Structure-Activity Relationships of a Novel Capsid Targeted Inhibitor of HIV-1 Replication was written by Kortagere, Sandhya;Xu, Jimmy P.;Mankowski, Marie K.;Ptak, Roger G.;Cocklin, Simon. And the article was included in Journal of Chemical Information and Modeling in 2014.Recommanded Product: 5496-35-5 This article mentions the following:
Despite the considerable successes of highly active antiretroviral therapy (HAART) for the treatment of HIV/AIDS, cumulative drug toxicities and the development of multidrug-resistant virus necessitate the search for new classes of antiretroviral agents with novel modes of action. The HIV-1 capsid (CA) protein has been structurally and functionally characterized as a druggable target. We have recently designed a novel small mol. inhibitor I-XW-053 using the hybrid structure based method to block the interface between CA N-terminal domains (NTD-NTD interface) with micromolar affinity. In an effort to optimize and improve the efficacy of I-XW-053, we have developed the structure activity relationship of I-XW-053 compound series using ligand efficiency methods. Fifty-six analogs of I-XW-053 were designed that could be subclassified into four different core domains based on their ligand efficiency values computed as the ratio of binding efficiency (BEI) and surface efficiency (SEI) indexes. Compound 34 belonging to subcore-3 showed an 11-fold improvement over I-XW-053 in blocking HIV-1 replication in primary human peripheral blood mononuclear cells (PBMCs). Surface plasmon resonance experiments confirmed the binding of compound 34 to purified HIV-1 CA protein. Mol. docking studies on compound 34 and I-XW-053 to HIV-1 CA protein suggested that they both bind to NTD-NTD interface region but with different binding modes, which was further validated using site-directed mutagenesis studies. In the experiment, the researchers used many compounds, for example, 4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoic acid (cas: 5496-35-5Recommanded Product: 5496-35-5).
4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoic acid (cas: 5496-35-5) belongs to imidazole derivatives. 1H-imidazole is an imidazole tautomer which has the migrating hydrogen at position 1. It is a conjugate base of an imidazolium cation. It is a conjugate acid of an imidazolide. It is a tautomer of a 4H-imidazole. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.Recommanded Product: 5496-35-5
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem