| abstract |
FIELD: chemistry. n SUBSTANCE: invention relates to a compound of formula , wherein R 1 is selected from -OR 7 and -NR 8 R 9 ; R 2 is H; X is -C 1 - 9 heteroaryl, selected from pyrazole, imidazole, triazole, benzotriazole, furan, tetrazole, pyrazine, thiophene, oxazole, isoxazole, thiazole, oxadiazole, pyridazine, pyridine, pyrimidine, benzoxazole, pyridylimidazole and pyridyltriazole; R 3 is absent or is selected from H; Halogen; -C 0 - 5 alkylene-OH; -NH 2 ; -C 1 - 6 alkyl; -CF 3 ; -C 3 - 7 cycloalkyl; -C 0 - 2 alkylene-O-C 1 - 6 alkyl; -C(O)R 20 ; -C 0 - 1 alkylene-COOR 21 ; -C (O) NR 22 R 23 ; -NHC(O)R 24 ; =O; -NO 2 ; -C(CH 3 ) =N(OH); Phenyl optionally substituted with one or two groups independently selected from halogen, -OH, -CF 3 , -OCH 3 , -NHC(O)CH 3 and phenyl; Naphthalenyl; Pyridinyl; Pyrazinyl; Pyrazolyl optionally substituted with methyl; Thiophenyl, optionally substituted by methyl or halogen; Furanyl; and -CH 2 -morpholinyl; and R 3 , when present, is attached to a carbon atom; R 4 is absent or is selected from H; -HE; -C 1 - 6 alkyl; -C 1 - 2 alkylene-COOR 35 ; -OCH 2 O(O)CH (R 36 )NH 2 ; -OCH 2 O(O)CH 3 ; -CH 2 CH(OH)CH 2 OH; and phenyl or benzyl optionally substituted with 1 to 3 groups selected from halogen, -COOR 35 , -OCH 3 , -OCF 3 and -SCF 3 ; and R 4 , when present, is attached to a carbon or nitrogen atom; or R 3 and R 4 are taken together to form -phenylene-O- (CH 2 ) 1-3- or -phenylene-O-CH 2 -CHOH-CH 2 -; A is 0 or 1; R 5 is halogen; B is 0 or an integer of 1 to 3; Each R 6 is independently selected from halogen, -OH, -CH 3 and -OCH 3 ; R 7 is selected from H, -C 1 - 8 alkyl, -[(CH 2 )2O]1-3CH 3 , -C 1 - 6 alkylene-OC(O)R 10 , -C 0 - 6 alkylenemorpholinyl, -C 1 - 6 alkylene-SO 2 -C 1 - 6 alkyl and the structure of formula (a); R 10 is -O-C 3 - 7 cycloalkyl; and R 32 is -C 1 - 6 alkyl; R 8 and R 9 are H; R 20 , R 21 and R 35 are independently selected from H and -C 1 - 6 alkyl; R 22 and R 23 are independently selected from H, -C 1 - 6 alkyl, -CH 2 COOH, -(CH 2 )2OH, -(CH 2 ) 2 OCH 3 , - (CH 2 ) 2 SO 2 NH 2 , -(CH 2 ) 2 N(CH 3 ) 2 , -C 0 - 1 alkylene-C 3 - 7 -cycloalkyl and -(CH 2 ) 2 -imidazolyl; or R 22 and R 23 are taken together to form a ring; R 24 is selected from -C 1 - 6 alkyl; -C 0 - 1 alkylene-O-C 1 - 6 alkyl; Phenyl optionally substituted by halogen or -OCH 3 ; and pyridinyl; and R 36 is -CH (CH3) 2; and wherein the methylene linker on the biphenyl is optionally substituted with one or two -C 1 - 6 alkyl groups; or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are prepared by combining a compound of formula with a compound of formula n 2 to provide a compound of formula I; Where P1 is also H. Also, the invention relates to an intermediate of formula 1, wherein P 1 is H. The compounds of formula (I) are intended for the preparation of a medicament or pharmaceutical composition having inhibitory activity against non-prolamin (NEP). (a). n EFFECT: compounds that have a non-lysine inhibitory enzyme activity. n 28 cl, 61 tbl, 25 ex |