AR052769A1 - BICYCLONONENE DERIVATIVES, PHARMACEUTICAL COMPOSITION BASED ON THE SAME AND USE OF THE COMPOUND IN THE PREPARATION OF MEDICINES - Google Patents

Abstract

This refers to biciclononene derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The present also deals with related aspects that include the processes of preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as renin inhibitors. These compounds are renin inhibitors, useful in the regulation of blood pressure, improving local pathophysiologically altered functions, such as renal, cardiac and vascular. Claim 1: A compound selected from the group consisting of biciclononene compounds of formula (1), wherein: X represents -NH-, -N (L) -, -CH2-, -CH (L) -, -O- or -S-; W represents 1,4-phenyl; V represents a group of formula -E1-Z-E2-; E1 represents a bond or methylene; E2 represents oxygen or -CH2-O-; Z represents a pyrrolidine or azetidine ring; U represents unsubstituted aryl; mono-, di-, tri- or tetra-substituted aryl, wherein the substituents are independently selected from the group consisting of halogen, -CF3, -OCF3, C1-7 hydroxyalkyl, R1COO-C1-7 alkyl and C1-alkyl -7; or five-membered heteroaryl containing two heteroatoms independently selected from nitrogen, oxygen and sulfur (preferably pyrazolyl or isoxazolyl), wherein said heteroaryl radical is optionally mono-, di- or tri-substituted, in which the substituents are independently selected from C1-7 alkyl, C1-7 alkoxy, -CF3, -OCF3 and halogen; T represents -CONR1-; Q represents methylene; M represents phenyl; mono- or di-substituted phenyl, where the substituents are independently selected from the group consisting of C1-7- alkyl, C1-7 alkoxy, -OCF3, -CF3, C1-7 hydroxyalkyl, halogen, C1-7-O-alkyl ( CH2) 0-4-CH2-, alkyl C1-7-O (CH2) 2-4-O-, and R42N- (CH2) 0-4-CH2-; or mono- or di-substituted pyridinyl, wherein the substituents are independently selected from the group consisting of halogen, C1-7 alkyl, -OCF3, -CF3, and C1-7 alkoxy; with the proviso that halogen substituents are not in position 2 or 6 of the pyridinyl ring; L represents -R3, -COR3, -COOR3, -CONR2R3, -SO2R3, or -SO2NR2R3; R1 and R1 'independently represent C1-7 alkyl or cycloalkyl; R2 and R2 'independently represent C1-7 alkyl, C2-7 alkenyl, cycloalkyl or C1-7 cycloalkylalkyl; R3 represents C1-7 alkyl, cycloalkyl, or C1-7 cycloalkylalkyl, in which these groups may be unsubstituted or mono-, di-, or tri-substituted, where the substituents are independently selected from hydroxy, -NH2, -OCOR2 , -COOR2, -SO3H, -SO2CH3, C1-7 alkoxy, cyano, -CONR2R2 ', -NH (NH) NH2, -NR1R1', tetrazolyl and C1-7 alkyl, with the proviso that a carbon atom is attached at most a heteroatom in case this carbon atom is hybridized sp3; and R4 represents hydrogen, C1-7 alkyl, cyclopropyl or -C (= O) -R ', where R' is C1-4 alkyl, - CF3, -CH2-CF3 or cyclopropyl; and optically pure enantiomers, mixtures of enantiomers such as racemates, diastereomers, mixtures of diastereomers, diastereomeric racemates, mixtures of diastereomeric racemates, and meso forms, as well as complexes of salts and solvents of such compounds and morphological forms.