N-formylhydroxylamines as neprilysin (NEP) inhibitors, in particular as mixed aminopeptidase N (APN) and neprilysin (NEP) inhibitors

A compound of following formula (II):

• wherein:
• R represents:
• a linear or branched hydrocarbon group comprising from 1 to 6 carbon atoms non-substituted or substituted by one or more aryl groups themselves non-substituted or substituted by one or more groups selected from aryls and linear or branched alkyl groups comprising from 1 to 4 carbons, or
• a Si(R10)3 group, R10 being a linear or branched alkyl group comprising from 1 to 4 carbon atoms,
• R1 represents a linear or branched hydrocarbon group comprising from 1 to 6 carbon atoms substituted by one or more groups selected from:
• an aryl non-substituted or substituted by one or more groups selected from halogens, a phenyl group, a benzyl group, an OR4 group, R4 being selected from hydrogen and a linear or branched alkyl group comprising from 1 to 4 carbon atoms, and combinations thereof,
• a 5 or 6 membered heteroaryl comprising 1 or 2 heteroatoms, each heteroatom being selected from oxygen, nitrogen and sulphur, and
• a 5 or 6 membered cycloheteroalkyl comprising 1 or 2 heteroatoms, each heteroatom being selected from oxygen, nitrogen and sulphur,
• R2 represents:
• a linear or branched hydrocarbon group comprising from 1 to 6 carbon atoms, non-substituted or substituted by one or more groups selected from:
• a group selected from ORS, SR5 and S(O)R5, R5 being selected from hydrogen and a linear or branched alkyl group comprising from 1 to 4 carbons,
• a CO2R6 group, R6 being selected from hydrogen, a linear or branched alkyl group comprising from 2 to 4 carbon atoms and a benzyl group,
• a 5 or 6 membered heteroaryl comprising 1 or 2 heteroatoms, each heteroatom being selected from oxygen, nitrogen and sulphur,
• a 5 or 6 membered cycloalkyl, and
• a 5 or 6 membered cycloheteroalkyl comprising 1 or 2 heteroatoms, each heteroatom being selected from oxygen, nitrogen and sulphur, or
• an aryl, non-substituted or substituted by one or more groups selected from halogens, an OR5 group, R5 having the same definition as above, and combinations thereof, or
• a heteroaryl comprising 1 or more heteroatoms, each heteroatom being selected from oxygen, nitrogen and sulphur, non-substituted or substituted by one or more groups selected from halogens, an OR5 group, R5 having the same definition as above, and combinations thereof,
• R3 represents:
• an OR7 group, R7 being selected from:
• hydrogen,
• a linear or branched alkyl group comprising from 2 to 6 carbon atoms a benzyl group, and
• a CHR8—COOR9, CHR8—O—C(═O)R9 or CHR8—O—C(═O)—OR9 group wherein R8 and R9 are, independently of each other, selected from an alkyl group, an aryl group, an arylalkyl group, a cycloalkyl group, a cycloheteroalkyl group, a heteroalkyl group, a heteroaryl group and a heteroarylalkyl group, and
• m and n are independently of each other an integer selected from 0 and 1,
• the carbon atom bearing R1 having an absolute configuration (R) or (S) and the carbon atom bearing R2 having an absolute configuration (S),
• as well as pharmaceutically acceptable salts and/or solvates thereof.

A pharmaceutical composition comprising at least one compound of following formula (I) and at least one pharmaceutically acceptable excipient;

• wherein:
• R1=(R)—CH2Ph;
• R2=(S)—CH3;
• R3=OH;
• n=m=0;
• R1=(S)—CH2Ph;
• R2=(S)—CH3;
• R3=OH;
• n=m=0;
• R1=(R)—CH2Ph;
• R2=(S)—CH2Ph;
• R3=OH;
• n=m=0;
• R1=(S)—CH2Ph;
• R2=(S)—CH2Ph;
• R3=OH;
• n=m=0;
• R1=(R)—CH2Ph;
• R2=(S)—CH2Ph;
• R3=OH:
• n=0;
• m=1;
• R1=(S)—CH2Ph;
• R2=(S)—CH3;
• R3=OH;
• n=0 m=1;
• R1=(R)—CH2Ph-4-Ph;
• R2=(S)—CH3;
• R3=OH;
• n=m=0;
• R1=(S)—CH2Ph-4-Ph;
• R2=(S)—CH3;
• R=OH;
• n=m=0;
• R1=(S)—CH2Ph;
• R2=(S)—CH2Ph;
• R3=OH;
• n=1;
• m=0,
• R1=(R)—CH2Ph;
• R2=(S)—CH2Ph;
• R3=OH;
• n=1;
• m=0.

A compound of following formula (I):

• wherein:
• R1 is CH2Ph,
• R2 is CH2Ph,
• R3 is OH,
• m=0, and
• n=0.