CB with an acyclic main chain 1 R receptor blocker

Abstract

The present invention generally relates to novel CB 1 receptor binding molecules and their uses.

Description

Technical Field

[0001] The present invention generally relates to novel peripherally restricted CB 1 receptor blockers and their uses.

[0002] Background

[0003] Obesity is a chronic disease that has reached epidemic proportions, with more than one-third (34.9% or 78.6 million) of US adults considered obese. Obesity has been described as a catalyst for many conditions, most notably cardiovascular disease, type 2 diabetes (T2DM), and non-alcoholic fatty liver disease (NAFLD). Although several metabolic factors have been associated with the development of obesity, the molecular mechanisms involved in metabolism have not been fully understood.

[0004] Endocannabinoids (eCBs) are endogenous lipid ligands that interact with the same cannabinoid receptors (CB 1 and CB 2 ), and the cannabinoid receptors (CB 1 and CB 2 ) also recognize the psychoactive component Δ 9 -tetrahydrocannabinol (THC) of the Cannabis genus and mediate its biological effects. By activating the CB 1 receptors, eCBs increase appetite ("the munchies") as well as lipogenesis in adipose tissue and the liver, and induce insulin resistance and dyslipidemia. These effects suggest that the overactive eCB / CB 1 receptor system contributes to the development of visceral obesity, T2DM, and its complications. Accordingly, this has prompted pharmaceutical companies to develop drugs that block the CB 1 receptors as potential treatments for obesity, T2DM, and NAFLD. The first such compound, rimonabant [a global CB 1 receptor antagonist (first generation)], not only effectively reduced the body weight of obese and overweight individuals but also effectively alleviated the associated metabolic abnormalities, including fatty liver, insulin resistance, and T2DM [1-6]. However, due to neuropsychiatric side effects (such as depression, anxiety, and suicidal ideation), rimonabant was withdrawn from the market globally, and the CB 1 receptor is no longer considered an effective therapeutic target for obesity, T2DM, or NAFLD.

[0005] References

[0006] [1]Van Gaal, L.F., Rissanen, A.M., Scheen, A.J., Ziegler, O. & Rossner, S.Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study.Lancet 365, 1389-1397 (2005).

[0007] [2]Pi-Sunyer, F.X., Aronne, L.J., Heshmati, H.M., Devin, J. & Rosenstock, J.Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial.JAMA 295, 761-775 (2006).

[0008] [3]Despres, J.P., Golay, A., Sjostrom, L. & Rimonabant in Obesity-Lipids Study, G.Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia.N Engl J Med 353, 2121-2134 (2005).

[0009] [4]Wierzbicki, A.S., et al.Rimonabant improves cholesterol, insulin resistance and markers of non-alcoholic fatty liver in morbidly obese patients: a retrospective cohort study.Int J Clin Pract 65, 713-715 (2011).

[0010] [5]Hollander,P.Endocannabinoid blockade for improving glycemic control and lipids in patients with type 2 diabetes mellitus.The American journal of medicine 120,S18-28;discussion S29-32(2007).

[0011] [6]Randall,M.D.,Kendall,D.A.,Bennett,A.J.&O′Sullivan,S.E.Rimonabantin obese patients with type 2 diabetes.Lancet 369,555(2007).

[0012] [7]US 2003 / 0199536

[0013] General description

[0014] The inventors of the technology disclosed herein have developed a method by which a peripherally restricted CB 1 receptor antagonist retains the therapeutic benefits of a globally acting CB 1 receptor blocker without causing CNS-mediated side effects; thus, the early promise of CB 1 receptor blockade for the treatment of metabolic syndrome is restored. To this end, the inventors have designed novel compounds that do not penetrate the blood-brain barrier and thus block CB 1 receptors only in peripheral organs such as adipose tissue, liver, skeletal muscle, pancreatic beta cells, and kidney without causing centrally mediated side effects.

[0015] The inventors have also demonstrated that lipophilic compounds that bind to CB 1 receptors and are P-gp substrates; and / or have a brain / plasma ratio below 0.3; and / or have a diphenylethylene or diphenylmethylene moiety exhibit therapeutic benefits without causing CNS-mediated side effects.

[0016] This novel compound is potent in affecting several features of metabolic syndrome.

[0017] Thus, in a first aspect of the invention disclosed herein, there is provided a lipophilic derivative of cannabinoid having a calculated LogP (partition coefficient between n-octanol and water) value in the range from 3 to 17.

[0018] The present invention also provides CB 1 receptor-binding lipophilic compounds, wherein:

[0019] - the compound is a substrate of P-glycoprotein (P-gp); and / or

[0020] - the compound has a brain / plasma ratio of less than 0.3; and / or

[0021] - the compound has a stilbene or bibenzylidene moiety of formula (A):

[0022]

[0023] wherein

[0024] R is a substituent or ring structure as defined in any of the following structures, X is a carbon-containing group (C, C═, CH), a nitrogen-containing group (N, N═, NH) or absent; provided that R is different from H.

[0025] In the compounds of formula (A), each of the phenyl groups may independently be substituted or unsubstituted by 1, 2, 3, 4 or 5 identical or different substituents.

[0026] In some embodiments, the CB 1 receptor-binding lipophilic compound is a substrate of P-gp.

[0027] In some embodiments, the CB 1 receptor-binding lipophilic compound has a brain / plasma ratio of less than 0.3.

[0028] In some embodiments, the CB 1 receptor-binding lipophilic compound comprises a stilbene or bibenzylidene moiety of formula (A), which may optionally be any compound of general formula (I) to general formula (XXXXI) or any of the specifically disclosed compounds.

[0029] As indicated, the compounds of the present invention exhibit therapeutic benefits without causing CNS-mediated side effects. The absence of CNS-mediated side effects is especially due to the interaction between the compounds of the present invention and P-gp (and thus are considered to be "P-gp substrates"), which limits or reduces their penetration into the brain. The absence or reduction of penetration into the brain can be determined qualitatively by means known in the art and, in some cases, quantitatively.

[0030] The brain-plasma concentration ratio, which represents one of the available tools for evaluating the pharmacokinetics of CNS, is a parameter indicating the blood-brain barrier availability of a compound. This value describes the free drug concentration of the compound in the brain, which is considered a parameter for eliciting a relevant pharmacological response at the target site. As indicated, the compounds of the present invention have shown substantially no brain penetration. In the context of this aspect of the present invention, the expression "substantially no brain penetration" means no brain penetration with a brain-plasma ratio in the range from 0.0001 to 0.3. The compounds of the present invention are also characterized by comprising a diphenylethylene or diphenylmethylene moiety of formula (A) as defined herein. In some embodiments, as disclosed herein, the compounds of formula (A) are compounds of formula (I).

[0031] The present invention also provides lipophilic CB 1 receptor-binding compounds having a calculated LogP (partition coefficient between n-octanol and water) value in the range from 3 to 17, wherein the compound comprises a diphenylethylene or diphenylmethylene moiety of formula (A) as defined herein, or is a compound of formula (I) as disclosed herein.

[0032] The present invention also provides compounds of formula (I):

[0033]

[0034] wherein

[0035] R 1 and R 2 each independently of the other is a group selected from -H, halide, -CN, -C 1 -C 5 alkyl-OH and -OH;

[0036] Each of n and m is independently an integer between 0 and 5, specifying the number of substituents on the ring;

[0037] X is selected from nitrogen and -CH-; or X-R 4 can optionally be N=R 4 or C=R 4 ;

[0038] R 3 is selected from H, an optionally substituted carbon-containing group having between 1 and 3 carbon atoms, and a nitrogen atom or nitrogen-containing group;

[0039] R 4 is selected from an optionally substituted carbon-containing group having between 1 and 3 carbon atoms, and a nitrogen atom or nitrogen-containing group;

[0040] or R 3 and R4 Together with the atoms to which they are bonded (carbon atom and X respectively), form a 5-membered or 6-membered carbon ring, which optionally contains heteroatoms selected from N, O, and S between 1 and 3;

[0041] or R 3 and R 4 Together with the atoms to which they are bonded, form a fused ring system, which optionally contains heteroatoms selected from N, O, and S between 1 and 6.

[0042] In some embodiments, X is N.

[0043] In some embodiments, X-R 4 is C=R 4 .

[0044] In some embodiments, X-R 4 is N=R 4 .

[0045] In some embodiments, X is a nitrogen atom and R 4 is a nitrogen-containing group. In such embodiments, the moiety X-R 4 can thus be selected from -N-NH-, -N=N-, and -N-N=(wherein in this selection, the left N is X and the right N is R 4 ).

[0046] In some embodiments, R 3 is a carbon-containing group and R 4 is a nitrogen-containing group.

[0047] In some embodiments, R 3 and R 4 Together with the atoms to which they are bonded, form a 6-membered carbon ring optionally containing 1 or 2 nitrogen atoms.

[0048] In some embodiments, R 3 and R 4 Together with the atoms to which they are bonded, form a 5-membered carbon ring optionally containing 1 or 2 nitrogen atoms.

[0049] In some embodiments, R 3 and R 4 Together with the atoms to which they are bonded, form a fused ring system optionally containing 1, 2, 3, 4, 5, or 6 heteroatoms such as nitrogen atoms.

[0050] In some embodiments, the fused ring system is a bicyclic fused system comprising a 5-membered ring fused to a 5-membered ring, or a 6-membered ring, or a 7-membered ring, or an 8-membered ring. In some embodiments, the fused ring system is a bicyclic fused system comprising a 5-membered ring fused to a 6-membered ring, wherein the fused system contains 1, 2, 3, 4 or 5 heteroatoms. The fused system may also be substituted.

[0051] In some embodiments, the compound has the general formula (II):

[0052]

[0053] wherein

[0054] One of L, L 1 and L 2 is a nitrogen atom, and each of the others of L, L 1 and L 2 is a carbon atom (selected from C, CH or CH 2 );

[0055] Each of R 5 , R 6 and R 7 is independently selected from -H, -C 1 -C 3 alkyl, -C(=O)-OH, -C(=O)-O-R 8 , -C(=O)-NR'R 8 , halide, -CN, -OH and -NR'R”; or

[0056] One of R 5 and R 6 or R 6 and R 7 together with the atom to which they are bonded may form a 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring, which 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring optionally contains from 1 to 3 heteroatoms selected from N, O and S;

[0057] The 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring is also optionally substituted with at least one functional group selected from: -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C1 -C 5 alkyl, -S-C 2 -C 5 alkenyl, -S-C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 2 -C 5 alkenyl, -C(=O)-O-C 2 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 2 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 2 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 1 -C 25Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C2 -C 25 -C≡C- 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 -C-C- 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 -C=C- 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 -C≡C- 3 -C 10 heteroaryl, 2,2,6,6-tetramethylpiperidin-1-yl-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenonyl derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0058] The 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring may optionally be substituted with at least one functional group selected from Structural Formulas (A) to (H):

[0059]

[0060]

[0061] Wherein in each of the functional groups (A) to (H), the wavy line indicates the point or bond of connectivity, j is 0 or 1, and Ra is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C(=O)-C 6 -C 10 aryl and -C(=O)-C 3 -C 10 heteroaryl,

[0062] Among functional group (G) and functional group (H), the side group -NH-Ra group can occur between 1 and 11 times at any position along the carbon ring (in some embodiments, it can be located at a ring atom that is one, two, or three ring atom moves away from an existing group or the N atom within the ring; in some embodiments, the position of the functional group is 1, 2 or 1, 3 or 1, 4, where 1 designates the position of the existing group or the N atom within the ring);

[0063] R 5 、R 6 and R 7 in one of them may be absent;

[0064] R 8 is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl and C 3 -C 10 heteroaryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 alkyl, -S-C 2 -C 5 alkenyl, -S-C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 2 -C 5 alkenyl, -C(=O)-O-C 2 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0065] R 10 selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 、-NO 2 、2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0066] Each of R', R” and R”' is independently selected from -H, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-C2 -C 25 alkyl, -C(=O)-C 2 -C 25 alkenyl, and C 5 -C 25 alkynyl; or one of R', R", and R''' does not exist; and wherein

[0067] N-L, L-L 1 , L 1 -L 2 and L 2 each bond between -C (designated ---) is a single bond or a double bond.

[0068] In some embodiments, R 8 is -C 1 -C 25 alkyl.

[0069] In some embodiments, R 8 is -C 2 -C 25 alkenyl.

[0070] In some embodiments, R 8 is -C 2 -C 25 alkynyl.

[0071] In some embodiments, R 8 is -C 6 -C 10 aryl.

[0072] In some embodiments, R 8 is C 3 -C 10 heteroaryl.

[0073] In some embodiments, R 8 is -C 1 -C 25 alkyl substituted with at least one functional group selected from: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 , -NH-C 2 -C 25 Alkenyl-NH2 、 -NH-C 2 -C 25 alkynyl-NH 2 、 -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl、 -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl、 -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl、 -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl、 -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl、 -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl、 -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl、 -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl、 -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl、 -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”'、 -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”'、 -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”'、 -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl、 -NH-C2 -C 25 Vinylene - C(=O) - O - C 1 -C 25 Alkyl, -NH - C 2 -C 25 Ethynylene - C(=O) - O - C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene - NR'R”R”', -NHC(=O)C 2 -C 25 Vinylene - NR'R”R”', -NHC(=O)C 2 -C 25 Ethynylene - NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene - OH, -NHC(=O)C 2 -C 25 Vinylene - OH, -NHC(=O)C 2 -C 25 Ethynylene - OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene - C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Vinylene - C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Ethynylene - C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene - C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25Vinylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Ethynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, Idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0074] In some embodiments, R 8 is -C substituted with at least one functional group selected from the following 2 -C 25 Alkenyl: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 -NH-NH2 、 -NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、 -NH-C 2 -C 25 Alkenyl-NH 2 、 -NH-C 2 -C 25 Alkynyl-NH 2 、 -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C2 -C 25 -alkynyl-NR'R”R”', -NHC(=O)C 1 -C 25 -alkyl-OH, -NHC(=O)C 2 -C 25 -alkenyl-OH, -NHC(=O)C 2 -C 25 -alkynyl-OH, -NHC(=O)C 6 -C 10 -aryl, -NHC(=O)C 3 -C 10 -heteroaryl, -NHC(=O)C 1 -C 25 -alkyl-C 6 -C 10 -aryl, -NHC(=O)C 2 -C 25 -alkenyl-C 6 -C 10 -aryl, -NHC(=O)C 2 -C 25 -alkynyl-C 6 -C 10 -aryl, -NHC(=O)C 3 -C 10 -heteroaryl, -NHC(=O)C 1 -C 25 -alkyl-C 3 -C 10 -heteroaryl, -NHC(=O)C 2 -C 25 -alkenyl-C 3 -C 10 -heteroaryl, -NHC(=O)C 2 -C 25 -alkynyl-C 3 -C 10 -heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0075] In some embodiments, R 8 is -C substituted with at least one functional group selected from the following 2 -C 25Alkynyl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 , -NH-C 2 -C 25 Alkenyl-NH 2 , -NH-C 2 -C 25 Alkynyl-NH 2 , -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkynylene-C 3 -C 10 heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivative, -pyridin-3-C(=O)-OH and -NR'R”R”'.

[0076] In some embodiments, R 8 is -C substituted with at least one functional group selected from the following 6 -C 10 aryl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25Alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkynylene-C 3 -C10 Heteroaryl, 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl radical, - NHC(=O)C(CH 3 ) 2 -O - aryl - Cl, - NHC(=O)CH 2 C(CH 3 ) 2 -O - aryl - Cl, idebenone derivatives, - pyridine - 3 - C(=O)-OH and - NR'R”R”'.

[0077] In some embodiments, R 8 is - C substituted with at least one functional group selected from the following 3 -C 10 heteroaryl: hydroxy, amine, halide, - ONO 2 , - NO 2 , - S -, - S - C 1 -C 5 alkyl, - S - C 1 -C 5 alkenyl, - S - C 1 -C 5 alkynyl, - C(=O)-, - C(=O)-C 1 -C 25 alkyl, - C(=O)-O - C 1 -C 5 alkyl, - C(=O)-O - C 1 -C 5 alkenyl, - C(=O)-O - C 1 -C 5 alkynyl, - C(=O)-NR'R”R”', - C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, - C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, - C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, - C(=O)-OR 10 , - O - C 1 -C 5 alkyl, - O - C 1 -C 5 alkenyl, - O - C 1 -C 5 alkynyl, - NH - NH 2 , - NH - NH - C(=O)-C 1 -C 25 alkyl, - NH - NH - C(=O)-C 2 -C25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C2 -C 25 Vinylene - OH, -NHC(=O)C 2 -C 25 Ethynylene - OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene - C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Vinylene - C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Ethynylene - C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene - C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Vinylene - C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Ethynylene - C 3 -C 10 Heteroaryl, 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl radical, -NHC(=O)C(CH 3 ) 2 -O - Aryl - Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O - Aryl - Cl, Idebenone derivative, -Pyridine - 3 - C(=O)-OH and -NR'R”R”'.

[0078] In some embodiments, among all the compounds of the present invention, those compounds in which R 8 is C 7 -C 12 alkyl are excluded. In this case, when R 8 is referred to as an alkyl having between 1 and 25 carbon atoms (including 1 and 25 carbon atoms), i.e., C 1 -C 25alkyl or C 1 -C 25 When the alkyl group is in the form of an alkylene group, taking into account the exclusions mentioned above, the alkyl group or alkylene group can be stated as C 1 -C 6 alkyl / alkylene and C 13 -C 25 alkyl / alkylene.

[0079] In some embodiments, the 5-membered carbocyclic ring, 6-membered carbocyclic ring, 7-membered carbocyclic ring or 8-membered carbocyclic ring is substituted with at least one functional group selected from Structure (A) to Structure (H):

[0080]

[0081] In some embodiments, in each of the functional groups (A) to (H), j is 0.

[0082] In some embodiments, in each of the functional groups (A) to (H), j is 1.

[0083] In some embodiments, the side group -NH-Ra group appears once. In some embodiments, -NH-Ra is located at a ring atom that is one move away from an existing group or an N atom within the ring. In some embodiments, -NH-Ra is located at a ring atom that is two moves away from an existing group or an N atom within the ring. In some embodiments, -NH-Ra is located at a ring atom that is three moves away from an existing group or an N atom within the ring.

[0084] The present invention also provides a compound of formula (II) as defined herein.

[0085] As used herein, a "carbon-containing group having between 1 and 3 carbon atoms" is any carbon chain or carbon-containing group or carbon-containing functional group that contains from 1 to 3 carbon atoms (including 1 and 3 carbon atoms), and the carbon atoms can be bonded to each other or can be separated or interrupted by one or more atoms that are not carbon. In some embodiments, the carbon-containing group is a group of a chain containing from 1 to 3 carbon atoms, and each carbon atom is connected to another atom. Non-limiting examples of such carbon groups include -CH, -CH 2 -, -CH 3 -, -CH-CH-, -CH 2 -CH-, -CH=CH-, -CH-CH 2 -, -CH 2 -CH 2 -CH 2 -, -CH 2 -CH-CH-, -CH 2-CH=CH- and others. Non-limiting examples of such carbon groups that include one or more atoms that are not carbon (e.g., heteroatoms such as nitrogen) include -CH-NH-, -C=N-, -CH 2 -NH-, -N-CH 3 -, -CH-NH-CH-, -CH 2 -CH-NH-, -CH=N-CH-, -CH-NH-CH 2 -, -CH 2 -NH-CH 2 -CH 2 -, -CH 2 -CH-NH-CH-, -CH 2 -CH=CH-NH-, -CH 2 -N=CH-NH-, -CH 2 -NH-CH=CH-NH-, -CH 2 -N=CH- and others. Such groups may be optionally substituted.

[0086] A carbon-containing group having between 1 and 3 carbon atoms may optionally be designated as -C 1 -C 3 alkyl, -C 2 -C 3 alkenyl or -C 2 -C 3 alkynyl, or any substituted form thereof.

[0087] "A nitrogen atom or nitrogen-containing group" is similarly any atomic group or functional group that contains one or more nitrogen atoms. The nitrogen atom may be substituted by a hydrogen atom or a carbon group or any other functional group. In some embodiments, the nitrogen-containing group is a group such as -NH-, -NH 2 -, -NHR′, NH 2 R′, NHR'R″, NR′R″R″′, where each of R′, R″, and R″′ is further defined herein. The nitrogen-containing group may alternatively be selected from nitrogen-containing rings. Non-limiting examples of such nitrogen-containing rings include aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, imidazolyl, pyrazolidinyl, pyrazolyl, triazolyl, piperidinyl, pyridyl, piperazinyl, diazinyl, triazinyl, trihydrotriazinyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, and others. The nitrogen atom or nitrogen-containing group may exist in the form of a charged nitrogen atom (ammonium).

[0088] As disclosed herein, for example with reference to variables R 3 and R 4, such that any two of the recited groups together with the atoms to which they are bonded (when referring to variables R 3 and R 4 , are a carbon atom and X, respectively) can form a 5-membered or 6-membered carbon ring, which 5-membered or 6-membered carbon ring optionally contains heteroatoms, such as between 1 and 3 heteroatoms (including 1 and 3 heteroatoms), where the heteroatoms can be selected from N, O, and S. Other non-carbon atoms may also be present. The 5-membered or 6-membered ring contains one or more carbon atoms in ring form (forming a carbocyclic structure). The carbon chain forming the carbocyclic ring can be interrupted by one or more heteroatoms, together forming a heterocyclic structure.

[0089] In some embodiments, the heterocycle can contain 1, 2, or 3 nitrogen atoms. In some embodiments, the heterocycle can contain 1, 2, or 3 oxygen atoms. In some embodiments, the heterocycle can contain 1, 2, or 3 sulfur atoms.

[0090] In some embodiments, the heterocycle can contain 1, 2, or 3 nitrogen atoms and / or oxygen atoms and / or sulfur atoms.

[0091] In some embodiments, the heterocycle can contain 1 or 2 nitrogen atoms.

[0092] Optionally, variables R 3 and R 4 together with the atoms to which they are bonded (when referring to variables R 3 and R 4 , are a carbon atom and X, respectively) can form a fused ring system as defined.

[0093] R 8 is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, and -C 3 -C 10 heteroaryl. As used herein with reference to R 8 or any other variable, alkyl, alkenyl, and alkynyl are each as known in the art.

[0094] When R 8 or any other group is C 1 -C 25 alkyl, it can be linear, branched, or cyclic, and can optionally be substituted by one or more substituents as defined. In some embodiments, R 8is a linear alkyl group that contains a number of carbon atoms selected from between 1 and 25, between 1 and 20, between 1 and 10, between 5 and 25, between 5 and 20, between 10 and 25, between 10 and 20, between 15 and 25, between 15 and 20, or between 20 and 25 carbon atoms. In some embodiments, the linear alkyl group contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. In some embodiments, the linear alkyl group contains 6, 10, 16, or 18 carbon atoms.

[0095] When the alkyl group is substituted at both ends, it can be considered an alkylene group.

[0096] In some embodiments, the alkyl group is non-linear, branched, or cyclic -C 5 -C 25 alkyl.

[0097] When R 8 or any other group is C 5 -C 25 alkenyl, it can be linear, branched, or cyclic and contains one or more double bonds in the cis or trans configuration. The double bond can be a double bond in the chain or a terminal double bond. When R 8 is a cyclic alkenyl, the double bond can be within the ring or outside the ring. In some embodiments, R 8 is a linear alkenyl that contains a number of carbon atoms selected from between 5 and 25, between 5 and 20, between 5 and 10, between 10 and 25, between 10 and 20, between 15 and 25, between 15 and 20, or between 20 and 25 carbon atoms. In some embodiments, the linear alkenyl contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. In some embodiments, the linear alkenyl contains between 1 and 10 double bonds, each of which can independently be in the cis or trans configuration. When the alkenyl group is substituted at both ends, it can be considered an alkenylene group. When R 8 or any other group is C 5 -C 25 alkynyl, it can be linear, branched, or cyclic and contains one or more triple bonds. The triple bond can be a bond in the chain or a terminal bond. When R 8 is a cyclic alkynyl, the triple bond can be within the ring or outside the ring. In some embodiments, R 8is a linear alkynyl group that contains a number of carbon atoms selected from among: between 5 and 25, between 5 and 20, between 5 and 10, between 10 and 25, between 10 and 20, between 15 and 25, between 15 and 20, or between 20 and 25. In some embodiments, the linear alkynyl group contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. In some embodiments, the linear alkynyl group contains between 1 and 5 triple bonds. When the alkynyl group is substituted at both ends, it can be considered an alkynylene group.

[0098] In some embodiments, the alkyl, alkenyl, or alkynyl group can be selected from CH 3 (CH 2 ) 3 -, CH 3 (CH 2 ) 4 -, CH 3 (CH 2 ) 5 -, CH 3 (CH 2 ) 6 -, CH 3 (CH 2 ) 7 -, CH 3 (CH 2 ) 8 -, CH 3 (CH 2 ) 9 -, CH 3 (CH 2 ) 10 -, CH 3 (CH 2 ) 11 -, CH 3 (CH 2 ) 12 -, CH 3 (CH 2 ) 13 -, CH 3 (CH 2 ) 14 -, CH 3 (CH 2 ) 15 -, CH 3 (CH 2 ) 16 -, CH 3 (CH 2 ) 17 -、CH3 (CH 2 ) 18 -, CH 3 (CH 2 ) 19 -, CH 3 (CH 2 ) 20 -, CH 3 (CH 2 ) 21 -, CH 3 (CH 2 ) 22 -, CH 3 (CH 2 ) 23 -, (CH 3 ) 2 CHCH 2 -, CH 3 (CH 2 ) 3 CH=CH(CH 2 ) 7 -, CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 7 -, CH 3 (CH 2 ) 8 CH=CH(CH 2 ) 4 -, CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 7 -, CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 7 -, CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 9 -, CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH 2 ) 7 -, CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH2 ) 7 -、CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 7 -、CH 3 (CH=CH) 2 -、CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CHCH 2 -CH=CHCH 2 CH=CH(CH 2 ) 3 -、CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 -CH=CH(CH 2 ) 3 -、CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 11 -、CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 CH=CH-CH 2 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 2 -、CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 CH=CH-CH 2 CH=CH(CH 2 ) 4 -、CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 4 -、CH 3 (CH 2 )4 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 6 -、CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 -CH=CH(CH 2 ) 5 -、CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 11 -、CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 9 -、CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 13 -、CH 3 (CH 2 ) 7 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 3 -、C 6 H 5 CH=CH-、CH 3 (CH 2 ) 3 C≡C(CH 2 ) 7 -、CH 3 (CH 2 ) 5 C≡C(CH 2 ) 7 -、CH 3 (CH 2 ) 8 C≡C(CH 2 ) 4 -、CH 3 (CH 2 ) 7 C≡C-(CH 2 ) 7 -、CH 3 (CH 2 ) 7C≡C(CH 2 ) 7 -、CH 3 (CH 2 ) 5 C≡C(CH 2 ) 9 -、CH 3 (CH 2 ) 4 C≡CCH 2 CH=CH(CH 2 ) 7 -、CH 3 (CH 2 ) 4 CH=CHCH 2 C≡C(CH 2 ) 7 -、CH 3 (CH 2 ) 4 C≡CCH 2 C≡C(CH 2 ) 7 -、CH 3 CH 2 C≡CCH 2 CH=CHCH 2 CH=CH(CH 2 ) 7 -、CH 3 (C≡C) 2 -、CH 3 (CH 2 ) 4 C≡CCH 2 CH=CHCH 2 -CH=CHCH 2 CH=CH(CH 2 ) 3 -、CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CHCH 2 C≡CCH 2 CH=CH(CH 2 ) 3 -、CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 C≡CCH 2 CH=CHCH 2 -CH=CH(CH 2 ) 3 -、CH 3 (CH2 ) 7 C≡C(CH 2 ) 11 -, CH 3 CH 2 C≡CCH 2 CH=CHCH 2 C≡CCH 2 CH=CHCH 2 C≡CCH 2 -CH=CH(CH 2 ) 2 -, CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 C≡C-CH 2 C≡C(CH 2 ) 4 -, CH 3 (CH 2 ) 4 C≡CCH 2 CH=CHCH 2 C≡C(CH 2 ) 4 -, CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CHCH 2 C≡C(CH 2 ) 6 -, CH 3 (CH 2 ) 4 C≡CCH 2 CH=CHCH 2 C≡CCH 2 -CH=CH(CH 2 ) 5 -, CH 3 (CH 2 ) 5 C≡C(CH 2 ) 11 -, CH 3 (CH 2 ) 7 C≡C(CH 2 ) 9 -, CH 3 (CH 2 ) 7 C≡C(CH 2 ) 13 -, CH 3 (CH 2 )7 C≡CCH 2 CH=CH-CH 2 C≡C(CH 2 ) 3 -C 6 H 5 C≡C- and alkenylene groups derived from DHA (all-cis-docosa-4,7,10,13,16,19-hexaenoic acid).

[0099] When R 8 or any other group is C 6 -C 10 aryl, as is known in the art, the aryl group can be any aromatic system containing between 6 and 10 atoms (usually carbon atoms). The aryl group can be a single aromatic ring, such as a phenyl ring or a benzyl ring; a group containing two or more ring structures, one or more of which are aromatic, such as a diphenyl group; or a fused ring system containing at least one aromatic ring, such as a fused phenyl ring and a naphthyl group.

[0100] When R 8 or any other group is C 3 -C 10 heteroaryl, the group contains one or more heteroatoms in the ring structure. Such groups can contain nitrogen, oxygen or sulfur atoms as ring atoms. Non-limiting examples include pyrrolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl, isoquinolinyl, furyl, thienyl, oxazolyl, benzoxazolyl, thiazolyl, benzothiazolyl, benzofuryl, benzodioxolyl, benzothienyl and others. Substitution of the heteroaryl group can occur at any position of the heteroaryl group, usually at any carbon atom. For example, the pyridyl group can be substituted at the ortho, meta or para positions to the N atom.

[0101] In some embodiments, in the compounds of formula (II), R 5 or R 6 or R 7 is -C(=O)-O-R 8 or -C(=O)-NR′R 8 , and R 8 is -C 1 -C 25 alkyl, which is, for example, selected from -(CH 2 ) 8 CH=CH(CH 2 ) 7 CH 3 、-(CH 2 ) 2 -、-(CH 2 )15 CH 3 、-(CH 2 ) 15 CH 3 and -(CH 2 ) 2 CH=CH(CH 2 CH=CH) 5 CH 2 CH 3 .

[0102] In some embodiments, in the compound of formula (II), R 6 or R 7 is -C(=O)-OR 8 or -C(=O)-NR′R 8 , and R 8 Selected from 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH, and -NR'R"R"'.

[0103] The group "2,2,6,6-tetramethylpiperidin-1-ol-4-yl" is a group having the following structure:

[0104] wherein z is 1, Rf is H, and wherein the dashed bond is a single bond. However, also included are groups wherein Z is zero, the dashed bond is a single bond or a double bond, and wherein Rf is H or selected from halide, -CN, -OH, -C 1 -C 25 Alkyl, -C 2 -C 25 Alkenyl, -C 2 -C 25 Alkynyl, -C 6 -C 10 Aryl, each of which is optionally substituted with at least one functional group selected from the group consisting of hydroxyl, amine, halide, -C 1 -C 5 Alkyl, -C 2 -C 5 Alkenyl, -C 2 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-OC 1 -C 5 Alkyl, -C(=O)-OC 1 -C5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR′R″R″′, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 , -NO 2 and -NR′R″R″′, as defined herein.

[0105] In some embodiments, in groups where Z is zero, the groups can be selected from:

[0106]

[0107] The group “-NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl” designates a substituted aryl group, wherein the chlorine atom and the ether group are substituted ortho, meta, or para to each other on the aryl structure. In some embodiments, the group has the following structure:

[0108]

[0109] “Idebenone group derivative” is a group having the following structure:

[0110] where k is an integer between 0 and 25.

[0111] In some embodiments, k is between 1 and 25, between 1 and 20, between 1 and 15, between 1 and 10, between 1 and 5, between 5 and 25, between 5 and 20, between 5 and 10, between 10 and 25, or between 10 and 20. In some embodiments, k is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. In some embodiments, k is 10.

[0112] The group “-pyridin-3-C(=O)-OH” is a nicotinic acid derivative, wherein the substitution on the pyridine ring can be at any position relative to the carboxylic acid group or relative to the ring nitrogen atom.

[0113] The group “-NR′R″R″′” designates an amine, which can be a primary, secondary, tertiary, or quaternary amine. Each of the R groups can be selected as disclosed herein. In some embodiments, each of R′, R″, and R″′ is independently -H, -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-C 2 -C 25 alkyl, -C(=O)-C 2 -C 25 alkenyl or C 5 -C 25 alkynyl. In the case where the group designates a charged nitrogen atom (ammonium), three R groups are present and can be selected as indicated. In the case where the group designates an uncharged nitrogen atom, one of R′, R″, and R″′ is absent, and the remaining two groups can each be selected as indicated herein.

[0114] As listed herein, in the compounds of formula (II), R 5 or R 6 or R 7 can be -C(=O)-O-R 8 or -C(=O)-NR′R 8 , where R 8 is selected as above. Each of the groups selected for R 8 can be substituted or unsubstituted. In some embodiments, the groups selected for R 8 , namely -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, and -C 6 -C 10 aryl, can be substituted with at least one functional group selected from the following: hydroxy (-OH), amine (primary, secondary, tertiary, or quaternary), halide (selected from F, Br, Cl, and I), -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -ONO 2 , -NO 2 , 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O - aryl - Cl, idebenone derivatives, -pyridine - 3 - C(=O)-OH and -NR'R”R”'.

[0115] In some embodiments, R 5 or R 6 or R 7 is -C(=O)-O - R 8 and R 8 is selected as described above. In some embodiments, R 8 is -C 1 -C 25 alkyl. In some embodiments, -C 1 -C 25 alkyl is selected from optionally substituted -(CH 2 ) 8 CH = CH(CH 2 ) 7 CH 3 , -(CH 2 ) 2 , -(CH 2 ) 15 CH 3 , -(CH 2 ) 15 CH 3 and -(CH 2 )2 CH=CH(CH 2 CH=CH) 5 CH 2 CH 3 。In some embodiments, the groups mentioned above are replaced by -NR'R”R”', where one of said R', R” and R”' is absent, and the other groups among R', R” and R”' are selected from -H, -C(=O)-, -C(=O)-C 1 -C 25 -alkyl, -C(=O)-O-C 1 -C 5 -alkyl, -C(=O)-O-C 1 -C 5 -alkenyl, -C(=O)-O-C 1 -C 5 -alkynyl, -C(=O)-NR'R”R”' and -C(=O)-OR 10 , as defined herein. In some embodiments, the group -NR'R”R”' is thus -NHR”' (R' is absent and R” = H), where R”' is -H, -C(=O)-, -C(=O)-O-C 1 -C 5 -alkyl, -C(=O)-O-C 1 -C 5 -alkenyl, -C(=O)-O-C 1 -C 5 -alkynyl, -C(=O)-NR'R”R”' or -C(=O)-OR 10 。In some embodiments, R”' is -C(=O)-, -C(=O)-C 1 -C 25 -alkyl, -C(=O)-O-C 1 -C 5 -alkyl, -C(=O)-O-C 1 -C 5 -alkenyl or -C(=O)-O-C 1 -C 5 -alkynyl. In some embodiments, R”' is -C(=O)- or -C(=O)-C 1 -C 25 -alkyl.

[0116] In some embodiments, R 5 or R 6 or R 7 is -C(=O)-O-R 8 and R 8 is selected from -(CH 2 ) 8 CH=CH(CH2 ) 7 CH 3 、-(CH 2 ) 2 -、-(CH 2 ) 15 CH 3 、-(CH 2 ) 15 CH 3 、-(CH 2 ) 2 -NHC(=O)(CH 2 ) 7 CH=CH(CH 2 ) 7 CH 3 and -(CH 2 ) 2 CH=CH(CH 2 CH=CH) 5 CH 2 CH 3 .

[0117] In some embodiments, R 5 or R 6 or R 7 is -C(=O)-O-(CH 2 ) 8 CH=CH(CH 2 ) 7 CH 3 、-C(=O)-O-(CH 2 ) 2 -、-C(=O)-O-(CH 2 ) 15 CH 3 、-C(=O)-O-(CH 2 ) 15 CH 3 、-C(=O)-O-(CH 2 ) 2 -NHC(=O)(CH 2 ) 7 CH=CH(CH 2 ) 7 CH 3 and -C(=O)-O-(CH 2 ) 2 CH=CH(CH 2 CH=CH) 5 -CH 2 CH 3 .

[0118] In some embodiments, R 5 or R6 or R 7 is -C(=O)-NR'R 8 and R 8 is selected as described above. In some embodiments, R 8 is -C 1 -C 25 alkyl. In some embodiments, -C 1 -C 25 alkyl is selected from optionally substituted -(CH 2 ) 8 CH=CH(CH 2 ) 7 CH 3 、-(CH 2 ) 2 -、-(CH 2 ) 15 CH 3 、-(CH 2 ) 15 CH 3 and -(CH 2 ) 2 CH=CH(CH 2 CH=CH) 5 CH 2 CH 3 .

[0119] In some embodiments, R 5 or R 6 or R 7 is -C(=O)-NR'R 8 and R 8 is selected from -(CH 2 ) 8 CH=CH(CH 2 ) 7 CH 3 、-(CH 2 ) 2 -、-(CH 2 ) 15 CH 3 、-(CH 2 ) 15 CH 3 、-(CH 2 ) 2 -NHC(=O)(CH 2 ) 7 CH=CH(CH 2 ) 7 CH 3 and -(CH 2 ) 2 CH=CH(CH 2(CH=CH) 5 CH 2 CH 3 。In some embodiments, R' is H.

[0120] In some embodiments, R 5 or R 6 or R 7 is -C(=O)-NH-(CH 2 ) 8 CH=CH(CH 2 ) 7 CH 3 、-C(=O)-NH-(CH 2 ) 2 -、-C(=O)-NH-(CH 2 ) 15 CH 3 、-C(=O)-NH-(CH 2 ) 15 CH 3 and -C(=O)-NH-(CH 2 ) 2 -NHC(=O)(CH 2 ) 7 CH=CH(CH 2 ) 7 CH 3 and -C(=O)-NH-(CH 2 ) 2 CH=CH-(CH 2 (CH=CH) 5 CH 2 CH 3 。

[0121] In some embodiments, in the compound of formula (II), L is a nitrogen atom (or a nitrogen atom-containing group), and each of L 1 and L 2 is a carbon atom (or a carbon atom-containing group).

[0122] In some embodiments, L is a nitrogen atom (or a nitrogen atom-containing group), each of L 1 and L 2 is a carbon atom (or a carbon atom-containing group), the bond between N and L is a single bond, the bond between L and L 1 is a double bond, and the bond between L 1 and L 2 is a single bond.

[0123] In some embodiments, R 5 is absent.

[0124] In some embodiments, the compound is a compound of formula (III):

[0125]

[0126] wherein R 1 、R 2 、n, m, R 6 and R 7 are each as defined herein, and wherein --- designates a single bond or a double bond (in the case where it is a double bond, the variable R 7 bearing a carbon atom does not bear a bond to a hydrogen atom).

[0127] As indicated herein, each of R 6 and R 7 can each independently be selected from -H, -C 1 -C 3 alkyl, -C(=O)-OH, -C(=O)-O-R 8 、-C(=O)-NR'R 8 、halide, -CN, -OH and -NR'R''; or

[0128] R 6 and R 7 together with the atoms to which they are bonded can form a 5-membered carbon ring, a 6-membered carbon ring, a 7-membered carbon ring or an 8-membered carbon ring, the 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring optionally containing from 1 to 3 heteroatoms selected from N, O and S. Substitution can be as indicated above.

[0129] In some embodiments, R 7 is H and R 6 is selected from -C 1 -C 3 alkyl, -C(=O)-O-R 8 、-C(=O)-NR'-R 8 、halide, -CN, -OH and -NR'R''; wherein R 8 is as defined herein.

[0130] In some embodiments, R 6 is -C(=O)-NR'R 8 ; and R 8 is as defined herein.

[0131] In some embodiments, R 6 is -C(=O)-NHR 8 ; and R 8 is as defined herein.

[0132] In some embodiments, the bond --- is a double bond.

[0133] In some embodiments, the bond --- is a single bond.

[0134] In some embodiments, the compound has the general formula (IV):

[0135]

[0136] wherein R 1 , R 2 , n, m and R 8 are each as defined herein.

[0137] In some embodiments, R 8 is an optionally substituted C 1 -C 25 alkyl, as disclosed and selected herein.

[0138] In some embodiments, n is 2 and m is 1.

[0139] In some embodiments, R 1 and R 2 are each a halide.

[0140] In some embodiments, each of R 1 and R 2 is a chlorine atom.

[0141] In some embodiments, the compound has the formula (V):

[0142]

[0143] wherein R 8 is as defined herein.

[0144] In some embodiments, for the compounds of formula (IV) and / or formula (V), R 8 can be:

[0145] -C 1 -C 25 alkyl substituted with at least one functional group selected from: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2, -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C10 Heteroaryl, -NHC(=O)C 2 -C 25 Vinylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Ethynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridin-3-C(=O)-OH and -NR'R”R”'; or

[0146] -C substituted with at least one functional group selected from the following 2 -C 25 Alkenyl: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 , -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C25 Vinylene - NR'R”R”', - NH C(=O) C 2 - C 25 Ethynylene - NR'R”R”', - NH C(=O) C 1 - C 25 Alkylene - OH, - NH C(=O) C 2 - C 25 Vinylene - OH, - NH C(=O) C 2 - C 25 Ethynylene - OH, - NH C(=O) C 6 - C 10 Aryl, - NH C(=O) C 3 - C 10 Heteroaryl, - NH C(=O) C 1 - C 25 Alkylene - C 6 - C 10 Aryl, - NH C(=O) C 2 - C 25 Vinylene - C 6 - C 10 Aryl, - NH C(=O) C 2 - C 25 Ethynylene - C 6 - C 10 Aryl, - NH C(=O) C 3 - C 10 Heteroaryl, - NH C(=O) C 1 - C 25 Alkylene - C 3 - C 10 Heteroaryl, - NH C(=O) C 2 - C 25 Vinylene - C 3 - C 10 Heteroaryl, - NH C(=O) C 2 - C 25 Ethynylene - C 3 - C 10 Heteroaryl, 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl radical, - NH C(=O) C(CH 3 ) 2 - O - Aryl - Cl, - NH C(=O) CH 2 C(CH 3 ) 2 - O - Aryl - Cl, idebenone derivative, - pyridine - 3 - C(=O) - OH and - NR'R”R”'; or

[0147] - C substituted with at least one functional group selected from the following 2 - C25 Alkynyl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkynylene-C 3 -C 10 heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivative, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0148] -C substituted with at least one functional group selected from the following 6 -C 10 aryl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10Heteroaryl, 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl radical, - NHC(=O)C(CH 3 ) 2 -O - aryl - Cl, - NHC(=O)CH 2 C(CH 3 ) 2 -O - aryl - Cl, idebenone - based derivatives, - pyridine - 3 - C(=O)-OH and - NR'R”R”'; or

[0149] -C substituted with at least one functional group selected from the following 3 -C 10 Heteroaryl: hydroxy, amine, halide, - ONO 2 , - NO 2 , - S -, - S - C 1 -C 5 Alkyl, - S - C 1 -C 5 Alkenyl, - S - C 1 -C 5 Alkynyl, - C(=O)-, - C(=O)-C 1 -C 25 Alkyl, - C(=O)-O - C 1 -C 5 Alkyl, - C(=O)-O - C 1 -C 5 Alkenyl, - C(=O)-O - C 1 -C 5 Alkynyl, - C(=O)-NR'R”R”', - C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, - C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, - C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, - C(=O)-OR 10 , - O - C 1 -C 5 Alkyl, - O - C 1 -C 5 Alkenyl, - O - C 1 -C 5 Alkynyl, - NH - NH 2 , - NH - NH - C(=O)-C 1 -C 25 Alkyl, - NH - NH - C(=O)-C 2 -C 25 Alkenyl, - NH - NH - C(=O)-C 2-C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C10 Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25Vinylene-OH, -NHC(=O)C 2 -C 25 Ethynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Vinylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Ethynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Vinylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Ethynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0150] In some embodiments, in the compound of formula (II), L is a nitrogen atom, L 1 and L 2 each is a carbon atom, the bond between N and L is a single bond, the bond between L and L 1 is a double bond, the bond between L 1 and L 2 is a single bond, and the bond between L 2 and C is a double bond.

[0151] In some embodiments, the compound has the general formula (VI):

[0152]

[0153] wherein R 1 、R 2 、n、m、R 6 and R 7 are each as defined herein.

[0154] In some embodiments, R 6 is selected from -C 1 -C 3 alkyl, -C(=O)-O-R 8 、-C(=O)-NR'-R 8 、halide, -CN, -OH and -NR'R”.

[0155] R 7 is C 1 -C 3 alkyl.

[0156] R 8 is as defined herein.

[0157] In some embodiments, R 6 is -C(=O)-NR'-R 8 ; and R 8 is C 1 -C 25 alkyl.

[0158] In some embodiments, the compound has the general formula (VII):

[0159]

[0160] wherein R 1 、R 2 、n、m and R 8 are each as defined herein.

[0161] In some embodiments, for the compound of formula (VII), R 8 can be:

[0162] -C 1 -C 25 alkyl substituted with at least one functional group selected from: hydroxyl, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2-C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3-C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, Idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0163] -C substituted with at least one functional group selected from the following 2 -C 25 Alkenyl: hydroxy, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1-C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-Aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2-O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH, and -NR'R”R”'; or

[0164] -C substituted by at least one functional group selected from the following 2 -C 25 Alkynyl: hydroxy, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-Aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-Aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0165] -C substituted with at least one functional group selected from the following 6 -C 10 Aryl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl -C(=O)-OH, -NH-C 2 -C 25 alkenyl -C(=O)-OH, -NH-C 2 -C 25 alkynyl -C(=O)-OH, -NH-C 1 -C 25 alkyl -C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl -C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl -C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl -NH 2 、-NH-C 2 -C 25 alkenyl -NH 2 、-NH-C 2-C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”'、-NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”'、-NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”'、-NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl、-NH-C 2 -C 25Vinylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Vinylidyne-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Vinylene-NR'R”R”', -NHC(=O)C 2 -C 25 Vinylidyne-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Vinylene-OH, -NHC(=O)C 2 -C 25 Vinylidyne-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Vinylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Vinylidyne-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Vinylene-C 3 -C10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-yl-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0166] -C substituted with at least one functional group selected from the following 3 -C 10 Heteroaryl: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C6 -C 10 Aryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25Alkynyl-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynyl-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynyl-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynyl-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0167] In some embodiments, the compounds of formula (all formulas generally or specifically listed herein) herein exclude those wherein R 8 is C 7 -C 12 alkyl compounds.

[0168] In some embodiments, R 8 is C 1 -C 25 alkyl.

[0169] In some embodiments, R 8 is 2,2,6,6-tetramethylpiperidin-1-ol-4-yl.

[0170] In some embodiments, the compound has the general formula (VIII):

[0171]

[0172] In some embodiments, n is 2 and m is 1.

[0173] In some embodiments, R 1 and R 2 are each a halide.

[0174] In some embodiments, R 1 and R 2 each is a chlorine atom.

[0175] In some embodiments, the compound has the formula (IX):

[0176]

[0177] wherein R 8 is as defined herein.

[0178] In some embodiments, for the compound of formula (IX), R 8 can be:

[0179] -C 1 -C 25 alkyl substituted with at least one functional group selected from: hydroxyl, amine, halide, -ONO 2 、-NO 2 、-S-、-S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1-C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C2 -C 25 -C≡C- 3 -C 10 heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridin-3-C(=O)-OH and -NR'R”R”'; or

[0180] -C substituted with at least one functional group selected from the following 2 -C 25 alkenyl: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C1 -C 25 Alkylene - OH, - NHC(=O)C 2 -C 25 Alkenylene - OH, - NHC(=O)C 2 -C 25 Alkynylene - OH, - NHC(=O)C 6 -C 10 Aryl, - NHC(=O)C 3 -C 10 Heteroaryl, - NHC(=O)C 1 -C 25 Alkylene - C 6 -C 10 Aryl, - NHC(=O)C 2 -C 25 Alkenylene - C 6 -C 10 Aryl, - NHC(=O)C 2 -C 25 Alkynylene - C 6 -C 10 Aryl, - NHC(=O)C 3 -C 10 Heteroaryl, - NHC(=O)C 1 -C 25 Alkylene - C 3 -C 10 Heteroaryl, - NHC(=O)C 2 -C 25 Alkenylene - C 3 -C 10 Heteroaryl, - NHC(=O)C 2 -C 25 Alkynylene - C 3 -C 10 Heteroaryl, 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl radical, - NHC(=O)C(CH 3 ) 2 -O - Aryl - Cl, - NHC(=O)CH 2 C(CH 3 ) 2 -O - Aryl - Cl, Idebenone derivative, - pyridine - 3 - C(=O)-OH and - NR'R”R”'; or

[0181] -C substituted with at least one functional group selected from the following 2 -C 25 Alkynyl: hydroxyl, amine, halide, - ONO 2 , - NO 2 , - S -, - S - C 1 -C5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 , -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2-C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6-C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkynylene-C 3 -C 10 heteroaryl, 2,2,6,6-tetramethylpiperidin-1-yl-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivative, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0182] -C substituted with at least one functional group selected from the following 6 -C 10 aryl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 , -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH, and -NR'R”R”'; or

[0183] -C substituted with at least one functional group selected from the following 3 -C 10 heteroaryl: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C1 -C 25 alkyl - C(=O)-OH, -NH - C 2 -C 25 alkenyl - C(=O)-OH, -NH - C 2 -C 25 alkynyl - C(=O)-OH, -NH - C 1 -C 25 alkyl - C(=O)-NR'R”R”', -NH - C 2 -C 25 alkenyl - C(=O)-NR'R”R”', -NH - C 2 -C 25 alkynyl - C(=O)-NR'R”R”', -NH - C 1 -C 25 alkyl - NH 2 、-NH - C 2 -C 25 alkenyl - NH 2 、-NH - C 2 -C 25 alkynyl - NH 2 、-NH - C 1 -C 25 alkyl - NH - C(=O)-C 1 -C 25 alkyl、-NH - C 2 -C 25 alkenyl - NH - C(=O)-C 1 -C 25 alkyl、-NH - C 2 -C 25 alkynyl - NH - C(=O)-C 1 -C 25 alkyl、-NH - C 1 -C 25 alkyl - NH - C(=O)-C 6 -C 10 aryl、-NH - C 2 -C 25 alkenyl - NH - C(=O)-C 6 -C 10 aryl、-NH - C 2 -C 25 alkynyl - NH - C(=O)-C 6 -C 10 aryl、-NH - C 1 -C 25 alkyl - NH - C(=O)-C 3 -C 10 heteroaryl、-NH - C 2 -C25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0184] In some embodiments, R 8 is 2,2,6,6-tetramethylpiperidin-1-ol-4-yl.

[0185] In some embodiments, the compound has formula (X):

[0186]

[0187] In some embodiments, in the compound of formula (I):

[0188] R 1 and R 2 each independently of the other is a group selected from H, halide, and -CN;

[0189] each of n and m independently of the other is an integer between 0 and 5, specifying the number of substituents on the designated ring;

[0190] X is selected from a nitrogen atom (or nitrogen-containing group) and CH; or X-R 4 may optionally be C=R 4 ;

[0191] and

[0192] R 3 is H or a carbon-containing group and R 4 is a nitrogen-containing group.

[0193] In some embodiments, X is CH, and R 4 is a carbon-containing group having between 1 and 3 carbon atoms.

[0194] In some embodiments, R 3 is H.

[0195] In some embodiments, the compound has the general formula (XI):

[0196]

[0197] wherein R 1 , R 2 , n, m, and R 8 are each as defined herein, optionally excluding compounds wherein R 8 is C 7 -C 12 alkyl.

[0198] In some embodiments, for the compound of formula (XI), R 8 may be:

[0199] -C 1 -C 25 alkyl substituted with at least one functional group selected from: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1-C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenylene, -NHC(=O)C 2 -C 25 alkynylene, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25Arylacetylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0200] -C substituted with at least one functional group selected from the following 2 -C 25 Alkenyl: hydroxy, amine, halide, -ONO 2 、-NO 2 、-S-、-S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-Aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-Aryl-Cl, idebenone derivative, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0201] -C substituted with at least one functional group selected from the following 2 -C 25 Alkynyl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2-C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3-C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0202] -C substituted with at least one functional group selected from the following 6 -C 10 Aryl: hydroxy, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1-C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C1 -C 25 Alkylene - NR'R”R”', - NH C(=O)C 2 -C 25 Alkenylene - NR'R”R”', - NH C(=O)C 2 -C 25 Alkynylene - NR'R”R”', - NH C(=O)C 1 -C 25 Alkylene - OH, - NH C(=O)C 2 -C 25 Alkenylene - OH, - NH C(=O)C 2 -C 25 Alkynylene - OH, - NH C(=O)C 6 -C 10 Aryl, - NH C(=O)C 3 -C 10 Heteroaryl, - NH C(=O)C 1 -C 25 Alkylene - C 6 -C 10 Aryl, - NH C(=O)C 2 -C 25 Alkenylene - C 6 -C 10 Aryl, - NH C(=O)C 2 -C 25 Alkynylene - C 6 -C 10 Aryl, - NH C(=O)C 3 -C 10 Heteroaryl, - NH C(=O)C 1 -C 25 Alkylene - C 3 -C 10 Heteroaryl, - NH C(=O)C 2 -C 25 Alkenylene - C 3 -C 10 Heteroaryl, - NH C(=O)C 2 -C 25 Alkynylene - C 3 -C 10 Heteroaryl, 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl radical, - NH C(=O)C(CH 3 ) 2 -O - Aryl - Cl, - NH C(=O)CH 2 C(CH 3 ) 2-O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH, and -NR'R”R”'; or

[0203] -C substituted with at least one functional group selected from the following 3 -C 10 heteroaryl: hydroxy, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 , -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-Aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-Aryl-Cl, idebenone derivatives, -pyridin-3-C(=O)-OH and -NR'R”R”'.

[0204] In some embodiments, R 8 is C 1 -C 25 alkyl.

[0205] In some embodiments, R 8 is 2,2,6,6-tetramethylpiperidin-1-ol-4-yl.

[0206] In some embodiments, the compound has the general formula (XII):

[0207]

[0208] In some embodiments, in the compound of formula (XI), R 8 is an idebenone derivative.

[0209] In some embodiments, the compound has the formula (XIII):

[0210]

[0211] wherein each of R 1 , R 2 , n and m is as defined above, and wherein k is an integer between 0 and 25.

[0212] In some embodiments, n is 2 and m is 1.

[0213] In some embodiments, R 1 and R 2 are each a halide.

[0214] In some embodiments, each of R 1 and R 2 is a chlorine atom.

[0215] In some embodiments, the compound has the general formula (XIV):

[0216]

[0217] wherein R 8 is as defined herein.

[0218] In some embodiments, for the compound of formula (XIV), R 8 can be:

[0219] -C 1 -C 25 alkyl substituted with at least one functional group selected from: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1-C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkynylene-C 3 -C 10Heteroaryl, 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl radical, - NHC(=O)C(CH 3 ) 2 -O - aryl - Cl, - NHC(=O)CH 2 C(CH 3 ) 2 -O - aryl - Cl, idebenone derivatives, - pyridine - 3 - C(=O)-OH and - NR'R”R”'; or

[0220] -C substituted by at least one functional group selected from the following 2 -C 25 Alkenyl: hydroxy, amine, halide, - ONO 2 、-NO 2 、-S -, - S - C 1 -C 5 Alkyl, - S - C 1 -C 5 Alkenyl, - S - C 1 -C 5 Alkynyl, - C(=O)-, - C(=O)-C 1 -C 25 Alkyl, - C(=O)-O - C 1 -C 5 Alkyl, - C(=O)-O - C 1 -C 5 Alkenyl, - C(=O)-O - C 1 -C 5 Alkynyl, - C(=O)-NR'R”R”', - C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, - C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, - C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, - C(=O)-OR 10 、-O - C 1 -C 5 Alkyl, - O - C 1 -C 5 Alkenyl, - O - C 1 -C 5 Alkynyl, - NH - NH 2 、-NH - NH - C(=O)-C 1 -C 25 Alkyl, - NH - NH - C(=O)-C 2 -C 25 Alkenyl, - NH - NH - C(=O)-C 2-C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 , -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C10 Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25Vinylene-OH, -NHC(=O)C 2 -C 25 Ethynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Vinylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Ethynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Vinylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Ethynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0221] -C substituted with at least one functional group selected from the following 2 -C 25 Alkynyl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl、-NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridin-3-C(=O)-OH and -NR'R”R”'; or

[0222] -C substituted with at least one functional group selected from the following 6 -C 10 Aryl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 , -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25Alkyl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C(=O)C 1 -C 25 Alkyl, -NH-C(=O)C 2 -C 25 Alkenyl, -NH-C(=O)C 2 -C 25 Alkynyl, -NH-C(=O)C 1 -C25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'; or

[0223] -C substituted by at least one functional group selected from the following 3 -C 10 Heteroaryl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylidene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylidene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-Aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH, and -NR'R"R"'.

[0224] In some embodiments, R 8 It is 2,2,6,6-tetramethylpiperidin-1-ol-4-yl.

[0225] In some embodiments, the compound has Formula (XV):

[0226]

[0227] In some embodiments, R 8 It is an idebenone-based derivative.

[0228] In some embodiments, the compound has Formula (XVI):

[0229]

[0230] wherein k is as defined above.

[0231] In some embodiments, in the compound of formula (IV), R 8is C optionally substituted with at least one functional group selected from the following 1 -C 25 alkyl: -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-OR 10 , where each of R', R”, R”' and R 10 is as defined above.

[0232] In some embodiments, the at least one functional group is selected from -C(=O)-NR'R”R”', -C(=O)-C 1 -C 25 alkyl and -C(=O)-OR 10 , where each of R', R”, R”' and R 10 is as defined above.

[0233] In some embodiments, R’ is H, R” is absent, and R’” is R 11 , where R 11 is selected from -H or -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5Alkynyl, -C(=O)-NR'R”R”', -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -ONO 2 , -NO 2 , 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O - aryl - Cl, idebenone derivatives, -pyridine - 3 - C(=O)-OH and -NR'R”R”', and wherein R', R”, R”' and R 10 are as defined above.

[0234] In some embodiments, the compound has the general formula (XVII):

[0235]

[0236] wherein R 1 , R 2 , n, m and R 11 are each as defined herein.

[0237] In some embodiments, n is 2 and m is 1.

[0238] In some embodiments, R 1 and R 2 are each halide.

[0239] In some embodiments, each of R 1 and R 2 is a chlorine atom.

[0240] In some embodiments, the compound has the general formula (XVIII):

[0241]

[0242] wherein R 11 is as defined herein.

[0243] In some embodiments, R 11Selected from -H or -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 、-NO 2 、2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0244] In some embodiments, in the compound of formula (XI), R 8 is -C optionally substituted with at least one functional group selected from the following 1 -C 25 alkyl: -C(=O)-, -C(=O)-C 1 -C 25Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-OR 10 wherein each of R', R”, R”' and R 10 is as defined above.

[0245] In some embodiments, the at least one functional group is selected from -C(=O)-NR'R”R”', -C(=O)-C 1 -C 25 alkyl and -C(=O)-OR 10 wherein each of R', R”, R”' and R 10 is as defined above.

[0246] In some embodiments, the compound has the general formula (XIX):

[0247]

[0248] wherein R 1 , R 2 , n, m and R 10 are each as defined herein.

[0249] In some embodiments, R 10 is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from: hydroxyl, amine, halide, -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -ONO 2 、-NO 2 、2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O - aryl - Cl, idebenone derivatives, -pyridine - 3 - C(=O)-OH and -NR'R”R”';

[0250] Each of R', R” and R”' is independently selected from -H, C 1 -C 5 Alkyl, C 2 -C 5 Alkenyl, C 2 -C 5 Alkynyl, -C(=O)-C 2 -C 25 Alkyl, -C(=O)-C 2 -C 25 Alkenyl and C 5 -C 25 Alkynyl; or one of R', R” and R”' is absent.

[0251] In some embodiments, n is 2 and m is 1.

[0252] In some embodiments, R 1 and R 2 are each a halide.

[0253] In some embodiments, R 1 and R 2 are each a chlorine atom.

[0254] In some embodiments, the compound has the general formula (XX):

[0255]

[0256] wherein R10 as defined herein

[0257] In some embodiments, R 10 is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 、-NO 2 、2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0258] Each of R', R” and R”' is independently selected from -H, C 1 -C 5 alkyl, C 2 -C 5Alkenyl, C 2 -C 5 Alkynyl, -C(=O)-C 2 -C 25 Alkyl, -C(=O)-C 2 -C 25 Alkenyl and C 5 -C 25 Alkynyl; or one of R', R", and R''' does not exist.

[0259] In some embodiments, in the compound of formula (IV), R 8 is C 10 -C 1 -C 25 alkyl optionally substituted with at least one functional group selected from hydroxyl, amine, -OR

[0260] In some embodiments, the at least one functional group is hydroxyl, amine, or -OR 10 , where the amine has the structure -NR'R"R''', and each of R', R", R''', and R 10 is as defined above.

[0261] In some embodiments, R' is H, R" does not exist, and R''' is R 11 , where R 11 is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R"R''', -C(=O)-OR 10 -O-C 1-C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 -NO 2 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”', and wherein R', R”, R”' and R 10 are as defined above.

[0262] In some embodiments, the compound has the general formula (XXI):

[0263]

[0264] wherein each of R 1 , R 2 , n, m and R 11 is as defined herein.

[0265] In some embodiments, R 11 is selected from -H or C 1 -C 25 alkyl, C 2 -C 25 alkenyl, C 2 -C 25 alkynyl, C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from: hydroxyl, amine, halide, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -ONO 2 、-NO 2 、2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine - 3 - C(=O)-OH and -NR'R”R”'.

[0266] In some embodiments, R' is H, R” is absent and R”' is R 11 where R 11 is -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl.

[0267] In some embodiments, the compound has the general formula (XXII):

[0268]

[0269] where R 1 、R 2 、n and m are each as defined herein.

[0270] In some embodiments, n is 2 and m is 1.

[0271] In some embodiments, R 1 and R 2 are each halide.

[0272] In some embodiments, each of R 1 and R 2 is a chlorine atom.

[0273] In some embodiments, the compound has the general formula (XXIII):

[0274]

[0275] wherein R 11 as defined herein.

[0276] In some embodiments, R 11 is selected from -H or C 1 -C 25 alkyl, C 2 -C 25 alkenyl, C 2 -C 25 alkynyl, C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 、-NO 2 、2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0277] In some embodiments, the compound has the formula (XXIV):

[0278]

[0279] In some embodiments, in the compound of formula (XI), R 8 is a C 10 -C 1 -C 25 alkyl optionally substituted with at least one functional group selected from hydroxyl, amine, -OR

[0280] In some embodiments, the at least one functional group is hydroxyl, amine or -OR 10 , wherein the amine has the structure NR'R”R”', where R', R”, R”' and R 10 are each as defined above.

[0281] In some embodiments, the compound has the general formula (XXV):

[0282]

[0283] wherein R 1 、R 2 、n, m and R 10 are each as defined herein.

[0284] In some embodiments, R 10 is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5Alkynyl, -C(=O)-NR'R”R”', -O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -ONO 2 , -NO 2 , 2,2,6,6 - tetramethylpiperidin - 1 - ol - 4 - yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O - aryl - Cl, idebenone derivatives, -pyridine - 3 - C(=O)-OH and -NR'R”R”';

[0285] Each of R', R” and R”' is independently selected from -H, C 1 -C 5 Alkyl, C 2 -C 5 Alkenyl, C 2 -C 5 Alkynyl, -C(=O)-C 2 -C 25 Alkyl, -C(=O)-C 2 -C 25 Alkenyl and C 5 -C 25 Alkynyl; or one of R', R” and R”' does not exist.

[0286] In some embodiments, n is 2 and m is 1.

[0287] In some embodiments, R 1 and R 2 are each a halide.

[0288] In some embodiments, R 1 and R 2 are each a chlorine atom.

[0289] In some embodiments, the compound has the general formula (XXVI):

[0290]

[0291] wherein R 10 is as defined herein.

[0292] In some embodiments, R 10 is selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 , -NO 2 , 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0293] Each of R', R” and R”' is independently selected from -H, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5Alkynyl, -C(=O)-C 2 -C 25 Alkyl, -C(=O)-C 2 -C 25 Alkenyl and C 5 -C 25 Alkynyl; or one of R', R", and R''' does not exist.

[0294] In some embodiments, the compound has the general formula (XXVII):

[0295]

[0296] Wherein each of R 1 , R 2 , n, m is as defined herein; R 5 Does not exist or is selected from H, -C 1 -C 3 Alkyl, -C(=O)-O-R 8 , -C(=O)-NR'-R 8 , halide, CN, and OH; and R 9 Is selected from -C(=O)-O-R 8 , -C(=O)-NR'-R 8 , -NH-C(=O)-O-R 8 , -NH-C(=O)-NR'-R 8 , -O-C(=O)-O-R 8 And -O-C(=O)-NR'-R 8 ; R 8 As defined herein.

[0297] In some embodiments, R 5 Is -C 1 -C 3 Alkyl and R 9 Is selected from -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-R 8 , -C(=O)-NR'-R 8 , -NH-C(=O)-O-R 8 , -NH-C(=O)-NR'-R 8 , -O-C(=O)-O-R 8 And -O-C(=O)-NR'-R 8 ; R 8 As defined herein.

[0298] In some embodiments, R 9 Is -NH-C(=O)-O-R8 、 -NH-C(=O)-NR'-R 8 、 -O-C(=O)-O-R 8 or -O-C(=O)-NR'-R 8 ; R 8 as defined herein.

[0299] In some embodiments, R 9 is -NH-C(=O)-O-R 8 or -O-C(=O)-O-R 8 ; R 8 as defined herein.

[0300] In some embodiments, the compound has the general formula (XXVIII):

[0301]

[0302] wherein R 1 、R 2 、n, m and R 8 each as defined herein.

[0303] In some embodiments, R 8 is -C 1 -C 25 alkyl.

[0304] In some embodiments, R 8 is -C 2 -C 25 alkenyl.

[0305] In some embodiments, R 8 is -C 2 -C 25 alkynyl.

[0306] In some embodiments, R 8 is -C 6 -C 10 aryl.

[0307] In some embodiments, R 8 is C 3 -C 10 heteroaryl.

[0308] In some embodiments, R 8 is -C 1 -C 25 alkyl substituted with at least one functional group selected from: hydroxyl, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1-C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 , -NH-C 2 -C 25 alkenyl-NH 2 , -NH-C 2 -C 25 alkynyl-NH 2 , -NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2-C 25 Vinylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Ethynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Vinylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Ethynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Vinylene-NR'R”R”', -NHC(=O)C 2 -C 25 Ethynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Vinylene-OH, -NHC(=O)C 2 -C 25 Ethynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Vinylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Ethynylene-C 6-C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-Aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-Aryl-Cl, Idebenone derivative, -Pyridine-3-C(=O)-OH and -NR'R”R”'.

[0309] In some embodiments, R 8 is -C substituted with at least one functional group selected from the following 2 -C 25 Alkenyl: Hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2-O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH, and -NR'R”R”'.

[0310] In some embodiments, R 8 is -C substituted with at least one functional group selected from the following 2 -C 25 alkynyl: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6-C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl -C(=O)-OH, -NH-C 2 -C 25 alkenyl -C(=O)-OH, -NH-C 2 -C 25 alkynyl -C(=O)-OH, -NH-C 1 -C 25 alkyl -C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl -C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl -C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl -NH 2 、-NH-C 2 -C 25 alkenyl -NH 2 、-NH-C 2 -C 25 alkynyl -NH 2 、-NH-C 1 -C 25 alkyl -NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl -NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl -NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl -NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl -NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl -NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25 alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 alkylene-OH, -NHC(=O)C 2 -C 25 alkenylene-OH, -NHC(=O)C 2 -C 25 alkynylene-OH, -NHC(=O)C6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 alkynylene-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 alkynylene-C 3 -C 10 heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivative, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0311] In some embodiments, R 8 is -C substituted with at least one functional group selected from the following 6 -C 10 aryl: hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1-C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl -C(=O)-OH, -NH-C 2 -C 25 alkenyl -C(=O)-OH, -NH-C 2 -C 25 alkynyl -C(=O)-OH, -NH-C 1 -C 25 alkyl -C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl -C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl -C(=O)-NR'R”R”', -NH-C 1 -C 25alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl、-NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”'、-NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”'、-NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”'、-NH-C 1 -C25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Vinylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Ethynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0312] In some embodiments, R 8 is a C substituted with at least one functional group selected from the following 3 -C 10 Heteroaryl: hydroxy, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 Alkyl, -O-C1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10 aryl, -NH-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkyl-C(=O)-OH, -NH-C 2 -C 25 alkenyl-C(=O)-OH, -NH-C 2 -C 25 alkynyl-C(=O)-OH, -NH-C 1 -C 25 alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkyl-NH 2 、-NH-C 2 -C 25 alkenyl-NH 2 、-NH-C 2 -C 25 alkynyl-NH 2 、-NH-C 1 -C 25 alkyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1-C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25 alkyl, -NHC(=O)C 2 -C 25 alkenyl, -NHC(=O)C 2 -C 25 alkynyl, -NHC(=O)C 1 -C 25Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”'.

[0313] In some embodiments, each of n and m is 1.

[0314] In some embodiments, R 1 is CN, and R 2 is a halide.

[0315] In some embodiments, R 2 is a chlorine atom.

[0316] In some embodiments, the compound has formula (XXIX):

[0317]

[0318] wherein R 8 is as defined herein.

[0319] In some embodiments, in the compound of formula (I), each of R 1 and R 2 is independently a group selected from H, a halide, and -CN;

[0320] Each of n and m is independently an integer between 0 and 5, specifying the number of substituents on the designated ring;

[0321] X is CH, CH 2 or wherein the group C-R 4 is C=R 4 ;

[0322] R 3 is H or a carbon-containing group having between 1 and 3 carbon atoms, which is further optionally substituted;

[0323] R 4 is a nitrogen atom or a nitrogen-containing group or a carbon-containing group having between 1 and 3 carbon atoms, which is further optionally substituted;

[0324] or R 3 and R 4 together with the atoms to which they are bonded (carbon atom and X, respectively) form a 5-membered or 6-membered carbon ring, which 5-membered or 6-membered carbon ring optionally contains between 1 and 3 heteroatoms selected from N, O, and S;

[0325] In some embodiments, X-R 4 is C=R 4 ; and R 4 is a nitrogen atom.

[0326] In some embodiments, R 3 is a carbon-containing group and R 4 is a nitrogen-containing group.

[0327] In some embodiments, R 3 and R 4 together with the atoms to which they are bonded form a 5-membered carbon ring optionally containing 1 or 2 nitrogen atoms.

[0328] In some embodiments, the compound has the general formula (XXX):

[0329]

[0330] wherein

[0331] L 1 and L 2 one of them is a nitrogen atom, and L 1 and L 2 the other one is a carbon atom (selected from C, CH or CH 2 );

[0332] R 5 、R 6 and R 7 each of them can independently be absent or selected from -H, C 1 -C 3 alkyl, -C(=O)-O-R 8 、-C(=O)-NR'-R 8 、halide, CN, OH and NR'R”;

[0333] and wherein R 8 、R', R” and R”' are as defined above. And wherein each bond (designated as ---) between C-N, N-L 1 、L 1 -L 2 and L 2 -C is a single bond or a double bond.

[0334] In some embodiments, L 1 is a nitrogen atom, and L 2 is a carbon atom.

[0335] In some embodiments, L 1 is a nitrogen atom and L 2 is a carbon atom, the bond between C and N is a double bond, the bond between N and L 1 is a single bond, and the bond between L 1 and L 2 is a single bond.

[0336] In some embodiments, the compound has the formula (XXXI):

[0337]

[0338] wherein R 1 、R 2 、n、m、R 6 and R 7 each is as defined herein.

[0339] In some embodiments, R 7 is H and R 6 is selected from -C 1 -C 3 alkyl, -C(=O)-O-R 8 、-C(=O)-NR'-R 8 、halide, -CN, -OH and -NR'R''; and wherein R 8 is as defined above.

[0340] In some embodiments, R 6 is substituted -C 1 -C 3 alkyl and R 7 is H.

[0341] In some embodiments, the compound has formula (XXXII):

[0342]

[0343] wherein R 8 is as defined herein.

[0344] In some embodiments, the compound has formula (XXXIII):

[0345]

[0346] wherein R 9 is selected from -O-R 8 and -NR'-R 8 ; R 8 is as defined herein.

[0347] In some embodiments, the compound has formula (XXXIV):

[0348]

[0349] wherein R 9 is selected from -O-R 8 and -NR'-R 8 ; wherein each of R' and R 8 is as defined herein.

[0350] In some embodiments, the compound has formula (XXXV):

[0351]

[0352] wherein R 9 is selected from -O-R 8 and -NR'-R 8 ; wherein each of R' and R 8 is as defined herein.

[0353] In some embodiments, the compound has the formula (XXXVI):

[0354]

[0355] wherein R 9 is selected from -O-R 8 and -NR'-R 8 ; wherein each of R' and R 8 is as defined herein.

[0356] As described herein, the present invention provides compounds having the general formula (II) as defined herein. In other words, the compound has the following formula:

[0357]

[0358] wherein

[0359] one of L, L 1 and L 2 is a nitrogen atom, and the others of L, L 1 and L 2 are each independently a carbon atom (selected from C, CH or CH 2 );

[0360] R 5 , R 6 and R 7 each independently can be selected from -H, -C 1 -C 3 alkyl, -C(=O)-OH, -C(=O)-O-R 8 , -C(=O)-NR'R 8 , halide, -CN, -OH and -NR'R''; or

[0361] R 5 and R 6 or R 6 and R 7 together with the atom to which they are bonded can form a 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring, which 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring optionally contains from 1 to 3 heteroatoms selected from N, O and S;

[0362] The 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring is further optionally substituted by at least one functional group B selected from the following: -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, hydroxyl, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 alkyl, -S-C 2 -C 5 alkenyl, -S-C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 2 -C 5 alkenyl, -C(=O)-O-C 2 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 2 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 2 -C 25 alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25 alkynyl, -NH-NH-C(=O)-C 6 -C 10Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C3 -C 10 Hetaryl, -NH-C 2 -C 25 Alkenyl -NH-C(=O)-C 3 -C 10 Hetaryl, -NH-C 2 -C 25 Alkynyl -NH-C(=O)-C 3 -C 10 Hetaryl, -NH-C 1 -C 25 Alkylene -C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene -C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene -C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene -C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene -C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene -C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene -NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene -NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene -NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene -OH, -NHC(=O)C 2 -C 25 Alkenylene -OH, -NHC(=O)C 2 -C 25 Alkynylene -OH, -NHC(=O)C 6 -C10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-Aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-Aryl-Cl, Idebenone derivative, -Pyridin-3-C(=O)-OH and -NR'R”R”';

[0363] The 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring may optionally be substituted with at least one functional group B selected from Structure (A) to Structure (H):

[0364]

[0365] Wherein in each of the functional groups (A) to (H), the wavy line indicates the point or bond of connectivity, j is 0 or 1, and Ra is selected from -H, -C 1 -C 25 Alkyl, -C 2 -C 25 Alkenyl, -C 2 -C 25Alkynyl, -C(=O)-C 6 -C 10 Aryl and -C(=O)-C 3 -C 10 Heteroaryl,

[0366] wherein in functional group (G) and functional group (H), the side group -NH-Ra group can occur between 1 and 11 times at any position along the carbocyclic ring (in some embodiments, it can be located at a ring atom that is one, two, or three ring atom displacements from an existing group or an in-ring N atom; in some embodiments, the position of the functional group is 1, 2 or 1, 3 or 1, 4, where 1 indicates the position of the existing group or the in-ring N atom);

[0367] R 5 、R 6 and R 7 One of them may be absent;

[0368] R 8 is selected from -H, -C 1 -C 25 Alkyl, -C 2 -C 25 Alkenyl, -C 2 -C 25 Alkynyl, -C 6 -C 10 Aryl and C 3 -C 10 Heteroaryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, -ONO 2 、-NO 2 、-S-, -S-C 1 -C 5 Alkyl, -S-C 1 -C 5 Alkenyl, -S-C 1 -C 5 Alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 Alkyl, -C(=O)-O-C 1 -C 5 Alkyl, -C(=O)-O-C 1 -C 5 Alkenyl, -C(=O)-O-C 1 -C 5 Alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 Alkyl, -C(=O)-NR'-C(=O)-C 1 -C 25Alkenyl, -C(=O)-NR'-C(=O)-C 1 -C 25 Alkynyl, -C(=O)-OR 10 、-O-C 1 -C 5 Alkyl, -O-C 1 -C 5 Alkenyl, -O-C 1 -C 5 Alkynyl, -NH-NH 2 、-NH-NH-C(=O)-C 1 -C 25 Alkyl, -NH-NH-C(=O)-C 2 -C 25 Alkenyl, -NH-NH-C(=O)-C 2 -C 25 Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C1 -C 25 alkyl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 1 -C 25 alkyl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 6 -C 10 aryl, -NH-C 1 -C 25 alkyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkenyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 2 -C 25 alkynyl-NH-C(=O)-C 3 -C 10 heteroaryl, -NH-C 1 -C 25 alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 alkylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkenylene-C(=O)-O-C 1 -C 25 alkyl, -NH-C 2 -C 25 alkynylene-C(=O)-O-C 1 -C 25 alkyl, -NHC(=O)C 1 -C 25Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C 2 -C 25 Alkynylene-OH, -NHC(=O)C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkenylene-C 6 -C 10 Aryl, -NHC(=O)C 2 -C 25 Alkynylene-C 6 -C 10 Aryl, -NHC(=O)C 3 -C 10 Heteroaryl, -NHC(=O)C 1 -C 25 Alkylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkenylene-C 3 -C 10 Heteroaryl, -NHC(=O)C 2 -C 25 Alkynylene-C 3 -C 10 Heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2-O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0369] R 10 selected from -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, each of which is optionally substituted with at least one functional group selected from the following: hydroxyl, amine, halide, -C 1 -C 5 alkyl, -C 2 -C 5 alkenyl, -C 2 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 1 -C 5 alkenyl, -C(=O)-O-C 1 -C 5 alkynyl, -C(=O)-NR'R”R”', -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -ONO 2 -NO 2 、2,2,6,6-tetramethylpiperidin-1-ol-4-yl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivatives, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0370] Each of R', R'' and R''' is independently selected from -H, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-C 2 -C 25 alkyl, -C(=O)-C 2 -C 25 alkenyl and C 5 -C 25 alkynyl; or one of R', R'' and R''' is absent; and wherein

[0371] N-L, L-L 1 、L 1 -L 2 and L 2 -C each bond (designated ---) between is a single bond or a double bond.

[0372] In some embodiments, in the compounds of formula (II), L 2 is a nitrogen atom, and each of L and L is a carbon atom. In some embodiments, R 7 is absent, and R 5 and R 6 together with the atoms to which they are bonded form a 5-membered carbocyclic ring, 6-membered carbocyclic ring, 7-membered carbocyclic ring or 8-membered carbocyclic ring optionally containing from 1 to 3 heteroatoms selected from N, O and S. In some embodiments, the compound has the formula (XXXVII):

[0373]

[0374] wherein R 1 、R 2 、R 5 、R 6 、n and m are each as defined above.

[0375] In some embodiments, R 5 and R 6 together with the atoms to which they are bonded can form a 5-membered carbocyclic ring, 6-membered carbocyclic ring, 7-membered carbocyclic ring or 8-membered carbocyclic ring, the 5-membered carbocyclic ring, 6-membered carbocyclic ring, 7-membered carbocyclic ring or 8-membered carbocyclic ring optionally containing from 1 to 3 heteroatoms selected from N, O and S.

[0376] In some embodiments, the compound has the formula (XXXVIII):

[0377]

[0378] wherein R1 , R 2 and each of m is as defined above, ring A is a 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring, the 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring optionally contains heteroatoms selected from N, O and S between 1 and 3, and is further optionally substituted by a group B selected from: -H, -C 1 -C 25 alkyl, -C 2 -C 25 alkynyl, -C 6 -C 10 aryl, hydroxyl, amine, halide, -ONO 2 , -NO 2 , -S-, -S-C 1 -C 5 alkyl, -S-C 1 -C 5 alkenyl, -S-C 1 -C 5 alkynyl, -C(=O)-, -C(=O)-C 1 -C 25 alkyl, -C(=O)-O-C 1 -C 5 alkyl, -C(=O)-O-C 2 -C 5 alkenyl, -C(=O)-O-C 2 -C 5 alkynyl, -C(=O)-NR'R”R”', -C(=O)-NR'-C(=O)-C 1 -C 25 alkyl, -C(=O)-NR'-C(=O)-C 2 -C 25 alkenyl, -C(=O)-NR'-C(=O)-C 2 -C 25 alkynyl, -C(=O)-OR 10 , -O-C 1 -C 5 alkyl, -O-C 1 -C 5 alkenyl, -O-C 1 -C 5 alkynyl, -NH-NH 2 , -NH-NH-C(=O)-C 1 -C 25 alkyl, -NH-NH-C(=O)-C 2 -C 25 alkenyl, -NH-NH-C(=O)-C 2 -C 25Alkynyl, -NH-NH-C(=O)-C 6 -C 10 Aryl, -NH-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkyl-C(=O)-OH, -NH-C 2 -C 25 Alkenyl-C(=O)-OH, -NH-C 2 -C 25 Alkynyl-C(=O)-OH, -NH-C 1 -C 25 Alkyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenyl-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynyl-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkyl-NH 2 、-NH-C 2 -C 25 Alkenyl-NH 2 、-NH-C 2 -C 25 Alkynyl-NH 2 、-NH-C 1 -C 25 Alkyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 1 -C 25 Alkyl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 6 -C 10 Aryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 6 -C 10Aryl, -NH-C 1 -C 25 Alkyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkenyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 2 -C 25 Alkynyl-NH-C(=O)-C 3 -C 10 Heteroaryl, -NH-C 1 -C 25 Alkylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkenylene-C(=O)-NR'R”R”', -NH-C 2 -C 25 Alkynylene-C(=O)-NR'R”R”', -NH-C 1 -C 25 Alkylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkenylene-C(=O)-O-C 1 -C 25 Alkyl, -NH-C 2 -C 25 Alkynylene-C(=O)-O-C 1 -C 25 Alkyl, -NHC(=O)C 1 -C 25 Alkyl, -NHC(=O)C 2 -C 25 Alkenyl, -NHC(=O)C 2 -C 25 Alkynyl, -NHC(=O)C 1 -C 25 Alkylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkenylene-NR'R”R”', -NHC(=O)C 2 -C 25 Alkynylene-NR'R”R”', -NHC(=O)C 1 -C 25 Alkylene-OH, -NHC(=O)C 2 -C 25 Alkenylene-OH, -NHC(=O)C2 -C 25 -alkynyl-OH, -NHC(=O)C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 -alkylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 -alkenylene-C 6 -C 10 aryl, -NHC(=O)C 2 -C 25 -alkynyl-C 6 -C 10 aryl, -NHC(=O)C 3 -C 10 heteroaryl, -NHC(=O)C 1 -C 25 -alkylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 -alkenylene-C 3 -C 10 heteroaryl, -NHC(=O)C 2 -C 25 -alkynyl-C 3 -C 10 heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical, -NHC(=O)C(CH 3 ) 2 -O-aryl-Cl, -NHC(=O)CH 2 C(CH 3 ) 2 -O-aryl-Cl, idebenone derivative, -pyridine-3-C(=O)-OH and -NR'R”R”';

[0379] The 5-membered carbon ring, 6-membered carbon ring, 7-membered carbon ring or 8-membered carbon ring may optionally be substituted with at least one functional group B selected from Structures (A) to (H):

[0380]

[0381] Wherein in each of the functional groups (A) to (H), the wavy line indicates the point or bond of connectivity, j is 0 or 1, and Ra is selected from -H, -C 1 -C 25 alkyl, -C2 -C 25 alkenyl, -C 2 -C 25 alkynyl, -C(=O)-C 6 -C 10 aryl and -C(=O)-C 3 -C 10 heteroaryl,

[0382] wherein in functional group (G) and functional group (H), the side group -NH-Ra group can occur between 1 and 11 times at any position along the carbocyclic ring (in some embodiments, it can be located at a ring atom that is one, two, or three ring atom moves away from an existing group or an N atom within the ring; in some embodiments, the position of the functional group is 1, 2 or 1, 3 or 1, 4, where 1 indicates the position of the existing group or the N atom within the ring).

[0383] In some embodiments, ring A is a 5-membered ring. In some embodiments, the ring is a heterocyclic ring containing one or more heteroatoms selected from N, O, and S.

[0384] In some embodiments, ring A is a 6-membered ring. In some embodiments, the ring is a heterocyclic ring containing one or more heteroatoms selected from N, O, and S. In some embodiments, the ring is an aromatic ring or a heteroaryl ring.

[0385] In some embodiments, ring A is a 7-membered ring. In some embodiments, the ring is a heterocyclic ring containing one or more heteroatoms selected from N, O, and S.

[0386] In some embodiments, ring A contains one or more double bonds.

[0387] In some embodiments, the compound is a compound of formula (XXXIX):

[0388]

[0389] wherein R 1 、R 2 、n, m, and B are each as defined above.

[0390] In some embodiments, the compound is a compound of formula (XXXX):

[0391]

[0392] wherein R 1 、R 2 、n, m, and B are each as defined above.

[0393] In some embodiments, the compound is a compound of formula (XXXXI):

[0394]

[0395] wherein R 1 and R 2 each of n, m, and B is as defined above.

[0396] In some embodiments, the compound of formula (II) is a compound having the structure of formula (XXXXII):

[0397]

[0398] wherein R 1 and R 2 each of m and B is as defined above.

[0399] In some embodiments of the compounds of the present invention, n is 2 and m is 1, or m is 2 and n is 1, or each of m and n is 2 or 1. In some embodiments, R 1 and R 2 are each a halide. In some embodiments, R 1 and R 2 each is a chlorine atom.

[0400] In some embodiments of the compounds of the present invention, n and m together represent 2 or 3 halide atoms. In some embodiments, the halide atoms are each a chlorine atom.

[0401] In some embodiments, the following compounds of the present invention are provided:

[0402]

[0403]

[0404]

[0405]

[0406]

[0407]

[0408]

[0409]

[0410]

[0411]

[0412]

[0413]

[0414] In some embodiments, in each compound of the present invention, R 8 is a lipophilic moiety.

[0415] The compounds of the present invention can be used as modulators of peripheral cannabinoid receptors, including peripherally restricted CB 1 receptors and CB 2 receptors. In some embodiments, the compound is a modulator (e.g., an inhibitor) of the peripherally restricted CB 1 receptor. In some embodiments, the compound is a neutral antagonist or inverse agonist. In some embodiments, the compound is a modulator (e.g., an activator) of the CB 2 receptor.

[0416] As used herein, the expression "peripherally restricted CB 1 receptor blocker" refers to an agent / material according to the present invention that is an antagonist or blocker of the CB 1 receptor present in peripheral organs and tissues (including adipose tissue, liver, skeletal muscle, pancreatic β-cells, and kidney), without causing centrally mediated side effects. In other words, these blockers or antagonists retain the therapeutic benefits of a globally acting CB 1 receptor blocker without causing CNS-mediated side effects.

[0417] "CB 1 receptor blocker" or antagonist is a compound according to the present invention that, most generally, partially or completely blocks, inhibits, or neutralizes the biological function of the peripheral CB 1 receptor. By partially or completely blocking, inhibiting, or neutralizing the biological function of the receptor, prevention or treatment of various metabolic syndromes can be achieved. These metabolic syndromes include obesity, insulin resistance, diabetes, coronary heart disease, fatty liver, cirrhosis, chronic kidney disease, and cancer.

[0418] The present invention also provides compounds of formula (I) as inverse agonists of the peripherally restricted CB 1 receptor.

[0419] The present invention also provides a composition comprising the compound of the present invention. In some embodiments, the composition is a pharmaceutical composition in a form suitable for administration to a human or animal subject. As used herein, a "pharmaceutical composition" comprises a therapeutically effective amount of the compound of the present invention, optionally together with suitable additives such as diluents, preservatives, solubilizers, emulsifiers, adjuvants, and / or carriers. The composition can be a liquid or lyophilized preparation or otherwise dried preparation, and includes diluents of various buffer contents (e.g., Tris-HCl, acetate, phosphate), pH and ionic strength, additives such as albumin or gelatin to prevent absorption to surfaces, detergents (e.g., Tween 20, Tween 80, Pluronic F68, bile salts), solubilizers (e.g., glycerol, polyethylene glycol), antioxidants (e.g., ascorbic acid, sodium metabisulfite), preservatives (e.g., Thimerosal, benzyl alcohol, parabens), and others.

[0420] Compositions suitable for oral administration can include (a) liquid solutions, such as a solution of an effective amount of the compound dissolved in a diluent such as water, saline, or orange juice; (b) capsules, sachets, tablets, lozenges, and troches, each containing a predetermined amount of the active ingredient as a solid or granule; (c) powders; (d) suspensions in a suitable liquid; and (e) suitable emulsions or self-emulsifying formulations. Liquid formulations can include diluents such as water and alcohols, alcohols such as ethanol, benzyl alcohol, and polyethylene alcohol, with or without pharmaceutically acceptable surfactants, suspending agents, or emulsifying agents. Capsule forms can be of the ordinary hard-shell gelatin type or soft-shell gelatin type, containing, for example, surfactants, lubricants, and inert fillers. Tablet forms can contain one or more of the following: lactose, sucrose, mannitol, corn starch, potato starch, alginic acid, microcrystalline cellulose, acacia, gelatin, guar gum, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, calcium stearate, zinc stearate, stearic acid, and other excipients, coloring agents, diluents, buffers, disintegrants, wetting agents, preservatives, flavoring agents, and pharmaceutically compatible carriers. Lozenge forms can contain the active ingredient in a flavor (usually sucrose and acacia or tragacanth), and pastilles, which contain the active ingredient in an inert matrix such as gelatin and glycerol, or sucrose and acacia, emulsions, gels, and the like, and pastilles contain carriers known in the art in addition to the active ingredient.

[0421] Compositions suitable for parenteral administration include sterile nanoemulsions, aqueous and non-aqueous isotonic sterile injection solutions, and aqueous and non-aqueous sterile suspensions. The aqueous and non-aqueous isotonic sterile injection solutions may contain antioxidants, buffers, bacteriostatic agents, and solutes that render the preparation isotonic with the blood of the intended recipient; the aqueous and non-aqueous sterile suspensions contain suspending agents, solubilizing agents, thickening agents, stabilizing agents, and preservatives.

[0422] The compounds of the present invention can be administered in a physiologically acceptable diluent in a pharmaceutical carrier, such as a sterile liquid or a mixture of liquids, including water, saline, dextrose aqueous solutions and related sugar solutions, alcohols such as ethanol, isopropanol or cetyl alcohol, diols such as propylene glycol or polyethylene glycol, glycerol ketals such as 2,2-dimethyl-1,3-dioxolane-4-methanol, ethers such as poly(ethylene glycol) 400, oils, fatty acids, fatty acid esters or glycerides, or acetylated fatty acid glycerides, with or without the addition of pharmaceutically acceptable surfactants such as soaps or detergents, suspending agents such as pectin, carbomer, methylcellulose, hydroxypropyl methylcellulose or carboxymethylcellulose, or emulsifying agents and other pharmaceutical adjuvants. Oils that can be used in parenteral formulations include petroleum, animal oils, vegetable oils or synthetic oils. Specific examples of oils include peanut oil, soybean oil, sesame oil, cottonseed oil, corn oil, olive oil, petrolatum and mineral oil. Suitable fatty acids for parenteral formulations include oleic acid, stearic acid and isostearic acid.

[0423] The compounds of the present invention can be made into injectable formulations. The requirements for effective pharmaceutical carriers for injectable compositions are well known to those of ordinary skill in the art. See Pharmaceutics and Pharmacy Practice, J.B. Lippincott Co., Philadelphia, Pa., edited by Banker and Chalmers, pages 238-250 (1982), and ASHP Handbook on Injectable Drugs, Toissel, 4th edition, pages 622-630 (1986).

[0424] In some embodiments, the composition is suitable for oral administration.

[0425] In other embodiments, the composition is suitable for IV (intravenous) administration or IM (intramuscular) administration.

[0426] In some embodiments, the composition is a self-emulsifying oil formulation comprising a nanocarrier according to the present invention.

[0427] In another aspect of the present invention, the present invention provides a nanocarrier comprising at least one compound according to the present invention.

[0428] The nano - carriers can be nanoparticles, nanocapsules or mixtures thereof. The "nano - carriers" of the present invention are particulate materials that are biocompatible and resistant enough to chemical and / or physical destruction such that a sufficient amount of the nano - carriers remains substantially intact after being administered into the human or animal body and persists for a sufficient time to reach the desired target tissue (or target organ). Generally, the nano - carriers have an average diameter of up to 700 nm.

[0429] Depending on various parameters related to the compounds of the present invention (such as solubility, molecular weight, polarity, charge, reactivity, chemical stability, biological activity, and others), the compounds can be incorporated (encapsulated) in nanocapsules (NC) and / or embedded in the matrix constituting the nanoparticles (NP). For the selected applications, the nano - carriers can thus be in the form of a core / shell (also referred to hereinafter as a nanocapsule), which has a polymer shell and a core containing at least one compound of the present invention.

[0430] Optionally, the nanoparticles can have a substantially uniform composition and are not characterized by an obvious core / shell structure. These nano - carriers are referred to herein as nanoparticles (NP).

[0431] In some embodiments, the average diameter of the nano - carriers is between about 100 nm and 200 nm. In some embodiments, the average diameter is between about 200 nm and 300 nm. In some embodiments, the average diameter is between about 300 nm and 400 nm, between 400 nm and 500 nm. In some embodiments, the average diameter is between about 600 nm and 700 nm.

[0432] In some other embodiments, the average diameter of the nano - carriers is between about 50 nm and 700 nm. In other embodiments, the average diameter is between about 50 nm and 500 nm. In other embodiments, the average diameter is between about 50 nm and 400 nm. In additional embodiments, the average diameter is between about 50 nm and 300 nm. In additional embodiments, the average diameter is between about 50 nm and 200 nm. In additional embodiments, the average diameter is between about 50 nm and 100 nm.

[0433] Materials suitable for forming nano - carriers such as nanocapsules and / or nanoparticles according to the present invention are polyesters, including polylactic acid (PLA), polyglycolic acid (PGA), polyhydroxybutyrate and polycaprolactone, poly(ortho esters), polyanhydrides, polyamino acids, poly(alkyl cyanoacrylates), polyphosphazenes, copolymers of (PLA / PGA) and aspartic acid or polyethylene oxide (PEO).

[0434] In some embodiments, the nanocarrier is a nanoparticle that comprises a first matrix, wherein the compound of the invention is embedded in the matrix. In other embodiments, the nanocarrier is a nanocapsule that comprises a first shell that encapsulates the compound of the invention or encapsulates a composition that contains the compound.

[0435] The nanocarrier can also be surrounded by another encapsulating layer to form a double protection. Thus, in some embodiments, the nanocarrier is also encapsulated within a second shell layer, which can contain the same or different material as the material of the first shell layer. In some embodiments, the nanocarrier is also embedded in a second matrix, and the first matrix and the second matrix can contain the same or different materials.

[0436] To increase the amount of the active compound that reaches the target tissue or target organ, it is sometimes necessary to provide a product that contains more than one nanocarrier, which is packaged in a single outer shell. Thus, in another aspect, there is provided a nanocapsule or microcapsule that contains more than one nanocarrier of the invention.

[0437] According to another aspect, there is provided a nanoparticle or microparticle that contains more than one nanocarrier of the invention. Such a nanoparticle or microparticle can confer a long-acting dosage form when administered parenterally, or can be used as a powder for oral, inhaled, or pulmonary delivery of the compound of the invention. In some embodiments, the nanoparticle or microparticle that contains more than one nanocarrier of the invention can be formed from a hydrophobic polymer.

[0438] The compounds of formula (I) and the formulations or compositions that contain them can also be used in a method for preventing or treating metabolic syndrome. Thus, the invention also provides the use of the compounds of the invention in a method for therapeutically preventing or treating diseases and disorders related to CB 1 receptor activity, such as metabolic syndrome as defined herein.

[0439] The invention also provides a method for preventing and treating metabolic diseases and metabolic disorders, which method comprises administering to a human or animal subject an amount of the compound of the invention. The compound can be:

[0440] - a highly lipophilic derivative of cannabinoid that has a LogP (partition coefficient between n-octanol and water) value in the range from 3 to 17;

[0441] - a compound of formula (I) and any derivative formula as defined herein.

[0442] As described above, the metabolic disease or metabolic disorder or metabolic syndrome can be selected from obesity, insulin resistance, diabetes, coronary heart disease, cirrhosis, and cancer.

[0443] Accordingly, the present invention provides a method of treating a subject to reduce body fat, or reduce body weight, or treat insulin resistance, or treat diabetes, or reduce or control hypertension, or improve an adverse lipid profile having elevated LDL cholesterol, low HDL cholesterol and elevated triglycerides, or treat fatty liver disease, or alleviate chronic kidney disease, or treat metabolic syndrome as defined herein, the method comprising administering to the subject a compound of the present invention. The compound may be in a form suitable for oral administration, parenteral administration, subcutaneous administration, intravenous administration, intramuscular administration or intraperitoneal administration. BRIEF DESCRIPTION OF THE DRAWINGS

[0445] To better understand the subject matter disclosed herein and to illustrate how the subject matter may be practiced in practice, embodiments will now be described by way of non-limiting example only with reference to the drawings, in which:

[0446] Figures 1A - 1C Depicts the results of a radioligand displacement assay. BNS-002 is more lipophilic than rimonabant (estimated partition coefficient [log P], 17 versus 6.4 for rimonabant), but has high affinity and selectivity for the CB 1 receptor. In the radioligand displacement assay, BNS-002 has a Ki of 4.96 nM for the CB 1 receptor, similar to the Ki of rimonabant ( Figure 1A ). Like rimonabant, BNS-002 reduces GTPγS binding in mouse meninges ( Figure 1B ), and is able to attenuate the effects of the potent CB 1 receptor agonist HU-210 ( Figure 1C ), indicating that it is an inverse agonist.

[0447] Figures 2A - 2B Shows the reduced brain permeability of BSN002. BSN002 shows significantly reduced brain permeability, as reflected by its reduced brain levels and elevated serum levels after administration of the compound at two different doses (3 mg / kg and 10 mg / kg, ip).

[0448] Figures 3A - 3EProvide a comparison of the effects of BNS002 and rimonabant on ambulation. Test whether the reduced brain permeability of BNS-002 is associated with a decrease in behavioral effects. To this end, evaluate the effects of BNS-002 and rimonabant in antagonizing cannabinoid-induced hypomotility. The significant increase in immobility induced by the cannabinoid agonist HU-210 (30 μg / kg, ip) in mice was completely blocked by rimonabant (10 mg / kg, ip), but not affected by similar and even higher doses of BNS-002 (10 mg / kg, 20 mg / kg, and 50 mg / kg; Figures 3A - 3E )

[0449] Figures 4A - 4D Show the increased activity profile of rimonabant compared to BNS002. Rimonabant (10 mg / kg, ip) induced a significant increase in the activity profile of mice, but BNS-002 (at 10 mg / kg, 20 mg / kg, and 50 mg / kg, ip) did not induce ( Figures 4A - 4D )

[0450] Figures 5A - 5B Show the metabolic profiles of BNS-002 and rimonabant. The metabolic profiles of BNS-002 and rimonabant were examined in mice with diet-induced obesity (DIO). Male C57BL / 6 mice fed a high-fat diet (HFD) for 14 weeks became obese and then started daily ip injections of vehicle, rimonabant, or BNS002 (all at 10 mg / kg / d) for an additional 28 days. Age-matched and sex-matched standard-fed mice were used as controls. The overweight and increased obesity of HFD mice were significantly reduced only by rimonabant ( Figures 5A - 5B )

[0451] Figures 6A - 6C Show that both rimonabant and BNS002 upregulate the reduction of HFD-induced VO 2 , total energy expenditure, and fat oxidation, as measured by using indirect calorimetry.

[0452] Figures 7A - 7B Demonstrate the potency of rimonabant over BNS002 in reducing food intake. The greater potency of rimonabant over BNS-002 in reducing body weight may be related to its ability to reduce total calorie intake ( Figures 7A - 7B )

[0453] Figures 8A - 8C Show the potencies of rimonabant and BNS-002 in alleviating HFD-induced hyperglycemia and glucose tolerance. BNS-002 completely reversed HFD-induced hyperglycemia and glucose intolerance in a manner similar to rimonabantFigures 8A - 8B )。A trend of decreasing serum insulin levels was also recorded for both compounds ( Figure 8C ).

[0454] Figure 9 Shows the efficacy of rimonabant and BNS-002 in reversing HFD-induced hepatic steatosis. HFD-induced hepatic steatosis, as reflected by elevated lipid vesicles in the liver, was completely reversed by rimonabant and partially reversed by BNS-002.

[0455] Figure 10 Shows the efficacy of rimonabant and BNS-002 in reversing HFD-induced renal hyperfiltration. In addition, HFD-induced renal hyperfiltration was completely normalized by BNS-002 ( Figure 10 ), indicating the enhanced ability of this novel compound to mitigate obesity-induced renal dysfunction.

[0456] Figures 11A - 11B Demonstrates the efficacy of higher doses of BNS002 in DIO mice. Next, the efficacy of higher doses of BNS-002 (15 mg / kg and 30 mg / kg, ip for 7 days) compared to rimonabant (10 mg / kg / d) was tested in DIO mice. Age-matched and sex-matched standard chow-fed mice were used as controls. Rimonabant and BNS-002 at a dose of 30 mg / kg significantly reduced the overweight of HFD mice ( Figure 11A and Figure 11B ), while no effect on weight loss was observed in the group treated with 15 mg / kg of BNS-002.

[0457] Figure 12 Provides the Ki value determined for TMP using the 3 [3H]CP-55,940 radioligand displacement assay.

[0458] Figure 13 Provides the Ki value determined for EST using the 3 [3H]CP-55,940 radioligand displacement assay.

[0459] Figure 14 Provides the Ki value determined for IDB using the 3 [3H]CP-55,940 radioligand displacement assay.

[0460] Figure 15Shows the ability of IDB, EST, TMP, and rimonabant (as a positive control) to induce centrally mediated hyperactivity in mice. Wild-type male C57B1 / 6J mice received a single dose of rimonabant (10 mg / kg, IP), IDB, EST, TMP (at 20 mg / kg, 40 mg / kg, and 35 mg / kg, IP, respectively), or vehicle. Locomotor activity was measured by the Promethion metabolic system (Sable Instruments, Inc). Data represent the mean ± SEM from 4 - 8 mice per group. *P < 0.05 relative to vehicle-treated controls.

[0461] Figure 16 Demonstrates the ability of IDB, EST, TMP, and rimonabant (as a positive control) to inhibit the hypomotility induced by the CB 1 receptor agonist (HU210). Wild-type male C57B1 / 6J mice received a single dose of rimonabant (10 mg / kg, IP), IDB, EST, TMP (at 20 mg / kg, 40 mg / kg, and 35 mg / kg, IP, respectively), or vehicle. Half an hour later, the mice received a single dose of HU210 (30 μg / kg, IP), and their locomotor activity was evaluated by the Promethion metabolic system (Sable Instruments, Inc). Data represent the mean ± SEM from 4 - 10 mice per group. *P < 0.05 relative to vehicle-treated controls, #P < 0.05 relative to HU210.

[0462] Figures 17A - 17B Shows that IDB has a CB 1 binding affinity (Ki) of 256.3 nM (A), and shows the inverse agonist profile as determined by the GTPγS binding assay (B). Data represent the mean ± SEM of at least three independent experiments performed in triplicate.

[0463] Figures 18A - 18F Shows that in DIO mice, IDB (20 mg / kg / day for 20 days) reduces body weight (A, B), decreases daily food intake and total food intake (C, D), and reduces fat mass and increases lean mass (E, F). Data represent the mean ± SEM from 5 mice per group. *P < 0.05 relative to vehicle-treated controls.

[0464] Figures 19A - 19FExhibit that long-term IDB administration (20 mg / kg / day for 20 days) induces significant changes in metabolic parameters within a 24-hour period, which are measured by the Promethion high-resolution behavioral phenotyping system (Sable Instruments, Inc.). Respiratory quotient (A), VO 2 (B), VCO 2 (C), total energy expenditure (D), fat oxidation (E), and carbohydrate oxidation (F). Data are mean ± SEM from 4 mice per group. *P < 0.05 versus vehicle-treated control.

[0465] Figures 20A - 20D Exhibit that long-term IDB administration (20 mg / kg / day for 20 days) affects locomotion in DIO mice. Locomotor activity (A), ability to run on a rotarod (B), ambulatory activity (C), and total distance (D). Methods: Mice were monitored over a 24-hour period by the Promethion high-resolution behavioral phenotyping system (Sable Instruments, Inc.). Data are mean ± SEM from 4 mice per group.

[0466] Figures 21A - 21I Illustrate the effect of long-term IDB administration (20 mg / kg / day for 20 days) on glycemic control. Mice on a high-fat diet for 20 weeks were treated long-term with IDB or vehicle, and glucose homeostasis was evaluated. Note that IDB decreased glucose tolerance (A - B), improved insulin sensitivity (C - F), and decreased fasting (G) and fed (H) glucose levels. In addition, IDB increased glucosuria (I). Data represent mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control.

[0467] Figures 22A - 22B Illustrate that long-term IDB administration (20 mg / kg / day for 20 days) reduces HFD-induced hepatic steatosis and liver injury in mice. Elevated vacuolar lipid deposition measured by H&E staining was evident in DIO mice treated with vehicle compared to IDB-treated animals on the same diet (A). In addition, a decrease in liver weight (B) and a decrease in liver enzymes (AST, ALT, and ALP) measured by the COBAS chemistry analyzer were significant in IDB-treated mice. Data represent mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control.

[0468] Figures 23A - 23ELong-term IDB administration (20 mg / kg / day for 20 days) was shown to improve dyslipidemia in DIO mice. IDB was able to reduce total cholesterol (A), triglycerides (B), HDL (C), and LDL (D) and increase the ratio of HDL to LDL (E). Data are expressed as the mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control. Detailed Description of the Invention

[0469] As disclosed herein, "EST" is designated herein as compound "I". "TMP" is designated herein as compound "H". "IDB" is designated herein as compound "K". "BNS-002" is designated herein as compound "D".

[0470] Synthesis and Characterization of 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-octadecyl-1H-pyrazole-3-carboxamide (BNS-002-)

[0471] Synthesis Procedure. A solution of ethyl chloroformate (0.25 mL, 2.6 mmol) in dichloromethane (10 mL) was added to 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (1 g, 2.6 mmol) in dry THF (150 mL). The mixture was added to a solution of stearylamine (0.7 g, 2.6 mmol) and triethylamine (0.38 ml, 2.8 mmol) in dry THF (200 mL). The addition was carried out slowly and dropwise at a rate of 10 ml / min at room temperature. The reaction mixture was stirred at room temperature for 4 hours. A pale yellow solution and a white precipitate were formed. The mixture was filtered through a white paper filter and washed with dry THF (50 ml). After filtration, THF was evaporated and the crude product was dissolved in hexane (150 ml), poured into a separatory funnel, and washed three times with DDW (100 ml). The hexane layer was collected, dried over anhydrous sodium sulfate, filtered through a white paper filter, and the resulting pale yellow liquid was removed via evaporation. A 70% yield was obtained prior to column chromatography. The precipitate was redissolved in 10 ml of dichloromethane and combined with silica powder (Silica Gel 60), dried and loaded onto a pre-prepared silica column (radius 5 cm, length 25 cm). Separation and purification were completed as follows: The column was washed with hexane for 2 times the volume of the column capacity; subsequently, the column was washed with hexane for 2 volumes of the column capacity.

[0472]

[0473] Characterization. LC-MS spectra and H-NMR spectra confirmed the structure of the title compound. HPLC showed a purity of greater than 98%.

[0474] Compounds with longer or shorter alkyl chains can be prepared similarly. Non-limiting examples of such compounds include:

[0475]

[0476] Radioligand binding assay. Using 3 [[H]]CP-55,940 as the radioligand for the CB 1 receptor and crude membranes from mouse brain, the binding of BNS-002 to the CB 1 receptor was evaluated in a competitive displacement assay. All data were in triplicate, and the Ki values were determined from three independent experiments.

[0477] 35 [[S]]GTPγS binding. Mouse brains were dissected, and P2 membranes were prepared and resuspended at ~6 μg protein / μL in 1 ml of assay buffer (50 mM Tris HCl, 9 mM MgCl 2 , 0.2 mM EGTA, 150 mM NaCl; pH 7.4). Ligand-stimulated 35 [[S]]GTPγS binding was assayed as previously described (Tam et al., JCI, 2010). Briefly, membranes (10 μg protein) were incubated in silanized glass tubes in assay buffer containing 100 μM GDP, 0.05 nM 35 [[S]]GTPγS, 1 nM - 1 μM of the test compound, and 1.4 mg / mL fatty acid-free BSA. Bound and free ligands were separated by vacuum filtration. Nonspecific binding was determined using 10 μM GTPS. Basal binding was assayed in the absence of ligand and in the presence of GDP.

[0478] Tissue levels of the antagonist. Mice received a single dose (3 mg / kg or 10 mg / kg, ip) of BNS-002 or rimonabant and were sacrificed 1 hour later. Blood was collected, and mice were perfused with phosphate-buffered saline for 1 min to remove the drug from the intravascular space before removing the brain and liver. Drug levels in tissue homogenates and plasma were determined using LC-MS / MS.

[0479] Locomotor activity. Locomotor activity was quantified by the number of interruptions of an infrared XYZ beam array with a beam spacing of 0.25 cm in a Promethion high-resolution behavioral phenotyping system (Sable Instruments, Inc., Las Vegas, NV, USA).

[0480] ​Mice. The experimental protocol used was approved by the Institutional Animal Care and Use Committee of the Hebrew University, an AAALAC International-accredited institution. Male 6-week-old C57B1 / 6J mice were obtained from Harlan Laboratories. Mice were maintained on a 12-h light / dark cycle and fed ad libitum. To induce diet-induced obesity, C57Bl6 / J mice were fed a high-fat diet (HFD) (60% of calories from fat, 20% from protein, and 20% from carbohydrates; Research Diet, D12492) or a standard laboratory diet (STD, 14% fat, 24% protein, 62% carbohydrates; NIH-31 rodent diet) for 14 weeks.

[0481] As indicated in the figure, HFD-fed obese mice received vehicle (1% Tween 80, 4% DMSO, 95% saline), BNS-002, IDB, or rimonabant daily by intraperitoneal (ip) injection at 10 mg / kg, 15 mg / kg, 20 mg / kg, and 30 mg / kg for 7 days - 28 days. Age-matched STD control mice received vehicle daily. Body weight and food intake were monitored daily. Total body fat mass and lean mass were determined by EchoMRI-100H TM (Echo Medical Systems LLC, Houston, TX, USA). 24-h urine was collected for 1 week before euthanasia using a mouse metabolic cage (CCS2000 refrigeration system, Hatteras Instruments, NC, USA). At 20 weeks, mice were euthanized by cervical dislocation under anesthesia, the kidneys, brain, liver, fat pads, and muscle were removed and weighed, and the samples were snap-frozen or fixed in buffered 4% formalin. Trunk blood was collected for determination of biochemical parameters.

[0482] Multi-parameter metabolic assessment. The metabolic profiles of mice were evaluated by using the Promethion high-resolution behavioral phenotyping system (Sable Instruments, Inc., Las Vegas, NV, USA). Data acquisition and instrument control were performed using MetaScreen software version 2.2.18.0, and the raw data obtained were processed using ExpeData version 1.8.4 with an analysis script that detailed all aspects of data conversion. Mice with free access to food and water were subjected to a standard 12h light / 12h dark cycle, which consisted of a 48h acclimation period followed by 24h of sampling. Respiratory gases were measured using a pull-mode negative pressure system with a GA-3 gas analyzer (Sable Systems, Inc., Las Vegas, NV, USA). Airflow was measured and controlled by an FR-8 (Sable Systems, Inc., Las Vegas, NV, USA), with the set flow rate being 2000 mL / min. Water vapor was continuously measured, and its dilution effect on O 2 and CO 2 was compensated mathematically. The effective mass was calculated by [body mass] 0.75 . Fat oxidation (FO) and carbohydrate oxidation (CHO) were calculated as FO = 1.69 × VO 2 - 1.69 × VCO 2 and CHO = 4.57 × VCO 2 - 3.23 × VO 2 , and were expressed as g / d / kg 有效质量 .

[0483] Glucose tolerance (ipGTT) test and insulin sensitivity test (ipIST). Mice fasted overnight were injected with glucose (1.5 g / kg, ip), and then tail blood was collected at 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, and 120 min. Blood glucose levels were determined using an Elite glucometer (Bayer, Pittsburgh, PA). On the next day, the mice fasted for 6 h before receiving insulin (0.75 U / kg, i.p.; Eli Lilly, DC, USA or vial, novo nordisk A / S, Denmark), and blood glucose levels were determined at the same time intervals as above.

[0484] Blood and urine biochemistry. Serum levels of creatinine and urine levels of creatinine, as well as serum levels of ALT, AST, ALP, HDL, LDL, TG, and cholesterol were determined using a Cobas C-111 chemistry analyzer (Roche, Switzerland). Creatinine clearance rate (CCr mL / h = urine creatinine mg / dL × urine volume / serum creatinine mg / dL × 24 hours) was calculated using urine creatinine level and serum creatinine level. Serum insulin level was measured using an ELISA kit (Crystal Chem, Inc., Downers Grove, IL, USA). Fasting blood glucose was measured using an Elite glucometer (Bayer, Pittsburgh, PA).

[0485] Histopathological analysis. Five-micrometer paraffin-embedded liver sections from 5 animals per group were stained with hematoxylin-eosin staining. Liver images were captured using a Zeiss AxioCam ICc5 color camera mounted on a Zeiss Axio Scope.A1 light microscope, and 10 random 40× fields were taken from each animal.

[0486] Results:

[0487] BNS-002 is more lipophilic than rimonabant (estimated partition coefficient [log P], 17 vs. 6.4 for rimonabant), but retains high affinity and selectivity for the CB 1 receptor. In radioligand displacement assays, BNS-002 had a Ki of 4.96 nM for the CB 1 receptor, similar to the Ki of rimonabant ( Figure 1A ). Like rimonabant, BNS-002 decreased GTPγS binding in mouse meninges ( Figure 1B ), and was able to attenuate the effects of the potent CB 1 receptor agonist HU-210 ( Figure 1C ), indicating that it is an inverse agonist.

[0488] Importantly, BSN002 showed significantly reduced brain permeability, as reflected by its decreased brain levels and increased serum levels after administration of the compound at two different doses (3 mg / kg and 10 mg / kg, ip; Figures 2A - 2B ).

[0489] Next, the inventors tested whether the reduced brain permeability of BNS-002 was associated with a blunting of the behavioral effects. To this end, we compared the effects of BNS-002 and rimonabant in antagonizing cannabinoid-induced hypomotility. The significant increase in immobility induced by the cannabinoid agonist HU-210 (30 μg / kg, ip) in mice was completely blocked by rimonabant (10 mg / kg, ip), but not by similar and even higher doses of BNS-002 (10 mg / kg, 20 mg / kg, and 50 mg / kg; Figures 3A - 3E )

[0490] In addition, rimonabant (10 mg / kg, ip) also induced a significant increase in the activity profile of mice, but BNS-002 (at 10 mg / kg, 20 mg / kg, and 50 mg / kg, ip) did not induce ( Figures 4A - 4D )

[0491] The metabolic profiles of BNS-002 and rimonabant were next examined in mice with diet-induced obesity (DIO). Male C57BL / 6 mice fed a high-fat diet (HFD) for 14 weeks became obese and then began daily ip injections of vehicle, rimonabant, or AM6545 (all at 10 mg / kg / d) for an additional 28 days. Age-matched and sex-matched standard chow-fed mice were used as controls. The overweight and increased adiposity of HFD mice were significantly reduced only by rimonabant ( Figures 5A - 5B )

[0492] However, a significant increase in the metabolic profiles of DIO mice treated with both antagonists was demonstrated using indirect calorimetry. As Figures 6A - 6C shown, both rimonabant and BNS-002 were able to upregulate the reduction of HFD-induced VO 2 2, total energy expenditure, and fat oxidation.

[0493] The greater potency of rimonabant over BNS-002 in reducing body weight may be related to its ability to reduce total caloric intake ( Figures 7A - 7B )

[0494] However, BNS-002 completely reversed HFD-induced hyperglycemia and glucose intolerance in a manner similar to rimonabant ( Figures 8A - 8B ). Both compounds also showed a trend towards reduced serum insulin levels ( Figure 8C )

[0495] In addition, HFD-induced hepatic steatosis, as reflected by elevated lipid vacuoles in the liver, was completely reversed by rimonabant and partially reversed by BNS-002 ( Figure 9 )

[0496] In addition, HFD-induced renal ultrafiltration was completely normalized by BNS-002( Figure 10 ), indicating the enhanced ability of this novel compound to mitigate obesity-induced renal dysfunction.

[0497] Next, the efficacy of higher doses of BNS-002 (15 mg / kg and 30 mg / kg, ip for 7 days) was tested in DIO mice compared to rimonabant (10 mg / kg / d). Age- and sex-matched standard chow-fed mice were used as controls. Rimonabant and BNS-002 at a dose of 30 mg / kg significantly reduced the overweight of HFD mice( Figure 11A and Figure 11B ), while no effect on weight loss was observed in the group treated with 15 mg / kg of BNS-002.

[0498] Synthesis and Characterization of 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(2,2,6,6-tetramethyl-1-oxo-1-piperidin-4-yl)-1H-pyrazole-3-carboxamide (BB1+TMP)

[0499] Synthesis procedure. N,N'-Dicyclohexylcarbodiimide (DCC, 1.08 g, 5.24 mmol) was added to 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (BB1, 1 g, 2.26 mmol) in CH 2 Cl 2 (70 ml). The resulting mixture was stirred for 10 min and then 4-Amino TEMPO (radical) (TMP, 0.45 g, 2.62 mmol) was added. The reaction mixture was stirred at room temperature for 24 h. An orange solution and a white precipitate formed. The mixture was filtered through a white paper filter and washed with CH 2 Cl 2 (50 ml). After filtration, CH 2 Cl 2 was evaporated and the crude product was redissolved in CH 2 Cl 2 (50 ml). An orange solution and a white precipitate formed. The mixture was filtered through a white paper filter and washed with CH 2 Cl 2 (50 ml). After filtration, CH 2 Cl 2 was evaporated.

[0500] A 74% yield was obtained prior to column chromatography. The orange viscous oil was redissolved in 10 ml of CH 2 Cl 2In, and combined with silica powder (silica gel 60), dried and loaded into a pre-prepared silica column (radius 5 cm, length 25 cm). Separation and purification were carried out as follows: The column volume was washed 2-fold with hexane; subsequently, the column volume was washed 2-fold with hexane:ethyl acetate (90:10), and the washing was terminated after washing the column volume 4-fold with hexane:ethyl acetate (80:20).

[0501]

[0502] Characterization. LC-MS and elemental analysis confirmed the structure of the title compound. HPLC showed a purity higher than 98%.

[0503] Elemental analysis

[0504]

[0505] Table 1

[0506] Synthesis and Characterization of 2,2,6,6-Tetramethyl-1-piperidin-4-yl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylate (BB1 + EST)

[0507] Synthesis procedure. N,N'-Dicyclohexylcarbodiimide (DCC, 1.08 g, 5.24 mmol) was added to 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (BB1, 1 g, 2.26 mmol) in CH 2 Cl 2 (70 ml). The resulting mixture was stirred for 10 min and then 4-hydroxy TEMPO (radical) (EST, 0.45 g, 2.62 mmol) was added. The reaction mixture was stirred at room temperature for 24 h. An orange solution and a white precipitate were formed. The mixture was filtered through a white paper filter and washed with CH 2 Cl 2 (50 ml). After filtration, CH 2 Cl 2 was evaporated, and the crude product was redissolved in CH 2 Cl 2 (50 ml). An orange solution and a white precipitate were formed. The mixture was filtered through a white paper filter and washed with CH 2 Cl 2 (50 ml). After filtration, CH 2 Cl 2 .

[0508] A yield of 70% was obtained prior to column chromatography. The orange viscous oil was redissolved in 10 ml of CH 2 Cl 2 and combined with silica powder (Silica Gel 60), dried and loaded onto a pre-prepared silica column (radius 5 cm, length 25 cm). Separation and purification were completed as follows: the column was washed with hexane for 2 column volumes; subsequently, it was washed with hexane∶ethyl acetate (90∶10) for 2 column volumes and the washing was ended after washing with hexane∶ethyl acetate (80∶20) for 4 column volumes.

[0509]

[0510] Characterization. LC-MS and elemental analysis confirmed the structure of the title compound. HPLC showed a purity of higher than 98%.

[0511] Elemental analysis

[0512]

[0513] Table 2

[0514] Synthesis and Characterization of 10-(4,5-Dimethoxy-2-methyl-3,6-dioxacyclohex-1,4-dien-1-yl)decyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylate (BB1 + IDB)

[0515] Synthesis procedure. N,N'-Dicyclohexylcarbodiimide (DCC, 1.3 g, 5.91 mmol) was added to 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (BB1, 1.12 g, 2.95 mmol) in CH 2 Cl 2 (70 ml). The resulting mixture was stirred for 10 min and then idebenone (IDB, 1, 2.95 mmol) was added. The reaction mixture was stirred at room temperature for 24 h. An orange solution and a white precipitate were formed. The mixture was filtered through a white paper filter and washed with CH 2 Cl 2 (50 ml). After filtration, CH 2 Cl 2 was evaporated and the crude product was redissolved in CH 2 Cl 2 (50 ml). An orange solution and a white precipitate were formed. The mixture was filtered through a white paper filter and washed with CH 2 Cl 2 (50 ml). After filtration, CH2 Cl 2 。

[0516] A 70% yield was obtained prior to column chromatography. The orange viscous oil was redissolved in 10 ml of CH 2 Cl 2 and combined with silica powder (Silica Gel 60), dried and loaded onto a pre-prepared silica column (radius 5 cm, length 25 cm). Separation and purification were completed as follows: The column was washed with hexane for 2 column volumes; subsequently, it was washed with hexane∶ethyl acetate (90∶10) for 2 column volumes, and the washing was ended after washing with hexane∶ethyl acetate (80∶20) for 4 column volumes.

[0517]

[0518] Characterization. LC-MS and H-NMR confirmed the structure of the title compound. HPLC showed a purity above 98%.

[0519] TMP, EST and IDB - In vitro binding report

[0520] Radioactive ligand binding assay. Using 3 H]CP-55,940 as the radioactive ligand for the CB 1 receptor and the crude membrane from mouse brain, the test compounds were evaluated for their binding to the CB 1 receptor in a competitive displacement assay. Membranes were extracted according to the established protocol previously described by Catani V.M. and Gasperi V. [8]. The test compounds were tested at different concentrations (10M - 5M - 10M - 11M), and their ability to displace 3 H]CP-55,940 was evaluated. Membranes with bound 3 H]CP-55,940 were separated from the free ligand by vacuum filtration and washed, and the radioactivity of the bound 3 H]CP-55,940 was measured using a β-counter. All data were in triplicate, and the Ki values were extracted by non-linear regression analysis using GraphPad Prism software.

[0521] Results

[0522] In the radioactive ligand displacement assay, all three test compounds were found to have high affinity for the CB 1 receptor. The Ki values for each substance varied, being in the range of 1.69 nM - 446 nM for TMP ( Figure 12 ), in the range of 0.37 nM - 7.81 nM for EST ( Figure 13 ), and for IDB ( Figure 14)In the range from 1.9 nM - 134.6 nM.

[0523] TMP, EST, and IDB - In Vivo Safety Report (Lack of CNS Central Activity)

[0524] Central - mediated hyperactivity profile. Wild - type male C57Bl / 6J mice (n = 4 - 8) received a single dose of rimonabant (10 mg / kg, IP), TMP (35 mg / kg, IP), EST (40 mg / kg, IP), IDB (20 mg / kg, IP), or vehicle only (IP). The mice were placed in metabolic cages and their activity profiles were evaluated. Locomotor activity was quantified by the number of interruptions of an infrared XYZ beam array with a beam spacing of 0.25 cm in a Promethion high - resolution behavioral phenotyping system (Sable Instruments, Inc., Las Vegas, NV, USA).

[0525] Antagonism of cannabinoid - induced hypomotility. The ability of different compounds to inhibit hypomotility induced by HU210 (a cannabinoid agonist) was evaluated. Wild - type male C57Bl / 6J mice (n = 4 - 10) received a single dose of rimonabant (10 mg / kg, IP), TMP (35 mg / kg, IP), EST (40 mg / kg, IP), IDB (20 mg / kg, IP), or vehicle only (IP). Half an hour later, the mice received a single dose of HU210 (30 μg / kg, IP), and their locomotor activity was evaluated as described above.

[0526] Results

[0527] Rimonabant (10 mg / kg) induced a significant increase in the activity profile of mice ( Figure 15 ), but no significant hyperactivity was recorded after injection of TMP (35 mg / kg, IP), EST (40 mg / kg, IP), and IDB (20 mg / kg, IP) compared to the vehicle group ( Figure 15 ). The significant hypomotility induced by the cannabinoid agonist HU210 (30 μg / kg, IP) in mice was significantly blocked by rimonabant, but not affected by the test compounds ( Figure 16 ).

[0528] Figure 17 shows that IDB has a CB 1 binding affinity (Ki) of 256.3 nM (A), and shows the inverse agonist profile as measured by the GTPγS binding assay (B). Data represent the mean ± SEM of at least three independent experiments performed in triplicate.

[0529] In Figure 18, in DIO mice, IDB (20 mg / kg / day for 20 days) reduced body weight (A, B), decreased daily food intake and total food intake (C, D), and decreased fat mass and increased lean mass (E, F). Data represent mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control.

[0530] In Figure 19, long-term IDB administration (20 mg / kg / day for 20 days) induced significant changes in metabolic parameters measured by the Promethion high-resolution behavioral phenotyping system (Sable Instruments, Inc.) over a 24-hour period. Respiratory quotient (A), VO 2 (B), VCO 2 (C), total energy expenditure (D), fat oxidation (E), and carbohydrate oxidation (F). Data are mean ± SEM from 4 mice per group. *P < 0.05 versus vehicle-treated control.

[0531] In Figure 20, long-term IDB administration (20 mg / kg / day for 20 days) did not affect locomotion in DIO mice. Locomotor activity (A), ability to run on a rotarod (B), ambulatory activity (C), and total meters (D). Methods: Mice were monitored over a 24-hour period by the Promethion high-resolution behavioral phenotyping system (Sable Instruments, Inc.). Data are mean ± SEM from 4 mice per group.

[0532] In Figure 21, the effect of long-term IDB administration (20 mg / kg / day for 20 days) on glucose control is shown. Mice on a high-fat diet for 20 weeks were treated long-term with IDB or vehicle, and glucose homeostasis was evaluated. Note that IDB decreased glucose tolerance (A - B), improved insulin sensitivity (C - F), and decreased fasting (G) and fed (H) glucose levels. In addition, IDB increased glucosuria (I). Data represent mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control.

[0533] Long-term IDB administration (20 mg / kg / day for 20 days) shown in Figure 22 reduced HFD-induced hepatic steatosis and liver injury in mice. An elevation in lipid vacuole deposition measured by H&E staining was evident in DIO mice treated with vehicle compared to IDB-treated animals on the same diet (A). In addition, a decrease in liver weight (B) and a decrease in liver enzymes (AST, ALT, and ALP) measured by the COBAS chemistry analyzer were significant in IDB-treated mice. Data represent mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control.

[0534] Long-term IDB administration (20 mg / kg / day for 20 days) shown in Figure 23 improved dyslipidemia in DIO mice. IDB was able to reduce total cholesterol (A), triglycerides (B), HDL (V), and LDL (D) and increase the ratio of HDL to LDL (E). Data represent mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control.

[0535] A very important difference between BNS-002 and IDB lies in their different effects on liver and kidney function. As can be seen in Figure 10 , HFD-induced renal ultrafiltration was completely normalized by BNS-002, indicating the ability of this novel compound to mitigate the enhanced obesity-induced renal dysfunction. In contrast, IDB had no effect compared to the control. In addition, HFD-induced hepatic steatosis, as reflected by elevated lipid vacuoles in the liver, was completely reversed by rimonabant and partially reversed by BNS-002 ( Figure 9 ). However, long-term IDB administration (20 mg / kg / day for 20 days) of IDB reduced HFD-induced hepatic steatosis and liver injury in mice. An elevation in lipid vacuole deposition measured by H&E staining was evident in DIO mice treated with vehicle compared to IDB-treated animals on the same diet ( Figure 22A ). In addition, a decrease in liver weight ( Figure 22B ) measured by the COBAS chemistry analyzer and a decrease in liver enzymes (AST, ALT, and ALP) were significant in IDB-treated mice. Data represent mean ± SEM from 5 mice per group. *P < 0.05 versus vehicle-treated control.

Claims

1. A compound of general formula (VI): wherein R 1 and R 2 each independently of one another is a halide; each of n and m is independently an integer between 0 and 5, specifying the number of halide substituents on the ring; R 6 selected from -C(=O)-O-R 8 and -C(=O)-NR'R 8 ; R 7 is -CH 3 ; R 8 selected from -NHC(=O)C 3 -C 10 heteroaryl-substituted linear -C 1 -C 25 alkyl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical or idebenone-based derivatives, wherein The group 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical has the structure: where z is 1, Rf is H, and where the dashed bond is a single bond, and where The idebenone-based derivative is a group having the following structure: where k is an integer between 0 and 25; and R' is selected from H, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, -C(=O)-C 2 -C 25 alkyl, -C(=O)-C 2 -C 25 alkenyl and C 5 -C 25 alkynyl.

2. A compound of general formula (VII): wherein R 8 Selected from 2,2,6,6-tetramethylpiperidin-1-yl-4-yl radical, idebenone derivatives or linear -C 3 -C 10 substituted by heteroaryl -C 1 -C 25 alkyl, wherein The group 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical has the structure: where z is 1, Rf is H, and where the dashed bond is a single bond, and where The idebenone-based derivative is a group having the following structure: where k is an integer between 0 and 25; R 1 and R 2 each of which is independently a halide; and each of n and m is independently an integer between 0 and 5, specifying the number of halide substituents on the ring.

3. A compound of general formula (VIII): wherein R 1 and R 2 each of which is independently a halide; and each of n and m is independently an integer between 0 and 5, specifying the number of halide substituents on the ring.

4. A compound of formula (IX): wherein R 8 Selected from 2,2,6,6-tetramethylpiperidin-1-yl-4-yl radical, idebenone derivatives or linear -C 3 -C 10 substituted by heteroaryl -C 1 -C 25 alkyl, wherein The group 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical has the structure: where z is 1, Rf is H, and where the dashed bond is a single bond, and where The idebenone-based derivative is a group having the following structure: where k is an integer between 0 and 25.

5. A compound of general formula (XI): wherein R 8 is a 2,2,6,6-tetramethylpiperidin-1-yl-4-yl radical or idebenone-based derivative, wherein The group 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical has the structure: where z is 1, Rf is H, and where the dashed bond is a single bond, and where The idebenone-based derivative is a group having the following structure: where k is an integer between 0 and 25; R 1 and R 2 each of which is independently a halide; and each of n and m is independently an integer between 0 and 5, specifying the number of halide substituents on the ring.

6. A compound of general formula (XII): wherein R 1 and R 2 each of which is independently a halide; and each of n and m is independently an integer between 0 and 5, specifying the number of halide substituents on the ring.

7. A compound of formula (XIII): wherein R 1 and R 2 each independently of one another is a halide; each of n and m is independently an integer between 0 and 5, specifying the number of halide substituents on the ring; and wherein k is an integer between 0 and 25.

8. A compound of general formula (XIV): wherein R 8 is a 2,2,6,6-tetramethylpiperidin-1-yl-4-yl radical or idebenone derivative, wherein The group 2,2,6,6-tetramethylpiperidin-1-ol-4-yl radical has the structure: where z is 1, Rf is H, and where the dashed bond is a single bond, and where The idebenone-based derivative is a group having the following structure: where k is an integer between 0 and 25.

9. A compound of formula (XVI): wherein k is an integer between 0 and 25.

10. A compound having any of the following structures:

11. A pharmaceutical composition comprising the compound according to any one of claims 1 to 10.

12. A nanocarrier comprising at least one compound according to any one of claims 1 to 10.

13. Use of the compound according to any one of claims 1 to 10, or the pharmaceutical composition according to claim 11, or the nanocarrier according to claim 12, in the manufacture of a medicament for the prevention or treatment of metabolic syndrome and metabolic disorders.

14. Use according to claim 13, wherein the metabolic syndrome or metabolic disorder is selected from obesity, insulin resistance, diabetes, coronary heart disease, cirrhosis and cancer.

15. Use of the compound according to any one of claims 1 to 10, or the pharmaceutical composition according to claim 11, or the nanocarrier according to claim 12, in the manufacture of a medicament for treating metabolic syndrome in a subject.

16. Use of the compound according to any one of claims 1 to 10, or the pharmaceutical composition according to claim 11, or the nanocarrier according to claim 12, in the manufacture of a medicament for reducing body fat, or reducing body weight, or treating insulin resistance, or treating diabetes, or reducing or controlling hypertension, or improving an adverse lipid profile having elevated LDL cholesterol, low HDL cholesterol and elevated triglycerides in a subject.

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