DE2232735B2 - 1-ethyl-3-aminoadamantane and its salts, its preparation and medicinal products containing these compounds - Google Patents

Description

The invention relates to l-EthyI-3-amino- «Damanlan and its salts, its preparation and medicinal products containing these compounds, as in the preceding claims.

In the Journal of Medicinal Chemistry. Vol. 14 (1971). Pp. 535-543, are substituted aminoadamantanes and the effects of different substitution The virostatic activity of corresponding compounds is described. l-methyl-3-aminoadamantane fiCl is said to have moderate activity while others substituted products are inactive, so that on the extremely bad effects of such substitution has been closed.

In contrast, it is surprising that I-ethyl-3-aminoadamantane and its salts have good pharmaceutical activity and are therefore suitable for medicinal products, in particular for the treatment of Parkinson's vision disease (which is presumably due to an influencing of the catecholamine metabolism) and are suitable for antivirals.

l-Ethyl-3-aminoadamanlan can be used as a free base Either as a component of a pharmaceutically acceptable salt, as the only active ingredient or together with other substances can be used orally or parenterally: for example in the form of solutions in an iso-ionic Saline solution, in the form of tablets. Coated tablets. Gelatin capsules and the like • Is a strong base, the use as SaI / is prohibited. for example in the form of the hydrohalides.

To produce the commercially available 1-bromadamanlan with ethylene according to Steller and (iocbcl (Chemical Reports. Vol. 95 [l% 2 |. S.! 039 to IO42) / u l - (.; - Bromoälhyl) -adamanlan implemented.

For this is with hydrogen in the presence of Rancy-Nieke! split off the bromine. The obtained I-Almanlan is brominated again and that at the same time resulting l-eth \ l-3-bromadamanian according to the »rit

⁷³⁵ 2 -

ler reaction «. converted to l-ethyl-3-aminoadamanlan; the latter can be isolated as salts _n free base or in the form Vo.

example

l - (/; - Bro.mäthyi) -adamantan was at normal pressure and room temperature in the presence of Raiiev nickel with hydrogen according to the method Vn _n L. H ο r η e r. L. Schläfer and H. Kämmerer (Ber. 92 [1959]. Pp. 1700 to 17041 hydrogenated dehalosening. 1-Ethyl-adamantane with a boiling point of 91 C at a pressure of 12 mm H ·. · -.Vurde in a yield of 81% of theory.

The] -AthyI-adamanlan was made with bromine according to the Procedure by H. Steller. M. Schwarz and A. Hirschhorn (Ber.92 [! 959], pp. 1629 to 1635) treated. l-ethyl-3-bromadamanlan with a boiling point of 105 ° C. at a pressure of 0.2 mm Hg was obtained in a yield of 70% of theory.

The 1-ethyl-3-bromadamanlan was prepared according to the Ritter reaction by the method of H. Steller. J. Mayer. M. Schwär / and K. W u 1 ff (Ber. 93 [1960]. Pp. 226 to 230) with acetonitrile implemented. The base formed was immediately converted into the hydrochloride and then isolated l-ethyl-3-aminoadamantane-HC! with a sublimation point over 190 C was obtained with a bulge of 70% of theory.

(1-EthyI-3-aminoadamantane) ₂ -H, SO ₄ with a boiling point of 240 ° C. and 1-Ethyi-3-aminoadamantane-HBr with a decomposition temperature above 300 ° C. were obtained in an analogous manner.

Since the anti-Parkinson's effectiveness in vivo me can be determined indirectly, the superior effectiveness of the invention l-ethyl-aminoadamantane hydrochloride on the 1-aminoadamantane hydrochloride known for this effect through studies according to the spiroperidol model, which is known to be suitable for this purpose. According to this testing technique (Int. J. Neuropharmacol., Vol. 7 [1968]. P. 39!) Were Vistar rats by i. p. Application of 0.4 mg kp put into catalepsy and after injecting different doses of l-ethyl-3-aminoadamantane sulphide the antagonism established: the results are given in Table 1 below:

Table 1

preparation DlISIS KalalcpMC 1.7
1.7
1.6 iiismu ' (mg kp) (Λ I .S \ | 0.0
0.0
2.9
0.0 ("..I I-aminoadaman-
tan hydrochloride 10
20th
40 20.1 1
18.9 4
3.8 i 33.0
37.0
87.3 l-ethyl-3-amino-
adamanlan-hydro-
chloride 10
20th
40 30.0 i
30.0 i
8.4 i
0.0 ± 0.0
0.0
72.0
100.0

As can be seen from the test results. will on application of 20 (40) mg kp l-Alhal-3-aminoadamanlanliulrochlorid the spiroperidol catalepsy / u 72.0 "(, (100'Ίι) postponed during administration the corresponding amounts of I-amino.ulamantane hydrochloride this catalepsy only occurs in 37.0% (87.3%).

The superior vuoNtaiischc effect compared to the back viroslatics was demonstrated on influenza A and herpes viruses after plaque-reading (Ar / neimiuelforschung. Vol. 23 [W'.H S. " ⁷ IS)

Table 2

respective infection after applying the \\ - rk-Moffe observed inhibitions in the following: Table 2 listed:

l'.n /.'iv I mm!

Influencing / a

l-Aminoadamanian hydrochloride none 20

no none

no none

| -Alhyl-3-aiTiinoadanianianh \ dro- 20 -U)

chloride

also 20 35

no none

Herpes

»Tromantandin« *) no 20

1-ethyl-3-aminoadanianianhvdro- 25 40

chloride

* l N '- (- ΠimcIh> l.llHlllo.ιllu'> \\) -. iα ■ I \ l-.ιIl! mo: ι ^ !. lnl.! nI.ι! lll \ drlKh! o! κi.

2iX) \ 0.02 ml

HX1_ \ u.u2m!

50 \ 0.02 ml

200 \ 0.02 ml

KX) \ 0.02 mi 50 \ 0.02 nil

2tX) y 0.02 ml 2 <X) \ 0.02 ml

The l-Ätli \ l-3-aminoadamanian hydrochloride according to the invention has compared to the used \ erleichssubsta / s a stronger virosial effect. because leads with the same applied amounts bigger inhibitions.

Claims (3)

22 claims: 1. l-ethyl-3-aminoadamanlan and its salts. especially its hydrohalides. 2. Process for the preparation of 1-Ätliyl-3-aminoadamantan unJ its salts, characterized in that in a manner known to them a) 1 - (// - Bromoethyl) adamantane with hydrogen in the presence of Raney nickel to 1-ethyladamantane is hydrogenated dchalogenated, b) 1-ethyladamantane with bromine to 1-ethyl-3-bromadamantane is brominated, c) the l-ethyl-3-bromadamantane after the Ritter reaction with acetonitrile to I-ethyl-3-aminoadamantane is implemented, which is isolated in the form of the free base or as its salt. 3. Medicines, particularly suitable for treatment Parkinson's disease and diseases caused by viruses, characterized by a content of 1-ethyl-3-aminoadamantane or its pharmaceutically acceptable salts.