Cathepsin Y for the development of a medicament for the treatment of pain

A pharmaceutical composition for the treatment of pain, comprising a compound having a general formula:

• 11
• wherein:
• R is selected from the group consisting of hydrogen, alkyl of from 1 to 6 carbon atoms, and where R and R2 are joined to form a ring structure of from 4 to 10 carbon atoms,
• R′ is selected from the group consisting hydrogen, alkyl of from 1 to 6 carbon atoms, and where R′ and R3 are joined to form a ring structure of from 4 to 10 carbon atoms,
• R1 is selected from the group consisting of alkyl of from 1 to 4 carbon atoms substituted with from 1 to 5 substituents selected from the group consisting of (a) aryl of from 6 to 10 carbon atoms, (b) aryl of from 6 to 10 carbon atoms substituted with 1 to 3 substituents selected from the group consisting of alkyl of from 1 to 6 carbon atoms, aryl of from 6 to 10 carbon atoms, alkoxy of from 1 to 6 carbon atoms, aryloxy of from 6 to 10 carbon atoms, hydroxy, cyano, halo and amino, (c) cycloalkyl of from 3 to 8 carbon atoms and (d) heterocycles of from 3 to 14 carbon atoms having from 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein said substituted alkyl group is optionally further substituted with from 1 to 2 hydroxyl groups, alkenyl of from 2 to 4 carbon atoms substituted with from 1 to 4 substituents selected from the group consisting of (a) aryl of from 6 to 10 carbon atoms, (b) aryl of from 6 to 10 carbon atoms substituted with 1 to 3 substituents selected from the group consisting of alkyl of from 1 to 6 carbon atoms, aryl of from 6 to 10 carbon atoms, alkoxy of from 1 to 6 carbon atoms, aryloxy of from 6 to 10 carbon atoms, hydroxy, cyano, halo and amino, (c) cycloalkyl of from 3 to 8 carbon atoms and (d) heterocycles of from 3 to 14 carbon atoms having from 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, aryl of from 6 to 10 carbon atoms, aryl of from 6 to 10 carbon atoms substituted with 1 to 3 substituents selected from the group consisting of alkyl of from 1 to 6 carbon atoms, aryl of from 6 to 10 carbon atoms, alkoxy of from 1 to 6 carbon atoms, aryloxy of from 6 to 10 carbon atoms, hydroxy, cyano, halo and amino, fluorenyl, heterocycles of from 3 to 14 carbon atoms having from 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• R2 and R3 are independently D- or L-amino acid side chains of at least 2 carbon atoms with the proviso that said amino acid side chains do not include the proline side chain;
• R4 is selected from the group consisting of —C(O)CH═N═N, —CH2OH, —C═NOH, and —C(O)R5, where R5 is hydrogen, alkyl of from 1 to 6 carbon atoms, haloalkyl of from 1 to 6 carbon atoms and 1 to 2 halo groups, alkoxy of from 1 to 6 carbon atoms, —NR6R7 where R6 and R7 are independently selected from the group consisting of hydrogen and alkyl of from 1 to 6 carbon atoms, and aryl of from 6 to 10 carbon atoms, and —N(CH3)OCH3;
• X is selected from the group consisting of —O—, —NR9—, and —S— where R9 is selected from the group consisting of hydrogen, alkyl of from 1 to 6 carbon atoms and aryl of from 6 to 10 carbon atoms;
• Y is selected from the group consisting of—C(O)— and —C(S)—;
• m is equal to zero or one;
• and
• n is equal to zero, one or two, or pharmaceutically acceptable salts thereof with the proviso that when R1 is 1-naphthyl, R2 is —CH(CH3)2 (L-isomer), R3 is —CH2-Ø (L-isomer), Y is —C(O)—, m is zero and n is one, then R4 is not —N(CH3)OCH3, with the further proviso that when R′ is diphenylmethyl, R2 is p-(benzyloxy)benzyl (L-isomer), Y is —C(O)—, and m and n are zero, then R4 is not —N(CH3)OCH3, and with still the further proviso that when R1 is (1,2diphenyl)ethenyl, Y is —C(O)—, R2 is —CH2-Ø- (L-isomer), and m and n are zero, then R4 is not —N(CH3)OCH3;
• wherein said compound downregulates Cathepsin Y activity.