174740-41-1Relevant articles and documents
Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site
Coric, Pascale,Turcaud, Serge,Souquet, Florence,Briant, Laurence,Gay, Bernard,Royer, Jacques,Chazal, Nathalie,Bouaziz, Serge
, p. 453 - 465 (2013/06/26)
Bevirimat (2), the first-in-class HIV-1 maturation inhibitor, shows a low efficacy due essentially to the natural polymorphism of its target, the CA-SP1 junction. Moreover, its low hydrosolubility makes it difficult to study its interaction with the CA-SP1 junction. We have synthesized new derivatives of bevirimat by adding different hydrophilic substituents at the C-28 position to improve their hydrosolubility and perform the structural study of a complex by NMR. Synthesis of the new derivatives, the effect of substituents at the C-28 position and their hydrosolubility are discussed. The ability of these molecules to inhibit viral infection and their cytotoxicity is assessed. Compared to the well-known bevirimat (2), one of our compounds (16) shows a higher hydrosolubility associated with a 2.5 fold increase in activity, a higher selectivity index and a better antiviral profile. Moreover, for the first time a direct interaction between a derivative of bevirimat (16) and the domain CA-SP1-NC is shown by NMR. Information from this study should allow us to decipher the mechanism by which bevirimat inhibits HIV-1 maturation and how the natural polymorphism of the spacer peptide SP1 triggers resistance to inhibitors.
Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on betulinic acid
Sun, I-Chen,Chen, Chin-Ho,Kashiwada, Yoshiki,Wu, Jiu-Hong,Wang, Hui-Kang,Lee, Kuo-Hsiung
, p. 4271 - 4275 (2007/10/03)
The betulinic acid derivative IC9564 inhibits human immunodeficiency virus (HIV)-1 entry. Among a series of IC9564 derivatives, 5 and 20 were the most promising compounds against HIV infection with EC50 values of 0.33 and 0.46 μM, respectively.
