112733-06-9

Basic information

• Product Name: Zenarestat
• Synonyms: Zenarestat;FR 74366;3-(2-Fluoro-4-bromobenzyl)-7-chloro-2,4(1H,3H)-dioxoquinazoline-1-acetic acid;3-[(4-Bromo-2-fluorophenyl)methyl]-7-chloro-3,4-dihydro-2,4-dioxo-1(2H)-quinazolineacetic acid;FK-366
• CAS NO: 112733-06-9
• Molecular Formula: C17H11BrClFN2O4
• Molecular Weight: 441.639
• Mol File: 112733-06-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 223-224°
• Boiling Point: 624.4°Cat760mmHg
• Flash Point: 331.4°C
• Appearance: /
• Density: 1.737
• Vapor Pressure: 1.86E-16mmHg at 25°C
• Refractive Index: 1.659
• PKA: 3.76±0.10(Predicted)
• CAS DataBase Reference: Zenarestat(CAS DataBase Reference)
• NIST Chemistry Reference: Zenarestat(112733-06-9)
• EPA Substance Registry System: Zenarestat(112733-06-9)

Safety Data

• Hazardous Substances Data: 112733-06-9(Hazardous Substances Data)

Usage

Originator

FK 366 ,Fujisawa Pharmaceutical

Uses

Treatment of diabetic neuropathy (aldose reductase inhibitor).

Manufacturing Process

To a solution of 4-bromo-2-fluorobenzylamine and triethylamine in chloroform was added dropwise a solution of 4-chloro-2-nitrobenzoyl chloride in chloroform at 0°C with stirring and the mixture was stirred at the same temperature for 1 h. The reaction mixture was washed in turn with diluted aqueous hydrochloric acid and water, and then dried. Evaporation of the solvent followed by recrystallization from diethyl ether gave N-(4-bromo-2- fluorobenzyl)-4-chloro-2-nitrobenzamide. A mixture of N-(4-bromo-2-fluorobenzyl)-4-chloro-2-nitrobenzamide and iron (1.45 g) in acetic acid (66 ml) was stirred at 100°C for 30 min. After cooling, iron was filtered off. The filtrate was evaporated to give a residue, which was made alkaline with aqueous 1 N sodium hydroxide and extracted with ethyl acetate. The extract was washed with water and dried. Removal of the solvent gave 2-amino-N-(4-bromo-2-fluorobenzyl)-4-chlorobenzamide. 2-Amino-N-(4-bromo-2-fluorobenzyl)-4-chlorobenzamide and N,N'- carbonyldiimidazole were dissolved in dioxane (50 ml). The solution was evaporated to give a residue, which was stirred at 150°C for 30 min. After cooling, the precipitates were collected by filtration and washed with ethanol to give 3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-2,4- dioxoquinazoline; melting point >280°C. To a suspension of 3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro- 2,4-dioxoquinazoline in N,N-dimethylformamide was added sodium hydride (60% in mineral oil) with stirring at 0°C and the mixture was stirred for 15 min at the same temperature. To this mixture was added ethyl bromoacetate and the mixture was stirred for 1 h at room temperature. The reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. The extract was washed with brine, dried and evaporated to give a residue. Thus obtained product was purified by recrystallization from isopropyl ether to give 2-[3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-2,4- dioxoquinazolin-1-yl]acetic acid melting point 223°-224°C.

Therapeutic Function

Aldose reductase inhibitor

InChI:InChI=1/C17H11BrClFN2O4/c18-10-2-1-9(13(20)5-10)7-22-16(25)12-4-3-11(19)6-14(12)21(17(22)26)8-15(23)24/h1-6H,7-8H2,(H,23,24)

Upstream product

• 112733-28-5 ethyl 2-[3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazoline-1-yl)acetate 
• 112733-45-6 ethyl 2-(7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazoline-1-yl)acetate 
• 76283-09-5 4-bromo-2-fluorobenzyl bromide 
• 188293-91-6 1,2,3,4-tetrahydro-7-chloro-2,4-dioxoquinazolin-1-ylacetic acid 
• 214288-97-8 4-chloro-2-ureido-benzoic acid 
• 89-77-0 2-Amino-4-chlorobenzoic acid 
• 13165-35-0 7-chloroquinazoline-2,4-dione 

Relevant articles and documents

The process development of a novel aldose reductase inhibitor, FK366. Part 1. Improvement of discovery process and new syntheses of 1-substituted quinazolinediones

This contribution describes part 1 of process development of a novel aldose reductase inhibitor FK366 (1). The original process applied on a laboratory scale was improved from the safety viewpoint to manufacture materials on 500-L scale suitable for toxic

Process for the preparation of 3-dihalobenzyl-2,4-quinazolinedione derivatives

A process for preparing a 3-dihalobenzyl-2,4-quinazolinedione derivative represented by the formula (V): (wherein X1, X2, X3are independently a halogen atom, and A is an alkylene group), which comprises: reacting a dihalob

Quinazoline derivatives, compositions thereof and their use in treating diabetic complications

The invention relates to compounds of the formula: STR1 in which R1 and R2 are each hydrogen, halogen, lower alkoxy or halo(lower)alkyl, R3 is dihalophenyl, naphthyl(lower)alkyl, phenyl(lower)alkyl substituted by one or two substituent(s) selected from the group consisting of halogen, lower alkoxy, halo(lower)alkyl and lower alkyl, or thienyl(lower)alkyl, R4 is carboxy or protected carboxy, Y is carbonyl, thiocarbonyl or sulfonyl and Z is lower alkylene, and pharmaceutically acceptable salts thereof, useful in the treatment of diabetic complications.