CS268644B1 - 2-Chloro-10- (1-pyrrolidinyl) -10,11-dihydrodibenzo / b, f / thiepine and its succinic acid salt - Google Patents

Abstract

The solution falls into the field of synthetic drugs. Its subject is 2-chloro- -10-(1-pyrrolidine1)-10,11-dihydrodibenzo/b,f/thiepine and its salts with succinic acid. With low acute toxicity, the named substance in the form of amber is effective in tests on mice and rats, which indicate the possibility of antidepressant action in patients, i.e. in particular in tests of antireserpine activity and in the test of potentiation of yohimbine toxicity. The named substance is prepared, for example, by reacting 2,10-dichloro-10,11- -dihydrodibenzo/b,f/thiepine with excess pyrrolidine in boiling chloroform. An oily base is obtained, which is converted into the corresponding salt by neutralization with succinic acid.

Description

The invention relates to 2-chloro-io- (1-pyrrolidinyl) -10,11-dihydrodibenzo [b, f] thiepine of the formula I

(I) and its salts with succinic acid.

The compound of formula I in the form of amber exhibits properties typical of antidepressants, i.e. drugs for dual depression. In the following tests, it was administered orally and the doses given are based on recalculations. It is not very toxic; its acute toxicity in mice, LD is 1,295 mg / kg. The substance is markedly effective in antireserpine tests: at doses of 25 and 50 mg / kg it antagonizes statistically significantly the hypothermic effect in mice. at a dose of 30 mg / kg inhibits statistically significantly the ulcerogenic effect of reserpine in rats. At a dose of 100 mg / kg, it shows an antireserpline effect in a mouse reserpine ptosis test. It further potentiates the toxicity of yohimbine in mice. The mean effective dose of Ε0 ₅ θ is 66.3 mg / kg. At the same time, it is incoordinatively ineffective in the rotating rod test in mice up to a dose of 250 mg / kg and is practically free of adrenolytic action (at a dose of 500 <sg / kg effect only in 20% of mice). exhibits affinity for desipramine binding sites in the rat hypothalamus, as evidenced by inhibition of 4 nM / ³ H / desipramine binding; IC ₅₀ = 755.9 nM. Its affinity is selective because the affinity for imipramine binding sites in the rat hypothalamus is much lower; IC-θ = 4 639 nu.

The compound of formula I according to the invention is new. It can be prepared, for example, by reacting 2,10-dichloro-10,11-dihydrodibenzo [b, f] thiepine (Pelz K. et al., Collect. Czech. Chem. Comun. 33, 1852 (1963)) with excess pyrrolidine in boiling The obtained oily base of formula I is converted by neutralization with succinic acid to acidic succinate (hydrogen succinate), which is crystalline and also forms part of the present invention.

Example

A mixture of 14.6 g of 2,10-dichloro-10,11-dihydrodibenzo [b, f] thiepine, 45 ml of chloroform and 14.6 g of pyrrolidine ae is mixed and refluxed for 5 h. The chloroform is then evaporated off under reduced pressure, the residue is dissolved in 200 ml of toluene, the solution is washed with water and then shaken with 100 ml of 2M HCl, whereby the basic product is converted into the aqueous phase as hydrochloride. The acidic aqueous layer was separated, basified with aqueous ammonia and the liberated base was isolated by extraction with toluene. The extract was dried over potassium carbonate and, after filtration, stripped off under reduced pressure. 11.7 g (71%) of crude, oily 2-chloro-10- (1-pyrrolidinyl) -1,11-dihydrodibenzo [b, f] thiepine (I) are obtained. This base is dissolved in 45 ml of acetone and neutralized to reflux with 4.4 g of succinic acid. On cooling, 12.2 g of hydrogen amber crystallize out, which compresses the crystal from acetone and melts in its pure state at 137-139 ° C.

Claims (2)

OBJECT OF THE INVENTION 2-Chloro-10- (1-pyrrolidinyl) -10,11-dihydrodibenzo [b, f] thiepine of formula I and its succinic acid salt.