Synthesis of new thienyl ring containing HIV-1 protease inhibitors: promising preliminary pharmacological evaluation against recombinant HIV-1 proteases.
A series of new thienyl ring containing analogues of nelfinavir and saquinavir with different substitution patterns were synthesized from suitable enantiopure diols. Their inhibitory activity against wild type recombinant HIV-1 protease was evaluated. In general thienyl groups spaced from the core by a methylene group gave products showing IC(50) in the nanomolar range, irrespective of the type and the substitution pattern of the heterocycle. The range of activity of the two most active compounds is substantially maintained or even increased against two commonly selected mutants, under drug pressure, such as V32I and V82A.
Bonini
Carlo
C
Dipartimento di Chimica, Università degli Studi della Basilicata, Via Nazario Sauro 85, 85100 Potenza, Italy. bonini@unibas.it
Chiummiento
Lucia
L
De Bonis
Margherita
M
Di Blasio
Nadia
N
Funicello
Maria
M
Lupattelli
Paolo
P
Pandolfo
Rocco
R
Tramutola
Francesco
F
Berti
Federico
F
D001216:Asparagine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D016333:HIV Protease / Q000737:chemistry* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D009154:Mutation; D019888:Nelfinavir / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D019258:Saquinavir / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D017320:HIV Protease Inhibitors; D011804:Quinolines; D011994:Recombinant Proteins; D001216:Asparagine; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; D019888:Nelfinavir; D019258:Saquinavir