CLASS OF BIFUNCTIONAL COMPOUNDS WITH QUATERNARY AMMONIUM SALT STRUCTURE Russian patent published in 2020 - IPC C07D403/12 C07D453/00 C07D453/02 C07D487/08 A61P11/08 

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) with bifunctional structure of quaternary ammonium salt with agonist activity β₂-adrenoreceptor and muscarinic receptor antagonist, a pharmaceutically acceptable salt thereof and an optical isomer, as well as a pharmaceutical composition, a method for production thereof and use thereof. In general formula (I) L is (4-10C) aryl or heteroaryl, where heteroatom heteroaryl is selected from N, O and S, and said groups can be unsubstituted or optionally substituted with one or more substitutes selected from halogen, -OR¹, -SR¹, -NR¹R², -NHCOR¹, -CONR¹R², -CN, -NO₂, -COOR¹, -CF₃ and C₁-C₄ unbranched or branched hydrocarbyl; W is independently selected from substituted or unsubstituted (3-6C) cycloalkyl, substitute selected from halogen, (1-4C) alkyl, (1-4C) alkoxy, alkoxyhydrocarbyl and heterocycle; R1 is a divalent group -(R_1a)_d-(A₁)_e-(R_1b)_f-; where d, e and f are each independently selected from 0, 1, 2 or 3 and the number of adjacent atoms in the shortest chain between two nitrogen atoms, to which R₁ is attached, ranges from 3 to 14; R_1a and R_1b are each independently selected from (1-10C) alkylene, (2-10C) alkenylene, (1-4C) alkyleneoxy, alkyleneoxyalkyl, alkylene amido, alkyleneacyloxy and alkyleneamino, where each of alkylene, alkenylene, alkyleneoxy, alkyleneoxyalkyl, alkyleneamino, alkyleneacyloxy, alkylene amido is unsubstituted or substituted with substituents, independently selected from (1-4C) alkyl, chlorine, fluorine, hydroxy, phenyl and substituted phenyl, R_1a and R_1b can be identical or different; A₁ is independently selected from (3-7C) cycloalkylene, (2-7C) alkylene, (6-10C) arylene, (4-9C) heteroarylene and (3-8C) heterocycloalkylene, where cycloalkylene can be unsubstituted or substituted with 1–4 substitutes independently selected from (1-6C) alkyl; each of arylene, heteroarylene and heterocycloalkylene can be unsubstituted or substituted with 1–3 substitutes independently selected from halogen, (1-6C) alkyl, (1-6C) alkoxy, -S-(1-4C) alkyl, -S(O)-(1-4C) alkyl, -S(O)2-(1-4C) alkyl, -C(O)-O-(1-4C) alkyl, -NH-(1-4C) alkyl, -N=[(1-4C)alkyl]₂, carboxy, nitro, cyano, amido, ester group, trifluoromethyl and trifluoromethoxy; R₂ is independently selected from -NHCHO, -CH₂OH, -NH-; R₃ is independently selected from -H, -CH=CH-C(O)-, -OCH₂C(O)-; provided that R₂ is independently selected from -NHCHO or -CH₂OH, when R₃ is -H; provided that R₂ is -NH-, when R₃ is independently selected from -CH═CH-C(O)- or -OCH₂C(O)-, and R₂, R₃ and their carbon atoms are connected to form a ring; Y is selected from Br^-, Cl^-, I^-, bicarbonate, carbonate, bisulphate, sulphate, nitrate, phosphate, hydrophosphate, dihydrophosphate, phosphite, formate, acetate, propionate, isobutyrate, methanesulphonate, p-toluenesulphonate, benzoate, oxalate, tartrate, fumarate, malonate, succinate, suberate, mandelate, phthalate, benzene sulphonate, citrate, glucuronate, galactonate and amino acid radical; and T is the position of hydroxy on the benzene ring and is selected from the ortho- or meta-position of R₂ on the benzene ring.

EFFECT: compounds of the present invention are characterized by high selectivity with respect to the M-receptor subtype and have a lower adverse reaction and lower toxic and side effects on the treatment of pulmonary diseases, such as COPD and asthma.

14 cl, 8 tbl, 158 ex