SU1047148A1 - Benzylidene-derivatives of imidazo-/4,5-g/-indolysines possessing bacteriostatic and fungistatic activity - Google Patents

Abstract

Benzylidene derivatives of iiidazo 5 5-g indolysins of the general formula C (g H E. 2 (O

Description

SN-SOUK (SNN) 2 J

- w) 2, RZ and; (SI.),, R, - CgHs; to.

 SNZ, Kg ™

pbladayuschie bzkteriostatich s. and

/;

K (SNS) 2

fungistatic activity.

The invention oi mosits i-. -ciEbiM chemical compounds of a number of them / ha:; ochdolizika, and the name of the bezil: -;: Yenir (: with an imidazo derivative; 3-g. iein; :: ; activt: .k;, and can be used: 1: 5 in chemistry; -;) -, pharmaceutical technology,

In the patent of the 1st jTHTenaTyDe ornCiiii. Dodecyl -methimidazo f 4, 5-with ttiridinium bromide. exhibiting anti-mikoibgp and fungistatic chkgnvnost. However, he possesses in; K: s11: oh choxychpos; PH5 (13 mg / kg)

which receive; imidazo 4 "; formulas

1C;; where R. and R., - H,

 , R .- 1;

R, -N / R., - Cl ,,

 R, -H, R2 - Q H.-.

with aromatic al, 1; egi; 1amrt formula

../

 t :: H (}

 y

Hi j

310

, 4.00 s, 5 (2) -OCHJ, 4.24 (s, 5-CH ,,); 6.18 (s, 7-CH-); 6,757, 80 (m, aromatic protons).

Found,%: C 58.3; H 4.2; N 8.2; 3 23.4.

b L1 Calculated, 1-. C 58.1; H 4.5;

N 7.9; 3, 6.

Para: e p 2. 7 (pK, K -DiketylaminobenzylideO-8,9-diphenyl-2,3-dimethylimidazo 4, 5-glindoyl inium iodide (16).

Prepared analogously to Example 1, starting from 0.091 g (3. mol) of 8,9-diphenyl-2 .3-dimethylimidazo 4,5-gJ indolysin and 0.1 g (7 - Yu mol) of no-benzaldehyde p-dimethylamides. V'kod 0.088 g (55.3%), so pl. 300 ° C (with decomposition of ii-buganol).

PMR spectrum (o, md,):

3.20 (s, 2-CH,), 3.46 C, ČSHN,) „; 4.23 (s, 6.16 (s, 7-CH-), 7.00-8510 (m, aromatic nporibi)

Found,%: C 64.3; H 5.1; N9.4; 20.9.

Calculated,%: C 64.4, H 4.9, N 9.4, and 21.3.

At a measure of 3. 3. 7- (nN, N-Dimethyl-umylbenzylidene) -8-fsil-2,3,9-trimethylim1-dazo 4, 5-g indolysine UHD1 (1 h).

Prepared analogously to example 1, starting from 0. 1 g (3.6-10 mol) 8 - phenyl-2, 3, 9-trimethylimidazo 4,5-g indolysin and 0.1 g (7 10 mol) p-dimethylaminobenz; dehydrate, yield 0.16 g (82.5%), so pl. (with decomposition, n-bug; 1ol).

Spectrum IMP (S, MD, CF, COOH):

2.15 (s,); 2.75 (s, 2-CH,); 2.87 s, K (CH.). J, 3.74 (s, H-CH); 6.8 1-7,1 6;, aromatic protons), 7.69 d. 4 (5) -and; J 6 TiiJ, 8.36 d, 5 (4) -N, J 6 Hz.,

Found,%: C 60.6, - H 5.4; N 10.7; 3 23.5.

Calculated; eno, C 60, /; H 5.1; N 10.5; -J 23.7., 50

Example 4. 7- (nN, N-Dimethylaminobenzylidene) -8-phenyl-2,3-dimethylimidazo 4, 5-g 1i1 and cholisinium iodine (1 g).

 similar to the example of 1.55

starting from 0.1 g (3.8 Yu mol) 8-fenst-2 5 W-dimethlimidazo 4. 5-g; c; olysine and 0.12 g (810 mol) p-dimethylAV4

am1 nobei; aldehyde. Yield 0.19 g (95;). mt ::. 319-320 ° C (n-butanol).

Spectrum (5, ppm, CF, COOH): 3.20 (s, 2-CHJ, 3.44 with% FSP),, D, 25 (s, 3-CH.); 6.16 (s, 7-CH-); 7.10-8.05 (m, aromatic protons)

Found,%: C 57.7; H 5.4, N 10.0; L 23.2.

,,, n 1

Bbr-iHcneVo,%: C 58.0; H 5.1; K 10,4; J 23.6.

Example 5. 9- (nN, N -Dimethylaminobenzylidene) -8-phenyl-2,3,7-trimeth. Imididazo 4,5-g HHAonH3HHHftiodide (1d).

Prepared analogously to example 1, starting from 0.1 g (3.6 mol) of 8-phenyl-2, 3,7-trimethyl imide 30 of 4.5-glindolysin and 0.1 g (7 1 O mol) of p-dimethyl: obensaldehyde . Yield 1.5 g (77.3%), so pl. 300 ° C (with a decomposition,:. Ri-butanol).

PMR spectrum (S, MD, CFjCOOH): 2.16 (s, 7-CHJ; 2.75 (s, 2-CH5) -, 2.84 s, FSP), 3.77 (s, W-CH), 6.80-7.00 (m, aromatic protons) 7.99 Gd, 4 (5) -H; J 6 Hz, 8.52 d, 5 (4) -N, J BGD.

Found,%: C 60.5; H 5.3; N 10.2, 3 23.4.

c.fi .-. i

Calculated,%: C 60.7j H 5.1; N 10.5; a 23.7.

1 zakteriostaticheskuyu activity of compounds was studied by the method of two-fold dilutions in a liquid medium. Hottinger's broth (pH 7.2-7.4) was used to cultivate the bacteria. Microbial load for bacteria 5 x X 10 cells agar 18-h. culture 3 1 ml of medium. The maximum concentration tested was 200 µg / ml.

D. mushroom cultivation used Saburo medium (pH 6.0-6.8). The load of 500 thousand reproductive bodies in 1. The maximum concentration tested is 200 μg / ml. The antimicrobial activity of the compounds was evaluated by: iginal bacteriostatic or nicoetic concentration,

The test results are shown in table.

The LDjo of compounds 1a-1d is 7710-419, 6510 ± 377,, 3500 + ± 148, 1040 ± 76 mg / kg, respectively.

Thus, the benzylidene derivatives of imidazo 4,5-g indolizinov have a high bacteriostatic

and mycostatic activity and are low toxic substances. leading to high therapeutics of microorganisms and fungi

Staphylococcus aureus 209P Bacillus antracoides 1312

Esherichia coli 675 B. pyocyaneum

Shigella flexneri

Trichophyton mentag. Ш1-124768

Microsporum lanosum 257

CI1.) Indices in relationships of a whole range of gram-negative and gram-negative bacteria, as well as fungi.

Minimal bacteriostatic or mycostatic concentration, µg / ml

L, about unity

T

sixteen

1c

Over 200

200 200

Same 6.25 6.25

s e e 200

6, .25

100 Over 25,200

25

Also

Claims (1)

The test results are shown in the table. The LD _{50 of} compounds 1a-1d is 7710-419, 65108377, 1120 * 59, 3500+ ± 148, 1040 + 76 mg / kg, respectively. Thus, the benzylidene derivatives of imidazo [4,5-ё] indolizines have high bacteriostatic ft and mycostatic activity and are low toxic substances, which leads to high therapeutic indices for a number of gram-positive and gram-negative bacteria, as well as fungi. Strains of microorganisms and fungi Minimum bacteriostatic or mycostatic concentration, μg / ml Connections