Prodrugs of Succinic Acid for Increasing ATP Production

A compound according to Formula (I)

• or a pharmaceutically acceptable salt thereof, where the dotted bond denotes an optional bond between A and B to form a cyclic structure, and wherein
• Z is —CH2—CH2— or >CH(CH3),
• A and B are independently different or the same and are selected from the group consisting of —OR, —O—R′, —NHR″, —SR′″ and —OH, both A and B are not —OH, wherein R is
• R′ is selected from:
• R′, R″ and R′″ are independently different or identical and is selected from:
• R1 and R3 are independently different or identical and are selected from the group consisting of H, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, O-acyl, O-alkyl, N-acyl, N-alkyl, Xacyl, CH2Xalkyl, CH2CH2CH2OC(═O)CH2CH2COX6R8, and
• X is selected from the group consisting of O, NH, NR6, and S,
• R2 is selected from the group consisting of Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, C(O)CH3, C(O)CH2C(O)CH3, and C(O)CH2CH(OH)CH3,
• p is an integer and is 1 or 2,
• R6 is selected from the group consisting of H, alkyl, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, acetyl, acyl, propionyl, benzoyl, formula (II), and formula (VIII),
• X5 is selected from the group consisting of —H, —COOH, —C(═O)XR6, CONR1R3,
• R9 is selected from the group consisting of H, Me, Et and O2CCH2CH2COXR8,
• R10 is selected from the group consisting of Oacyl, NHalkyl, NHacyl, and O2CCH2CH2COX6R8,
• X6 is O or NR8, and R8 is selected from the group consisting of H, alkyl, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, acetyl, acyl, propionyl, benzoyl, formula (II), and formula (VIII),
• R11 and R12 are independently the same or different and are selected from the group consisting of H, alkyl, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, acetyl, acyl, propionyl, benzoyl, acyl, —CH2Xalkyl, and —CH2Xacyl, where X is selected from the group consisting of O, NR6 and S,
• R13, R14 and R15 are independently different or identical and are selected from the group consisting of H, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, —COOH, O-acyl, O-alkyl, N-acyl, N-alkyl, Xacyl, and CH2Xalkyl,
• Rc and Rd are independently CH2Xalkyl or CH2Xacyl, where X=O, NR6 or S, and alkyl is H, Me, Et, propyl, i-propyl, butyl, iso-butyl, or t-butyl, and acyl is formyl, acetyl, propionyl, isopropionyl, byturyl, tert-butyryl, pentanoyl, benzoyl or the like,
• Rf, Rg and Rh are independently selected from the group consisting of Xacyl, —CH2Xalkyl, —CH2X-acyl and R9,
• alkyl is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, isopentyl, hexyl, isohexyl, heptyl, octyl, nonyl or decyl, and acyl is selected from the group consisting of formyl, acetyl, propionyl, butyryl pentanoyl, benzoyl and the like,
• R20 and R21 are independently different or identical and are H lower alkyl, or R20 and R21 together may form a C4-C7 cycloalkyl or an aromatic group, both of which may optionally be substituted with halogen, hydroxyl or a lower alkyl, or
• R20 and R21 are
• CH2X-acyl, F, CH2COOH, or CH2CO2alkyl, and
• when there is a cyclic bond present between A and B the compound is
• and acyls and alkyls may be optionally substituted,
• with the proviso that the compound is not any one of
• wherein R2 is Me, Et, i-Pr, t-Bu or cycloalkyl and R3 is H and R1 is Me, Et, n-Pr or iso-Pr,