MEDICINAL CHEMISTRY

NH
H 2N C NH (CH 2) n
NH
HN C NH 2
Synthalin A (202) ; decamethylene; n=10
Synthalin B (203) ; dodecamethylene; n=12
Biguanides also reduce the GIT absorption of amino acids and other ingredients of
dietary energy value. They also lower the plasma levels of triglycerides and cholesterol.
In the treatment of maturity onset diabetes, biguanides thus offer two fold advantage.
They induce weight loss and reduce obesity along with their hypoglycemic action.
In patients with cardiac (myocardial infarction) or renal disease, phenformin treatment
was found to increase blood lactic acid level. This lactic acidosis sometimes induces
severe fatalities in patients. Lactic acidosis is characterized by dehydration, acidosis and a
bicarbonate deficiency. This complication demands contraindication of phenformin in
patients having liver, heart and kidney diseases. Along with acidosis, prolonged use of
phenformin is found to induce malabsorption of cyanocobalamin. On the creditable sides,
biguanides sometime have been used in combination with insulin preparation for
smoother control of brittle diabetes in some patients. They are also used in combination
with sulfonylureas, in cases where treatment with either agent alone, fails.
Mechanism of Action: The mechanism of action include-
• Inhibition of intestinal transport and absorption of sugars.
• Inhibition of hepatic gluconeogenesis potentiation of action of insulin on glucose
transport process into cell.
• Enhancement of glucose utilisation process.
e.g. Synthalin A; Decamethylene (H=10)
Synthalin B: Dodecamethylene (H=12)
b) First, Second and Third Generation Sulfonylureas
1 st Generation 2 nd Generation 3 rd Generation
Tolbutamide Glyburide (Glibenclamide) Glybormuride
Chlorpropamide Glipizide Glypizide
Tolazamide Glimepirides
Acetohexamide Repaglinide
The clinically used sulfonylureas are represented above. In all effective compounds, a
substituted aryl sulfonyl moiety is attached to N 1 of urea molecule. These derivatives are
structurally similar and bear essentially the similar properties. They differ in their
duration of action and chemically in the nature of the substituent at para position (-X-)
and R. The substitution of aliphatic side-chain present in the first generation
hypoglycemic sulfonylurea by cyclopentyl or cyclohexyl group and addition of yet
another ring structure to the aromatic nucleus resulted into development of more potent
second generation series.