Substituted oxazole benzenesulfonamides as potent human β3 adrenergic receptor agonists

H. O OK; L. B REIGLE; C. D STRADER; L TOTA; P WANG; M. J WYVRATT; M. H FISHER; A. E WEBER; M. R CANDELORE; M. A CASCIERI; L. F COLWELL; L DENG; W. P FEENEY; M. J FORREST; G. J HOM; D. E MACINTYRE

doi:10.1016/S0960-894X(00)00277-8

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Substituted oxazole benzenesulfonamides as potent human β3 adrenergic receptor agonists

Journal article

Peer reviewed

Substituted oxazole benzenesulfonamides as potent human β3 adrenergic receptor agonists

H. O OK, L. B REIGLE, C. D STRADER, L TOTA, P WANG, M. J WYVRATT, M. H FISHER, A. E WEBER, M. R CANDELORE, M. A CASCIERI, …

Bioorganic & medicinal chemistry letters, Vol.10(14), pp.1531-1534

07/17/2000

DOI: https://doi.org/10.1016/S0960-894X(00)00277-8

PMID: 10915043

Abstract

Biological and medical sciences

Catecholaminergic system

Medical sciences

Neurotransmitters. Neurotransmission. Receptors

Pharmacology. Drug treatments

Neuropharmacology

As a part of our investigation into the development of orally bioavailable β3 adrenergic receptor agonists, we have identified a series of substituted oxazole derivatives that are potent β3 agonists with excellent selectivity against other β receptors. Several of these compounds showed excellent oral bioavailability in dogs. One example, cyclopentylethyloxazole 5f is a potent β3 agonist (EC50=14 nM, 84% activation) with 340-fold and 160-fold selectivity over β1 and β2 receptors, respectively, and has 38% oral bioavailability in dogs.

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Title: Substituted oxazole benzenesulfonamides as potent human β3 adrenergic receptor agonists
Creators: H. O OK - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
L. B REIGLE - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
C. D STRADER - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
L TOTA - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
P WANG - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
M. J WYVRATT - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
M. H FISHER - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
A. E WEBER - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
M. R CANDELORE - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
M. A CASCIERI - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
L. F COLWELL - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
L DENG - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
W. P FEENEY - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
M. J FORREST - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
G. J HOM - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
D. E MACINTYRE - Departments of Medicinal Chemistry, Biochemistry and Physiology, Pharmacology, and comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, United States
Publication Details: Bioorganic & medicinal chemistry letters, Vol.10(14), pp.1531-1534
Publisher: Elsevier; Oxford
Identifiers: 9923972926901921
Academic Unit: Department of Chemistry
Language: English
Resource Type: Journal article

Substituted oxazole benzenesulfonamides as potent human β3 adrenergic receptor agonists

Abstract

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