Originator
DBI ,Geigy, US ,1959
Uses
N-Phenethylbiguanide is used in cancer treatment methods using thermotherapy and/or enhanced immunotherapy.
Definition
ChEBI: A member of the class of biguanides that is biguanide in which one of the terminal nitrogen atoms is substituted by a 2-phenylethyl group. It was used as an anti-diabetic drug but was later withdrawn from the market due to potential risk of lactic acidos
s.
Manufacturing Process
15.76 g of β-phenylethylamine hydrochloride and 8.4 g of dicyandiamide were ground and intimately mixed. The mixture was heated in an oil bath in a 3neck flask fitted with a thermometer and stirrer, and the mixture began to melt at a bath temperature of 125°C and was completely fluid at 130°C. Further heating at 145°C to 150°C initiated an exothermic reaction and the temperature of the fusion mixture (156°C) exceeded the oil bath temperature (150°C) by 6°. Heating was continued for one hour at bath temperature of 148°C to 150°C. The reaction mixture was cooled, dissolved in about 100 cc of methanol and filtered. The methanol filtrate was concentrated under reduced pressure, cooled and the product (β-phenylethylbiguanide hydrochloride) filtered off and recrystallized from 95% isopropanol.
Brand name
DBI (Ciba-Geigy);Adibetin;Antipond;Bi-uglucon ud87;D bretard;Daopar;Db comb.;Db retard;De be;Debej;Diaformin;Dibein retard;Dibenide;Dibinyl;Dibolin;Dibophen;Dibun;Diebin retard;Diguabet;Dobeom;Fenguanide;Gluciferne;Glucifrene;Glucopstin;Kataglicina;Ls 6030;Oraleo;Prontoformin;Tolbrtaphen.
Therapeutic Function
Antidiabetic
World Health Organization (WHO)
Phenformin, a biguanide with oral hypoglycaemic activity, was
introduced in 1957 for the management of diabetes mellitus. By 1970 its use had
been associated with incidences of lactic acidosis and by 1976 clinical studies had
conclusively demonstrated that the hazards of phenformin treatment outweighed
the benefits. Preparations containing phenformin were withdrawn in several
countries and their use restricted in others. Elsewhere, however, proprietary
preparations containing this drug may remain available. The related biguanide,
buformin, has been also associated with lactic acidosis and has been subjected to
similar restrictions as phenformin, whereas there is some evidence that metformin
is less liable to induce lactic acidosis.
(Reference: (WHODI) WHO Drug Information, 2, 4, 1977)
Safety Profile
Poison by intraperitoneal, subcutaneous, and intravenous routes. Moderately toxic by ingestion. When heated to decomposition it emits toxic fumes of NOx.
Enzyme inhibitor
This oral, biguanide-class antidiabetic (FWhydrochloride = 241.72 g/mol; M.P. = 175-178°C; typically supplied as the water-soluble hydrochloride salt), also known as phenethylbiguanide and phenylethylbiguanide, and named systematically as N’-b-phenethylformamidinyliminourea, was withdrawn from the U.S. market in 1977 due to high risk of inducing often fatal lactic acidosis. Target(s): cholesterol biosynthesis; 7-dehydrocholesterol reductase; diamine oxidase; glucose transport; insulysin; pyruvate kinase; and ubiquinol:cytochrome c reductase. Phenformin is an activator of AMP-stimulated protein kinase, and like ther AMPK activators also induce nucleoli re-organization, with attendanty changes in cell proliferation. Among the compounds tested, phenformin and resveratrol had the most pronounced impact on nucleolar organization. 1. McDonald & Dalidowicz Biochemistry
