Koteswar Rao Yeleswarapu

Conformationally restricted 3,4-diarylfuranones (2,3a,4,5-tetrahydronaphthofuranones) as selective cyclooxygenase-2 inhibitors.

A number of naphthofuranones were synthesized and tested for COX-1 and COX-2 inhibition. Few of them were identified as selective COX-2 inhibitors. Structure-activity relationship studies within the series are discussed.

A high speed parallel synthesis of 1,2-diaryl-1-ethanones via a clean-chemistry C–C bond formation reaction

Abstract In this report, we describe the parallel as well as conventional synthesis of 1,2-diaryl-1-ethanones via environmentally benign acylation of arenes with in situ generated arylacetyl trifluoroacetates. A wide variety of arylacetic acids I participated in trifluoroacetic anhydride/ phosphoric acid mediated C–C bond formation reaction when reacted with arenes of type II to give 1,2-diaryl-1-ethanones III in good to excellent yield. Under the solvent-free conditions these chemical transformations that normally require longer reaction time can be performed within minutes in good yield.

Regioselective aluminium chloride induced heteroarylation of pyrrolo[1,2-b]pyridazines: its scope and application☆

Abstract We describe a detailed study on the novel synthesis of 6,7-disubstituted pyrrolo[1,2-b]pyridazines through AlCl3 induced C–C bond formation reactions. A wide variety of 6-aryl substituted azolopyridazines was reacted with 3,6-dichloropyridazine to give 7-pyridazinyl substituted pyrrolopyridazines regioselectively in good to excellent yield. The mechanism and regiochemistry of the reaction along with applications of the methodology are discussed.

A simple and rapid entry to 5-alkyl (aryl)-5-hydroxy-3,4-diarylfuranones and 3a-hydroxy-1-aryl-2,3a,4,5-tetrahydronaphthofuranones via a tandem esterification and oxidative cyclization process ☆

A synthesis of 5-hydroxy-3,4-diarylfuranones and related derivatives is accomplished by the reaction of arylacetic acid with α-bromoketone in the presence of base and atmospheric oxygen. A variety of compounds were synthesized in good to excellent yield and many are of potential biological interest.

Synthesis and Cyclooxygenase-2 (COX-2) Inhibiting Properties of 1,5 - Diarylpyrazoles Possessing N-Substitution on the Sulfonamide (-SO2NH2) Moiety †

A number of novel 1,5-diarylpyrazoles possessing N-substitution on the sulfonamide (-SO2NH2) moiety were synthesized and tested for COX-1/COX-2 inhibition in vitro. Many of these 1,1-dioxo-2,3- dihydrobenzo(d)isothiazolyl substituted 1,5-diarylpyrazoles, where the SO2NH2 group was a part of the fused ring, showed COX inhibitory activity. Few of them were identified as selective COX-2 inhibitors. Structure Activity Relationship study within the series are discussed.

2-Hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide (DRF-4367): an orally active COX-2 inhibitor identified through pharmacophoric modulation

Analogs of 1,5-diarylpyrazoles with a novel pharmacophore at N1 were designed, synthesized and evaluated for the in-vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The variations at/around position-4 of the C-5 phenyl ring in conjunction with a CF3 and CHF2 groups at C-3 exhibited a high degree of potency and selectivity index (SI) for COX-2 inhibition. The in-vivo evaluation of these potent compounds with a few earlier ones indicated the 4-OMe-phenyl analog and the 4-NHMe-phenyl analog with a CF3, and the 4-OEt-phenyl analog with a CHF2 group at C-3 to possess superior potency than celecoxib. In addition to its impressive anti-inflammatory, antipyretic, analgesic and anti-arthritic properties, compound (DRF-4367) was found to possess an excellent pharmacokinetic profile, gastrointestinal (GI) safety in the long-term arthritis study and COX-2 potency in human whole blood assay. Thus, compound was selected as an orally active anti-inflammatory candidate for pre-clinical evaluation.