Two series of peptidomimetics containing a novel C2 pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV-1 Pr) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1I benzyl and P2/P2I Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC50 = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC50 = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture (ED50 = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.
Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1-hydroxypropanes and 2,4 diamino-1-hydroxybutanes
MARASTONI, Mauro;SALVADORI, Severo;
1999
Abstract
Two series of peptidomimetics containing a novel C2 pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV-1 Pr) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1I benzyl and P2/P2I Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC50 = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC50 = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture (ED50 = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
