Author/Authors :
Jeffrey A. Campbell، نويسنده , , Viola Bordunov، نويسنده , , Chris A. Broka، نويسنده , , Michelle F. Browner، نويسنده , , James M. Kress، نويسنده , , Tara Mirzadegan، نويسنده , , Chakk Ramesha، نويسنده , , Bong F. Sanpablo، نويسنده , , Russell Stabler، نويسنده , , Patricia Takahara، نويسنده , , Armando Villasenor، نويسنده , , Keith A.M. Walker، نويسنده , , Jin-Hai Wang، نويسنده , , Mary Welch، نويسنده , , Paul Weller، نويسنده ,
Abstract :
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.
Keywords :
COX-2 , X-ray structure.* Corresponding author at present address: PTC Therapeutics , 100Corporate Court , South Plainfield , Selective COX-2 inhibitor , NJ 07080 , USA. Tel.: +1-908-2227000x122 , fax: +1-908-2227231 , e-mail: jcampbell@ptcbio.com , Indole
