Discovery of an orally bioavailable alkyl oxadiazole beta3 adrenergic receptor agonist

D D Feng; T Biftu; M R Candelore; M A Cascieri; 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(00)00267-5

Discovery of an orally bioavailable alkyl oxadiazole beta3 adrenergic receptor agonist

Bioorg Med Chem Lett. 2000 Jul 3;10(13):1427-9. doi: 10.1016/s0960-894x(00)00267-5.

Authors

D D Feng¹, T Biftu, M R Candelore, M A Cascieri, 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. [email protected]

PMID: 10888324
DOI: 10.1016/s0960-894x(00)00267-5

Abstract

5-n-Pentyl oxadiazole substituted benzenesulfonamide 8 is a potent and selective beta3 adrenergic receptor agonist (beta3 EC50 = 23 nM, beta1 IC50 = 3000 nM, beta2 IC50 = 3000 nM). The compound has high oral bioavailability in dogs (62%) and rats (36%) and is among the most orally bioavailable beta3 adrenergic receptor agonists reported to date.

MeSH terms

Administration, Oral
Adrenergic beta-3 Receptor Agonists*
Adrenergic beta-Agonists / administration & dosage
Adrenergic beta-Agonists / chemistry
Adrenergic beta-Agonists / pharmacokinetics*
Adrenergic beta-Agonists / pharmacology*
Animals
Biological Availability
CHO Cells
Cricetinae
Dogs
Drug Design
Humans
Molecular Structure
Oxadiazoles / administration & dosage
Oxadiazoles / chemistry
Oxadiazoles / pharmacokinetics*
Oxadiazoles / pharmacology*
Rats
Structure-Activity Relationship

Substances

Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Oxadiazoles