RU2469023C1 - 4-[2-(4-benzylpiperidin-1-yl)-hydroxypropyl] phenol uniformly labelled with tritium - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to 4-[2-(4-benzylpiperidin-1-yl)-hydroxypropyl] phenol of formula

which is uniformly labelled with tritium.

EFFECT: 4-[2-(4-benzylpiperidin-1-yl)-hydroxypropyl] phenol which is uniformly labelled with tritium, which can be useful in studying physiologically active compounds, is obtained and described.

1 cl, 1 ex

Description

The invention relates to the field of organic chemistry and may find application in analytical chemistry and biological research.

In the study of physiologically active compounds, their labeled analogues are necessary.

It is known that replacing the atoms of compounds with their labeled analogues does not lead to a change in any properties of the starting compound (Evans EA - Tritium and its compounds London Butterworths, 1974, p. 48) [1].

Known 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol of the formula:

This compound is a selective inhibitor and antagonist of the NMDA receptor (Reynolds I.J., Miller R.J. // Mol. Pharmacol. 36 (5), 758-765 (1989) [2]).

However, its uniformly labeled with tritium is not described.

The technical result achieved by the present invention is to expand the range of labeled analogues of physiologically active compounds.

This technical result is achieved by obtaining uniformly labeled with tritium 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol of the formula:

The following is an example implementation of the invention.

Example I.

A solution of 4 μmol of 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol in 300 μl of methanol was mixed with 170 mg of 5% Pd / BaSO ₄ . Under reduced pressure, the solvent was evaporated and the residue was lyophilized.

The dried residue was placed in an ampoule. The ampoule was evacuated and filled with gaseous tritium to a pressure of 400 hPa. The reaction was carried out at 150 ° C for 10 min. The ampoule was again evacuated, the catalyst was applied to a filter, the substance was extracted with methanol (5 × 0.5 ml). The extracts were evaporated, the residue was dissolved in methanol (3 × 1 ml) and again evaporated to remove labile tritium.

The analysis was performed on Milichrome A-02, ProntoSIL-120-5-C ₁₈ AQ DB-2003 column, 2.0 × 75 mm, 5 μm, 0.2 ml / min, 35 ° C, detection - 210 nm, A - 0.2 M LiClO ₄ + 0.005 M HClO ₄ buffer, B - methanol, gradient B → (0-100) for 12.5 minutes, retention time of 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol - 8.75 minutes. The retention time of 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol when analyzed under the same conditions, but with a gradient of B → (50-100) for 12.5 min, was 2.46 min.

Evenly labeled 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol was purified by preparative high performance liquid chromatography. Chromatography was performed on a Kromasil 100C ₁₈ , 8 × 150 mm, 7 μm column, system: A — methanol — 25 mM phosphate buffer (30:70), B — methanol, gradient B → (0-100) in 30 min, flow rate - 2 ml / min, retention time - 11.2 min, the content of the labeled drug is not less than 98%, the yield is 35-40%. The molar radioactivity of the uniformly labeled 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol is 220 Ci / mmol.

Thus, 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol uniformly labeled with tritium was obtained.

Claims (1)

Uniformly labeled with tritium 4- [2- (4-benzylpiperidin-1-yl) -hydroxypropyl] phenol of the formula