Document Detail


Synthesis and evaluation of novel phenylethanolamine derivatives containing acetanilides as potent and selective beta3-adrenergic receptor agonists.
MedLine Citation:
PMID:  20410638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemical & pharmaceutical bulletin     Volume:  58     ISSN:  1347-5223     ISO Abbreviation:  Chem. Pharm. Bull.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-07-27     Revised Date:  2011-03-08    
Medline Journal Info:
Nlm Unique ID:  0377775     Medline TA:  Chem Pharm Bull (Tokyo)     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  533-45     Citation Subset:  IM    
Affiliation:
Drug Discovery Research, Astellas Pharma Inc, Tsukuba, Ibaraki, Japan. tatsuya.maruyama@jp.astellas.com
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/Adrenergic Agonists; 0/Adrenergic beta-3 Receptor Agonists; 0/Blood Glucose; 0/Hypoglycemic Agents; 0/Phenethylamines; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; 0/Receptors, Adrenergic, beta-3

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