Synthesis of N-(3,6-dihydro-1(2H)-pyridinyl)benzamides with hyperglycemic-hypoglycemic activity.
A group of N-(3,6-dihydro-1(2H)-pyridinyl)benzamides 7 were synthesized to determine the effect that the position and physicochemical properties of substituents attached to the heterocyclic ring have on blood glucose levels. 5-Methyl-N-(3,6-dihydro-1(2H)-pyridinyl)benzamide 7b was the most active hyperglycemic agent, elevating blood glucose 124% and 116% at 2 and 4 h, respectively, after a 100 mg/kg po dose. The most active hypoglycemic agent was the 4-acetyl analogue 7o, which was about 50% as active as chlorpropamide, lowering blood glucose 19% at 4 h after a 100 mg/kg po dose. A correlation between blood glucose levels and the partition coefficient P was not observed.
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001549:Benzamides; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D011725:Pyridines