SU722911A1 - 4-nicotinoylamido-2,2,6,6-tetramethyl-pyperidine-1-oxyl as inhibitor of enzymic lactate oxidation - Google Patents

Description

The mixture is neutralized by the gradual addition of dry soda to a pH of 7.5-8.0. The precipitate is separated by filtration and washed with ice water and used for further work without further purification,. .

B, 4-Nicotinoyl-amido-2,2, b, b-tetramethylpiperidine-1-oxyl,

17.1 g (0.1 mol) of 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl and 6.0 g of sodium hydroxide are dissolved in 400 ml of water and this solution is gradually stirred during 1 Nicotinic azide prepared from 17.3 g (0.125 mol) of nicotinic hydrazide is added. During the reaction, the pH is maintained in the range of 9.0-10.0 by the addition of small amounts of dry soda. The amide precipitates as yellow crystals. After the addition of Aside is completed, the mixture is allowed to stand. 1.5-2.0 hours, saturate the reaction mixture, potash to completely release the amide, separate the precipitate, cool with water and air dry. 21 g (76.0%) yield. After recrystallization from water, chromatographically homogeneous is obtained. product (SiPufofi 254}, chloroform alcohol system (20: 1), t, sh1,.

Found,%: C 65.08; H 7.99; N 15.35,

C, 5. ,

From $ 5.19; H 8.02;

Calculated% N 15.21.

Example 2, Compound 1 is prepared as in Example 1, using a solution of sodium carbonate instead of sodium hydroxide solution. The amide yield of 79.0% .1

The ability of a compound of the above formula to inhibit the reaction of lactate oxidation, catalyzed by the isoenzyme LDH-M pig muscle

studied in 1 m phosphate buffer at pH 7.0 at 35 s. The concentrations of the substances in the solution were: niko-4

Tinamida 8.0-10 - 2.0

ten

lakta10 ildg 1,4-

that sodium 4.0

active centers. Constant values

inhibitions amounted to 3.2 MO

for nicotinamide and 1,1

compounds of the above formula.

A 3-fold decrease in the inhibition constant with the introduction of an amino radical residue into the nicotinamide molecule makes it possible to rely on a high pharmacological effect.

In the study of the toxicity of 4-nicotinoyl-amido-2, 2,6, b7 tetramethyl 5 piperidine-1-oxyl with subcutaneous administration of a 10% solution of white non-breed rats at doses of 600 700 mg / kg, it was established that the drug does not cause pathological changes in the animal organism.

Invention Formula

254-Nicotinoyl-amido-2,2,6,6-tetramethylpiperidine-1-oxyl

II

ABOUT

s

as an inhibitor of enzymatic oxidation of lactate.

Sources of information taken into account in the examination

1. Vorontsov E, A, et al. Interaction of N-nicotinoyl amino acids, Biochem, 1974, 39, No. 2, 252,

2, Chemistry of biologically active natural compounds, under, ed., Preobrazhensky N.A. and Evstigneeva R.I.M. Chemistry; 1970, p. 232.

Claims (2)

Claim 25 4-Nicotinoylamido-2,2,6,6-tetramethylpiperidin-1-oxyl N as an inhibitor of the enzymatic oxidation of lactate. 35 Sources of information taken into account during the examination · 1. Vorontsov EA et al. Interaction of N-nicotiyoylamino acids. Biochemistry, 1974, 39, No. 2, 252. 2. Chemistry of biologically active ⁴⁰ natural compounds, edited by N. Preobrazhensky and R. Evstigneev. I.M Chemistry ') 197.0, p. 232.