Rhoda Weber Joseph

Discovery and SAR of a series of 4,6-diamino-1,3,5-triazin-2-ol as novel non-nucleoside reverse transcriptase inhibitors of HIV-1.

The discovery and SAR study of a series of 4,6-diamino-1,3,5-triazin-2-ol compounds as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are reported. The lead compounds in this series showed excellent activity against wild-type and drug-resistant RT enzymes and viral strains. In addition, compounds from this series demonstrated favorable pharmacokinetic profile in rat. A preliminary modeling study was conducted to understand the binding mode of this series of compounds.

Structure-based design of substituted biphenyl ethylene ethers as ligands binding in the hydrophobic pocket of gp41 and blocking the helical bundle formation.

A series of substituted biphenyl ethylene ether compounds has been designed to target the gp41N-trimer in order to inhibit formation of the six-helical bundle that represents the end state of gp41-mediated viral fusion. A size exclusion HPLC based helical bundle formation (HBF) assay was developed to evaluate in vitro inhibitory affinity of the inhibitors. The most potent compound 1 had an IC(50) of 31microM. The binding of compound 1 to the proposed hydrophobic pocket of gp41 was further validated by site-directed peptide mutagenesis experiments.

Benzaldehyde-derived chloroformates and their application towards the synthesis of methoxyfenozide-N-[(acyloxy)benzyloxy]carbonyl derivatives

Abstract The synthesis of a series of substituted benzaldehyde-derived chloroformates and their application towards the synthesis of a diverse series of novel insecticidally active carboxylic acid [ N ′- tert -butyl- N ′-(3,5-dimethylbenzoyl)- N -(3-methoxy-2-methylbenzoyl)hydrazinocarbonyloxy]phenylmethyl esters, prepared in a parallel synthesis fashion, is reported.