SU1095594A1 - N-[4-(3,3-dimethyltriazeno)-pnenylsulfonyl]-benzamide displaying diuretic activity - Google Patents

Description

This invention relates to a novel chemical compound, in particular, an N-4- (3,3-dimethyltriazeno) fest; benzamide sulfonech exhibiting I diuretic activity. () (O) -S0 which exhibits diuretic activity and is a structural analogue of the proposed compound. HCl / NaNOi. / -X, W,. ) S07NHCOCH3 This property suggests the possibility of its use in medical practice as a diuretic. Known 4-piperidinoazo-N, N-diacetylbenzosulfamid formula 2N (COCH3h (i) However, the structural analogue is not stable (6 months) and it is obtained by -3-stage synthesis according to the following scheme: ... SGSOSnz / -h 1y, N {COCH3) 2

 1095594

The aim of the invention is to find; What is more simple, which new triazen derivatives are obtained:

benzenesulfonamides, which exhibit high diuretic activity, low toxicity and increased stability (CH3) 2 N-N - § S02NHC (

The method for the preparation of the proposed compound, based on the acylation of the corresponding benzenesulfamide with carboxylic acid halide (I), is that 4- (3,3-dimethyltriazeno) benzenesulfamide is dissolved in acetone, and added to the resulting

HCl / NQNO

M.11.

-S02NH2

() -SO, NH The yield of the desired product is 56.4%. Elemental analysis data, GO 1P-spectrum, and so pl. presented in the example. The method for preparing the compound of formula (II) is illustrated by the following example. Primer p. 4.56 g (0.02 gmol) of 4- (3,3-dimethyltriazeno) benzene sulphamide is dissolved in 250 ml of acetone, 27.6 g (0.2 gmol) is added. mixing and. 5.2 ml (0.04 g-mol) of benzoyl chloride is added dropwise at room temperature. The reaction mixture was boiled for 6 hours with constant stirring. The product and excess potash are filtered, washed with acetone and placed in 300 ml of water and 0.2 kg of ice. The resulting suspension is neutralized with conc. HCl to pH The product is filtered, washed with hot water and the crystallized wet from ethanol. 3.7 g (56.4%) of (3, 3-dimethyltriazeno) phenylsulfonyl benzamide are obtained with a melting point of 174 - 176 ° C. Molecular Weight 332.38 PMR spectrum (ppm, 5): N (CH3) 3.21; 3.54; SbN 7.51; 8, J2; NH 10.8 CgHg. 7.2; 8.0 (D - acetone). Found,%: C 54.37; H 5.20; N 16.75; S 9.55. , BY450 Calculated,%: C 54.20; H 4.85; N 16.86; S 9.66.

technology.

The goal is achieved by the proposed compound of the formula

(Ii)

benzoyl chloride is added while transferring at room temperature and the reaction mixture is boiled for 6 h. and select the desired product.

j. ,

The starting 4- (3,3-dimethyltriazeno) benzenesulfamide is obtained according to the following scheme: Diuretic activity was studied in chronic experiments in rats, in which diuresis, water intake, excretion of sodium, potassium, uric acid, and creatinine. The latter serves as a measure of j glomerular filtration. The compound is administered once and for a long time (7 days). With long-term administration, the indicated indices are determined before the beginning of administration, then, at 1, 3, 5, and 7 days of administration and 2 and 5 hours after the water load. All obtained values are processed statistically according to conventional formulas. The maximum effects of the compound in single and long-term administration of 50 mg / kg orally are presented in Table 1. Tabl 1 51 The if sign indicates the absence of statistically significant changes. From Table 1 it can be seen that with a single administration of the compound (25, 50, 75 mg / kg orally) a dose-dependent effect is obtained; increased diuresis, natriuresis and to a lesser extent potassium cleavage. With prolonged administration (7 days at 50 mg / kg orally), diurnal diuresis and natriuresis gradually increase and remain reliably more 2-5 days after the end of the infusions. Kaliuresis with prolonged administration does not change significantly. Creatinine levels in all series of experiments remain stable. Water diuresis does not change when a dose of 30 mg / K is taken orally. Urinary acid excretion is not significantly altered. When comparing the activities of the proposed compound, dichlothiazide (3) and the closest structural analogue of formula (I) (10 mg / kg) for the main indicators, the following results are obtained (in percent K; initial values, taken over 100), given in Table . 2. Table. Daily diuresis with a single dose of 160-200 190 n. 4 Continuation of the table.2 i I: IEI: E ::: Daily diuresis with long-term. administration of 190 180 250 sodium intake with prolonged administration 480 600 850 Potassium excretion during prolonged administration 100 100 175 Acute toxicity (LD) when ingested into mice turned out to be b. 1500 mg / kg, for dichlothiazide and for the closest structural analogue. 1500 mg / kg. As can be seen from Table 2, the activity of the proposed compound is at the level of the structural analogue, and in the case of daily diuresis with long-term administration, the proposed compound prevails over the analogue in structure. The advantage of the proposed compound is also high. stability (more than 2 years), and in the structural analogue it is 6 months, as well as the simplicity of the synthesis due to the two-stage implementation against the three-stage method of obtaining the structural analogue. Thus, the proposed compound, due to its properties, may be of interest for medicine as diuretic agents.

Claims (1)

Ν- [4- (3,3-dimethyltriazeno) phenylsulfonylZbenzamide of the formula (CH ₃ ) ₂ ·-Ν = Ν - @ - 3Ο ₂ ΝΗΟθ | - @> exhibiting diuretic activity.