Pyranone compounds useful to modulate OMA1 protease

A compound of the formula I

• wherein R1 and R2 taken together are a double bond;
• wherein R3 is the moiety of formula II
• wherein R5 and R6 taken together are forming a 5-, 6- or 7-membered saturated or unsaturated ring;
• wherein R7 is a) cyclopropyl, b) CH3—CH2—, or c) t-butyl;
• wherein R9 is
• a) —NR12SO2-het,
• b) —NR12SO2-phenyl unsubstituted or substituted by one (1) R11,
• c) —CH2—SO2-phenyl unsubstituted or substituted by one (1) R11,
• or d) —CH2—SO2-het;
• wherein het is a 5-, 6- or 7-membered saturated or unsaturated ring containing from one (1) to three (3) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• or any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring or another heterocycle;
• unsubstituted or substituted by one (1) R10;
• wherein R10 is a) —CH3, b) —CN, c) —OH, d) —C(O)OC2H5, e) —CF3, f) —NH2, or g) —C(O)—NH2;
• wherein R11 is a) —CN, b) —F, c) —OH, or d) —NO2;
• and
• wherein R12 is a) —H, or b) —CH3;
• or a stereochemically isomeric form thereof or a pharmaceutically acceptable salt thereof, wherein said compound is provided in an effective amount for the treatment of a mitochondrial disease characterized by OPA1 alterations, wherein the effective amount is obtained after detecting inhibition of OMA1 protease and/or OPA1 cleavage.

A compound of the formula I

• wherein R1 is H—;
• wherein R2 is a) C3-C5 alkyl, b) phenyl-(CH2)2—, c) het-SO2NH—(CH2)2—, d) cyclopropyl-(CH2)2—, e) F-phenyl-(CH2)2—, f) het-SO2NH-phenyl-, or g) F3C—(CH2)2—;
• or
• wherein R1 and R2 taken together are a double bond;
• wherein R3 is the moiety of formula II
• wherein R5 and R6 taken together are forming a 5-, 6- or 7-membered saturated or unsaturated ring;
• wherein R7 is a) cyclopropyl, b) CH3—CH2—, or c) t-butyl;
• wherein R9 is
• a) —NR12SO2-het,
• b) —NR12SO2-phenyl unsubstituted or substituted by one (1) R11,
• c) —CH2—SO2-phenyl unsubstituted or substituted by one (1) R11,
• or d) —CH2—SO2-het;
• wherein het is a 5-, 6- or 7-membered saturated or unsaturated ring containing from one (1) to three (3) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• or any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring or another heterocycle;
• unsubstituted or substituted by one (1) R10;
• wherein R10 is a) —CH3, b) —CN, c) —OH, d) —C(O)OC2H5, e) —CF3, f) —NH2, or g) —C(O)—NH2;
• wherein R11 is a) —CN, b) —F, c) —OH, or d) —NO2;
• and
• wherein R12 is a) —H, or b) —CH3;
• or a stereochemically isomeric form thereof or a pharmaceutically acceptable salt thereof, wherein said compound does not activate OMA1 protease, and wherein said compound is provided in an effective amount for the treatment of a mitochondrial disease characterized by OPA1 alterations, wherein the effective amount is obtained after detecting inhibition of OMA1 protease and/or OPA1 cleavage.