CS209608B1 - D-1-hydroxyethyl-8-methoxycarbonyl-6-methylergoline i-formula - Google Patents

Abstract

New D-1-hydroxyethyl-8-methoxycarbones 1-6-methylergoline-I of formula I and its salts with pharmaceutically acceptable acids inhibit adenohypophyseal secretion prolactin is produced by being known in the art 1-carboxymethyl-dimethyl ester -9,1O-dihydrolysergic-I selectively reduces ester function at position 1 of the molecule.

Description

The present invention relates to D-1-hydroxyethyl-8-methoxycarbonyl-6-methylergoline-X of the formula

and salts thereof with pharmaceutically acceptable organic and inorganic acids such as tartaric, maleic, hydrochloric, sulfuric and the like.

D-1-hydroxyethyl-8-methoxycarbonyl-6-methylergoline-1, a novel substance not yet described, has remarkable biological properties, such as inhibiting adenohypophyseal prolactin secretion in rats, which is manifested by anti-lactation and anti-oxidation effects. For example, the anti-lactation effect of the compound in lactating rats (Wistar Konarovice strain) still appears at a dose of 2 mg / kg administered orally in the form of an aqueous solution of acid tartrate. In addition, D-1-hydroxyethyl-8-methoxycarbonyl-6-methylergoline-I is a valuable starting product for the synthesis of other pharmacodynamically active compounds.

For example, a compound of the formula I can be prepared by reacting dimethyl D-1-carboxylic acid 1-9, 10-dihydrolysyl ester with an inert organic solvent such as methanol with borohydride Sodium, in an amount of not more than 10 mol equivalents, at temperatures from -10 ° C to the boiling point of the reaction mixture. After pouring the reaction mixture into water, the precipitated product is isolated and worked up in a conventional manner.

The starting ester is a substance known and readily prepared in good yield and of satisfactory quality from D-9,10-dihydrolysergic acid-I / MS. author's certificate no. 190240 /.

Conversion of the compound of the formula into salts with pharmaceutically acceptable organic and inorganic acids such as tartaric, malic, malonic, succinic, maleic, sulfuric, methane and ethanesulfonic acids, etc., can be accomplished by reacting equimolar amounts of both components in an inert inert solvent, for example ethanol.

The melting point of the novel compound of the invention was determined on a Boeti block and is not corrected. The specified specific rotation value refers to a crystal-free substance.

Details of the preparation of D-1-hydroxyethyl-8-methoxycarbonyl-6-methylergoline-I are given in the following example.

Exemplary embodiment

To a solution of 3.6 g (0.01 mol) of D-1-methoxycarbonylmethyl-9,10-dihydrolysergic acid methyl ester was added 1.9 g of sodium borohydride at 30 ° C. After stirring for 1 hour at 30 [deg.] C., an additional 1.9 g of sodium borohydride, i. total 3.8 g (0.10 mol). The reaction mixture is then heated at reflux for 1 hour, cooled to 20 ° C and poured into 400 ml of water. The precipitated product is filtered off with suction, washed with water and dried. Crystallization from methanol gave D-1-hydroxyethyl-8-methoxycarbonyl-6-methylergoline-I as colorless crystals of m.p. t.

174 DEG-176 DEG C. [.alpha.] D @ 20 = -100.6 DEG / c 0.4; pyridine /.

Claims (2)

SUBJECT OF THE INVENTION D-1-hydroxyethyl-8-methoxycarbonyl-6-methylergoline-I of the formula and salts thereof with pharmaceutically acceptable organic and inorganic acids.