Carbohydrate biguanides as potential hypoglycemic agents.
A series of monosaccharides containing a biguanide functionality was prepared and evaluated for hypoglycemic activity. Among the analogues prepared were those involving D-glucose substituted on the 6- or 1-position (19 and 24), D-galactose substituted on the 6-position (7), and D-arabinose (31). The target compounds were evaluated in a modified rat glucose-tolerance test (oral glucose load/oral drug, 100 mg/kg). Compounds 8 [6-biguanidino-1,2:3,5-bis-O-(1-methylethylidene)-6-deoxy-al pha-D- glucofuranose] and 23 [methyl 6-biguanidino-6-deoxy-2,3,4-O-tribenzyl-alpha-D-glucopyra nos ide] were the most active, exhibiting nearly equivalent hypoglycemic activity to that of phenformin (1) and metformin (2), as measured by the inhibition of the rise of blood glucose. Compound 31 was somewhat less active with 26% inhibition, as compared to 64% inhibition with 1 and 41% inhibition with 2.
Department of Chemical Research, McNeil Pharmaceutical, Spring House, Pennsylvania 19477-0776.
A B
AB
Reitz
R W
RW
Tuman
C S
CS
Marchione
A D
AD
Jordan
C R
CR
Bowden
B E
BE
Maryanoff
D000284:Administration, Oral; D000818:Animals; D001645:Biguanides / Q000008:administration & dosage / Q000138:chemical synthesis*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000138:chemical synthesis*; D008297:Male; D013058:Mass Spectrometry; D008687:Metformin / Q000008:administration & dosage; D009005:Monosaccharides / Q000008:administration & dosage / Q000138:chemical synthesis*; D010629:Phenformin / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001645:Biguanides; D007004:Hypoglycemic Agents; D009005:Monosaccharides; D008687:Metformin; D010629:Phenformin