DE1955386C3 - 2- (5'-Nitro-2'-furfurylidene) indanones and processes for their preparation, and pharmaceuticals containing these compounds - Google Patents

Description

H ₂ C

in which R has the meaning given in claim 1 or a corresponding acid addition salt converts the same and then, optionally, the compound obtained in a pharmacological Compatible acid addition salt transferred.

4. Medicament, characterized by a content of a compound according to claim 1 in addition to customary, inert carriers or diluents.

The invention relates to 2- (5'-nitro-2'-furfurylidene) indanones of the general formula

O ₂ N-CjL-CH

35

40

45 prepared by reacting in a manner known per se 5-nitrofurfurol or a functional derivative thereof with a compound of the general formula

in which R denotes an N-alkyl or Ν, Ν-dialkylaminoethoxy group with 1 to 5 carbon atoms in the alkyl part or a pyrrolidino, piperidino or morpholinoethoxy group and their pharmacologically acceptable acid addition salts, a process for their preparation and drugs containing these compounds.
The compounds of the above formula are

55

60 H ₃ C

in which R has the meaning given above or a corresponding acid addition salt thereof converts and then optionally the compound obtained into a pharmacologically acceptable Acid addition salt transferred.

The process is carried out at room temperature or at an elevated temperature in an acidic medium, preferably in Glacial acetic acid carried out in the presence of concentrated sulfuric acid or in orthophosphoric acid. When Functional derivative of 5-nitrofurfural, the diacetate is preferably used.

The compounds according to the invention, in particular their acid addition salts, are crystalline compounds. The free bases can be removed from the reaction mixtures by pouring them into ice water and optionally Isolate neutralize with a base. By treating with acids, the corresponding acid addition salts are obtained. The acid addition salts are made from the reaction mixtures isolated by evaporation under reduced pressure Acid addition salts recrystallized from alcohols or alcohol / water mixtures

Physiologically compatible acids are suitable for salt formation, for example hydrochloric acid, sulfuric acid, Phosphoric acid, acetic acid, propionic acid, succinic acid, citric acid, benzoic acid, salicylic acid.

The compounds of the invention have a broad antimicrobial effect, such as. B. against gram positive and gram-negative germs and protozoa such as Trichomonas vaginalis. To prove their effectiveness they were in comparison tests against known compounds from the South African patent 68 05 902 checked. The minimum inhibitory concentrations (MIC) were determined using the known serial dilution technique determined in liquid media, which is described in detail in the following book: "Analytical Microbiology, F. Kavanagh, Edit, Academic Press, New York & London 1963". From the The table below shows that the compounds according to the invention

2- (5'-nitro-2'-furfurylidene) -5- (2-dimethylaminoethoxy) -1 indanone hydrochloride and 2- (5'-nitro-2'-furfurylidene) -5- (2-pyrrolidinoethoxy) -1 indanone sulfate

are superior to the prior art with regard to their antimicrobial effect.

In addition to a significantly better activity against Trichomonas vaginalis, those according to the invention are notable Compounds mainly due to their effectiveness against problem germs such as Proteus mirabilis or Pseudomonas aeruginosa. those caused by the comparison substances either not at all or only moderately be inhibited. The compounds according to the invention are suitable because of their properties, and in some cases also against others Germs (S. aureus, E. coli, P. vulgaris and Kl. Pneumoniae)

superior effect especially as medicinal substances for the treatment of such trichomonas infections, which are accompanied by bacterial infections from the urinary ducts.

MIC (r / ml)

connection Staphylo Escheri Proleus Klebsieila pseudo Proteus Tricho- coccus chia coli vulgaris pneumo- monas mirabilis monas aureus niae aerugi- vagi- nosa nalis

2 - {. 5'-nitro-2'-furfurylidene) -5- (2-di-0.1

methylaminoethoxy) -l-indanone,
Hydrochloride (example 1)

2- (5'-nitro-2'-furfurylidene) -5- (2-pyrro-0.1
lidinoethoxy) -l-indanone, sulfate
(Example 3) "

Comparison substances accordingly
ZA-PS 68 05902

2- (5-nitro-2-furfuryldene) -5-methoxy-0.2
1-indanon

2- (5-nitro-2-furfurylidene) -4-methyl-0.1
l-indanon

2- (5-nitro-2-furfurylidene) -5-hydroxy-0.01
1-indanon

0.02 0.4

0.2 3.1

1.6
1.6

3.1 6.2 0.00075

6.2 12.5

0.049

0.2 - - - - 0.05 0.1 3.1 0.8 > 12.5 - 0.8 0.1 0.8 0.8 6.2 - 0.2

The compounds according to the invention can be used in the pharmaceutically customary application forms, such as pills, Dragoes, capsules, tablets, juices, solutions, etc., can be administered.

example 1

2- (5'-nitro-2'-furfurylidene} 5- (2-dimethylaminoethoxy) -1 indanone hydrochloride

300 mg (31% of theory) 2- (5'-nitro-2'-furfurylidene) -5- (2-diethylaminoethoxy) -1-indanone sulfate obtained from the m.p. 248 ° C.

Weight analysis in 0 / OfUrC ₂₀ H ₂₂ N ₂ O ₅ · H ₂ SO ₄
(MG 468.5):

Calculated: N 5.98, S 6.84;

found: N 5.87, S 6.73.

35

1.5 g of 5-) 2-dimethylaminoethoxy) -l-indanone hydrochloride and 1.92 g of 5-nitro-furfural diacetate are stirred in 20 ml of orthophosphoric acid at 50 ° C. for 20 hours. The mixture is then poured into ice water, neutralized with NaOH, extracted with ethyl acetate and the glacial acetic ester solution washed with water, then _{dried with Na 2} SO ₄ and evaporated. The 2- (5'-nitro-2'-furfurylidene) -5- (2-dimethylaminoethoxy) -1-indanone obtained as a residue is taken up in methanol, mixed with alcoholic HCl and evaporated. The residue is recrystallized from methanol. 1.1 g (50% of theory) of 2- (5'-nitro-2'-furfurylidene) -5- (2-dimethylaminoethoxy) -1-indanone hydrochloride with a melting point of 238 ° are obtained C (decomposition).
Weight analysis in% for Ci ₈ Hi _{9 ClN 2} O ₅
(MG 378.8):

Calculated: Cl 936, N 7.39; found: Cl 9.41, N 7.42.

Example 2

2- (5'-nitro-2'-furfurylidene) -5- (2-diethylaiminoethoxy) -1 -indanone sulfate

600 mg 5- (2-diethylaminoethoxy) -l-indanom-hydrochicrid and 300 mg 5-nitrofuro! will be in 10 m! Acetic acid in the presence of 0.112 ml of concentrated H ₂ SO _{4 was} stirred at 100 ° C. for 6 hours. The mixture is then evaporated in vacuo and the residue is recrystallized from ethanol / water (3: 1). There are B is ρ i e.1 3

2- (5'-nitro-2'-furfurylidene) -5- (2-pyrrolidinoethoxy) -1 -indanone sulfate

The preparation takes place analogously to Example 2 from 245 mg of 5- (2-pyrrolidinoethoxy) -1-indanone and 141 mg of 5-nitrofuran. The residues obtained after evaporation are recrystallized from methanol 200 mg (43% theory) 2- (5'-nitro-2'-fuifurylidene) -5- (2-pyrrolidinoethoxy) -1-indanone sulfate obtained from the mp 234 ° C.

Weight analysis in% for C ₂ OH ₂ ON ₂ Os · H ₂ SO ₄
(MG 466.5):

Calculated: N 6.01, S 6.87;

found: N 5.79, S 6.76.

Example 4

2- (5'-nitro-2'-furfurylidene) -5- (2-piperidinoethoxy) -1 -indanone sulfate

Production takes place analogously to Example 2 from 450 mg of 5- (2-piperidinoethoxy) -1-indanone hydrochloride and 250 mg of 5-nitrofurfurol. After recrystallization of the residue from ethanol, 200 mg (27% of theory) of 2- (5'-nitro-2'-furfurylidene) -5- (2-piperidinoethoxy) -! - indanon-su! Fats from F. 165 ° C.
Weight analysis in% WrC ₂ IH ₂₂ N ₂ O ₅ · H ₂ SO ₄
(MG 480.5):

Calculated: N 5.83, S 6.67;

found: N 5.63, S 6.30

Example 5

2- (5'-Nit! O-2'-furfurylidene) -5- (2-morpholinoethoxy) -1-indanone sulfate

The preparation takes place according to Example 2 from 600 mg of 5- (2-morpholinoethoxy) -1-indanone hydrochloride and 280 mg of 5-nitrofurfurol. Recrystallization of the residue from methanol / water (1 : \) gives 400 mg (41% of theory) of 2- (5'-nitro-2'-furfurylidene) -5- (2-morpholinoethoxy) -l-indanone sulfate from F. 262 C (decomposition).

Weight analysis in% for C ₂₀ H ₂₀ N ₂ O ₆ · H ₂ SO ₄
(MG 482.4):

15th

Calculated: N 5.81, S 6.64;
found: N 5.58, S 6.43.

Example! 6th

2- (5'-nitro-2'-furfurylidene) -5- (2-n-butylaminoethoxy) -1 -indanonsulf at

0.7 g of 5- (2-n-butylamino-ethoxy-l-indanone hydrochloride and 0.35 g of 5-Nitrofurfurol are stirred for 6 hours at 100 ⁰ C in 10 ml of acetic acid in the presence of 0.13 ml kenzentrierter H2SO4. The mixture is then completely concentrated, the oil obtained is treated several times with ether and freed from all volatile substances in vacuo, giving 550 mg of 2- (5'-nitro-2'-furfurylidene) -5- (2-n-butylamino) ethoxy) -1-indanone sulfate.

Weight analysis in ° / o for C20H24N2O9S
(MC- 468.5):

Calculated: N 5.98, S 6.85;

found: N 5.73, S 6.54.

Claims (3)

Patent claims: 1. 2- (5'-Nitro-2'-furfurylidene) indanones of the general formula in which R is an N-alkyl or N.N-dialkylaminoethoxy group with 1 to 5 carbon atoms in the alkyl part • or a pyrrolidino, piperidino or morpholinoethoxy group means and their pharmacologically acceptable acid addition salts. 2. 2- (5'-Nitro-2'-furfurylidene) -5- (2-dimethylaminoethoxy) -1 indanone hydrochloride. 3. A process for the preparation of the compounds specified in claim 1, characterized in that that one in a conventional manner 5-nitrofurfurol or a functional derivative the same with a compound of the general formula