Hypoglycemic activity of a series of alpha-alkylthio and alpha-alkoxy carboxylic acids related to ciglitazone.
The thiazolidinedione moiety of ciglitazone and its analogues can be replaced by an alpha-alkoxy or alpha-thioether carboxylic acid group. The influence of the nature of the R group, the length of the connector to the aromatic backbone of the molecule, and the stereochemistry have been studied. The most potent compounds have glucose-lowering activity at doses as low as 0.01 mg/kg.
Hulin
B
B
Central Research, Pfizer Inc., Groton, Connecticut 06340, USA.
Newton
L S
LS
Lewis
D M
DM
Genereux
P E
PE
Gibbs
E M
EM
Clark
D A
DA
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D051379:Mice; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*; D045162:Thiazolidinediones
D001572:Benzofurans; D002264:Carboxylic Acids; D007004:Hypoglycemic Agents; D010080:Oxazoles; D013844:Thiazoles; D045162:Thiazolidinediones; C101722:2-ethoxy-3-(2-((5-methyl-2-phenyloxazol-4-yl)methyl)benzofuran-5-yl)propionic acid; C101721:3-(2-((5-methyl-2-phenyloxazol-4-yl)methyl)benzofuran-5-yl)-2-(propylsulfanyl)propionic acid; C039671:ciglitazone