The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one in mice.
(-)-Multiflorine (1), which was isolated from leguminous plants, produced a hypoglycemic effect when administered to mice with streptozotocin-induced diabetes. (-)-Multiflorine has an enaminone type conjugation on the A-ring, which is unusual in lupine alkaloids. Proceeding on the assumption that the A-B ring is responsible for the activity, several compounds bearing quinolizidin-2-one were synthesized and their hypoglycemic effects were examined. The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one was approximately 4 times stronger than that of (-)-multiflorine measured by oral glucose tolerance test in normal mice. This result indicates that compounds possessing the quinolizidin-2-one ring system as the basic structure may be possible lead compounds for a new type of diabetes drug.
Kubo
H
H
Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan. kubo@hoshi.ac.jp
Kobayashi
J
J
Higashiyama
K
K
Kamei
J
J
Fujii
Y
Y
Ohmiya
S
S
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013237:Stereoisomerism; D013311:Streptozocin; D013329:Structure-Activity Relationship; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D007004:Hypoglycemic Agents; D013311:Streptozocin; C417683:multiflorine; D000093843:Quinolizidine Alkaloids