RU2491281C1 - Uniformly tritiated 4-iodo-n-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzensuphonamide - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to uniformly tritiated 4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzensulphonamide of formula:

.

EFFECT: what is prepared is a uniformly tritiated analogue of 4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzensulphonamide which can find application in analytical chemistry, biological studies and medicine for treating schizophrenia and Alzheimer's disease.

1 cl, 1 ex

Description

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

When studying 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 E. A. — Tritium and its compounds London Butterworths, 1974, p. 48) [1].

Known 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide of the formula:

This compound exhibits nootropic, antidepressant and anxiolytic properties (Stean T.O., Hirst WD, Thomas DR, Price GW, Rogers D., Riley G., Bromidge SM, Serafmowska HT, Smith DR, Bartlett S., Deeks N., Duxon M., Upton N. // Pharmacology, Biochemistry, and Behavior. 2002. V.71. N 4. P.645-654 [2]; Loiseau F., Dekeyne A., Millan MJ // Psychopharmacology. 2008. V.196. N 1. P.93-104 [3]; Wesolowska A., Nikifbruk A., Stachowicz K. // Behavioural Pharmacology. 2007. V.18. N 5-6. P.439-446 [4 ]). Also 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide is the strongest antagonist of 5-HT6 receptors (Hirst WD, Minton JA, Bromidge SM, Moss SF, Latter AJ, Riley G., Routledge C., Middlemiss DN, Price GW // British Journal of Pharmacology. 2000. V.130. N 7. P.1597-1605 [5]) and a promising drug that can be used in such cognitive disorders, like schizophrenia and Alzheimer's disease.

However, its counterpart 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.

The technical result is achieved by obtaining uniformly labeled with tritium 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide of the formula:

The following is an example implementation of the invention.

Example I.

A solution of 1.5 mg of 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide in 75 μl of methanol was mixed with 37.5 mg of aluminum oxide. Under reduced pressure, the solvent was evaporated and the residue was lyophilized.

The dried residue and 15 mg of a Lindlar catalyst based on 5% Pd / BaSO ₄ were placed in a vial and mechanically mixed. The ampoule was evacuated and filled with gaseous tritium to a pressure of 400 hPa. The reaction was carried out at 240 ° C for 5 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 a Milichrome A-02 chromatograph, 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 + 0.005M HClO ₄ buffer, B - methanol, gradient B → 0-100 for 12.5 min: retention time of 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide - 8.89 minutes Uniformly labeled 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide 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 - 27.7 min.

The radiochemical purity of the uniformly labeled 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide after chromatography is not less than 98%, yield 20-25%, molar radioactivity 15 Ci / mmol .

Thus, 4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzene sulfonamide uniformly labeled with tritium was obtained.

Claims (1)

4-iodo-N- [4-methoxy-3- (4-methyl-1-piperazinyl) phenyl] benzensulfonamide uniformly labeled with tritium of the formula: