Substituted propanamides as inhibitors of nucleases

A method of treatment of MRE11-related cancer, MRE11-related premature aging and/or MRE11-related neurological diseases, the method comprising the step of administering the compound of general formula (1):

• or pharmaceutically acceptable salts, or solvates thereof, wherein:
• R1 is selected from the group consisting of alkyl;
• aryl;
• cycloalkyl;
• heterocyclyl;
• and heteroaryl;
• wherein each of the alkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of F, Cl, Br, I, OH, CN, N3, ═O, O(C1-C6-alkyl), ═S, SH, S(C1-C6-alkyl), S(O)C1-C6-alkyl, S(O)2C1-C6-alkyl, CF3, C2F5, OCF3, OC2F5, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, ═N—OH, ═N—O(C1-C6-alkyl), NO2, COOH, COO(C1-C6-alkyl), CO(C1-C6-alkyl), CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, (C1-C6-alkyl)-S(O)2—NH—, (C1-C6-alkyl)-S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—(SO)2—, (C1-C6-alkyl)2N—(SO)2—, (C1-C6-alkyl)-CO—NH—, (C1-C6-alkyl)-CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-OCO—NH—, (C1-C6-alkyl)-OCO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-CO—NH—CO—, (C1-C6-alkyl)-CO—N(C1-C6-alkyl)-CO—, NH2—CO—NH—, (C1-C6-alkyl)-NH—CO—NH—, (C1-C6-alkyl)2N—CO—NH—, NH2—CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)2N—CO—N(C1-C6-alkyl)-, NH2—S(O)2—NH—, (C1-C6-alkyl)-NH—S(O)2—NH—, (C1-C6-alkyl)2N—S(O)2—NH—, NH2—S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)2N—S(O)2—N(C1-C6-alkyl)-, C1-C6-alkyl, O—C1-C6-alkyl, O-phenyl, phenyl;
• whereas the C1-C6-alkyl, O-phenyl, phenyl in these moieties can optionally be further substituted by one or more substituents selected independently from:
• F, Cl, Br, C1-C6-alkyl, OH, O—C1-C6-alkyl, SH, SCH3, S(O)C1-C6-alkyl, S(O)2C1-C6-alkyl, CF3, OCF3, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, NO2, COOH, COO(C1-C6-alkyl), CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, NHC(O)C1-C6-alkyl, or NHC(O)NH2;
• R2 is selected from the group consisting of aryl;
• heteroaryl;
• heterocyclyl;
• alkyl and cycloalkyl;
• wherein each of the aryl, heterocyclyl, heteroaryl, alkyl, cycloalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of F, Cl, Br, I, OH, CN, N3, ═O, O(C1-C6-alkyl), ═S, SH, S(C1-C6-alkyl), S(O)C1-C6-alkyl, S(O)2C1-C6-alkyl, CF3, C2F5, OCF3, OC2F5, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, ═N—OH, ═N—O(C1-C6-alkyl), NO2, COOH, COO(C1-C6-alkyl), CO(C1-C6-alkyl), CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, (C1-C6-alkyl)-S(O)2—NH—, (C1-C6-alkyl)-S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—(SO)2—, (C1-C6-alkyl)2N—(SO)2—, (C1-C6-alkyl)-CO—NH—, (C1-C6-alkyl)-CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-OCO—NH—, (C1-C6-alkyl)-OCO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-CO—NH—CO—, (C1-C6-alkyl)-CO—N(C1-C6-alkyl)-CO—, NH2—CO—NH—, (C1-C6-alkyl)-NH—CO—NH—, (C1-C6-alkyl)2N—CO—NH—, NH2—CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)2N—CO—N(C1-C6-alkyl)-, NH2—S(O)2—NH—, (C1-C6-alkyl)-NH—S(O)2—NH—, (C1-C6-alkyl)2N—S(O)2—NH—, NH2—S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)2N—S(O)2—N(C1-C6-alkyl)-, C1-C6-alkyl, O—C1-C6-alkyl, O-phenyl, phenyl, heterocyclyl, heteroaryl;
• whereas the C1-C6-alkyl, O-phenyl, phenyl, heterocyclyl, heteroaryl in these moieties can optionally be further substituted by one or more substituents selected independently from:
• F, Cl, Br, C1-C6-alkyl, OH, O—C1-C6-alkyl, SH, SCH3, S(O)C1-C6-alkyl, S(O)2C1-C6-alkyl, CF3, OCF3, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, NO2, COOH, COO(C1-C6-alkyl), CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, NHC(O)C1-C6-alkyl, or NHC(O)NH2,
• R3 is selected from the group consisting of H;
• aryl;
• cycloalkyl;
• halogen;
• alkyl;
• and heteroaryl,
• wherein each of the aryl, cycloalkyl, alkyl or heteroaryl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of F, Cl, Br, I, OH, CN, N3, ═O, O(C1-C6-alkyl), ═S, SH, S(C1-C6-alkyl), S(O)C1-C6-alkyl, S(O)2C1-C6-alkyl, CF3, C2F5, OCF3, OC2F5, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, ═N—OH, ═N—O(C1-C6-alkyl), NO2, COOH, COO(C1-C6-alkyl), CO(C1-C6-alkyl), CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, (C1-C6-alkyl)-S(O)2—NH—, (C1-C6-alkyl)-S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—(SO)2—, (C1-C6-alkyl)2N—(SO)2—, (C1-C6-alkyl)-CO—NH—, (C1-C6-alkyl)-CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-OCO—NH—, (C1-C6-alkyl)-OCO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-CO—NH—CO—, (C1-C6-alkyl)-CO—N(C1-C6-alkyl)-CO—, NH2—CO—NH—, (C1-C6-alkyl)-NH—CO—NH—, (C1-C6-alkyl)2N—CO—NH—, NH2—CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—CO—N(C1-C6-alkyl)-, (C1-C6-alkyl)2N—CO—N(C1-C6-alkyl)-, NH2—S(O)2—NH—, (C1-C6-alkyl)-NH—S(O)2—NH—, (C1-C6-alkyl)2N—S(O)2—NH—, NH2—S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)-NH—S(O)2—N(C1-C6-alkyl)-, (C1-C6-alkyl)2N—S(O)2—N(C1-C6-alkyl)-, C1-C6-alkyl, O—C1-C6-alkyl, O-phenyl, phenyl;
• whereas the C1-C6-alkyl, O-phenyl, phenyl in these moieties can optionally be further substituted by one or more substituents selected independently from:
• alkyl, O-phenyl, phenyl being optionally substituted by F, Cl, Br, C1-C6-alkyl, OH, O—C1-C6-alkyl, SH, SCH3, S(O)C1-C6-alkyl, S(O)2C1-C6-alkyl, CF3, OCF3, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, NO2, COOH, COO(C1-C6-alkyl), CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, NHC(O)C1-C6-alkyl, or NHC(O)NH2,
• R2 and R3 together with the carbon atoms to which they are bound may also form an aliphatic or aromatic ring structure;
• R4 is selected from the group consisting of H and C1-C6-alkyl;
• R5 is selected from the group consisting of H;
• C1-C6-alkyl;
• and aryl;
• R6 is selected from the group consisting of H and C1-C6-alkyl;
• or R5 and R6 together with the carbon atoms connecting these two substituents may form a cyclopropyl ring, unsubstituted or optionally substituted with alkyl, O-phenyl, phenyl being optionally substituted by F, Cl, Br, C1-C6-alkyl, OH, O—C1-C6-alkyl, SH, SCH3, S(O)C1-C6-alkyl, S(O)2C1-C6-alkyl, CF3, OCF3, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, COOH, COO(C1-C6-alkyl), CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, NHC(O)C1-C6-alkyl, or NHC(O)NH2 to a subject in need thereof.