HIV protease inhibitor HOE/BAY 793, structure-activity relationships in a series of C2-symmetric diols.
A detailed structure-activity relationship of C2-symmetric diol inhibitors of HIV-1 protease leads to inhibitor 6 (HOE/BAY 793) which is outstanding in the inhibition of the enzyme and in the inhibition of viral replication in HIV infected cell culture (IC50: 0.3 nM; EC50: 3 nM). There are well defined steric requirements for the design of the side chains P1-P3 of the inhibitors. In addition, all three side chains need to be lipophilic. While the enzyme tolerates hydrophilic substituents in some cases, drastic reductions in anti-HIV activity are observed in cell culture, most likely due to insufficient cell penetration.
Budt
K H
KH
Hoechst AG, Pharma Research, Frankfurt, Germany.
Peyman
A
A
Hansen
J
J
Knolle
J
J
Meichsner
C
C
Paessens
A
A
Ruppert
D
D
Stowasser
B
B
D002244:Carbon; D002478:Cells, Cultured; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D013329:Structure-Activity Relationship; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D017320:HIV Protease Inhibitors; C095310:Hoe-Bay 793; D002244:Carbon; D014633:Valine