NEPRILYSIN INHIBITORS Russian patent published in 2017 - IPC C07C233/56 C07C243/26 C07C271/22 C07C231/02 C07C241/04 C07D317/40 A61K31/216 A61K31/27 A61K31/365 A61P9/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to formula I compounds, or pharmaceutically acceptable salts thereof, which have the ability to inhibit neprilysin activity (NEP). In formula I, R¹ is selected from H, -C₁-₈alkyl, -C₁-₆alkylene-OC(O)R¹⁰, -CH₂-pyridinyl, -(CH₂)₂-pyridinyl and ; R¹⁰ is selected from -C₁-₆alkyl, -OC₁-₆alkyl and -CH(R¹⁵)-NHC(O)O-C₁-₆alkyl; R¹⁴ is -C₁-₆alkyl; R¹⁵ is -CH(CH₃)₂; R² is -OR²¹ or -CH₂OR²¹; and R³ is H or -CH₃; where R²¹ is H; or R² is taken with R³ to form -CH₂-CH₂-; Z is selected from -CH- and -N-; R⁴ is selected from H, -C₁-₈alkyl, -C₁-₃alkylene-O-C₁-₈alkyl, -C₁-₃alkylene-C₆-₁₀aryl, -[(CH₂)₂O]₁-₃CH₃ and ; R⁴⁴ is-C₁-₆alkyl; A is 0 or 1; R⁵ is selected from halogen, -CH₃, -CF₃ and -CN; b is 0 or an integer of 1 to 3; each R⁶ are independently selected from halogen, -OH, -CH₃, -OSN₃, -CN and -CF₃. Each alkyl group in R¹ and R⁴ is optionally substituted with 1 to 8 fluorine atoms and the methylene linker on biphenyl is optionally substituted with one or two -C₁-₆alkyl groups. The invention also relates to a method for the preparation of formula I compounds containing their pharmaceutical composition and application of the said compounds for preparation of a medicament for treatment of hypertension, heart failure or kidney disease.

EFFECT: improved compounds properties.

40 cl, 16 ex