CS235188B1 - 4,9-Dihydro-1- (2,3-dihydroxypropyl) -3-methyl-4-oxo-1H-pyrazolo- (3,4-b) quinoline and its method of preparation - Google Patents

Abstract

The invention relates to 4,9-dihydro-1-(2,3-dihydroxypropyl)-3-methyl-4-oxo-1H-pyrazolo(3,4- -b)quinoline of formula I and a process for its preparation. This new, previously undescribed substance exhibits antiviral activity against the A2-Hong Kong influenza virus and against the mouse encephalomyocarditis virus.

Description

The invention relates to 4,9-dihydro-1- (2,3-dihydroxypropyl) -3-methyl-4-oxo-1H-pyrazolo (3,4-quinoline of the formula I)

and a process for its preparation. This novel drug, not yet described, exhibits antiviral activity against the influenza A-Honkong virus and the encephalomyocarditis virus in mice.

The present invention relates to 4,9-dihydro 1- (2,3-dihydroxypropyl) -3-methyl-4-oxo-1H-pyrazolo (3,4-b) quinolines of formula I

and a process for its preparation.

This novel drug, not yet described, exhibits antiviral activity against the influenza A-Honkong virus and the encephalomyocarditis virus in mice.

The compound of formula (I) may be obtained by acid hydrolysis of a compound of formula (II)

where

R represents an alkyl group having 1 to 5 carbon atoms, preferably ethyl.

Said compound of the formula I according to the invention belongs to the group of substances having antiviral effects. These effects were evaluated against the A2-Honkong influenza virus and the encephalomyocarditis virus (EMC) in mice.

Evaluation of efficacy against A2-Honkong influenza virus in mice:

Female white SPF mice (Velaz) weighing 10 to 11 g were used. The virus was administered to mice under light ether anesthesia intranasally. The amount of LD 50 of the virus was determined in a separate experiment and was calculated according to REED and MUENCH [Reed L.}, Muench H .: Amer. J. Hyg. 27, 493 (1938)]. Three virus concentrations differing by order were chosen for testing. 7 mice were used for each concentration. Test substances were suspended with oleic acid monoester with tripolyethylene glycol anhydride sorbitol (Tween 80). Animals were administered per os by gavage, or were administered subcutaneously into the skin lash on the back in a volume of 0.2 ml each. Mice were treated orally or subcutaneously 2 times daily for 5 days (1 day before and 4 days after injection). The daily dose was 2X150 mg / kg. Efficacy was assessed by increasing the average survival time compared to the untreated control.

Compound I prolongs the survival of mice against 5 LD 50 virus by subcutaneous administration by 52%.

Evaluation of efficacy against EMC in mice:

Female white SPF mice (Velaz) weighing 10-11 g were used. The virus was administered subcutaneously in mice in a volume of 0.2 ml. Untreated mice died depending on virus concentration 3 to 7 days after injection. The amount of virus was determined as described for efficacy against influenza virus. Subcutaneous treatment was performed with four doses of 100 mg / kg each 28, 22, 2 hours before and 2 hours after infection. Oral treatment was performed with a single dose of 400 mg / kg 24 hours prior to infection. The efficacy evaluation was performed as in the efficacy against influenza virus.

Compound I prolongs the survival of mice after subcutaneous administration against 5 LD 50 virus by 60 percent, against 50 LD 50 by 29 percent.

As can be seen from the above data, the compound of formula I is active against the A2-Honkong influenza virus and the encephalomyocarditis virus in mice. The process for the preparation of this substance is simple and was carried out by the process according to the invention. Further details will be apparent from the following exemplary embodiment.

Example

4,9-Dihydro-1- (2,3-dihydroxypropyl) -3-methyl-4-oxo-1H-pyrazolo (3,4-b) quinoline

To a solution of 13 g of 5- (1-ethyl-2-hydroxyethylamino) -3-methyl-1 - [(2,2-dimethyl-1,3-dioxolan-4-ylmethyl) -ΙΗ-pyrazolo (3 4-b) -quinoline (37 mmol) in 65 ml of ethanol was added 65 ml of 20% hydrochloric acid, and the mixture was refluxed for 2 hours. 4.6 g (52.6%) of mp 236-239 ° C were obtained.

Claims (2)

1. 4,9-Dihydro-1- (2,3-dihydroxypropyl) -3-methyl-4-oxo-1H-pyrazolo (3,4-b) quinoline of the formula I 2. A process for the preparation of a compound according to claim 1, which comprises 4- (1-alkyl-2-hydroxyethylamino) -3-methyl-1 - [(2,2-dimethyl-1,3-dioxolane-4)]. 1-Methyl-1H-pyrazolo [3,4-b] quinoline, wherein alkyl is C1 -C5 alkyl, preferably ethyl, is hydrolyzed by boiling with aqueous ethanolic hydrochloric acid.