BETA-LACTAMASE INHIBITORS AND APPLICATION THEREOF Russian patent published in 2021 - IPC C07D471/08 A61K31/439 A61P31/04 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a compound by the formula (1) or a pharmaceutically acceptable salt thereof, wherein each R¹ is independently selected from C_1–6 alkyl, or each R¹ and the geminal carbon atom whereto they are attached forms a C_3–6 cycloalkyl ring or a C_3–6 heterocycloalkyl ring containing one oxygen atom and substituted by 1-3 groups independently selected from =O and C_1–6 alkyl; R² is selected from a single bond, C_1–6 alkanediyl, C_1-6 heteroalkanediyl containing one or two oxygen atoms, C_1–6 alkanediyl substituted with 1 to 2 C_1–6 alkyls, C_1–6 heteroalkanediyl containing one or two oxygen atoms and substituted by =O; R³ is selected from a C_1–6 alkyl, –O–C(O)–R⁴, –S–C(O)–R⁴, –C(O)–O–R⁴, C₆ aryl substituted by –O-C(O)-R⁴, wherein R⁴ is selected from C_1-8 alkyl, C_1–8 heteroalkyl containing one oxygen atom, C₆ aryl, C_7–10 arylalkyl, C_1–8 alkyl substituted with C_1–6 alkoxy, C_1–8 heteroalkyl containing one oxygen atom and substituted by -COOH and =O, methyl-5-methyl-1,3-dioxol-2-one, C₆ aryl substituted by 1 to 3 substituents independently selected from halogen, C_1–6 alkyl and C_1–6 alkoxy; R⁵ is selected from hydrogen, 4-yl-piperidine and C_2–6 heteroalkyl containing an oxygen atom and substituted by —NH₂; R⁶ constitutes hydrogen; and A constitutes a single bond (–) and R⁷ constitutes hydrogen, or A constitutes a double bond (=) and R⁷ constitutes C_1–3 alkyl; or the compound constitutes: (2S, 5R)–2–carbamoyl–7–oxo–1,6–diazabicyclo[3.2.1]octan–6–yl 1H–imidazole–1–sulfonate (34); 3–((((2S, 5R)–2–carbamoyl–7–oxo–1,6–diazabicyclo[3.2.1]octan–6–yl)oxy)sulfonyl)oxy)–2,2–dimethylpropyl adamantane–1–carboxylate (55); diethyl 2–((((((2S, 5R)–2–carbamoyl–7–oxo–1,6–diazabicyclo[3.2.1]octan–6–yl)oxy)sulfonyl)oxy)methyl)–2–methylmalonate (56); 4–((((2S, 5R)–2–carbamoyl–7–oxo–1,6–diazabicyclo[3.2.1]octan–6–yl)oxy)sulfonyl)oxy)–3,3–dimethylbutyl adamantane–1–carboxylate (63); 2–(((((2S, 5R)–2–carbamoyl–7–oxo–1,6–diazabicyclo[3.2.1]octan–6–yl)oxy)sulfonyl)oxy)methyl)–2–methylpropane–1,3–diyl dibenzoate (70); 2–(((((2S, 5R)–2–carbamoyl–7–oxo–1,6–diazabicyclo[3.2.1]octan–6–yl)oxy)sulfonyl)oxy)methyl)–2–methylpropane–1,3–diyl diacetate (71); ethyl 3–((((2S, 5R)–2–carbamoyl–7–oxo–1,6–diazabicyclo[3.2.1]octan–6–yl)oxy)sulfonyl)oxy)–2,2–dimethylbutanoate (73). The invention also relates to a pharmaceutical composition for inhibition of beta-lactamase based on the described compounds.

EFFECT: technical result is production of new compounds and a pharmaceutical composition based thereon, potentially applicable in medicine for treatment of bacterial infections.

30 cl, 79 ex