Synthesis and evaluation of novel phenylethanolamine derivatives containing acetanilides as potent and selective beta3-adrenergic receptor agonists.

Abstract

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential pharmacotherapies for the treatment of obesity and non-insulin dependent (type II) diabetes, we prepared a novel series of phenylethanolamine derivatives containing acetanilides and evaluated their biological activities at the human beta3-, beta2-, and beta1-ARs. Among these compounds, the 6-amino-2-pyridylacetanilide (36b), 2-amino-5-methylthiazol-4-ylacetanilide (36g), and 5-amino-1,2,4-thiadiazol-3-ylacetanilide (36h) derivatives showed potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In addition, these compounds exhibited significant hypoglycemic activity in a rodent diabetic model.

• Authors: Tatsuya Maruyama, Kenichi Onda, Masahiko Hayakawa, Takayuki Suzuki, Tetsuya Kimizuka, Tetsuo Matsui, Toshiyuki Takasu, Itsuro Nagase, Noritaka Hamada, Mitsuaki Ohta
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 58 Issue 4 Pg. 533-45 (Apr 2010) ISSN: 1347-5223 [Electronic] Japan
• PMID: 20410638 (Publication Type: Journal Article)

Chemical References

• Adrenergic Agonists
• Adrenergic beta-3 Receptor Agonists
• Blood Glucose
• Hypoglycemic Agents
• Phenethylamines
• Receptors, Adrenergic, beta-1
• Receptors, Adrenergic, beta-2
• Receptors, Adrenergic, beta-3

Topics

• Adrenergic Agonists (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Adrenergic beta-3 Receptor Agonists
• Animals
• Blood Glucose (drug effects)
• Humans
• Hypoglycemic Agents (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Male
• Mice
• Models, Molecular
• Molecular Conformation
• Phenethylamines (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Receptors, Adrenergic, beta-1 (metabolism)
• Receptors, Adrenergic, beta-2 (metabolism)
• Receptors, Adrenergic, beta-3 (metabolism)