9α-fluoro-16α-hydroxyprednisolon [3h]-acetonide highly labeled with tritium

FIELD: organic chemistry, steroids, labeled compounds.

SUBSTANCE: invention relates to highly labeled analog of physiologically active compound, i. e. to 9α-fluoro-16α-hydroxyprednisolon [3H]-acetonide highly labeled with tritium of the formula (I): . The highly tritium-labeled compound of the formula (I) is necessary for investigation of active non-labeled analog.

EFFECT: valuable properties of compound.

2 cl, 1 ex

 

The invention relates to the field of organic chemistry and can find application in analytical chemistry, Bioorganic chemistry, biochemistry and applied medicine.

For the study of physiologically active compounds necessary for their labeled counterparts and how they are received.

It is known that substitution of atoms of compounds for their labeled counterparts does not change any properties of the original compounds, including their biological activity (Evans E.A. - Tritium and its compounds London Butterworths,1974, p.48) [1].

Known acetonide 9α-fluorescent-16α-hydroxyprednisolone formula:

This connection is known biologically active compound and is used for the treatment of chronic asthma

(K.FIorey, Anal. Profiles Drug Subs. 1, 397 1972) [2].

However, tritium-labeled analogue not described.

The technical result achieved by the present invention, is expanding the range labeled analogs of the physiologically active substances.

Achieved the specified technical result obtaining a new labeled physiologically active compounds - vysokobarnogo tritium [3N]-acetonide 9α-fluorescent-16α-hydroxyprednisolone formula:

The following is an example implementation of the invention.

Example 1.

In the first chamber of the reaction dokume the Noah ampoules were placed catalyst: 30 mg of palladium oxide and 30 mg of 5% PdO/BaSO 4in another 225 ál of absolute dioxane, 25 μl of triethylamine and 5 mg acetonide 9α-fluorescent-16α-hydroxyprednisolone. The second camera was frozen with liquid nitrogen, the vial was evacuated to a pressure of 0.1 PA and filled with gaseous tritium to pressure 333 hPa. Then, the first chamber was heated to 70°With the result that the oxide of palladium was recovered. Received tritium water was peremarazhival the second chamber. The reaction vial was evacuated to a pressure of 0.1 PA, continuing to heat the first ampoule up to 70°and filled with argon. Then the contents of the second chamber is transferred into the first chamber, which was sealed. Thus, the reaction mixture consisted of the recovered catalyst, tritium water, triethylamine and a solution of acetonide 9α-fluorescent-16α-hydroxyprednisolone in dioxane. The contents of the ampoules were heated for 30 min at 140°C. Then, the ampoule was opened, the reaction mixture was diluted with 0.5 ml of methanol, the catalyst was separated by filtration and washed with methanol (5×1 ml). Tritium water, dioxane and triethylamine drove on the rotor. Labile tritium was removed and the resulting product was repeatedly dissolved in methanol (5 x 2 ml), pariva last.

The first stage of the treatment received [3H]-acetonide 9α-fluorescent-16α-hydroxyprednisolone was performed by thin layer chromatography. Reactionuses was dissolved in 0.1 ml of methanol and applied on silicagel plate Sorbfil (JSC Carbolines", PTSH-P-A-UV). Mobile phase : chloroform-acetone (10:1) Rf=0.26. The zone containing [3H]-acetonide 9α-fluorescent-16α-hydroxyprednisolone, cut and were extracted with methanol (5×5 ml). The methanol was evaporated and analyzed by HPLC.

HPLC [3H]-acetonide 9α-fluorescent-16α-hydroxyprednisolone was performed on column Kromasil 100 C18, 7 μm, 4×150 mm, in the system methanol-water (70:30), the rate of eluent - 1.0 ml/min, retention time - 4,19 minutes For receiving and processing the chromatographic data were used hardware-software complex "Multichrome" (CJSC "ampersand character", Russia) based on IBM PC/AT. Radioactivity was measured by scintillation counter with an efficiency of registration of tritium 30% in dioxane scintillator.

Output [3H]-acetonide 9α-fluorescent-16α-hydroxyprednisolone after treatment was 22%, the molar radioactivity of 1.3 CI/mmol. Radiochemical purity of 97-99%.

The thus obtained new visokomernoe tritium physiologically active compound.

Viscometry tritium [3N]-acetonide 9α-fluorescent-16α-hydroxyprednisolone formula



 

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4 cl, 3 sch, 1 tbl, 8 ex

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12 cl, 17 ex, 5 dwg, 21 tbl

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