L-770,644: a potent and selective human beta3 adrenergic receptor agonist with improved oral bioavailability

T L Shih; M R Candelore; M A Cascieri; S H Chiu; L F Colwell Jr; L Deng; W P Feeney; M J Forrest; G J Hom; D E MacIntyre; R R Miller; R A Stearns; C D Strader; L Tota; M J Wyvratt; M H Fisher; A E Weber

doi:10.1016/s0960-894x(99)00182-1

L-770,644: a potent and selective human beta3 adrenergic receptor agonist with improved oral bioavailability

Bioorg Med Chem Lett. 1999 May 3;9(9):1251-4. doi: 10.1016/s0960-894x(99)00182-1.

Authors

T L Shih¹, M R Candelore, M A Cascieri, S H Chiu, L F Colwell Jr, L Deng, W P Feeney, M J Forrest, G J Hom, D E MacIntyre, R R Miller, R A Stearns, C D Strader, L Tota, M J Wyvratt, M H Fisher, A E Weber

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.

PMID: 10340609
DOI: 10.1016/s0960-894x(99)00182-1

Abstract

L-770,644 (9c) is a potent and selective agonist of the human beta3 adrenergic receptor (EC50 = 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 (ED50 = 0.21 mg/kg). Based on its desirable in vitro and in vivo properties, L-770,644 was chosen for further preclinical evaluation.

MeSH terms

Administration, Oral
Adrenergic beta-Agonists / administration & dosage*
Adrenergic beta-Agonists / chemical synthesis*
Adrenergic beta-Agonists / pharmacology*
Animals
Biological Availability
Dogs
Humans
Inhibitory Concentration 50
Kinetics
Rats
Sulfonamides / administration & dosage*
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology*
Tetrazoles / administration & dosage*
Tetrazoles / chemical synthesis*
Tetrazoles / pharmacology*

Substances

Adrenergic beta-Agonists
Sulfonamides
Tetrazoles
L 770644