DE2547572C2 - Dihydroxy-dithio-decahexane derivative and medicinal products containing it - Google Patents

Description

IK) (CHi) ₂ -S- (CM.) ,, .- S- (CIb) ₂ OI I

κ, (which is known per se, for example by condensation of a dihulogenated derivative with a Alkali metal salt of the corresponding mercaptoalkanol can be obtained) with the acid chloride

P-CI-C ₆ H ₅ -OC (CHj) ₂ -COCI

lets react, the acid chloride preferably in

slight excess is used.

The lipid depressive activity of the invention Compound was detected in pharmacological comparative tests, the results of which are given in

are shown in the table below.

For the experiments 200-30Og were heavy

male rats used; the test animals, divided into lots of 10 each, received during

the following diet for a period of 14 days:

Part T: normal diet, consisting of grainy

Fodder,

, o Part A: Hyperlipid Diet,
"Lot B: Hyperlipidic Diet + 125 mg / kg / day of the

compound (II) according to the invention,
Lot C: Hyperlipid diet + 125 mg / kg / day of known compound (I).

After 14 days, the animals were sacrificed and all of the lipids in the blood (method N. Z o 11 mer et al .: Z. Ges. Exp. Med., 135, 545 [1962]) and the cholesterol (D. Watson: Clin . Chim. Acta, 5,637 [1960]).
The results obtained are shown in Table I.

Table 1

Diet (trial) Lipid depressant substance dose Total lipids Cholesterol total mg / kg / day mg / 100 ml% cont. mg / 100 ml % Inh. Normal (T) _ 226.83 - 55.1 _ Hyperlipid Control (Lot A) 246.52 - 60.3 - substance according to the invention (II) 125 150.8 38.8 39.8 33.7 (Game B) known substance (I) 125 178.7 27.5 54.3 9.7 (Game C)

The determination of the toxicities was carried out according to the graphic methods of Miller and Tainter (Proc. Soc. Exp. Biol. Med., 57, 261 [1944]) or by L i t c h F i e 1 d and W i 1 c ο χ ο η (J. Pharm. Exp. Therp., 96, 99 [1949]). The results obtained are shown in Table II.

Table II

LD50 (mg / kg)

Substance according to the invention (II)
Known substance (I)

8200
1540

To produce a medicament according to the invention, compound (11) is mixed with a conventional one Carriers, for example lactose, silicon dioxide, semi-synthetic glycerides, magnesium stearate, gelatin.

Exemplary embodiments of suitable pharmaceutical forms with the active ingredient according to the invention are:

1. Soft gelatin capsules with an active ingredient content of 0.200 to 0.500 g.

2. Capsules made of hard gelatine, which are made from a homogeneous mixture of 60% active ingredient and 40% S1O2 and 4% gelatin consist.

J. Emulsions have the following compositions:

Connection (I I) log Peanut oil 40 g Polyoxyethylene sorbitan Munostearal 3.6 ml Sorbitan monostearai 8.4 ml Sodium benzoal 0.2 g Flavor 0.3 g Water, missing amount 100 ml

4. Glycerin suppositories with an active ingredient ratio of 0.600-0.80Og.

example 1

In a 1 liter reaction vessel with a stirrer and RüL'kflusskühler, whose outlet opening through a CljCa tube is protected, 66.7 g of l, 10-bis (/ 3-hydroxyethyl-thio) -decanes are added and add 530 ml of anhydrous benzene.

The mixture is heated to 50 ° C. while stirring, during which the product dissolves. Then 53 ml of pyridine are added and then the p-chloro-phenoxy-isobutyryl chloride is added dropwise, taking care that the temperature does not exceed ^{70 ° C.}

After all the chloride has been added, the mixture is stirred for a further 50 minutes and left at room temperature for 20 minutes Stand for hours.

The precipitate obtained is filtered off and washed with

50 ml of benzene.
The solution obtained is with 250 ml of water and with

100 ml of 10% HCl solution washed.
Then it is extracted twice with 250 ml each time

saturated sodium bicarbonate solution and twice more

each with 3Ü0 ml of distilled water. One separates the ίο pale yellow organic layer, dries on anhydrous Magnesium sulfate, filtered and evaporated in vacuo

a.
In this way 121-124 g of one are obtained

light yellow oil of high viscosity, boiling point 224-226 ° C / 0.5 Torr (decomposition), with the following Elemental analysis:

Calculated
C 59.38, H 6.98, Cl 10.36, S 9.31%;
, found:

C 59.21, H 7.09, Cl 10.41, S 9.42%.

Yield: 80%.

In fine-layer chromatography, the product shows a single spot with an Rf = 0.79, with as Eluent ethyl acetate / chloroform / formic acid

(4G: 60: 1) is used and in its infrared specirum bands at 1740 cm- ¹ and at 1240 and 1140 cm- '(ester linkage).

Claims (2)

Patent claims: 1. Diester of 1,16-dihydroxy-3,14-dithic) -n-decahexanesder formula RO (CH ₂ ) ;, S- (CH ₂ I ₁₀ -S- (CH ₂ I ₂ OR, in the cn, R (P) -Cl-CJI ₅ -OC-CO represents. 2. Medicament, characterized by a content of the compound according to claim 1 as Active ingredient and a common additive. Substances that lower the concentration of lipids in the blood (cholesterol and triglycerides), play an important role in the therapy of atherosclerosis, as they inhibit its spread and also reduce the frequency of thrombosis. p-chloro-phenoxy-ethyl isobutyrate (hereinafter referred to as "Connection (1)") is one of the most important known connections for this purpose. Of the The discovery of further compounds with a lipid-depressive effect is of considerable importance. This is the object of the invention. It relates to the one defined in more detail in the claims Object. The compound according to the invention is also referred to below as “compound (II)”. Compound (II) surprisingly exhibits antihypercholesterolemic and normolipidemic properties similar to those of the known compound (I) surpass; in addition, it has a lower toxicity and a more favorable therapeutic ratio. s Compound (II) is obtained by adding to it.!, known way the dialcohol