IL44304A

IL44304A - 3-benzyl-pyrido(3,4-e)-as-triazine derivatives and their preparation

Info

Publication number: IL44304A
Application number: IL44304A
Authority: IL
Original assignee: Morton Norwich Products Inc
Priority date: 1973-06-06
Filing date: 1974-02-27
Publication date: 1977-05-31
Also published as: DK302274A; AU473797B2; FR2232322B1; SE7405655L; CH591479A5; AU6884674A; ZA741277B; NL7403598A; BE816006A; JPS5019772A; DE2427382A1; IL44304A0; GB1391900A; FR2232322A1; US3883526A

Abstract

The titled compounds are effective antifungal agents adapted to be combined in pharmaceutical forms for use in the eradication of fungus infections. [US3883526A]

Description

derivatives and This invention is concerned with the compounds and These compounds are effective antifungal and lower derivatives thereof are known from Patent Specification The in these known compounds are to lower alkyl and lower carboalkoxy and thus could not have suggested the specific according to the present The compounds of the present invention are readily prepared in accordance with the following EXAMPLE I 3 Hydrochloride Ethyl Hydrochloride To a solution of 91 g of in 600 of phenol was added 62 g of ethyl carbazate at using mechanical The reaction was exothermic over ca 5 with a temperature rise to The reaction solution was heated on the v steam bath for cooled to and added to of anhydrous After standing at room temperature for ca 10 the supernatant solution was and the resultant amorphous solid was washed twice with anhydrous The solid was treated with 500 ml of heating on the steam bath with affording a light crystalline Upon cooling in an ice bath for ca 10 the initial product was washed well With isopropanol and in a vacuum dessicator 55 g The product was recrystallized from 700 ml of 40 for O Hydrochlorldo Ά solution of 87 g mole of in 520 of concentrated HC1 was heated to dryness over 23 hr on a steam The yellow residue was slurried in 200 ml of refluxed for 20 and filtered The red crystalline solid was washed with 100 ml of 200 ml of and 39 g The crude product was recrystalized from 1050 ml of washed with five portions of 250 ml of and 24 g for Hydrochloride A 22 g portion of was slurried in 170 ml of treated with g of and subjected to hydrogenation at 50 hydrogen uptake was 30 lb in 4 The reduction mixture was cooled for 2 hr and The product plus catalyst was washed with three portions of and 17 g This procedure was repeated more to give a combined total of 34 g of the product plus The crude 34 was recrystallized from of methanol washed with 170 ml of 300 ml of ether and 23 g for y pyr o Hydrochloride A mixture of g of and 60 g of acetic acid was heated in a bath for 2 It was then cooled and shaken with a mixture of ml of chloroform and 400 ml of water layer was washed with 300 ml portions of chloroform and evaporated to dryness under The resulting red oil was dissolved in 400 ml of absolute A precipitate formed which was filtered and washed with ethanol and then 30 This was recrystallized from anhydrous methanol to yield for 13 12 4 EXAMPLE II To a solution of 20 g of the compound of Example I in 400 ml of water and 100 ml of ethanol was added a solution of g of in 50 ml of Manganese dioxide was added and the reaction was stirred for The reaction was filtered and the residue was washed with chloroform until the washings were colorless The chloroform layer was washed with filtered through anhydrous and to 16 g for 13 10 4 The compounds of this invention are potent antifungal are capable in small concentration of inhibiting the growth of pathogenic fungi such as Candida albicans and Mlcrosoorum canis Such capabilities are represented in the table herebelow which reflects results secured in the commonly used in antifungal test employing dextrose agar as the medium supportive of fungal growth and measuring the amount of inhibition of such growth in millimeters over a period of eight insufficientOCRQuality

Claims

Diameter of Zone of Inhibition in mm at Days *Conc in C. albicans M. canis Compound mc /ml 2 4 6 8 4 6 0 Example I 2000 33 32 52 Example II 1860 33 33 10 * The diluent carrier for the compound in this test is 50% ethanol which exhibits no antifungal activity. A noteworthy characteristic of the compounds of this invention is their lack of irritation to the skin. When applied daily in the form of a suspension at concentrations up to 4% in a vehicle of aqueous methyl cellulose* no skin irritation was observed over a period of three days. For convenience in administration the compounds of this invention can be compounded in various pharmaceutical forms such as ungents, solutions, suspensions, powders and sprays using readily available and commonly used excipients with which there is no incompatibility. What Is claimed is;

1. Λ compound selected from the group consisting of l,2-dihydro-3-benzylpyrido [3,4-e]-as-triazine hydrochloride and 3-benzylpyrido[3,4-e]-as-triazine.

2. The compound l,2-dihydro-3-benzylpyrido- [3,4-e]-as-triazine hydrochloride .

3. The compound 3-benzylpyrido(3,4-e]-as-triazine.

4. The method of preparing l,2-dihydro-3-benzylpyrido(3,4-e]-as-triazine hydrochloride which consists in reacting 3-amino-4-hydrazinopyridine hydrochloride and phenylacetic acid.

5. The method of preparing 3-benzylpyrido[3,4-e]-as-triazine which consists in oxidizing l,2-dihydro-3-ben.-!ylpyrido[3,4-e]-as-triazine hydrochloride with manganese dioxide.