Oxalic acid amides as inhibitors of neprilysin, pharmaceutical composition based on them and their preparation

A compound of formula I: ** ** Formula wherein: R1 is selected from H, C1-8 -alkyl, C1-3 -alkylene-C6-10aryl, C1-3 -alkylene-heteroaryl C1-9, -cycloalkyl C3-7, - [(CH2) 2O] 1-3CH3, -C 1-6 alkyl-OC (O) R10, -C 1-6 NR11R12, C1-6alkylC 10 -C (O) R13, -C C0-6-morpholinyl, C1-6 -alkylene-SO2-C1-6 alkyl, ** ** Formula R10 is selected from -C1-6alkyl, -O-C1-6alkyl, -C3-7cycloalkyl, -O -C3-7cycloalkyl, phenyl, -O-phenyl, -NR11R12, -CH (R15) -NH2, -CH (R15) -NHC (O) O-C1-6 alkyl and -CH (NH2) CH2COOCH3; and R11 and R12 are independently selected from H, -C1-6alkyl, and benzyl; or R11 and R12 are taken together as - (CH2) 3-6-, -C (O) - (CH2) 3- or - (CH2) 2O (CH2) 2-; R13 is selected from -C1-6alkyl, -O-benzyl and -NR11R12; and R14 is -C1-6alkyl or -C 1-6 alkyl- C6-10 aryl, R15 is H, -CH3, -CH (CH3) 2, phenyl or benzyl; R2 is -OR21 or -CH2OR21; and R3 is H or -CH3; where R21 is H, -C (O) -C1-6alkyl, -C (O) -CH (R22) -NH2, -C (O) - CH (R22) -NHC (O) O-C1-6 alkyl or -P (O) (oR 23) 2; R22 is H, -CH3, -CH (CH3) 2, phenyl or benzyl; R23 is H, -C1-6alkyl or phenyl; or R2 taken together with R1 to form -OCR15R16- or -CH20-CR15R16-, and R3 is selected from H and -CH3, wherein R15 and R16 are independently selected from H, -C1-6alkyl and -O-C3 -7, or R15 and R16 are taken together to form> = O; or R2 taken together with R3 to form -CH2-O-CH2- or -CH2-CH2-; or R2 and R3 are both -CH3; Z is selected from -CH- and -N-; R4 is selected from H, C1-8 -alkyl, C1-3 -alkylene-O-C1-8alkyl, C6-10aryl-C1-3 -alkylene, C1-3 -alkylene-O-C6-10aryl, - C1-9 heteroaryl C1-3 alkylene, C3-7 -cycloalkyl, - [(CH2) 2O] 1-3CH3, -C 1-6 alkyl-OC (O) R40, -C 1-6 NR41R42, -C1 -6-C (O) R43, C0-6 -alkylene-morpholinyl, C1-6 -alkylene-SO2-C1-6 alkyl, ** ** Formula R40 is selected from -C1-6alkyl, -O-C1 -6, -C3-7cycloalkyl, -O-C3-7cycloalkyl, phenyl, -O-phenyl, -NR41R42, -CH (R45) -NH2, -CH (R45) -NHC (O) O-C1 6 and -CH (NH2) CH2COOCH3; and R41 and R42 are independently selected from H, -C1-6alkyl, and benzyl; or R41 and R42 are taken together as - (CH2) 3-6-, -C (O) - (CH2) 3- or - (CH2) 2O (CH2) 2-; R43 is selected from -O-C1-6alkyl, -O-benzyl and -NR41R42; and R44 is -C1-6alkyl or -alkylene C0-6- C6-10 aryl; R45 is H, -CH3, -CH (CH3) 2, phenyl or benzyl; a is 0 or 1; R5 is selected from halo, -CH3, -CF3 and -CN; b is 0 or an integer of 1 to 3; each R6 is independently selected from halo, -OH, -CH3, -OCH3, -CN and -CF3; wherein each alkyl group in R1 and R4 is optionally substituted by 1 to 8 fluorine atoms; and wherein the connector methylene biphenyl is optionally substituted with one or two C1-6 alkyl or cyclopropyl; or pharmaceutically acceptable salt thereof.