6-Alkyl, alkoxy, or alkylthio-substituted 3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones: a novel class of diarylheterocyclic selective cyclooxygenase-2 inhibitors

• Published in: Bioorganic & medicinal chemistry letters 2003-07, Vol.13 (13), p.2205-2209
• Main Authors: Rao, P.N.Praveen, Amini, Mohsen, Li, Huiying, Habeeb, Amgad G., Knaus, Edward E.
• Format: Article
• Language: English
• Subjects: Alkanes - chemical synthesis; Alkanes - pharmacology; Binding Sites - drug effects; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - chemical synthesis; Cyclooxygenase Inhibitors - pharmacology; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - pharmacology; Hydrogen Bonding; Indicators and Reagents; Isoenzymes - metabolism; Magnetic Resonance Spectroscopy; Medical sciences; Models, Molecular; Molecular Conformation; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Pyrones - chemical synthesis; Pyrones - pharmacology; Structure-Activity Relationship; Sulfones - chemical synthesis; Sulfones - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00391-3

A novel class of 3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones possessing a central six-membered lactone (pyran-2-one) ring system, in conjunction with C-6 alkyl (Me, Et or i-Pr), alkoxy (OMe, OEt or O- i-Pr), and alkylthio (SMe, SEt or S- i-Pr) substituents, were designed for evaluation as selective COX-2 inhibitors. Design, synthesis, and evaluation of a novel class of diarylheterocycles as selective cyclooxygenase-2 inhibitors ( 10a– c, 11a– c and 12a– c) are described.