Rational design of 6-methylsulfonylindoles as selective cyclooxygenase-2 inhibitors
| Autor: | Ramesha Chakk S, Jin-Hai Wang, Russell Stephen Stabler, Paul Weller, Bong F. Sanpablo, Armando G. Villaseñor, Campbell Jeffrey Allen, Tara Mirzadegan, Viola Bordunov, Chris Allen Broka, Patricia Takahara, James M. Kress, Michelle F. Browner, Keith A. M. Walker, Mary Welch |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Indoles Stereochemistry Clinical Biochemistry Administration Oral Pharmaceutical Science Drug design Carrageenan Biochemistry Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Humans Potency Cyclooxygenase Inhibitors Sulfones Molecular Biology Inflammation Indole test Binding Sites Cyclooxygenase 2 Inhibitors biology Organic Chemistry Rational design Membrane Proteins Rats chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Enzyme inhibitor biology.protein Molecular Medicine Cyclooxygenase |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 14:4741-4745 |
| ISSN: | 0960-894X |
| Popis: | The introduction of 3-arylmethyl, 3-aryloxy and 3-arylthio moieties into a 6-methylsulfonylindole framework using rational drug design led to potent, selective COX-2 inhibitors having efficacy in a rat carrageenan air pouch model. Incorporation of a conformationally more rigid 3-aroyloxy substituent onto the 6-methylsulfonylindole scaffold led to selective, but considerably less potent COX-2 inhibitors. Variation of the hydrophilicity and size of the indole 2-substituent of 3-arylthio-6-methylsulfonylindole inhibitors led to modulation of the COX-2 human whole blood (HWB) potency and selectivity. |
| Databáze: | OpenAIRE |
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