507271-44-5Relevant academic research and scientific papers
Rational design of 6-methylsulfonylindoles as selective cyclooxygenase-2 inhibitors
Campbell, Jeffrey A.,Bordunov, Viola,Broka, Chris A.,Browner, Michelle F.,Kress, James M.,Mirzadegan, Tara,Ramesha, Chakk,Sanpablo, Bong F.,Stabler, Russell,Takahara, Patricia,Villasenor, Armando,Walker, Keith A.M.,Wang, Jin-Hai,Welch, Mary,Weller, Paul
, p. 4741 - 4745 (2007/10/03)
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. 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.
A new synthesis of 3-arylthioindoles as selective COX-2 inhibitors using PIFA
Campbell, Jeffrey A.,Broka, Chris A.,Gong, Leyi,Walker, Keith A. M.,Wang, Jin-Hai
, p. 4073 - 4075 (2007/10/03)
The direct 3-arylthiolation of 2-substituted indoles using phenyliodine(III)bis trifluoroacetate (PIFA) in (CF3)2CHOH with a wide variety of benzenethiols has been accomplished. In particular, indoles bearing a 6-MeSO2 and either a 2-methyl or 2-carboxymethyl substituent could be 3-arylthiolated in good to excellent yields to afford the corresponding 3-arylthioindoles as selective COX-2 inhibitors. In a study varying the electronic nature of the 5-substituent of 2-CO2Et indoles, it was discovered that the yield of the reaction improved as the substituent became more electron withdrawing. This result was consistent with a proposed mechanism involving benzenethiol displacement of an intermediate 3-IPh indole complex.
Indole derivatives as anti-inflammatory agents
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, (2008/06/13)
This invention relates to compounds, which are generally anti-inflammatory and analgesic compounds, and which are represented by Formula I: wherein A is a —CH2—, —O—, —S—, or —S(O)—; and the other substituents are as defined in the specification; or individual isomers, mixtures of isomers, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents
