SU1676448A3 - Method of producing sulfonamide - Google Patents

Abstract

The invention relates to sulphonamides, in particular the preparation of a compound of the O NH-S-CH U compound exhibiting anti-arrhythmic activity, which can be used in medicine. The goal is to create a new more active compound of the specified class. Synthesis is carried out by acylation of the corresponding diamine methanesulfonylchloride in the presence of a hydrogen chloride acceptor (better than pyridine). The new compound has ToPL "177-1 / 9 ° C, gross f-lu C 2rH NaOrS, active dose EDg 1 c.f f-crystals, 1 tab. 2N05-5g, 10 mol. Yo

Description

The invention relates to sulfonamides, in particular the production of compounds f-ly

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II

Η ₃ £ -δ-ΝΗ

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exhibiting antiarrhythmic activity,

what can be used in medicine. The goal is to create a new, more active compound of the specified class. The synthesis is carried out by acylation of the corresponding diamine with methanesulfonylchloride in the presence of an acceptor of hydrogen chloride (preferably pyridine). The new compound has mp 1771/9 ° C, gross-f-C _2o H lu _gu Ak 5 tive dose of ₂ U £ ⁼ 1,3 · 10 ^"7 mol. To

1 s.p. crystals, 1 tab.

The invention relates to the production of sulfonamides, in particular, to a method for producing a new Ν-μθτηπ-Ν- (5-μθtansulfone | ^ idobenzofur-2-yl-methyl) -4-methanesulfonamidophenethylamine of the formula

which exhibits antiarrhythmic activity and may find application in medicine "

The aim of the invention is to develop a method for producing a new compound in the series of sulfonamides, which exhibits higher antiarrhythmic activity and does not exert a toxic effect on a living organism.

Example 1. Obtaining Ν-methyl-Ν- (5-methanesulfonamidobenzofur-2-yl-methyl) -4-methane ulpho namidophenethylamine.

Methanesulfonyl chloride (0.76 g,

6.6 mmol) was added dropwise to the solution to 0.9 g (3.0 mmol) of Ν-methyl-Ν- (5-aminobenzofur-2-yl-methyl) -4-aminophenethylamine in 25 ml of pyridine, and the mixture was stirred 18 h at room 1676448 AZ

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temperature ”Then the solvent is evaporated, the residue diluted with an aqueous solution of sodium bicarbonate is extracted three times with methylene chloride. The combined organic extracts were dried (magnesium sulfate) and evaporated, and the residue was purified by chromatography on silica gel eluted with ethyl acetate. Fractions: d

containing the product, combine, evaporate, and the resulting solid is subjected to recrystallization from a mixture of ethyl acetate and methanol, get the specified substance "Yield 0.35 g]] 5 Top" 177-179 ° C "

Calculated,%: C 53.2; H 5.6;

N, 9.3;

Found,%: C 53.2; Η 5,7; Ν 9,0 _a ^ H NMR data (SPST ^) for soedi7,20 (5H, m) 4, b5 (2H, q), 2.95 (2H, t), 2.90 (SH, d )

20

25

nenia (I):

7.55 (2H, m)

3.30 (2H, m)

2.85 (ZN, d) 2.45 (ZN, s)

The starting material of Example 1 is prepared by restoring the corresponding dinitro compound with hydrogen in the presence of Raney nickel in ethanol, pressure 344.7 kPa, room temperature, reaction time 4 hours

To assess the biological activity of the compounds of formula (I) on the atrial immunity, the right atrium of the guinea pig is placed in a bath containing a solution of physiological salt, and one end of it is connected to a force transducer. ”Tissues are stimulated at a frequency of 1 Hz, field electrodes are used. The effective immunity peribd (PEN) is measured by introducing a premature stimulus (5 ^) after every eighth main stimulus (5 <). The joint interval 5 ^ 5 ₂ gradually increases until 5 ₂ does not extract a common response with reproducibility. This interval is defined as PENo. Then, the concentration of the substance required to increase the PEN by 25% (AU ₃₅ ) is determined. AU 25 is obtained - PEN = 1.3. 10 ^-7 mol. In addition, the PEN of the right guinea pig capillary muscle in physiological salt is measured. »A muscle is stimulated from the ONE end using bipolar electrodes, and a common electrogram is recorded from the opposite end through

35

40

45

fifty

55

unipolar surface electrode "PEN is determined similarly using the methodology of external stimuli. The travel time is determined using a storage digital oscilloscope by measuring the interval between the stimulating artifact and the peak of the electrogram, ie. the time required for the pulse to travel along the length of the muscle "

In addition, the PEN values of the atria and ventricles of dogs that are conscious or anesthetized are measured using an external stimulus technique, while the atria or right ventricle contract at a constant rate. ”

Compared to known compounds of the formula

Π ^ Ο> -Χ-Ν0Ν-Κ4 ^(1g)

the compound of formula (I) is more effective (see table), the value of ED ₂₅ for known compounds is determined in a similar way "

Claims (1)

The compounds of formula (I) can be entered as a clock, but usually they are prescribed in a mixture with a pharmacological carrier selected in accordance with the intended method of administration and standard pharmaceutical practice. They can be prescribed to patients suffering from arrhythmias, as well as prophylactically, to those patients who are likely to develop arrhythmias. For example, they can be administered orally in the form of tablets containing such medication media as starch, lactose, or in capsules, or as such, or in a mixture with the medication media, or in the form of elixirs, or suspensions containing flavoring or coloring agents. They can be administered, for example, intravenously, intramuscularly or subcutaneously. For administration, it is best to use these substances in the form of a sterile aqueous solution, which may contain others: solutes, such as enough salts or glucose, to make the solution isotonic. ” For administration to a person in the healing or prophylactic treatment of cardiac conditions such as ventricular or extraventricular arrhythmias, including atrial fibrillation 16/6448