Discovery of a Novel, Potent and Selective Human β₃‐Adrenergic Receptor Agonist.

Abstract

Urea derivatives Q 0640Discovery of a Novel, Potent and Selective Human β 3 -Adrenergic Receptor Agonist. -A variety of analogues of compound (I) are prepared and tested for their β3-adrenergic receptor activity and selectivity. Compound (I) is the most potent and selective β3-adrenergic receptor agonist in this series. -(NAKAJIMA*, Y.; HAMASHIMA, H.; WASHIZUKA, K.-I.; TOMISHIMA, Y.; OHTAKE, H.; IMAMURA, E.; MIURA, T.; KAYAKIRI, H.; KATO, M.; Bioorg. Med. Chem. Lett. 15 (2005) 2, 251-254; Med. Chem. Res. Lab., Fujisawa Pharm. Co., Ltd., Yodogawa, Osaka 532, Japan; Eng.) -R. Staver 19-099

Dehydrogenases/Reductases for the Synthesis of Chiral Pharmaceutical Intermediates

“…Therefore, to make these chiral drugs, asymmetric synthesis of 1, 2, 3 is highly valuable. Chiral halohydrins play an important role in the synthesis of a wide range of biologically compounds [53][54][55]. For example, (S)-3-chloro-1-phenylpropanol (4) can be used as a key chiral intermediate required for the synthesis of 1, 2, 3.…”

β3-Adrenoceptor Agonists and (Antagonists as) Inverse Agonists

“…LHS is typically an arylethanolamine or aryloxypropanolamine (Perrone et al, 2006(Perrone et al, , 2008b, LK has various structures including both aromatic and aliphatic moieties (Perrone et al, 2009), RHS typically contains polar and/or ionizable functionalities including ureas, acylamides, sulfonamides and sulfonic, phosphonic, and carboxylic groups (Dow et al, 2004;Nakajima et al, 2005). LHS is typically an arylethanolamine or aryloxypropanolamine (Perrone et al, 2006(Perrone et al, , 2008b, LK has various structures including both aromatic and aliphatic moieties (Perrone et al, 2009), RHS typically contains polar and/or ionizable functionalities including ureas, acylamides, sulfonamides and sulfonic, phosphonic, and carboxylic groups (Dow et al, 2004;Nakajima et al, 2005).…”

Subject Index to Volume 12

“…In addition, this compound had significantly superior pharmacokinetics and its oral bioavailability was found to be 27% in both dogs and rats. Despite its high selective profile for monkey β 3 -AR (EC 50 tachycardia. Among them, 4-(trifluoromethyl)phenyl thiazole analogue 9 (L-796,568) was a potent and selective agonist (EC 50 = 3.6 nM, IA = 94% for β 3 -AR; >1300 and >600fold selectivity against β 1 -and β 2 -ARs, respectively) [26].…”

“…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].…”