62605-98-5Relevant articles and documents
Synthesis, Biological Evaluation, and Computational Analysis of Biaryl Side-Chain Analogs of Solithromycin
Daher, Samer S.,Lee, Miseon,Jin, Xiao,Teijaro, Christiana N.,Wheeler, Steven E.,Jacobson, Marlene A.,Buttaro, Bettina,Andrade, Rodrigo B.
supporting information, p. 3368 - 3373 (2021/09/06)
There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π-stacking and H-bonding) between from the biaryl side-chain of the drug and key residues in the 50S ribosomal subunit. We have designed and synthesized a library of solithromycin analogs to study their structure-activity relationships (SAR) in tandem with new computational studies. The biological activity of each analog was evaluated in terms of ribosomal affinity (Kd determined by fluorescence polarization), as well as minimum inhibitory concentration assays (MICs). Density functional theory (DFT) studies of a simple binding site model identify key H-bonding interactions that modulate the potency of solithromycin analogs.
Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase
Jorgensen, William L.,Bollini, Mariela,Thakur, Vinay V.,Domaoal, Robert A.,Spasov, Krasimir A.,Anderson, Karen S.
supporting information; experimental part, p. 15686 - 15696 (2011/12/03)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein-in
Substituted benzamide inhibitors of rhinovirus 3C protease
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Page column 13, (2010/01/31)
Nonpeptide benzamide-containing inhibitors of human rhinovirus (HRV) 3C protease are described.
Substituted benzamide inhibitors of human rhinovirus 3C protease: Structure-based design, synthesis, and biological evaluation
Reich, Siegfried H.,Johnson, Theodore,Wallace, Michael B.,Kephart, Susan E.,Fuhrman, Shella A.,Worland, Stephen T.,Matthews, David A.,Hendrickson, Thomas F.,Chan, Fora,Meador III, James,Ferre, Rose Ann,Brown, Edward L.,DeLisle, Dorothy M.,Patick, Amy K.,Binford, Susan L.,Ford, Clifford E.
, p. 1670 - 1683 (2007/10/03)
A series of nonpeptide benzamide-containing inhibitors of human rhinovirus (HRV) 3C protease was identified using structure-based design. The design, synthesis, and biological evaluation of these inhibitors are reported. A Michael acceptor was combined with a benzamide core mimicking the P1 recognition element of the natural 3CP substrate, α,β-Unsaturated cinnamate esters irreversibly inhibited the 3CP and displayed antiviral activity (EC50 0.60/μM, HRV-16 infected H1-HeLa cells). On the basis of cocrystal structure information, a library of substituted benzamide derivatives was prepared using parallel synthesis on solid support. A 1.9 A? cocrystal structure of a benzamide inhibitor in complex with the 3CP revealed a binding mode similar to that initially modeled wherein covalent attachment of the nucleophilic cysteine residue is observed. Unsaturated ketones displayed potent reversible inhibition but were inactive in the cellular antiviral assay and were found to react with nucleophilic thiols such as DTT.
