REN-1654

A scalable procedure for the conversion of nitriles to N-tert-butyl amides via the Ritter reaction was optimized employing tert-butyl acetate and acetic acid. The reaction has a broad scope for aromatic, alkyl, and alpha,beta-unsaturated nitriles.

Nitrone-related therapeutics (NRTs) represents a new class of mols. that may be effective in treating inflammatory conditions.The goal of this study was to examine the effect of CPI-1189 in a rat model of inflammatory bowel disease (IBD).Colonic inflammation was induced by an enema of trinitrobenzene sulfonic acid (TNBS).Saline-enema treated rats served as controls.After 3 days colonic damage was assessed morphol. using a validated scoring system and through measurement of myeloperoxidase (MPO), an enzymic marker of inflammation.We found that a dose-dependent protection from TNBS-induced colonic damage was observed in rats given 10-70 mg kg^-1 of CPI-1189 treated p.o. 1 h. before the TNBS enema.Consistent with the 55% absolute oral bioavailability of CPI-1189, greater protection (77%) was seen when CPI-1189 (30 mg kg^-1) was administered i.v. 1 h. before the TNBS enema.In a sep. series of healing experiments where CPI-1189 was administer after the TNBS inflammatory response had peaked, CPI-1189 at a dose of 90 mg kg^-1 p.o. reduced the TNBS colitis.CPI-1189 prevents and heals TNBS-induced colonic damage in rats suggesting that CPI-1189 may be a novel agent for the treatment of IBD.