DUAL-ACTING ANTIHYPERTENSIVE COMPOUNDS, METHODS FOR PREPARING THEM, BASED PHARMACEUTICAL COMPOSITIONS AND INTERMEDIATE COMPOUNDS Russian patent published in 2013 - IPC C07D213/64 C07D231/10 C07D249/08 C07D233/64 C07D233/68 C07D233/70 C07D401/10 C07D401/12 C07D409/06 C07D405/06 A61K31/4164 A61K31/4178 A61K31/4412 A61P9/00 

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts wherein r represents 1; Ar is specified in and , R¹ is specified in -COOR^1a, -NHSO₂R^1b, -SO₂NHR^1d, -SO₂OH, -O-CH(R^1e)-COOH and tetrazol-5-yl, R^1a represents H, -C_1-6alkyl, -C_1-3alkylenaryl, -C_1-3alkyleneheteroaryl, - C_3-7cycloalkyl, -CH(C_1-4alkyl)OC(O)R^1aa, or R^1aa represents -O-C_1-6alkyl or -O-C_3-7cycloalkyl; R^1b represents R^1c; R^1d represents -C_1-6alkyl or -C_0-4alkylenaryl; R^1d represents -C(O)R^1c or -C(O)NHR^1c; R^1e represents -C_1-4alkyl; Y represents -C(R³)-, Z represents -N-, Q represents -C(R²)-, and W represents a bond; Y represents -N-, Z represents -C(R³)-, Q represents -C(R²)-, and W represents a bond; Y represents -C(R³)-, Z represents -N-, Q represents -N-, and W represents a bond; or Y represents -C(R³)-, Z represents -CH-, Q represents -C(R²)-, and W represents -C(O)-; R² is specified in H, halogen, -C_1-6alkyl, -C_3-6dicloalkyl, and -C_0-5alkylene-OR^2b; wherein R^2b is specified in H and -C_1-6alkyl; R³ is specified in -C_1-10alkyl and -C_0-5alkylene-O-C_0-5alkylene-R^3b; and R^3b represents -C_1-6alkyl; X represents -C_1-12alkylene-, where at least one group -CH₂- in alkylene is substituted by the group -NR^4a-C(O)- or -C(O)-NR^4a-, wherein R^4a is specified in H, -OH, and -C_1-4aalkyl; R⁵ is specified in -C_0-3 alkylene-SR^5a, -C_0-3alkylene-C(O)NR^5bR^5c, -C_0-3alkylene-NR^5b-C(O)R^5d, -NH-C_0-1alkylene-P(O)(OR^5e)2, -C_0-2alkylene-CHR^5g-COOH and -C_0-3alkylene-C(O)NR^5h-CHR⁵ⁱ-COOH; R^5a represents H or -C(O)-R^5aa; R^5aa represents -C_1-6alkyl, -C_0-6alkylene-C_3-7cycoalkyl, -C_0-6alkylenaryl, or -C_0-6alkylenemorpholine; R^5b represents -OH, -OC(O)R^5ba, -CH₂COOH or -OC(S)NR^5bbR^5bc; R^5ba represents -C_1-6alkyl, -OCH₂-aryl or -CH₂O-aryl; R^5bb and R^5bc independently represents -C_1-4alkyl; R^5c represents H; R^5d represents H; R^5e represents H; R^5g represents H or -CH₂-O-(CH₂)₂-O-CH₃; R^5h represents H; R⁵ⁱ represents -C_0-3alkylenaryl; R⁶ is specified in -C_1-6alkyl, -C_0-3alkylenaryl, -C_0-3alkyleneheteroaryl and -C_0-3alkylene-C_3-7cycloalkyl; and R⁷ represents H or together with R⁶ to form -C_3-7cycloalkyl; where each ring in Ar and each aryl and heteroaryl in R^1-3 and R^5-6 are optionally substituted by 1-3 substitutes optionally specified in -C_1-6alkyl, -CN, halogen, -O-C_1-6alkyl, -phenyl, -NO₂, wherein each alkyl is optionally substituted by 1-5 fluorine atoms; each carbon atom in X is optionally substituted by one or more groups R^4b, and one group -CH₂- in X may be substituted by -C_4-8cycloalkylene- and -CH=CR^4d-; where R^4b is specified in -C₀-5alkylene-COOR^4c and benzene, where R^4c represents H; and R^4d represents -CH₂-thiophen; each alkyl and each aryl in R^1-3, R^4a-4d and R^5-6 are optionally substituted by 1-7 fluorine atoms; where aryl represents monovalent aromatic hydrocarbon having one ring or condensed rings, and contains 6-10 carbon atoms in the ring; and heteroaryl represents a monovalent aromatic group having one ring or two condensed rings, and having 5-10 atoms in large in the ring with one atom of the ring represents a heteroatom specified in nitrogen, oxygen and sulphur. Besides, the invention refers to a pharmaceutical composition based on the compound of formula

,

to a method for preparing the compound of formula (I), to intermediate compounds used in synthesis of the compound of formula (I), to the use of the compounds of formula (I).

EFFECT: there are prepared new compounds possessing activity of a type 1 angiotensin II (AT₁) receptor antagonist and activity of neprilysin inhibition.

38 cl, 36 ex