CHELATE COMPOUNDS OF MANGANESE BASED ON TETRAAZABICYCLO-MACROCYCLE, SUITABLE AS IMAGING AGENTS FOR MRI Russian patent published in 2022 - IPC C07D471/08 C07F13/00 A61K49/10 

FIELD: pharmaceutics.

SUBSTANCE: invention relates to a compound of formula I: in which X is O; Y is Q-R³, where Q is N, and R³ is selected from the group containing C_1-6alkyl or a hydrogen atom; Z is Q-R³-(L-R⁴), where Q is N or CH, and R³ is C_1-20hydroxyalkyl, C_1-6alkyl or hydrogen atom, and L is an optional linker, selected from a group comprising C_1-6alkylene, C_1-6hydroxyalkylene and polyethylene glycol (PEG) linker, R⁴ is selected from a group comprising C_1-6alkyl-R⁵, C_3-6aryl-R⁵, hydroxy, -O-C_1-3alkyl-R⁵, sulphonyl, 5–6-membered heterocyclic ring selected from an N-acetylneuraminic acid residue, dihydropyrimidine-2,4(1H,3H)-dione, tetrahydrothiophene-1,1-dioxide, imidazolidine-2,4-dione and morpholine, a carbohydrate group, selected from monosaccharide and disaccharide residues, chelate group amino acid group, wherein R⁵ is one or more optional substitutes, selected from hydroxy, amino, oxo, sulphonamide or -C(=O)-NH-C_1-6hydroxyalkyl; or Z itself forms part of a carbohydrate group selected from monosaccharide and disaccharide residues, or 5–6 membered heterocyclic ring selected from an N-acetylneuraminic acid residue, dihydropyrimidine-2,4(1H,3H)-dione, tetrahydrothiophene-1,1-dioxide, imidazolidine-2,4-dione and morpholine; R¹ is C_1-3alkyl; R² is absent; and each n is integer from 1 to 6; wherein the compound of formula I contains at least two hydroxy groups. Also disclosed is a pharmaceutical composition, a method of forming MR images and/or MR spectra using a compound of formula I.

EFFECT: disclosed compounds of formula (I) are a polyase-macrocycle with side "arms" in the form of carboxylic acid residues, which provide formation of a complex with manganese as a core metal, and are suitable for use as contrast agents in magnetic resonance imaging (MRI).

18 cl, 26 ex