Cyclic amine sulfonamides as linkers in the design and synthesis of novel human β3 adrenergic receptor agonists

The Tertiary Amine Nitrogen Atom of Piperazine Sulfonamides as a Novel Determinant of Potent and Selective β3‐Adrenoceptor Agonists

“…All the compounds belonging to this set were found to be less potent (EC 50 = 6.1-36.2 nm) than 7 a-d and almost always more potent than the aryloxypropanolamine [30] and were calculated and reported here if the percent inhibition was greater than 45 % (see the Results and Discussion section). piperidine sulfonamide analogues of Sum and colleagues, [26] even if 15 e and 15 g were found to be inactive.…”

“…The arylethanolamines 15 a-c and 15 e-g were prepared based on biological results obtained by assaying the corresponding aryloxypropanolamines, as reported by Sum et al [26] This research group also used a piperidine function as the LK in which the sulfonamide nitrogen atom is part of the ring. All the compounds belonging to this set were found to be less potent (EC 50 = 6.1-36.2 nm) than 7 a-d and almost always more potent than the aryloxypropanolamine [30] and were calculated and reported here if the percent inhibition was greater than 45 % (see the Results and Discussion section).…”

Four‐Membered Heterocycles: Structure and Reactivity

“…The presence of an aryl substituent at the 2-position seems to increase their reactivities; subsequent reactions lead, finally, to aziridines (Scheme 3.51) [105]. Instead of elimination, substitution occurs when 3-arylsulfonate-azetidines are reacted with benzylamine (Scheme 3.52) [106]. These substitutions, which occur with retention of configurations (due to the participation of the ring nitrogen) were also reported with sodium cyanide [107].…”

Subject Index to Volume 12

“…Several groups have explored aryloxypropanolamine derivatives and disclosed potent and selective agonists of human β 3 -AR [50,[71][72][73][74][75][76][77][78][79][80][81]. Several groups have explored aryloxypropanolamine derivatives and disclosed potent and selective agonists of human β 3 -AR [50,[71][72][73][74][75][76][77][78][79][80][81].…”

“…The Wyeth group has reported novel cyclic sulfonamide derivatives with aryloxymethyl groups on the LHS, 37 and 38, that are potent β 3 -AR agonists and have excellent selectivity against β 1 -and β 2 -AR [77,78]. Compound 37 was active in vivo in β 3 transgenic mice with a 30% increase in thermogenesis when dosed intraperitoneally at 10 mg/kg [77].…”