NEW β-LACTAMASE INHIBITOR AND A METHOD OF ITS PRODUCTION Russian patent published in 2023 - IPC C07D471/08 C07D211/60 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to intermediate compounds of formula (I), where A is Ra(Rb)N- or RcO-; B is NH; C is benzyl, H or SO₃M, where M is pyridinium or tetrabutylammonium; Ra and Rb are each, independently of each other, H, methyl, benzoyl, C_1-4 alkylcarbonyl, heterocyclylcarbonyl, where heterocyclyl is selected from tetrahydropyran, piperidine and pyrrolidine, and heteroarylcarbonyl, where heteroaryl is selected from furan, oxazole and pyridine; Rc is C_1-3 alkyl or 4–6-membered heterocyclyl having one nitrogen atom selected from azetidine, pyrrolidine and piperidine; A can be modified with 0 to 3 Fn1 substituents, where the Fn1 substituent that can modify A can be further modified with Fn1; Fn1 is C_1-6 alkyl which is selected from cyclopropylmethyl and cyclobutyl, O= or Rg-(CH₂)_0-1 — where Rg is a 4–7-membered heterocyclyl containing 1–2 heteroatoms selected from a nitrogen atom and an oxygen atom selected from azetidine, pyrrolidine, piperidine, morpholine, imizolidine, piperazine and diazepan, phenyl, a 5-membered heteroaryl having 1–2-nitrogen atoms, which is selected from pyrrole and imidazole, RdO₂S-, Re(Rf)N-, Re(Rf)NCO-, ReO-, ReOCO- or a protective group, where Rd is methyl; Re and Rf are each independently H or C_1-4 alkyl, and additionally Ra and Rb can be closed by bonding to give a 5–6 membered heterocyclyl having at least one nitrogen atom or nitrogen and oxygen, which is selected from pyrrolidine and morpholine, Rc and B can be closed by coupling to obtain a 5–6-membered heterocyclyl having a nitrogen atom and an oxygen atom, which is selected from oxazolidine and oxazinane, and Re and Rf can be closed by coupling with obtaining morpholine, the protective group is selected from tert-butoxycarbonyl, benzyloxycarbonyl and triisopropylsilyl, or pharmaceutically acceptable salts thereof. The invention also relates to intermediate compounds of formula (II), (IIa), (IIb) and (III), as well as to methods of their production.

EFFECT: invention provides methods of obtaining effective β-lactamase inhibitors and intermediate compounds for such inhibitors production for the treatment of bacterial infections.

13 cl, 5 dwg, 9 tbl, 122 ex