DE2133473A1 - Adenosine derivs - prepd by reaction 6-halo-purine riboside with amines, show activity on blood vessels and circulation and lipid- - Google Patents

Abstract

Cpds. of formula (I):- (where X = a valency bond or O; n = 1-5; A = lower alkyl or alkoxy); are prepd. by reacting a cpd. (II) with an amine (III):- opt. blocking the OH-gps. of the ribose. Cpds. (I) are active on blood-vessels and the circulation and have also lipid-lowering props. An examples of (I) is N(6)-/d,l-trans-2-(3-methoxyphenyl)-cyclohexyl/-adenosine.

Description

BOEIIRIHGEE MANNHEIM GMBH

I5IO a

Adenosine derivatives and processes for their production (addendum to patent application P 16 70 235-5)

Patent application P 16 70 235-5 relates to adenosine derivatives the general formula

(CH ₂ ) _n
CH-CH-X- / ^

(D,

HO OH

in which E is hydrogen or a lower alkyl group, X is a valence trio or an oxygen atom and η denotes the numbers 1-5,

which have particularly interesting cardiovascular effects and in particular can be used as coronary dilators .. These compounds are prepared by using a method known per se Way 6-halo-purine riboside of the general formula II

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Hal

in which Hal means a halogen atom ",

with amines of the general formula III

H-W-CH - CH-X

«/ Λ

in which R, X and η have the meaning given above

converts, if desired, the OH groups of the ribose residue intermediately after condensation has taken place, it can be split off Groups blocked.

It has now been found that in addition to those mentioned in the parent application Compounds of the general formula I, including compounds of the formula I a

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HO OH

CH-X

(I a),

in which X and η have the same meaning as in formula I, jedooh the phenyl radical contains a substituent A which means a lower alkyl or alkoxy radical, are vascular and circulatory and also lipid-lowering Possess properties. Subject of the present application are these substances as well as processes for the production of the same, whereby the methods of the main application are used come.

The substances and processes for their preparation are explained in more detail in the examples below.

2U9 88Λ / 1300

■ - 4 -

example 1

Ιί (6) - [d, l-trans-2- (3-methoxyphenyl) -cyclohexyl "j-adenoa in

6.2 g of triacetyl-6-chloro-9- (β-I'-ribofuranosyl) -purine become together with 3> 7 g d, l-trans-2- (3-methoxyphenyl) -cyclohexylamine and 2.5 ml of triaethylamine in 100 ml of isopropanol heated under reflux for 1 1/2 hours. Then im Concentrated in vacuo and the residue taken up with benzene and V / aseer. The benzene phase is twice more washed with water, dried and concentrated *

k. The residue is taken up in 80 ml of methanolic ammonia and the resulting solution is distilled off to dryness after standing over fold at room temperature; the remaining syrup is reprecipitated from ethyl acetate / ligroin. This gives 4 »3 g (63 io of theory) of N (6) - [d, l-trans-2- (3-methoxyphenyl) cyclohexyl] adenosine with a melting point of 110-112 C.

Example 2
N (6) - | d, 1-trans-2- (3-methoxyphenyl) -cyclopentyl 1-adenosine

In a manner analogous to that described in Example 1, 6.2 g of triaoetyl-6-chloro-9- (ß-D-ribofuranosyl) purine are obtained,

3.4 S d, l-trans-2- (3-methoxyphenyl) -cyclopentylamine and

2.5 ml of triethylamine 1.5 g (23 f ° of theory) N (6) - [d, l-trans-2- (3-methpxyphenyl) cyclopentyl] adenosine with a melting point of 78-8I ⁰ C.

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Example 3

N (6) - [d _t 1-trans -2- (2-methyl-phenyl) -cyclohexyl-1-adenosine

In a manner analogous to that described in Example 1, 4.1 g of triaoetyl-6-chloro-9- (ß-D-ribofuranosyl) -purine, 2.3 gd, l-trans-2- (2-methyl- phenyl) cyclohexylamine and 1.7 ml triethylamine 2.6 g (59 $ of theory) H "(6) - [d, l-trans-2- (2-methylphenyl) cyclohexyl] adenosine vom Melting point 138-14O ⁰ C.

Example 4 NC 6) - [d, l-trans -2- (2-methyl-phenyl) -cyclopentyl-1-adenosine

A solution of 4.1 g of triacetyl-6-chloro-9- (ß-D-ribofuranosyl) -purine, 2.1 gd, l-trans-2- (2-methyl-phenyl) -cyclopentylamine and 1.7 ml Triethylamine in 40 ml of isopropanol remains at room temperature for 3 days. Then, as described in Example 1, worked up. This gives 1.8 g (42 $ of theory) of N (6) - [d, l-trans-2- (2-methyl-phenyl) -cyclopentyl] -adenosine melting point of 110-112 ⁰ C.

Example 5 N (6) - [d, l-trans -2- (4-methoxyphenyl) -oyclohexyl-1-adenosine

In a manner analogous to that described in Example 4, 6.2 g of triaoetyl-6-chloro-9- (ß-D-ribofuranosyl) -purine, 3.7 gd, l-trans-2- (4-methoxy- phenyl) cyclohexylamine and 2.5 ml triethylamine 2.1 g (3I ^c / o of theory) N (6) - [d, l-trans-2- (4-methoxyphenyl) cyclohexyl] adenosine melting point 123-124 ° C.

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Example 6

U (6) - [d, l-trans-2- (2-methoxyphenyl) -cyclohexyl-1-adenosine

In a manner analogous to that described in Example 4, from 6.2 g of triacetyl-6-chloro-9- (β-D-ril3ofuranosyl) -purine, 3.7 g of d, l-trans-2- (2-methoxy) are obtained -phenyl) -cyclohexylamine and 2.5 ml of triethylamine 3.4 g (50 ^c /> d.Th.) N (6) - [d, 1-trans-2- (2-methoxyphenyl) -cyclohexyl] - adenosine having a melting point of 110-112 ⁰ C.

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Claims (4)

- 4fr _ Claims Adenosine derivatives of the general formula I a CH-X (I a), HO OH in which X is a valence stricium or an oxygen atom, η denotes the numbers 1-5 and A denotes a lower alkyl or alkoxy radical. 2. Process for the preparation of adenosine derivatives of the general PorEel I a, characterized in that 6-halo-purine ribosides of the general Formula II Shark HO OH iäi which means a halogen atom ", 2U988W 1300 with amines of the general formula III a H ₂ N-CH - in which X, A and η have the meaning given above, converts, viobei nan, if desired, the OH groups of Ribose residue blocked by groups that can easily be split off after condensation has taken place. 3. Use of compounds of the formula I a for the preparation of drugs with vascular and circulatory effects or lipid-lowering effects. 4. Medicines, characterized by a content of compounds of formula Ia. 2U9884 / 1300