Synthesis and evaluation of N-phenyl-(2-aminothiazol-4-yl)acetamides with phenoxypropanolamine moiety as selective β3-adrenergic receptor agonists.

Abstract

In the search for potent and selective human β3-adrenergic receptor (AR) agonists as potential drugs for use in treating obesity and non-insulin dependent (type 2) diabetes, a series of N-phenyl-(2-aminothiazol-4-yl)acetamides with phenoxypropanolamine moiety were prepared and their biological activities against human β3-, β2-, and β1-ARs were evaluated. Among these compounds, N-phenyl-(2-phenylaminothiazol-4-yl)acetamide (4 g), N-phenyl-(2-benzylaminothiazol-4-yl)acetamide (4j), and N-phenyl-[2-(3-methoxyphenyl)aminothiazol-4-yl]acetamide (6g) derivatives showed potent agonistic activity against the β3-AR with functional selectivity over the β1- and β2-ARs. In addition, these compounds exhibited significant hypoglycemic activity in a rodent model of diabetes.

• Authors: Tatsuya Maruyama, Kenichi Onda, Takayuki Suzuki, Masahiko Hayakawa, Takumi Takahashi, Tetsuo Matsui, Toshiyuki Takasu, Itsuro Nagase, Mitsuaki Ohta
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 60 Issue 5 Pg. 647-58 ( 2012) ISSN: 1347-5223 [Electronic] Japan
• PMID: 22689403 (Publication Type: Journal Article)

Chemical References

• Acetamides
• Adrenergic beta-3 Receptor Agonists
• Hypoglycemic Agents
• Phenoxypropanolamines
• Receptors, Adrenergic, beta-1
• Receptors, Adrenergic, beta-2
• Receptors, Adrenergic, beta-3

Topics

• Acetamides (chemistry)
• Administration, Oral
• Adrenergic beta-3 Receptor Agonists (chemical synthesis, chemistry, therapeutic use)
• Animals
• Diabetes Mellitus, Type 2 (drug therapy)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Humans
• Hypoglycemic Agents (chemical synthesis, chemistry, therapeutic use)
• Male
• Mice
• Obesity (drug therapy)
• Phenoxypropanolamines (chemistry)
• Receptors, Adrenergic, beta-1 (chemistry, metabolism)
• Receptors, Adrenergic, beta-2 (chemistry, metabolism)
• Receptors, Adrenergic, beta-3 (chemistry, metabolism)