Jigar Desai

Design, synthesis and biological evaluation of γ-lactam hydroxamate based TACE inhibitors

A new series of γ-lactam hydroxamate based TACE inhibitors was designed mainly by introducing various substitutions at the 2nd position of the quinoline nucleus to achieve high potency and good selectivity towards TACE over matrix metalloproteases (MMPs) and ADAM-10. In ex vivo TNF-α inhibitory activity assays, compounds 11o and 11p were identified as the most potent compounds. The in vitro TACE inhibitory activity, selectivity over MMPs and ADAM-10 and the in vivo TNF-α inhibitory activities of compounds 11o and 11p were assessed and lead compound 11p was identified. Preliminary toxicity and pharmacokinetic (PK) studies were conducted for compound 11p and it showed an improved PK and clean toxicological profile compared to standard compound 1. Altogether, these results demonstrated the discovery of highly potent and selective γ-lactam hydroxamate based TACE inhibitors which show potential for the safe and effective treatment of inflammatory diseases.

Novel and Efficient Route for the Synthesis of 4-Aryl-Substituted 2(5H)-Furanones

Abstract 4-Aryl-substituted 2(5H)-furanones were prepared by reaction of diethylphosphono acetic acid and phenacyl bromides, followed by an intramolecular Horner–Emmons-type cyclization. Both the reactions were carried out in situ to give the desired 4-aryl substituted 2(5H)-furanone derivatives.

One-Pot Synthesis of 3,4-Diaryl-Substituted 2(5H)-Furanone and Its Commercial Application

Abstract One-pot synthesis of 3,4-diaryl substituted 2(5H)-furanones was established and its commercial application has been demonstrated by accomplishing total synthesis of rofecoxib, under mild reaction conditions, with good yields and purity. GRAPHICAL ABSTRACT

Novel and Efficient Synthesis of tert-Butyl-2-(4-(2-aminoethyl)phenylthio)-2-methylpropanoate, a Key Intermediate in the Synthesis of Ureido Thioisobutyric Acid

Abstract A convenient and cost-effective synthesis of pharmacologically important tert-butyl-2-(4-2-aminoethyl)phenylthio)-2-methylpropanoate from commercially available 2-2-phenyl-1-ethanol is described.

Synthesis and Characterization of Homologue of Irganox 1076—Some Novel Observations

Abstract A convenient and high yielding preparation of Irganox 1076 homologue from 2,6-di-tert-butyl phenol is reported. 2,6-Di-tert-butyl phenol on Friedel–Crafts succinoylation in the presence of aluminium chloride leads to migration and elimination of tert-butyl group without tert-butyl acceptor along with O- and C-succinoylated products.