114-86-3 Usage
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 It was used as an anti-diabetic drug but was later withdrawn from the market due to potential risk of lactic acidos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 Preparations containing phenformin were withdrawn in several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
Check Digit Verification of cas no
The CAS Registry Mumber 114-86-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,1 and 4 respectively; the second part has 2 digits, 8 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 114-86:
(5*1)+(4*1)+(3*4)+(2*8)+(1*6)=43
43 % 10 = 3
So 114-86-3 is a valid CAS Registry Number.
InChI:InChI=1/C10H15N5/c11-9(12)15-10(13)14-7-6-8-4-2-1-3-5-8/h1-5H,6-7H2,(H6,11,12,13,14,15)
114-86-3Relevant articles and documents
Preparation method and crystal structure of 5-fluorouracil phenformin salt
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Paragraph 0026, (2020/01/08)
The invention provides a salt of 5-fluorouracil and phenformin as well as a preparation method and crystal structure of the salt, and relates to the field of medicinal chemistry. A molecular formula of the 5-fluorouracil phenformin salt is C14H18FN7O2, and a basic structure unit is composed of a phenformin cation and a 5-fluorouracil anion; the salt belongs to a monoclinic system, and the space group is P2/n; and the preparation method comprises the steps of using the 5-fluorouracil bulk drug and a phenformin free base as raw materials, mixing the 5-fluorouracil bulk drug and the phenforminfree base according to a molar ratio of 1:1, dissolving the mixture into a mixed solvent of methanol and acetonitrile for a reaction, performing recrystallization by using ethanol as a solvent to obtain the high-purity 5-fluorouracil phenformin salt. According to the 5-fluorouracil phenformin salt provided by the invention, the solubility of the 5-fluorouracil is improved, and the synergistic antitumor activity of the 5-fluorouracil and the phenformin is facilitated; and no crystalline solvent molecules exist in the salt structure, and the skeleton structure of the salt crystal can be maintained under long-term storage at room temperature.
A novel metformin derivative, HL010183, inhibits proliferation and invasion of triple-negative breast cancer cells
Koh, Minsoo,Lee, Jong-Cheol,Min, Changhee,Moon, Aree
, p. 2305 - 2313 (2013/05/09)
Mounting evidence suggests that metformin (N,N-dimethylbiguanide), a widely prescribed drug for the treatment of type II diabetes, exerts an anti-tumor effect on several cancers including breast cancer. Breast cancer has been estimated as one of the most commonly diagnosed types of cancer among women. In particular, triple-negative breast cancers are associated with poor prognosis and metastatic growth. In the present study, we synthesized a novel metformin derivative 5 (HL010183) and metformin salts, 9a, 9b, and 9c (metformin gamma-aminobutyric acid (GABA) salt, metformin pregabalin salt and metformin gabapentin salt), which exerted more potent inhibitory effects on the proliferation and invasiveness of Hs578T triple-negative breast carcinoma cells than metformin. Importantly, 5 showed approximately 100-fold more potent effects compared to metformin. In a triple-negative breast cancer xenograft model, 5 showed a comparable degree of inhibitory effect on in vivo tumor growth at the 100 mg/kg dose to that of metformin at 500 mg/kg. Our results clearly demonstrate that 5 exerts a potent anti-tumor effect both in vitro and in vivo, paving the way for a strategy for treatment of triple-negative breast cancer.
