Anti-Ischemic Activity of the Novel Benzazepine Calcium Antagonist SQ 31,486

A Dual Lewis Base Activation Strategy for Enantioselective Carbene-Catalyzed Annulations

“…25 Benzoazepinones with the same N,N -dimethylethyl side chain are related to the FDA-approved drug diltiazem, 26 a potent calcium channel blocker (Cardizem) and SQ 31,486, a candidate to reduce myocardial ischemia for cardioprotective treatments. 27 …”

“…24,25 Benzazepinones with the same N,N-dimethylaminoethyl side chain are related to the FDA-approved drug diltiazem, 26 a potent calcium channel blocker (Cardizem), and SQ 31,486, a candidate to reduce myocardial ischemia for cardioprotective treatments. 27 This report highlights the new integration of two distinct Lewis base activation modes to achieve an enantioselective organocatalytic formal [4 + 3] heterocycloaddition. This challenging "dual activation" concept was successfully realized through concomitant in situ generation of two reactive, transient species: a nucleophilic NHC−homonenolate and a highly electrophilic o-quinone methide.…”

“…In addition, the related benzoxepanes are known central nervous system depressants . The overall replacement of the O atom in 3a with a nitrogen substituent to give 8 was easily accomplished in four steps, providing access to benzazepinones that are structurally related to benzodiazepine drugs (e.g., Xanax, Valium). , Benzazepinones with the same N , N -dimethylaminoethyl side chain are related to the FDA-approved drug diltiazem, a potent calcium channel blocker (Cardizem), and SQ 31,486, a candidate to reduce myocardial ischemia for cardioprotective treatments …”