DE2105560A1 - Purine ribonucleoside derivatives and processes for making the same - Google Patents

Description

Purine ribonucleoside derivatives and processes for making the same.

The present invention relates to new nitric acid esters of purine ribonucleosides of the general formula I.

O ₂ NOH ₂ C

O ₂ NO

(D,

0-NO ₂

in the

R, a hydroxy or an amino group, R_ denotes hydrogen or halogen,

and processes for their production, their use for production of drugs, as well as pharmaceutical preparations containing purine carbonucleoside derivatives of the general Formula I.

It has been found that the new compounds of general formula I have an interesting cardiac activity that with that of nitroglycerine is comparable.

The process according to the invention for the preparation of the compounds of general formula I is characterized in that

1 7 fl

in a manner known per se, purine ribonucleosides of the general kind Formula II

HO-H2C

(II),

HO OH

in which

R, and R_ have the above meaning, nitrated.

The nitration is preferably carried out with highly concentrated (e.g. 95-100%) nitric acid. It is extremely surprising that the esterification can be carried out with "a strong mineral acid in this special case, since it is known that the glycosidic Binding in purine ribonucleosides easily attacked by acidic agents will.

The novel substances I according to the invention can be administered enterally and parenterally in liquid or solid form will. All common forms of application are possible, for example tablets, capsules, coated tablets, syrups, solutions, suspensions ate. Water is preferably used as the injection medium for application, which is the usual additives for injection solutions such as stabilizers, solubilizers and buffers. Such additives are e.g. Ttirrtrat and CLtrat buffers, Ethanol, complexing agents (such as ethylenediamine-tetra-acetic acid and their non-toxic salts), high molecular weight polymers (wio liquid polyethylene oxide) for viscosity recycling. Liquid Carriers for injection solutions must be and become sterile

2 0 9 8 3 7/117 8

preferably filled in ampoules. Solid carriers are e.g. starch, lactose, mannitol, methyl cellulose, talc, highly dispersed silicic acids, higher molecular fatty acids (such as stearic acid), Gelatine, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats, solid high molecular weight polymers (such as polyethylene glycols). Preparations suitable for oral administration can, if desired, contain flavorings and sweeteners contain.

^{Preparation 1 of} the compounds according to the invention is described in more detail in the following examples.

2 0 9837/1178

example Inosine-2 ', 3', 5'-trinitrate

10.0 g of inosine are added in portions to 100 ml of 100 % xge nitric acid with stirring and cooling to 0-5 ° C. The clear solution is stirred for a further 1 hour at 5 ° C. and then poured into 1.5 liters of ice water. When the solution is neutralized with sodium hydroxide solution, the product βμβ falls. The precipitate is filtered off with suction, washed with water and dried. After repeated recrystallization from methanol, 4.5 g (30 % of theory) of inosine-2 ¹ , 3 ', 5'-trinitrate are obtained, which melts at 177 ° C. with decomposition.

example

2-chloradenosine-2 ', 3', 5'-trinitrate

3.0 g of 2-chloroadenosine are introduced in portions into 30 ml of 95% strength nitric acid with stirring and cooling to 0-5 ° C. The clear solution is stirred for a further 4 hours at 5-10 ° C. and then neutralized by carefully dropping it into sodium bicarbonate solution while cooling. The deposited precipitate is filtered off with suction and recrystallized from water / methanol. 1.1 g (25 % of theory) of 2-chloradenosine-2 ', 3 ¹ , 5 * -trinitrate with a bp. 186-188 ° C. (decomp.) Are obtained.

In an analogous way one obtains

a) from adenosine
Adenosine 2 ', 3', 5'-trinitrate

of pp. 145 ° C (decomp.) (26 % of theory) «* ■

b) from bromadenosine

2-bromadenosine-2 ', 3', 5'-trinitrate
mp. 190 ⁰ C (dec.) (41% of theory).

209837 // 1178

Claims (4)

Claims 1. Purine ribonucleoside derivatives of the general formula I. R ₁ O ₂ NOH ₂ C O ₂ NO 0-NO ₂ in the R, a hydroxy or an amino group, R, hydrogen or halogen, and processes for their production, their use for production of drugs, as well as pharmaceutical preparations containing purine ribonucleoside derivatives of the general Formula I. 2. Process for the preparation of compounds of the general formula I, characterized in that purine ribonucleosides are used in a manner known per se of the general formula II 209837/1178 HO-H2C HO • OH (Ιϊ), in which and R _{2 have} the above meaning * nitrated. 3. Use of substances of the general formula I for the preparation of drugs that act on the heart. 4. Medicines, characterized "by a content of compounds fe of the general formula I. 2Ü9837 / 1178