114-86-3

Basic information

• Product Name: Phenformin
• Synonyms: (phenylethyl)biguanide;1-phenethyl-biguanid;azucaps;beta-PEBG;beta-Phenethybiguanide;beta-Phenethylbiguanide;Biguanide, 1-phenethyl-;cronoformin
• CAS NO: 114-86-3
• Molecular Formula: C₁₀H₁₅N₅
• Molecular Weight: 205.26
• EINECS: 204-057-4
• Mol File: 114-86-3.mol

Chemical Properties

• Melting Point: 176.5 °C
• Boiling Point: 333.94°C (rough estimate)
• Flash Point: 204 °C
• Appearance: white powder
• Density: 1.0541 (rough estimate)
• Vapor Pressure: 4.71E-07mmHg at 25°C
• Refractive Index: 1.6380 (estimate)
• PKA: pKa 3.1/12.9±0.01(H2O,t =25,I>0.1) (Uncertain)
• CAS DataBase Reference: Phenformin(CAS DataBase Reference)
• NIST Chemistry Reference: Phenformin(114-86-3)
• EPA Substance Registry System: Phenformin(114-86-3)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: DU2200000
• Hazardous Substances Data: 114-86-3(Hazardous Substances Data)

Usage

Uses

Phenformin has been found to have applications in various fields, particularly in the medical and pharmaceutical industries. Here are some of its uses:
1. Used in Cancer Treatment:
Phenformin is used as a therapeutic agent in cancer treatment methods that involve thermotherapy and/or enhanced immunotherapy. It has been shown to have potential anti-cancer properties, making it a valuable compound in the fight against cancer.
2. Used in Anti-diabetic Treatment (Historic):
Although Phenformin was withdrawn from the market due to safety concerns, it was initially used as an anti-diabetic drug. It helped in managing blood sugar levels in patients with diabetes by increasing the sensitivity of muscle cells to insulin and decreasing glucose production in the liver.
3. Used in Research and Development:
Phenformin's unique chemical structure and properties make it an interesting compound for researchers in the field of pharmaceuticals and medicinal chemistry. It can be used as a starting point for the development of new drugs with improved safety profiles and targeted applications.

Originator

DBI ,Geigy, US ,1959

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.

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

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)

Upstream product

• 156-28-5 2-phenylethylamine hydrochloride 
• 127099-85-8 N-Cyanoguanidine 
• 834-28-6 phenformin hydrochloride 

Downstream Products

• 79246-47-2 4-amino-6-phenethylamino-1H-[1,3,5]triazin-2-one 
• 2158-04-5 (2-phenylethyl)urea 
• 538-69-2 (2-phenylethyl)guanidine 
• 1429191-49-0 phenformin acetic acid salt 
• 104912-21-2 amino-phenethylamino-[1,3,5]triazine-2-carboxylic acid amide 
• 104621-88-7 amino-phenethylamino-[1,3,5]triazine-2-carboxylic acid 
• 109446-01-7 N-phenethyl-N'-sulfanilyl-guanidine 
• 30253-52-2 6-methyl-N-phenethyl-[1,3,5]triazine-2,4-diamine 

Related news

Metformin and Phenformin (cas 114-86-3) block the peripheral antinociception induced by diclofenac and indomethacin on the formalin test08/27/2019

AimsRecent evidence has shown that systemic administration of sulfonylureas and biguanides block the diclofenac-induced antinociception, but not the effect produced by indomethacin. However, there are no reports about the peripheral interaction between analgesics and the biguanides metformin and...detailed

Relevant articles and documents

Preparation method and crystal structure of 5-fluorouracil phenformin salt

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.

PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING IMMUNE DISEASES OR INFLAMMATORY DISEASES, CONTAINING BIGUANIDE DERIVATIVE COMPOUND AS ACTIVE INGREDIENT

The present invention relates to a biguanide derivative compound capable of effectively preventing and treating immune diseases. The biguanide-based derivative compound according to the present invention inhibits the generation of IL-17 and TNF-α, which are inflammatory cytokines, increases the activity of regulatory T cells having an immunomodulatory function, and exhibits excellent therapeutic effects in animal models of immune diseases. Accordingly, the biguanide-based derivative compound can be usefully used as an immunosuppressant or a pharmaceutical composition capable of preventing or treating various immune diseases, such as autoimmune diseases, inflammatory diseases, and transplant rejection, caused by the dysregulation of immune responses.

A novel metformin derivative, HL010183, inhibits proliferation and invasion of triple-negative breast cancer cells

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.

CURABLE COMPOSITION

The present invention has its object to provide a curable composition which comprises a guanidine compound as a non-organotin type catalyst, is less discolored, has good surface curability, depth curability, strength rise and adhesiveness, and can retain the curability even after storage; the above object can be achieved by a curable composition which comprises: (A) an organic polymer containing a silyl group capable of crosslinking under siloxane bond formation, the silyl group being a group represented by the general formula (1): -SiX 3 (1) (wherein X represents a hydroxyl group or a hydrolyzable group and the three X groups may be mutually the same or different), (B) a guanidine compound (B-1) as a silanol condensation catalyst, and (C) a plasticizer, wherein the content of the component (B-1) is not lower than 0.1 part by weight but lower than 8 parts by weight per 100 parts by weight of the component (A), and a non-phthalate ester plasticizer accounts for 80 to 100% by weight of the (C) component plasticizer.