N-phenpropylcyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase

A compound of formula (I), a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof;

• wherein
• R1 is C1-6alkyl which may be substituted by one or more substituents, which may be the same or different, selected from the list:
• halo, hydroxy, C1-6alkoxy, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkoxy, carbocyclyl, carbocyclyloxy, C1-4alkoxycarbocyclyloxy, heterocyclyl, heterocyclyloxy, —NR2R3, —NR4COR5, —NR4SO2R5, —CONR2R3, —S(O)pR6, —COR7 and —CO2(C1-4alkyl);
• or R1 is carbocyclyl or heterocyclyl, each of which may be substituted by one or more substituents from said list, which substituents may be the same or different, which list further includes C1-6alkyl;
• or R1 is hydrogen, C1-6alkoxy, —NR2 R3 or —NR4SO2R5;
• wherein
• R2 and R3, which may be the same or different, are carbocyclyl or heterocyclyl (each of which may be substituted by C1-4alkyl, hydroxy or C1-4alkoxy);
• or are hydrogen or C1-4alkyl;
• or R2 and R3 together with the nitrogen to which they are attached form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C1-4alkyl)piperazinyl group;
• R4 is hydrogen or C1-4alkyl;
• R5 is C1-4alkyl, CF3, carbocyclyl, C1-4alkylcarbocyclyl, C1-4alkoxycarbocyclyl, heterocyclyl, C1-4alkoxy or —NR2R3;
• R6 is C1-4alkyl, carbocyclyl, heterocyclyl or NR2R3;
• and
• R7 is C1-4alkyl, carbocyclyl or heterocyclyl;
• p is 0, 1, 2 or 3;
• X is the linkage —(CH2)n— or —(CH2)q—O—(wherein Y is attached to the oxygen);
• wherein one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy;
• hydroxy;
• hydroxyC1-3alkyl;
• C3-7cycloalkyl;
• carbocyclyl;
• heterocyclyl;
• or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups;
• n is 3, 4, 5, 6 or 7;
• and q is 2, 3, 4, 5 or 6;
• and
• Y is phenyl or pyridyl, each of which may be substituted by one or more groups R8 which may be the same or different, wherein R8 is hydroxy;
• mercapto;
• halogen;
• cyano;
• acyl;
• amino;
• mono(C1-4alkyl)amino;
• di(C1-4alkyl)amino;
• carbocyclyl or heterocyclyl (either of which is optionally substituted by C1-6alkyl, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C1-6alkylthio or halogen);
• C1-6alkoxy;
• phenoxy;
• C1-6alkylthio;
• phenylthio;
• or alkyl optionally substituted by C1-6alkoxy, haloC1-6alkoxy, C1-6alkylthio, halogen or phenyl;
• or
• two R8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused 5- or 6-membered carbocyclic or heterocyclyic ring, optionally substituted by C1-6alkyl, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C1-6alkylthio or halogen.