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 -COOR1a, -NHSO2R1b, -SO2NHR1d, -SO2OH, -O-CH(R1e)-COOH and tetrazol-5-yl, R1a represents H, -C1-6alkyl, -C1-3alkylenaryl, -C1-3alkyleneheteroaryl, - C3-7cycloalkyl, -CH(C1-4alkyl)OC(O)R1aa, or R1aa represents -O-C1-6alkyl or -O-C3-7cycloalkyl; R1b represents R1c; R1d represents -C1-6alkyl or -C0-4alkylenaryl; R1d represents -C(O)R1c or -C(O)NHR1c; R1e represents -C1-4alkyl; 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, -C1-6alkyl, -C3-6dicloalkyl, and -C0-5alkylene-OR2b; wherein R2b is specified in H and -C1-6alkyl; R3 is specified in -C1-10alkyl and -C0-5alkylene-O-C0-5alkylene-R3b; and R3b represents -C1-6alkyl; X represents -C1-12alkylene-, where at least one group -CH2- in alkylene is substituted by the group -NR4a-C(O)- or -C(O)-NR4a-, wherein R4a is specified in H, -OH, and -C1-4aalkyl; R5 is specified in -C0-3 alkylene-SR5a, -C0-3alkylene-C(O)NR5bR5c, -C0-3alkylene-NR5b-C(O)R5d, -NH-C0-1alkylene-P(O)(OR5e)2, -C0-2alkylene-CHR5g-COOH and -C0-3alkylene-C(O)NR5h-CHR5i-COOH; R5a represents H or -C(O)-R5aa; R5aa represents -C1-6alkyl, -C0-6alkylene-C3-7cycoalkyl, -C0-6alkylenaryl, or -C0-6alkylenemorpholine; R5b represents -OH, -OC(O)R5ba, -CH2COOH or -OC(S)NR5bbR5bc; R5ba represents -C1-6alkyl, -OCH2-aryl or -CH2O-aryl; R5bb and R5bc independently represents -C1-4alkyl; R5c represents H; R5d represents H; R5e represents H; R5g represents H or -CH2-O-(CH2)2-O-CH3; R5h represents H; R5i represents -C0-3alkylenaryl; R6 is specified in -C1-6alkyl, -C0-3alkylenaryl, -C0-3alkyleneheteroaryl and -C0-3alkylene-C3-7cycloalkyl; and R7 represents H or together with R6 to form -C3-7cycloalkyl; where each ring in Ar and each aryl and heteroaryl in R1-3 and R5-6 are optionally substituted by 1-3 substitutes optionally specified in -C1-6alkyl, -CN, halogen, -O-C1-6alkyl, -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 R4b, and one group -CH2- in X may be substituted by -C4-8cycloalkylene- and -CH=CR4d-; where R4b is specified in -C0-5alkylene-COOR4c and benzene, where R4c represents H; and R4d represents -CH2-thiophen; each alkyl and each aryl in R1-3, R4a-4d and R5-6 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
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Authors
Dates
2013-02-27—Published
2008-04-23—Filed