L-770,644: A potent and selective human β3 adrenergic receptor agonist with improved oral bioavailability

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 9; pp. 1251 - 1254
• Main Authors: Shih, Thomas L., Candelore, Mari R., Cascieri, Margaret A., Chiu, Shuet-Hing L., Colwell, Lawrence F., Deng, Liping, Feeney, William P., Forrest, Michael J., Hom, Gary J., MacIntyre, D.Euan, Miller, Randall R., Stearns, Ralph A., Strader, Catherine D., Tota, Laurie, Wyvratt, Matthew J., Fisher, Michael H., Weber, Ann E.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 03.05.1999; Elsevier
• Subjects: Biological and medical sciences; General and cellular metabolism. Vitamins; Medical sciences; Pharmacology. Drug treatments; Agonist; Tetrazole derivatives; Nitrogen heterocycle; Monkey; β-Adrenergic receptor agonist; Pyridine derivatives; β-Adrenergic receptor; Primates; Aromatic compound; Chemical synthesis; Dog; Fissipedia; Obesity; Carnivora; Aminoalcohol; Sulfonamide; Oral administration; Bioavailability; In vitro; Biological activity; In vivo; Vertebrata; Mammalia; Animal; Benzenic compound; Pharmacokinetics; Cyclopentane derivatives
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00182-1

L-770,644 ( 9c) is a potent and selective agonist of the human β 3 adrenergic receptor (EC 50 = 13 nM). It shows good oral bioavailability in both dogs and rats (%F = 27), and is a full agonist for glycerolemia in the rhesus monkey (ED 50 = 0.21 mg/kg). Based on its desirable in vitro and in vivo properties, L-770,644 was chosen for further preclinical evaluation. L-770,644 ( 9c) is a potent and selective agonist of the human β 3 adrenergic receptor (EC 50 = 13 nM), which has 27% oral bioavailability in both dogs and rats.