazine dipeptide isostere with N-(methoxycarbonyl)-L-tert-leucine increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives The bis(L-tert-leucine) derivatives I (R1 = Ph (CGP 75355), pyrid-2-yl (CGP 73547), thiazol-2-yl (CGP 75136), 2-methyl-2H-tetrazol-5-yl (CGP 75176); R2 = R3 = tert-butyl; R4 = OMe) combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clin. candidates.
Journal of Medicinal Chemistry published new progress about Antiviral agents. 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Formula: C10H7NOS.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica