Chinone-, hydrochinome- and naphthochinone-analogues of vatiquione for treatment of mitochondrial disorder diseases

Abstract

Abstract The disclosure provides therapeutic compositions (i.e., therapeutic agents) and methods of preventing or treating Friedreich's ataxia in a mammalian subject, reducing risk factors, signs and / or symptoms associated with Friedreich's ataxia (e.g. Complex I deficiency), and / or reducing the likelihood or severity of Friedreich's ataxia. The disclosure further provides novel intermediates for the production of said therapeutic compositions and related reduced versions of said therapeutic compositions, which reduce forms may also be used as therapeutic agents (or prodrugs of the therapeutic agent(s)). Abstract

Description

CROSS-REFERENCE TO RELATED APPLICATIONS 5 This application claims the benefit of and priority to U.S. Provisional Appl. No. 62 / 911,069, filed October 4, 2019, and U.S. Provisional Appl. No. 62 / 991,525, filed March 18, 2020, the contents of each of which are incorporated herein by reference in their entirety for any and all purposes. TECHNICAL FIELD 0 The present application relates generally to compositions and methods for preventing, ameliorating and / or treating mitochondrial disease, such as Friedreich's ataxia, and / or reducing the severity of such diseases. Furthermore, the present application relates to: 1) methods for the preparation of novel therapeutic compounds and related intermediates (e.g., chromanes (benzodihydropyrans), quinones, hydroquinones, benzoquinones and 15 hydroxybenzoquinones), and / or 2) administering an effective amount of a novel compound disclosed herein, alone or in combination with one or more other therapeutic agents, to a subject suffering from Friedreich's ataxia or other mitochondrial disease. INTRODUCTION The following description is provided to assist the understanding of the reader. None of the 20 information provided or references cited is admitted as being prior art to the compositions and methods disclosed herein. Friedreich's ataxia (FA) is a fatal, monogenic, autosomal recessive disease caused by mutations in the gene encoding the nuclear encoded mitochondrial protein frataxin. Tissues in both the peripheral and central nervous systems are affected in FA, and include the dentate 25 nucleus, Clark’s column, spinocerebellar tract and dorsal root ganglia. Progressive degeneration of these tissues leads to a worsening ataxia which for most patients ends in loss of independent ambulation by the third decade of life. The FXN gene encodes the protein frataxin. Frataxin is an iron binding protein responsible for forming iron-sulfur clusters. One result of frataxin deficiency is mitochondrial iron 30 overload. This data, for application number 2020358970, is current as of 2026-05-02 14:39 AEST 2026203365   02 May 2026 Frataxin is a highly conserved iron binding protein. Human frataxin is synthesized as a 210 amino acid precursor that is imported to the mitochondria via the mitochondrial targeting signal contained in the N-terminus. The frataxin precursor is subsequently cleaved to a mature 14 kDa protein (residues 81-210). 5 Frataxin binds both Fe2+ and Fe3+ ions in an electrostatic manner and functions as an iron chaperone during Fe-S cluster assembly. Frataxin directly binds to the central Fe-S cluster assembly complex, which is composed of Nfsl enzyme and Isu scaffold protein. Nfsl is a cysteine desulfurase used in the synthesis of sulfur bioorganic derivatives and Isu is the transient scaffold protein on which the Fe-S cluster assembles. Frataxin increases the 0 efficiency of Fe-S cluster formation, which is required to activate the mitochondrial Kreb cycle enzyme aconitase. Frataxin also plays a role in mitochondrial iron storage and heme biosynthesis by incorporating mitochondrial iron into protoporphyrin (PIX). Loss of frataxin function results in the disruption of iron-sulfur cluster biosynthesis, mitochondrial iron overload, oxidative stress, impaired aerobic electron transport chain 15 respiration and cell death in the brain, spinal cord, dorsal root ganglia and heart. Studies have also shown that frataxin protects dopaminergic neuronal cells against MPTP-induced toxicity in a mouse model of Parkinson’s disease. Ferroptosis is an iron-dependent type of cell death that is biochemically distinct from apoptosis and typically accompanied by a large amount of iron accumulation and lipid 20 peroxidation during the cell death process. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. Recent studies have shown that ferroptosis is closely related to the pathophysiological processes of many diseases, such as tumors, nervous 25 system diseases, ischemia-reperfusion injury, kidney injury, and blood diseases. Decreased expression of frataxin (FXN) is associated with mitochondrial dysfunction, mitochondrial iron accumulation, and increased oxidative stress. Recent studies have shown that frataxin, which modulates iron homeostasis and mitochondrial function, is a key regulator of ferroptosis. As such, ferroptosis as has been identified as a therapeutic target for Friedreich’s 30 ataxia. As described above, ferroptosis is associated with glutathione depletion and production of lipid peroxides, which are generated by lipoxygenase enzymes such as 2026203365   02 May 2026 lipoxygenase-15. Accordingly, targeting lipoxygenase-15 provides a therapeutic target for Friedreich’s ataxia. Mitochondrial iron overload leads to impaired intra-mitochondrial metabolism and a defective mitochondrial respiratory chain. A defective mitochondrial respiratory chain leads 5 to increased free radical generation and oxidative damage, which may be considered as mechanisms that compromise cell viability. Some evidence suggests that frataxin might detoxify ROS via activation of glutathione peroxidase and elevation of thiols. (See e.g., Calabrese et al., Journal of the Neurological Sciences, 233(1): 145-162 (June 2005)). Friedreich’s ataxia occurs when the FXN gene contains amplified intronic GAA repeats. The 0 mutant FXN gene contains expanded GAA triplet repeats in the first intron; in a few pedigrees, point mutations have also been detected. Since the defect is located in an intron, which is removed from the mRNA transcript between transcription and translation, the mutated FXN gene does not result in the production of abnormal proteins. Instead, the mutation causes gene silencing, i.e., the mutation decreases the transcription of the gene. 15 Symptoms typically begin between the ages of 5 and 15 years, although they sometimes appear in adulthood. The first symptom to appear is usually gait ataxia, or difficulty walking. The ataxia gradually worsens and slowly spreads to the arms and the trunk. There is often loss of sensation in the extremities, which may spread to other parts of the body. Other features include loss of tendon reflexes, especially in the knees and ankles. Most people with 20 Friedreich's ataxia develop scoliosis, which often requires surgical intervention for treatment. Dysarthria (slowness and slurring of speech) develops and can get progressively worse. Many individuals with later stages of Friedreich’s ataxia develop hearing and vision loss. Heart disease often accompanies Friedreich's ataxia, such as hypertrophic cardiomyopathy, myocardial fibrosis (formation of fiber-like material in the muscles of the heart), and cardiac 25 (heart) failure. Heart rhythm abnormalities such as tachycardia (fast heart rate) and heart block (impaired conduction of cardiac impulses within the heart) are also common. Other symptoms that may occur include chest pain, shortness of breath, and heart palpitations. Many patients with Friedreich’s ataxia will exhibit a slow decline in visual acuity in later stages of the disease. The most common ophthalmic manifestation of Friedreich’s ataxia is 30 optic neuropathy. In some cases, severe / catastrophic visual loss is experienced. 2026203365   02 May 2026 About 20 percent of people with Friedreich's ataxia develop carbohydrate intolerance and 10 percent develop diabetes. Most individuals with Friedreich’s ataxia tire very easily and find that they require more rest and take a longer time to recover from common illnesses such as colds and flu. 5 The rate of progression varies from person to person. Generally, within 10 to 20 years after the appearance of the first symptoms, the person is confined to a wheelchair, and in later stages of the disease individuals may become completely incapacitated. Friedreich's ataxia can shorten life expectancy, and heart disease is the most common cause of death. The five enzyme complexes (i.e. Complex I, Complex II, Complex III, Complex IV and 0 Complex V) of the oxidative phosphorylation (OXPHO S) system are located in the mitochondrial membrane and Complex I deficiency leading to decreased levels (and decreased production) of adenosine triphosphate (ATP) is believed to be associated with Friedreich’s ataxia. Indeed, it has been suggested that decreased frataxin expression in the cells of Friedreich’s ataxia patients increases the pool of non-bioavailable iron within the cell, 15 thereby leading to free radical generation, increased oxidative damage to the cell and decreased Complex I activity and associated decreases in intracellular ATP generation (Heidari et al., Complex I and ATP Content Deficiency in Lymphocytes from Friedreich’s Ataxia, Can. J. Neurol. Sci. 2009: 36: 26-31). There is no known cure for Friedreich’s ataxia. Generally, therapies involve treatment of the 20 symptoms. Because patients with Friedreich’s ataxia are at a risk of developing heart disease, they are often prescribed medications such as beta blockers, ACE inhibitors and / or diuretics. Because it is believed that damage caused by oxidative stress is involved in the progression of Friedreich’s ataxia, antioxidants such as vitamin E, idebenone and coenzyme Q10 are often co-administered to persons diagnosed or suspected of having Friedrich’s ataxia. These 25 compounds have been used in various clinical trials. Currently, EPL743 (a benzoquinone compound also known as vatiquinone) is currently in phase 2 clinical trials, has yet to initiate a phase 3 clinical trial for the treatment of refractory epilepsy and has been granted orphan drug designation and fast track status by the United States Food and Drug Administration (FDA). Vatiquinone is believed to reduce oxidative 30 stress and improve mitochondrial function. Omaveloxolone is a second generation synthetic oleanane triterpenoid that is believed to exhibit antioxidative and anti-inflammatory activity. Omaveloxolone is currently in phase 2 4 2026203365   02 May 2026 clinical development for treatment of a variety of indications, including Friedreich’s ataxia, mitochondrial myopathies and ophthalmic conditions / diseases. Several other therapies for the treatment of Friedreich’s ataxia are currently in clinical trials but there are no FDA approved drugs. Hence, there remains a need for better drug candidates 5 to address the needs of patients diagnosed with Friedreich’s ataxia. SUMMARY In an aspect, a compound of formula E-F,or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, is provided wherein E is 21 or 22: 10 22 and F is 13, 14, 15, 16, 17, 18, 19 or 20: 14 16 19 wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond 2026203365   02 May 2026 between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 5   of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if w=wis a single bond); each X is independently a group of formula -(CR12R13)-; each Y is independently absent or a group of formula -(CR12R13)-; each Z is independently a group of formula -(CR14)-; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 50 membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each Rs and R9 is each independently H, D, F, Cl, Br, I or C1-C4 alkyl; or taken together Rs and R9 form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; Rio is H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R11 is H, D or Ci-Ce alkyl; each of R12, R13 and Rm is independently H, D, F, 15 Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R20 is H, D, F or C1-C12 alkyl; each R21 is independently H, D, F, Cl, Br, I, or C1-C4 alkyl; n is an integer from 0 to 12; and *** indicates the point of attachment of E to F and ** indicates the point of attachment of F to E; and further provided that: (i) at least one group of formula Ri, R2, R3, R4, Rs, Re, R7, Rs, R9, Rio, R12, R13, R14, R20 or R21 comprises at least one fluorine atom; and / or (ii) Rs and R9 taken 20 together form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring. In any embodiment herein, it may be that E is 21 and F is 13, 14, 19 or 20. In any embodiment herein, it may be that E is 22 and F is 13, 14, 19 or 20. In any embodiment herein, it may be that E is 21 and F is 15, 16, 17 or 18. In any embodiment herein, it may be that E is 22 and F is 15, 16, 17 or 18. In any embodiment herein, it may be that J is O. In any embodiment 25 herein, it may be that J is S. In any embodiment herein, it may be that J is N-R11. In any embodiment herein, it may be that J is O or N-R11 and K is absent. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, 30   -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, each of K and L is independently -(CH2)-, 2026203365   02 May 2026 -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, L is -(CH2)-, - 5   (CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-,                 - 0   (C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, L is -(CH2)-, - (CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)-or -(C(CF3)2)-. In some embodiments, each of Ri, R2 and R3 is independently H, D, Cl, F, - 15 ch3, -och3, -cd3, -ocd3, -ch2f, -och2f, -chf2, -ochf2, -cf3, -ocf3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, 20   -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In 25 some embodiments, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2. In some embodiments, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2. In some embodiments, J is O; each of K and L is 30 independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CF3, 2026203365   02 May 2026 -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -ch2ch3, - OCH2CH3, or -CH(CH3)2 and Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments, E is 21 A, 21B, 21C, 21D, 21E or 21F: 21B             21C wherein each of Rie and R17 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, -CH(CH3)2, -OCH(CH3)2, -C(CH3)3 or - 10   O(CH3)3; and J” is O, S or N-Ris, wherein Ris is H, D, -CH3, -CH2F, -CHF2 or -CF3. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -ocf3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -cf2cf3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -ocd2cd3, 15   -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, 20 -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, and -CH(CH3)2, and 2026203365   02 May 2026 where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or is selected from H, D, methyl, ethyl, isopropyl and t-butyl. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2; and 5 where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -CH2CH3, and -CH(CH3)2, and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or is selected from H, D, methyl and ethyl. In some embodiments, each W is C and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF. In any embodiment herein, it may be that each of Rs and R9 is independently H, D, F, Cl, Br, I, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3 or 15   -CF(CF2CF3)2. In some embodiments, each of Rs and R9 is independently H, F, -CH3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CF2CH3, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CF3)3, - CH2CH2CH3, -CH(CH2CH3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In any embodiment herein, it may be that Rs and R9 taken together form a 3-, 4-, 5-, 6- or 720 membered carbocyclic or heterocyclic ring can be 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45,46 or 47: 31      32       33       34         35 36      37     38      39     40      41 42       43       44       45       46       47 2026203365   02 May 2026 wherein # indicates the point of attachment of the carbocycle or heterocycle to the remainder of the compound. In any embodiment herein, it may be that Rio is H, D, F, -CH3, -OCH3, -CD3, -0CD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, 5   -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CF2CF3, -CF(CF2CF3)2, -C(CH2CH3)3, -C(CD2CD3)3, -C(CF2CF3)3, -OCH2CH2CH3, -OCH(CH2CH3)2, 0 -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -CH(CH3)2. In any embodiment herein, it may be that R11 is H, methyl or ethyl. In any embodiment herein, it may be that each of R12, R13 or Rm is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, 15   -CH(CH3)2, -CH2CH2CH3, -CH(CH2CH3)2, -C(CH3)3, -OCH2CH3, -OCH(CH3)2, -OCH2CH2CH3, -OCH(CH2CH3)2 or -OC(CH3)3. In some embodiments, each of R12, R13 or R14 is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -OCH2CH3. In any embodiment herein, it may be that R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, 20 -CH2CH2CH2CH3, -CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH2CH3 or -CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3. In any embodiment herein, it may be that each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, 25   -CH(CH3)2, -CH2CH2CH2CH3 or -C(CH3)3. In any embodiment herein, it may be that n is 0, 1, 2, 3 or 4. In some embodiments, the compound is O 2026203365   02 May 2026 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is O or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, 5 a hydrate, and / or a solvate thereof. In some embodiments, the compound is or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 10 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is O or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 2026203365   02 May 2026 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 5 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is o HO, F Compound H o or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is Compound I or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is Compound J 2026203365   02 May 2026 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is Compound K or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, 5 a hydrate, and / or a solvate thereof. In some embodiments, the compound is or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 10 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In an aspect, a compound of formula C-D, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, is provided wherein C is 11 or 12: 15 2026203365   02 May 2026 and D is 13, 14, 15, 16, 17, 18, 19 or 20: 20 wherein, J’ is OH, SH or NH-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond 5 between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent (if w=Wis a double bond) or 10 selected from H, D and Ci-Ce alkyl (if w=wis a single bond); each X is independently a group of formula -(CR12R13)-; each Y is independently absent or a group of formula -(CR12R13)-; each Z is independently a group of formula -(CR14)-; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 5membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or 15 heteroaromatic ring or a 6-membered heterocyclic ring; each of Rs and R9 is each independently H, D, F, Cl, Br, I or C1-C4 alkyl; or taken together Rs and R9 form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; Rio is H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R11 is H, D or Ci-Ce alkyl; each of R12, R13 and Rm is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R19 is H, C1-C4 alkyl or benzyl; R20 is H, D, F, or Ci- 20   C12 alkyl; each R21 is independently H, D, F, Cl, Br, I, or C1-C4 alkyl; n is an integer from 0 to 12, inclusive; and *** indicates the point of attachment of C to D and ** indicates the 2026203365   02 May 2026 point of attachment of D to C; and further provided that: (i) at least one group of formula Ri, R2, R3, R4, Rs, Re, R7, Rs, R9, Rio, R12, Ri3, R14, R20 or R21 comprises at least one fluorine atom; and / or (ii) Rs and R9 taken together form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring. 5 In any embodiment herein, it may be that C is 11 and D is 13, 14, 19 or 20. In any embodiment herein, it may be that C is 12 and D is 13, 14, 19 or 20. In any embodiment herein, it may be that C is 11 and D is 15, 16, 17 or 18. In any embodiment herein, it may be that C is 12 and D is 15, 16, 17 or 18. In any embodiment herein, it may be that J’ is OH. In any embodiment herein, it may be that J’ is SH. In any embodiment herein, it may be that J’ 0 is NH-R11. In any embodiment herein, it may be that J’ is OH or NH-R11 and K is absent. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, 15   -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some 20 embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, 25   -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, L is -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, L is 30   -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -ocf3, -CH2CH3, -CH(CH3)2, -cd2cd3, 2026203365   02 May 2026 -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -ocf2ch3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, 5 -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, 0 -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2. In some embodiments, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2. In some embodiments, J’ is OH; each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, 15   -(C(CH3)2)- or -(C(CF3)2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2 and Ri and R2 taken together form a 5-, or 6-membered 20 carbocyclic or heterocyclic ring. In some embodiments, C is 11 A, 1 IB, 1 IC, 1 ID, 1 IE or 1 IF: 2026203365   02 May 2026 wherein each of Rie and R17 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -0CF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, -CH(CH3)2, -OCH(CH3)2, -C(CH3)3 or -O(CH3)3; and J” is OH, SH or NH-Ris, wherein Ris is H, D, -CH3, -CH2F, -CHF2 or -CF3. 5 In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), 0   -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, 15 -OCF2CF2CF3 or -OCF(CF2CF3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, and -CH(CH3)2, and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or is selected from H, D, methyl, ethyl, isopropyl and t-butyl. In some 20 embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently H, D, F, Cl, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2, and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is 25 independently absent or is selected from H, D, methyl and ethyl. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In any embodiment herein, it may be that each of Rs and R9 is independently H, D, F, Cl, Br, I, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, 30   -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3 or 2026203365   02 May 2026 -CF(CF2CF3)2. In some embodiments, each of Rs and R9 is independently H, F, -CH3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CF2CH3, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CF3)3, - CH2CH2CH3, -CH(CH2CH3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In any embodiment herein, it may be that Rs and R9 taken together form a 3-, 5   4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring selected from 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 and 47: 10 wherein # indicates the point of attachment of the carbocycle or heterocycle to the remainder of the compound. In any embodiment herein, it may be that Rio is H, D, F, -CH3, -OCH3, -CD3, -0CD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, 15   -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CF2CF3, -CF(CF2CF3)2, -C(CH2CH3)3, -C(CD2CD3)3, -C(CF2CF3)3, -OCH2CH2CH3, -OCH(CH2CH3)2, 20 -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -CH(CH3)2. In any embodiment herein, it may be that R11 is H, methyl or ethyl. In any embodiment herein, it may be that each of R12, R13 or Rm is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, 2026203365   02 May 2026 -CH(CH3)2, -CH2CH2CH3, -CH(CH2CH3)2, -C(CH3)3, -OCH2CH3, -OCH(CH3)2, -OCH2CH2CH3, -OCH(CH2CH3)2 or -OC(CH3)3. In some embodiments, each of R12, Ri3 or R14 is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -OCH2CH3. In any embodiment herein, it may be that R19 is H. In 5 any embodiment herein, it may be that R19 is -CH3. In any embodiment herein, it may be that R19 is -CH2CH3. In any embodiment herein, it may be that R19 is -C(CH3)3. In any embodiment herein, it may be that R19, is an unsubstituted or substituted benzyl group. In any embodiment herein, it may be that R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, 0 -CH2CH2CH2CH3, -CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH3, - CH2CH2CH2CH2CH2CH2CH2CH2CH3 or -CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3. In any embodiment herein, it may be that each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -15   CH(CH3)2, -CH2CH2CH2CH3 or -C(CH3)3. In any embodiment herein, it may be that n is 0, 1, 2, 3 or 4. In some embodiments, the compound is OH or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, 20 a hydrate, and / or a solvate thereof. In some embodiments, the compound is OH or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 2026203365   02 May 2026 OH or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is OH 5 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is OH or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 10                          OH or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is OH 2026203365   02 May 2026 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, 5 a hydrate, and / or a solvate thereof. In some embodiments, the compound is 0H Compound 1-2 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is Compound J-2 10 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is Compound K-2 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 2026203365   02 May 2026 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In some embodiments, the compound is 5 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In an aspect, a compound of formula A-B, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, or of formula A-H, or pharmaceutically acceptable salts, stereoisomers, mixtures of 10 stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein A is 1, 2, 3 or 4: B is 5, 6, 7 or 8: 2026203365   02 May 2026 and H is 25: Rs' l ** fQJ Rio' \ zp 25 wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each Q is 5 independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each W is independently C (carbon) or N (nitrogen) and wherein for each use of w=w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re 10 and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if w=wis a single bond); each X is independently a group of formula -(CR12R13)-; each Y is independently absent or a group of formula -(CR12R13)-; each Z is independently a group of 15 formula -(CR14)-; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or heteroaromatic ring or a 6-membered heterocyclic ring; each of Rs and R9 is each independently H, D, F, Cl, Br, I or C1-C4 alkyl; or taken together Rs and R9 form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; 20 Rio is H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; each of Rs’, R9’ and Rio’ is independently a C1-C4 alkyl, or taken together Rs’ and R9’ form a 3-, 4-, 5-, 6- or 7membered carbocyclic or heterocyclic ring; R11 is H, D or Ci-Ce alkyl; each of R12, R13 and Rm is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; Ris is H, C1-C4 alkyl or 2026203365   02 May 2026 PG, wherein PG is a phenol protecting group; R20 is H, D, F or C1-C12 alkyl; each R21 is independently H, D, F, Cl, Br, I, or C1-C4 alkyl; n is an integer from 0 to 12, inclusive; p is an integer from 0 to 20, inclusive; and *** indicates the point of attachment of A to B or to H and ** indicates the point of attachment of B to A or of H to A; and further provided that: (i) 5 at least one group of formula Ri, R2, R3, R4, R5, Re, R7, Rs, R9, Rio, R12, Ri3, R14, R20 or R21 comprises at least one fluorine atom; and / or (ii) Rs and R9 taken together form a 3-, 4-, 5-, 6-or 7-membered carbocyclic or heterocyclic ring. In any embodiment herein, it may be that A is 1 or 3 and B is 5 or 8. In any embodiment herein, it may be that A is 2 or 4 and B is 5 or 8. In any embodiment herein, it may be that A 0 is 1 or 3 and B is 6 or 7. In any embodiment herein, it may be that A is 2 or 4 and B is 6 or 7. In any embodiment herein, it may be that J is O. In any embodiment herein, it may be that J is S. In any embodiment herein, it may be that J is N-R11. In any embodiment herein, it may be that J is O or N-Ru and K is absent. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -15   (CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)-20 or -(C(CF2CF3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, L is -(CH2)-, 25   -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, 30   -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, L is -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In 2026203365   02 May 2026 some embodiments, L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, each of Ri, R2 and R3 is independently H, D, Cl, F, -ch3, -och3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -ochf2, -cf3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, 5   -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, 0 -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, 15    -OC(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2. In some embodiments, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2. In some embodiments, J is O; each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, 20   -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2, and Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments, A is 1A, IB, IC, ID, IE, IF, 3A, 3B, 3C, 3D, 3E 25 or3F: OR15 1C 2026203365   02 May 2026 3D             3E             3F wherein each of Rie and R17 is independently H, D, Cl, F, -CH3, -OCH3, 5   -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, -CH(CH3)2, -OCH(CH3)2, -C(CH3)3 or -O(CH3)3; and J” is O, S or N-Ris, wherein Ris is H, D, -CH3, -CH2F, -CHF2 or -CF3. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, 10 -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, 15   -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, 2026203365   02 May 2026 -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently H, D, F, Cl, Br, I, -CH3, -OCH3, -CD3, -OCD3, -CH2F, 5 -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2, and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or selected from H, D, methyl, ethyl, isopropyl and t-butyl. In some embodiments, R3 is H, D, Cl, F, -CH3, -0CH3, -CD3,-OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, or -CH(CH3)2; and 0   where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -CH2CH3, and -CH(CH3)2, and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or selected from H, D, methyl and ethyl. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or 15 -OCF3. In any embodiment herein, it may be that each of Rs and R9 is independently H, D, F, Cl, Br, I, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, 20   -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In some embodiments, each of Rs and R9 is independently H, F, -CH3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CF2CH3, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CF3)3, - CH2CH2CH3, -CH(CH2CH3)2, -CF2CF2CF3 or -CF(CF2CF3)2. 25 In any embodiment herein, it may be that Rs and R9 taken together form a 3-, 4-, 5-, 6- or 7membered carbocyclic or heterocyclic ring selected from 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 and 47: 31      32       33       34         35 2026203365   02 May 2026 36      37     38      39     40      41 42       43       44       45       46       47 wherein # indicates the point of attachment of the carbocycle or heterocycle to the remainder of the compound. In any embodiment herein, it may be that Rio is H, D, F, -CH3, -OCH3, 5   -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, - CD2CD3, -CD(CD3)2, -CF2CH3, -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, 10   -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CF2CF3, -CF(CF2CF3)2, -C(CH2CH3)3, -C(CD2CD3)3, -C(CF2CF3)3, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -CH(CH3)2. In any embodiment herein, it may be that R11 is H, methyl or ethyl. 15 In any embodiment herein, it may be that each of R12, R13 or Rm is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH(CH2CH3)2, -C(CH3)3, -OCH2CH3, -OCH(CH3)2, -OCH2CH2CH3, -OCH(CH2CH3)2 or -OC(CH3)3. In some embodiments, each of R12, R13 or R14 is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, 20   -CF3, -OCF3, -CH2CH3 or -OCH2CH3. In any embodiment herein, it may be that R15 is H. In any embodiment herein, it may be that R15 is -CH3. In any embodiment herein, it may be that R15 is a silyl-based phenol protecting group. In any embodiment herein, it may be that R15 is triphenylmethyl-based phenol protecting group. In any embodiment herein, it may be that R15, is an unsubstituted or substituted benzyl group. 25 In any embodiment herein, it may be that R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -CH2CH2CH2CH3, -CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH3, 2026203365   02 May 2026 -CH2CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH2CH3 or -CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3. In any embodiment herein, it may be that each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3 or -C(CH3)3. In any embodiment herein, it may 5 be that n is 0, 1, 2, 3 or 4. In an aspect, a compound of formula E-G, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, is provided wherein E is 21 or 22: O                R7 O 21              22 10 and G is 23 or 24: 23                   24 wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is independently C (carbon) or N (nitrogen) and wherein for each use of w=w, the bond between each W can be a single bond or double bond and further provided that if a single 15 bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent (if w=wis a double bond) or selected from H, D and Ci-Ce alkyl (if W=w is a single bond); each Q is independently a 20 group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each Rs’, R9’ and Rio’ is independently a C1-C4 alkyl; or taken together Rs’ 2026203365   02 May 2026 and R9’ form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; Rn is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R20 is H, D, F or C1-CI2 alkyl; p is an integer from 0 to 20, inclusive; and *** indicates the point of attachment of E to G and ** indicates the point of attachment of G to E. 5 In any embodiment herein, it may be that E is 21, J is O, K is -CH2-, L is -CH2- and each of Ri, R2 and R3 is independently selected from: H, D, F, -CEE, -OCEE and -OCF3. In any embodiment herein, it may be that the chiral center at the carbon to which R20 is linked is an S configuration, or it may be that the chiral center at the carbon to which R20 is linked is a R configuration. In any embodiment herein, it may be that each Q is -CH2-, or at least one Q is 0 O and each other Q is -CH2-. In some embodiments, the compound is of formula Compound M-0: u HV R2        R3 Compound M-0 wherein each of Ri, R2 and R3 is independently H, F, -CEE, -OCEE, -CH2CH3, -OCH2CH3, or -OCF3, p’ is an integer from 1 to 9, inclusive and p” is an integer from 1 to 9, inclusive. In 15 some embodiments, the compound is or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. In an aspect, a compound of formula C-G, or pharmaceutically acceptable salts, 20 stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, is provided wherein C is 11 or 12: 2026203365   02 May 2026 and Gis 23 or 24: ** wherein, J’ is OH, SH or NH-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 5 independently C (carbon) or N (nitrogen) and wherein for each use of w=w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 10 of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if w=w is a single bond); each Q is independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered 15 heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each Rs’, R9’ and Rio’ is independently a C1-C4 alkyl; or taken together Rs’ and R9’ form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; R11 is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R20 is H, D, F or C1-CI2 alkyl; p is an integer from 0 to 20, inclusive; and *** 20 indicates the point of attachment of E to G and ** indicates the point of attachment of G to E. In some embodiments, C is 11, J’ is OH, R19 is H, K is -CH2-, L is -CH2- and each of Ri, R2 and R3 is independently selected from: H, D, F, -CH3, -OCH3 and -OCF3. In any embodiment herein, it may be that the chiral center at the carbon to which R20 is linked is an S configuration, or that the chiral center at the carbon to which R20 is linked is a R 25 configuration. In any embodiment herein, it may be that each Q is -CH2-, or that at least one 2026203365   02 May 2026 Q is O and each other Q is -CH2-. In some embodiments, the compound is of formula Compound M-3: Compound M-3 wherein each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2CH3, - 5 OCH2CH3, or -OCF3, p’ is an integer from 1 to 9, inclusive and p” is an integer from 1 to 9, inclusive. In some embodiments, the compound is OH OH Compound M-2 or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof. 10 In an aspect, a compound is provided that comprises a substituted quinone or hydroquinone head group to which is covalently linked an aliphatic tail group that comprises at least one chiral center, at least one hydroxyl group and at least one silicon atom. In an aspect, the present technology a method for treating or preventing Friedreich’s ataxia or the signs or symptoms of reduced frataxin levels or activity in a subject in need thereof, the 15 method comprising administering to the subject a therapeutically effective amount of a compound of any aspect or embodiment of the present technology disclosed herein (hereafter collectively referred to as “a compound of the present technology” or the like) or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the subject 20 displays reduced levels of frataxin expression compared to a normal control subject. In any embodiment herein, it may be that the compound is administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is administered daily for 12 weeks or more. In any embodiment herein, it may be that the subject has been diagnosed as having Friedreich’s ataxia. In some embodiments, the Friedreich’s ataxia comprises one or more of 2026203365   02 May 2026 muscle weakness, loss of coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. In any embodiment herein, it may be that the subject is human. In any embodiment herein, it may be that the compound is administered orally, topically, intranasally, systemically, intravenously, subcutaneously, 5 intraperitoneally, intradermally, intraocularly, ophthalmically, intrathecally, intracerebroventricularly, iontophoretically, transmucosally, intravitreally, or intramuscularly. In an aspect, the present technology provides a method for reducing mitochondrial iron in a mammalian subject having or suspected of having Friedreich’s ataxia, the method comprising 0 administering to the subject a therapeutically effective amount of a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the mammalian subject has decreased expression of frataxin compared to a normal control subject. In any embodiment herein, it may be that the compound is administered daily for 6 15 weeks or more. In any embodiment herein, it may be that the compound is administered daily for 12 weeks or more. In any embodiment herein, it may be that the subject has been diagnosed as having Friedreich’s ataxia. In some embodiments, the Friedreich’s ataxia comprises one or more of muscle weakness, loss of coordination, motor control impairment, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and 20 heart disorders. In any embodiment herein, it may be that the subject is human. In any embodiment herein, it may be that the compound is administered orally, topically, intranasally, systemically, intravenously, subcutaneously, intraperitoneally, intradermally, intraocularly, ophthalmically, intrathecally, intracerebroventricularly, iontophoretically, transmucosally, intravitreally, or intramuscularly. 25 In an aspect, the present technology provides a method for treating Complex I deficiency in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the compound is administered daily for 6 weeks or more. 30 In any embodiment herein, it may be that the compound is administered daily for 12 weeks or more. In any embodiment herein, it may be that the subject has been diagnosed as having Friedreich’s ataxia. In some embodiments, the Friedreich’s ataxia comprises one or more of 2026203365   02 May 2026 muscle weakness, loss of coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. In any embodiment herein, it may be that the subject is human. In any embodiment herein, it may be that the compound is administered orally, topically, intranasally, systemically, intravenously, subcutaneously, 5 intraperitoneally, intradermally, intraocularly, ophthalmically, intrathecally, intracerebroventricularly, iontophoretically, transmucosally, intravitreally, or intramuscularly. In an aspect, a method is provided for reducing or inhibiting lipoxygenase-15 activity in a mammalian subject having or suspected of having Friedreich’s ataxia, the method comprising 0 administering to the subject a therapeutically effective amount of a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the compound is administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is administered daily for 12 weeks or more. In any embodiment herein, it 15 may be that the Friedreich’s ataxia comprises one or more of muscle weakness, loss of coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. In any embodiment herein, it may be that the subject is human. In any embodiment herein, it may be that the compound is administered orally, topically, intranasally, systemically, intravenously, subcutaneously, intraperitoneally, intradermally, 20 intraocularly, ophthalmically, intrathecally, intracerebroventricularly, iontophoretically, transmucosally, intravitreally, or intramuscularly. In an aspect, a method is provided for reducing or inhibiting ferroptosis in a mammalian subject having or suspected of having Friedreich’s ataxia, the method comprising administering to the subject a therapeutically effective amount of a compound of the present 25 technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the compound is administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is administered daily for 12 weeks or more. In any embodiment herein, it may be that the Friedreich’s ataxia comprises one or more of muscle weakness, loss of 30 coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. In any embodiment herein, it may be that the subject is human. In any embodiment herein, it may be that the compound is administered orally, topically, 2026203365   02 May 2026 intranasally, systemically, intravenously, subcutaneously, intraperitoneally, intradermally, intraocularly, ophthalmically, intrathecally, intracerebroventricularly, iontophoretically, transmucosally, intravitreally, or intramuscularly. In an aspect, the present technology provides a compound of the present technology, or 5 pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, for use in treating or preventing Friedreich’s ataxia in a subject in need thereof. In any embodiment herein, it may be that the compound is effective to increase or maintain frataxin levels in a subject suspected of having Friedreich’s ataxia. In any embodiment herein, it may be that the compound is effective to inhibit the reduction in 0 frataxin levels in a subject suspected of having Friedreich’s ataxia. In any embodiment herein, it may be that the compound is effective to treat one or more symptoms of Friedreich’s ataxia selected from the group consisting of: muscle weakness, loss of coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. In any embodiment herein, it may be that the compound is 15 effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is effective when administered daily for 12 weeks or more. In an aspect, the present technology provides a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, for use in increasing the levels of frataxin expression in a 20 subject in need thereof. In any embodiment herein, it may be that the compound is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is effective when administered daily for 12 weeks or more. In an aspect, the present technology provides a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, 25 hydrates, and / or solvates thereof, for use in treating Complex I deficiency in a subject in need thereof. In any embodiment herein, it may be that the compound is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is effective when administered daily for 12 weeks or more. In any embodiment herein, it may be that the compound is effective to increase intracellular adenosine 30 triphosphate (ATP) levels in tissue in a subject diagnosed as having Friedreich’s ataxia. 2026203365   02 May 2026 In an aspect, the present technology provides a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, for use in reducing or inhibiting lipoxygenase-15 activity in a mammalian subject having or suspected of having Friedreich’s ataxia. In any embodiment 5 herein, it may be that the compound is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is effective when administered daily for 12 weeks or more. In an aspect, the present technology provides a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, 0 hydrates, and / or solvates thereof, for use in reducing or inhibiting ferroptosis in a mammalian subject having or suspected of having Friedreich’s ataxia. In any embodiment herein, it may be that the compound is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the compound is effective when administered daily for 12 weeks or more. 15 In an aspect, use of a composition in the preparation of a medicament for treating or preventing Friedreich’s ataxia in a subject in need thereof is provided, wherein the composition comprises a therapeutically effective amount of a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the 20 medicament is effective to increase or maintain frataxin levels in a subject suspected of having Friedreich’s ataxia. In any embodiment herein, it may be that the medicament is effective to inhibit the reduction in frataxin levels in a subject suspected of having Friedreich’s ataxia. In any embodiment herein, it may be that the medicament is effective to treat one or more symptoms of Friedreich’s ataxia selected from the group consisting of: 25 muscle weakness, loss of coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. In any embodiment herein, it may be that the medicament is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the medicament is effective when administered daily for 12 weeks or more. 30 In an aspect, use of a composition in the preparation of a medicament for increasing the levels of frataxin expression in a mammalian subject compared to a normal control subject is provided, wherein the composition comprises a therapeutically effective amount of a 2026203365   02 May 2026 compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the medicament is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the medicament is effective when 5 administered daily for 12 weeks or more. In any embodiment herein, it may be that the medicament is effective to increase frataxin levels in a subject diagnosed as having Friedreich’s ataxia. In an aspect, use of a composition in the preparation of a medicament for treating Complex I deficiency in a mammalian subject compared to a normal control subject is provided, wherein 0 the composition comprises a therapeutically effective amount of a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the medicament is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the medicament is effective when administered daily for 12 weeks or 15 more. In any embodiment herein, it may be that the medicament is effective to increase intracellular adenosine triphosphate (ATP) levels in tissue in a subject diagnosed as having Friedreich’s ataxia. In an aspect, use of a composition in the preparation of a medicament for reducing or inhibiting lipoxygenase-15 activity in a mammalian subject having or suspected of having 20 Friedreich’s ataxia is provided, wherein the composition comprises a therapeutically effective amount of a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that the medicament is effective when administered daily for 6 weeks or more. In any embodiment herein, it may be that the medicament is effective when 25 administered daily for 12 weeks or more. In an aspect, use of a composition in the preparation of a medicament for reducing or inhibiting ferroptosis in a mammalian subject having or suspected of having Friedreich’s ataxia is provided, wherein the composition comprises a therapeutically effective amount of a compound of the present technology, or pharmaceutically acceptable salts, stereoisomers, 30 mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof. In any embodiment herein, it may be that wherein the medicament is effective when administered daily for 6 2026203365   02 May 2026 weeks or more. In any embodiment herein, it may be that the medicament is effective when administered daily for 12 weeks or more. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1A an illustration of a partial chemical scheme for the production of novel compositions 5 disclosed herein. Fig. IB is an illustration of a continuation of the chemical scheme shown in Fig. 1A for the production of novel compositions disclosed herein, wherein a species of compound 216 (i.e., 216a) is the starting material for the production of compound 226a. Fig. IC is an illustration of a continuation of the chemical scheme shown in Fig. 1A for the 0 production of novel compositions of formula I (and formula la-Ih). Fig. ID is an illustration of the continuation of the chemical scheme shown in Fig. IB, wherein compound 226a is converted to compositions of formula II (including formula Ila-Ild). Fig. 2A an illustration of a partial chemical scheme for the production of novel compositions 15 disclosed herein. Fig. 2B is an illustration of a continuation of the chemical scheme shown in Fig. 2A for the production of novel compositions disclosed herein, wherein a species of compound 316 (i.e., 316a) is the starting material for the production of compound 326a. Fig. 2C is an illustration of a continuation of the chemical scheme shown in Fig. 2A for the 20 production of novel compositions of formula III (including formula Illa-IIIh). Fig. 2D is an illustration of the continuation of the chemical scheme shown in Fig. 2B, wherein compound 316a is converted to compositions of formula IV (including formula IVa-IVd). Fig. 3 is an illustration of a chemical scheme for the production of intermediate compound 25   203 used / disclosed herein. Fig. 4 is an illustration of a chemical scheme for the reduction of certain therapeutic compositions disclosed herein. 2026203365   02 May 2026 Fig. 5 is a graphic illustration of data obtained for the analysis of the effects of various compounds disclosed herein on cells obtained from a patient confirmed to have Friedreich’s ataxia. Fig. 6A is an illustration of various known heterocycles that could be used as starting 5 materials in the methods of production of the novel compounds disclosed herein. Fig. 6B is an illustration of various known heterocycles that could be used as starting materials in the methods of production of the novel compounds disclosed herein. Fig. 6C is an illustration of various known heterocycles that could be used as starting materials in the methods of production of the novel compounds disclosed herein. 0 Fig. 7 is a bar graph summarizing the results obtained for a Nrf-2 activation assay comparing the activity of Ovameloxolone with various of the novel compounds disclosed herein. DETAILED DESCRIPTION I. Chemical Definitions: Definitions of specific functional groups and chemical terms are described in more detail 15 below. The chemical elements are identified in accordance with the Periodic Table of the Elements, GAS version, Handbook of Chemistry and Physics, 7Sh Ed., inside cover. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th 20 Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987. The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are intended to comply 25 with the standard rules of chemical valency known in the chemical arts. When a range of values is listed, it is intended to encompass each value and subrange within the range. For example "Ci-Ce alkyl" is intended to encompass, Ci, C2, C3, C4, C5, Ce, Ci-Ce, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6 alkyl. When a group or moiety is referred to as “substituted”, one or more of the hydrogen atoms 30 of the group has been replaced with a substituent. Possible “substituents” include, for 2026203365   02 May 2026 example one or more: (i) deuterium (D), fluorine (F), chlorine (Cl), bromine (Br) or iodine (I) atoms (individually each of F, Cl, Br and I is a “halogen” and collectively F, Cl, Br and I are “halogens”); or (ii) methyl, ethyl, propyl, tri chloromethyl, trifluoromethyl, carbonyl (i.e., C=O), nitrile (i.e., -C =N), hydroxyl or protected hydroxyl (i.e., -OH or -OPG, wherein PG is 5 a protecting group), alkoxy (i.e., -OR”), nitro (i.e., -NO2) groups or amino (in protected or unprotected form, i.e., -NH2 or -NHPG, wherein PG is a protecting group), each independently chosen for each possible position for substitution of a hydrogen atom. Other substituents are contemplated, such as azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carboxyl, silyl, ether, 0 sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, fluoroalkyl (such as trifluoromethyl), cyano, or the like. A group or moiety that is not substituted is unsubstituted. Certain compounds of the present application can exist in unsolvated forms as well as solvated forms, including hydrated forms. Solvated forms can exist, for example, because it is 15 difficult or impossible to remove all the solvent from the compound post synthesis. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present application. Certain compounds of the present application may exist in multiple crystalline or amorphous forms. Certain compounds of the present application may exist in various tautomeric forms. Certain compounds of the present application may 20 exist in various salt forms. In general, all physical forms are equivalent for the uses contemplated by the present application and are intended to be within the scope of the inventive compositions disclosed herein. As used herein “alkoxy” is one example of a heteroalkyl group and refers to an alkyl, cycloalkyl, heteroalkyl or cycloheteroalkyl group linked to a terminal oxygen of general _Q_2 25 formula:         ?, wherein R” is the alkyl, cycloalkyl, heteroalkyl or cycloheteroalkyl group and -~w identifies the bond that forms the point of attachment of the alkoxy group to another compound or moiety. Each instance of an alkoxy group may be independently optionally unsubstituted (an "unsubstituted alkoxy") or substituted (a "substituted alkoxy") with one or more substituents. For example, the substituent can be a halogen such as fluorine. A few 30 non-limiting examples of fluorine substituted alkoxy groups used herein include: fluoromethoxy (“-OCH2F”), difluoromethoxy (“-OCHF2”) and trifluoromethoxy (“-OCF3”). 2026203365   02 May 2026 As used herein, "alkyl" refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms ("C1-C20 alkyl"). In some embodiments, an alkyl group has 1 to 12 carbon atoms ("C1-C12 alkyl"). In some embodiments, an alkyl group has 1 to 10 carbon atoms ("C1-C10 alkyl"). In some 5 embodiments, an alkyl group has 1 to 8 carbon atoms ("Ci-Cs alkyl"). In some embodiments, an alkyl group has 1 to 6 carbon atoms ("Ci-Ce alkyl"). In some embodiments, an alkyl group has 1 to 5 carbon atoms ("C1-C5 alkyl"). In some embodiments, an alkyl group has 1 to 4 carbon atoms ("C1-C4 alkyl"). In some embodiments, an alkyl group has 1 to 3 carbon atoms ("C1-C3 alkyl"). In some embodiments, an alkyl group has 1 to 2 carbon 0 atoms ("C1-C2 alkyl"). In some embodiments, an alkyl group has 1 carbon atom ("Ci alkyl"). Examples of Ci-Ce alkyl groups include methyl (Ci), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), iso-butyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), and n-hexyl (Ce). Additional examples of higher order alkyl groups (e.g. C1-C12) include n-heptyl (C7), n-octyl 15   (Cs), nonyl (C9), decyl (C10), undecyl (Cn) and dodecyl (C12) and the like. Each instance of an alkyl group may be independently optionally unsubstituted (an "unsubstituted alkyl") or substituted (a "substituted alkyl") with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents or just 1 substituent. For example, the substituent can be a halogen such as fluorine. A few non-limiting examples 20 of substituted alkyl groups used herein include: fluoromethyl (“-CH2F”), difluoromethyl (“CHF2 ) and trifluoromethyl (“-CF3”). As used herein, "alkenyl" refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 12 carbon atoms, one or more carbon-carbon double bonds, and no triple bonds ("C2-C12 alkenyl"). In some embodiments, an alkenyl group has 1-10 carbon 25 atoms ("C2-C10 alkenyl"). In some embodiments, an alkenyl group has 2 to 8 carbon atoms ("C2-C8 alkenyl"). In some embodiments, an alkenyl group has 2 to 6 carbon atoms ("C2-C6 alkenyl"). In some embodiments, an alkenyl group has 2 to 5 carbon atoms ("C2-C5 alkenyl"). In some embodiments, an alkenyl group has 2 to 4 carbon atoms ("C2-C4 alkenyl"). In some embodiments, an alkenyl group has 2 to 3 carbon atoms ("C2-C3 30 alkenyl"). In some embodiments, an alkenyl group has 2 carbon atoms ("C2 alkenyl"). The one or more carbon-carbon double bonds can be internal (such as in 2-butenyl) or terminal (such as in 1-butenyl). Examples of C2-C4 alkenyl groups include ethenyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), and the like. Examples 41 2026203365   02 May 2026 of C2-C6 alkenyl groups include the aforementioned C2-C4 alkenyl groups as well as pentenyl (C5), pentadienyl (C5), hexenyl (Ce), and the like. Additional examples of alkenyl include heptenyl (Ci), octenyl (Cs), octatrienyl (Cs), and the like. Each instance of an alkenyl group may be independently optionally unsubstituted (an "unsubstituted alkenyl") or substituted (a 5 "substituted alkenyl") with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents or just 1 substituent. For example, the substituent can be a halogen such as fluorine. As used herein, the term "alkynyl" refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 12 carbon atoms, one or more carbon-carbon triple 0 bonds ("C2-C12 alkynyl"). In some embodiments, an alkynyl group has 2 to 10 carbon atoms ("C2-C10 alkynyl"). In some embodiments, an alkynyl group has 2 to 8 carbon atoms ("C2-C8 alkynyl"). In some embodiments, an alkynyl group has 2 to 6 carbon atoms ("C2-C6 alkynyl"). In some embodiments, an alkynyl group has 2 to 5 carbon atoms ("C2-C5 alkynyl"). In some embodiments, an alkynyl group has 2 to 4 carbon atoms ("C2-C4 15 alkynyl"). In some embodiments, an alkynyl group has 2 to 3 carbon atoms ("C2-C3 alkynyl"). In some embodiments, an alkynyl group has 2 carbon atoms ("C2 alkynyl"). The one or more carbon-carbon triple bonds can be internal (such as in 2-butynyl) or terminal (such as in 1-butynyl). Examples of C2-C4 alkynyl groups include ethynyl (C2), 1- propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), and the like. Each instance of an 20 alkynyl group may be independently optionally unsubstituted (an "unsubstituted alkynyl") or substituted (a "substituted alkynyl") with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents or just 1 substituent. For example, the substituent can be a halogen such as fluorine. As used herein, “aprotic solvent” refers to an organic solvent that has no O-H or N-H bonds. 25 Non-limiting examples of aprotic solvents include: acetonitrile (abbreviated as ACN or MeCN), tetrahydrofuran (THF), dioxane, dichloromethane (DCM), N,N-dimethylformamide (DMF) and dimethylsulfoxide (DMSO). As used herein, "aryl" (sometimes abbreviated as “Ar”) refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 71 30 electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system ("C6-C14 aryl"). In some embodiments, an aryl group has six ring carbon atoms ("Ce aryl"; e.g., phenyl). In some embodiments, an aryl group has 2026203365   02 May 2026 ten ring carbon atoms ("Cio aryl"; e.g., naphthyl such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has fourteen ring carbon atoms ("C14 aryl"; e.g., anthracyl). An aryl group may be described as, e.g., a Ce-Cio-membered aryl, wherein the term "membered" refers to the non-hydrogen ring atoms within the moiety. Aryl groups include phenyl, 5 naphthyl, indenyl, and tetrahydronaphthyl. Each instance of an aryl group may be independently optionally unsubstituted (an "unsubstituted aryl") or substituted, (a "substituted aryl") with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents or just 1 substituent. For example, the substituent can be a halogen such as fluorine or chlorine. In some embodiments, the 0 aromatic ring may be substituted at one or more ring positions with one or more substituents, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl or protected hydroxyl (i.e., -OH or -OPG, wherein PG is a protecting group), alkoxy (i.e., -OR”), nitro, amino (in protected or unprotected form, i.e., -NH2 or -NHPG, wherein PG is a protecting group), sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, 15 sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, fluoroalkyl (such as trifluoromethyl, difluoromethyl and trifluoromethyl), cyano, or the like. An aryl group is sometimes referred to as an aromatic group (or aromatic moiety). As used herein, the term "arylalkyl" refers to a radical of an aryl or heteroaryl group (which aryl or heteroaryl group may be substituted or unsubstituted) that is attached to a (Ci- 20 C2o)alkyl group (which alkyl group may be substituted or unsubstituted) via an alkylene linker. The term "arylalkyl" refers to a group that may be substituted or unsubstituted. The term "arylalkyl" is also intended to refer to those compounds wherein one or more methylene groups in the alkyl chain of the arylalkyl group can be replaced by a heteroatom such as O, N, P, Si, and S, and wherein the nitrogen, phosphorus and sulfur atoms may optionally be 25 oxidized and the nitrogen heteroatom may optionally be quaternized with one or more appended alkyl and / or aryl groups. Arylalkyl groups include for example, benzyl (in substituted or unsubstituted form). As used herein, the term “arylheteroalkyl” refers to a radical of aryl group (which aryl group may be substituted or unsubstituted) linked to a non-cyclic stable straight or branched chain, 30 or combinations thereof, alkyl group including at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, and wherein the nitrogen, phosphorus and sulfur atoms may optionally be oxidized, and the nitrogen 2026203365   02 May 2026 heteroatom may optionally be quatemized with one or more appended alkyl and / or aryl groups. As used herein, the term “benzyl group” refers to a group of formula: 5 wherein each Ai is independently H, D, F, Cl, Br, I, -CH3, -OCH3, -CH2CH3, -OCH2CH3, chloromethyl, dichloromethyl, tri chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, nitrile (-C=N), hydroxyl / phenol (i.e., -OH or -OPG, wherein PG is a protecting group) or nitro (-NO2). If each Ai is H, then the benzyl group is unsubstituted. If at least one Ai is not H, then the benzyl group is substituted. 10 As used herein, the term “carbocyclic ring” or “carbocycle” refers to a ring formed by linked carbon atoms. A carbocyclic ring may be independently optionally unsubstituted (e.g. an "unsubstituted cycloalkyl") or substituted (e.g. a "substituted cycloalkyl") with one or more substituents. For example, the substituent can be a halogen such as fluorine. A cycloalkyl group comprises a carbocyclic ring. An aryl group such as benzene comprises a 15 carbocyclic ring. A carbocyclic ring can comprise 3 carbon atoms (a “C3 carbocycle”), 4 carbon atoms (a “C4 carbocycle”), 5, carbon atoms (a “C5 carbocycle”), 6 carbon atoms (a “Ce carbocycle”), 7 carbon atoms (a “C7 carbocycle”) or 8 carbon atoms (a “Cs carbocycle”). A carbocyclic ring can be aromatic and therefore comprise 6 carbon atoms (a “Ce carbocycle”), 10 carbon atoms (a “C10 carbocycle”) or 14 carbon atoms (a “C14 20 carbocycle”). As used herein, “chiral chromatography” refers to the use of a chiral column (i.e. chiral stationary phase) for the separation of racemic, and sometimes diastereomeric, mixtures to obtain an optically enriched or optically pure product from the chromatographic separation. As used herein, "cycloalkyl" refers to a radical of a non-aromatic cyclic hydrocarbon group 25 having from 3 to 12 ring carbon atoms ("C3-C12 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 10 ring carbon atoms ("C3-C10 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms ("C3-C8 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some 44 2026203365   02 May 2026 embodiments, a cycloalkyl group has 4 to 6 ring carbon atoms ("C4-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms ("Cs-Ce cycloalkyl"). In some embodiments, a cycloalkyl group has 5 to 7 ring carbon atoms ("C5-C7 cycloalkyl"). In some embodiments, a cycloalkyl group has 6 to 7 ring carbon atoms ("C6-C7 cycloalkyl"). A 5 cycloalkyl group maybe described as, e.g., a C4-C7-membered cycloalkyl, wherein the term "membered" refers to the non-hydrogen ring atoms within the moiety. Exemplary C3-C6 cycloalkyl groups include, without limitation, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (Ce), cyclohexenyl (Ce), cyclohexadienyl (Ce), and the like. Exemplary C3-C7 cycloalkyl groups 0 include, without limitation, the aforementioned C3-C6 cycloalkyl groups as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), and cycloheptatrienyl (C7), bicyclo[2.1.1]hexanyl (Ce), bicyclo[3.1.1 ]heptanyl (C7), and the like. Exemplary C3-C10 cycloalkyl groups include, without limitation, the aforementioned C3-C7 cycloalkyl groups as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro- 15    1 H-indenyl (C9), decahydronaphthalenyl (C10), spiro[4.5]decanyl (C10), and the like. As the foregoing examples illustrate, in certain embodiments, the cycloalkyl group is either monocyclic ("monocyclic cycloalkyl") or contain a fused, bridged or spiro ring system such as a bicyclic system ("bicyclic cycloalkyl") and can be saturated or can be partially unsaturated. Non-limiting examples of bicyclic cycloalkyl groups include 1 20 ethylbicyclo[l.l.l]pentane, l-ethylbicyclo[2.2.2]octane and (3r,5r,7r)-l-ethyladamantane. "Cycloalkyl" also includes ring systems wherein the cycloalkyl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is on the cycloalkyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the cycloalkyl ring system. Each instance of a cycloalkyl group may be independently 25 optionally unsubstituted (an "unsubstituted cycloalkyl") or substituted (a "substituted cycloalkyl") with one or more substituents. For example, the substituent can be a halogen such as fluorine. As used herein, “cycloheteroalkyl” refers to a radical of a cycloalkyl group comprising at least one heteroatom (wherein the heteroatom is substituted in the ring for a carbon atom) 30 selected from the group consisting of O, N, P, Si, and S, and wherein the nitrogen, phosphorus and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized with appended alkyl and / or aryl groups. The heteroatom(s) O, N, P, S, and Si may be placed at any position of the cycloheteroalkyl group but generally each 45 2026203365   02 May 2026 heteroatom is linked to at least two carbon atoms of the cycloalkyl group. As used herein, the term "heteroalkyl" refers to a radical of a non-cyclic stable straight or branched chain, or combinations thereof, including at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, and wherein the 5 nitrogen, phosphorus and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized with appended alkyl and / or aryl groups. The heteroatom(s) O, N, P, S, and Si may be placed at any position of the heteroalkyl group but generally each heteroatom is linked to at least two carbon atoms of the radical group. Exemplary heteroalkyl groups include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-0 NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2-S(O)-CH3, -CH2-CH2- S(O)2-CH3, -CH2-CH2-P(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, and -O-CH2-CH3. Up to two heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3, -CH2CH2-S-S-CH2CH3 and -CH2-O-Si(CH3)3. Each instance of heteroalkyl group may be independently optionally unsubstituted 15 (an "unsubstituted heteroalkyl") or substituted (a "substituted heteroalkyl") with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents or just 1 substituent. For example, the substituent can be a halogen such as fluorine. As used herein, the term "heteroaryl" refers to a radical of an aromatic heterocycle that 20 comprises 1, 2, 3 or 4 heteroatoms selected, independently of the others, from nitrogen, sulfur and oxygen. As used herein, the term "heteroaryl" refers to a group that may be substituted or unsubstituted. For example, the substituent can be a halogen such as fluorine. A heteroaryl may be fused to one or two rings, such as a cycloalkyl, an aryl, or a second heteroaryl ring. The point of attachment of a heteroaryl to a molecule may be on the heteroaryl, cycloalkyl, 25 heterocycloalkyl or aryl ring, and the heteroaryl group may be attached through carbon or a heteroatom. Examples of heteroaryl groups include imidazolyl, furyl, pyrrolyl, thienyl, thiazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolinyl, indazolyl, benzoxazolyl, benzisooxazolyl, benzofuryl, benzothiazolyl, indolizinyl, imidazopyridinyl, pyrazolyl, triazolyl, oxazolyl, tetrazolyl, 30 benzimidazolyl, benzoisothiazolyl, benzothiadiazolyl, benzoxadiazolyl, indolyl, tetrahydroindolyl, azaindolyl, imidazopyridyl, quinazolinyl, purinyl, pyrrolo[2,3]pyrimidyl, pyrazolo[3,4]pyrimidyl or benzo(b)thienyl, each of which can be optionally substituted. The 2026203365   02 May 2026 aromatic heterocycle may be substituted at one or more ring positions with one or more substituents, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl or protected hydroxyl (i.e., -OH or -OPG, wherein PG is a protecting group), alkoxy (i.e., -OR”), nitro, amino (in protected or unprotected form, i.e., -NH2 or -NHPG, wherein PG is a 5 protecting group), sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, fluoroalkyl (such as trifluoromethyl), cyano, or the like. A heteroaryl group is sometimes referred to as a heteroaromatic group (or moiety). As used herein, the term “heterocyclic ring” or “heterocycle” refers to a ring of atoms of at 0 least two different elements, one of which is carbon. Additional reference is made to: Oxford Dictionary of Biochemistry and Molecular Biology, Oxford University Press, Oxford, 1997 as evidence that the term “heterocyclic ring” is a term well-established in field of organic chemistry. A heterocyclic ring can be aliphatic (e.g. tetrahydrofuran) or aromatic (e.g. pyridine). 15 As used herein, the term "hydrate" refers to a compound which is associated with water. The number of the water molecules contained in a hydrate of a compound may be (or may not be) in a definite ratio to the number of the compound molecules in the hydrate. As used herein, the term "pharmaceutically acceptable salt" refers to a salt of a therapeutically active compound that can be prepared with relatively nontoxic acids or bases, 20 depending on the particular substituents found on the compounds described herein. When compounds of the present application contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. When compounds of the present application contain relatively basic functionalities, acid addition salts can be obtained 25 by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Salts derived from pharmaceutically acceptable inorganic bases include ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, and zinc salts, and the like. Salts derived from pharmaceutically acceptable organic bases include salts of primary, secondary and tertiary 30 amines, including substituted amines, cyclic amines, naturally-occurring amines and the like, such as arginine, betaine, caffeine, choline, N,N'-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N- 2026203365   02 May 2026 methylmorpholine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperadine, polyamine resins, procaine, purines, theobromine, triethylamine (NEts), trimethylamine, tripropylamine, tromethamine and the like, such as where the salt includes the protonated 5 form of the organic base (e.g., [HNEt3]+). Salts derived from pharmaceutically acceptable inorganic acids include salts of boric, carbonic, hydrohalic (hydrobromic, hydrochloric, hydrofluoric or hydroiodic), nitric, phosphoric, sulfamic and sulfuric acids. Salts derived from pharmaceutically acceptable organic acids include salts of aliphatic hydroxyl acids (e.g., citric, gluconic, glycolic, lactic, lactobionic, malic, and tartaric acids), aliphatic 0 monocarboxylic acids (e.g., acetic, butyric, formic, propionic and trifluoroacetic acids), amino acids (e.g, aspartic and glutamic acids), aromatic carboxylic acids (e.g., benzoic, p-chlorobenzoic, diphenylacetic, gentisic, hippuric, and triphenylacetic acids), aromatic hydroxyl acids (e.g., o-hydroxybenzoic, p-hydroxybenzoic, l-hydroxynaphthalene-2-carboxylic and 3-hydroxynaphthal ene-2-carboxylic acids), ascorbic, dicarboxylic acids (e.g., 15 fumaric, maleic, oxalic and succinic acids), glucuronic, mandelic, mucic, nicotinic, orotic, pamoic, pantothenic, sulfonic acids (e.g., benzenesulfonic, camphorsulfonic, edisylic, ethanesulfonic, isethionic, methanesulfonic, naphthalenesulfonic, naphthalene-l,5-disulfonic, naphthalene-2,6-disulfonic and p-toluenesulfonic acids (PTSA)), xinafoic acid, and the like. In some embodiments, the pharmaceutically acceptable counterion is selected from the group 20 consisting of acetate, benzoate, besylate, bromide, camphorsulfonate, chloride, chlorotheophyllinate, citrate, ethanedi sulfonate, fumarate, gluceptate, gluconate, glucoronate, hippurate, iodide, isethionate, lactate, lactobionate, laurylsulfate, malate, maleate, mesylate, methyl sulfate, naphthoate, sapsylate, nitrate, octadecanoate, oleate, oxalate, pamoate, phosphate, polygalacturonate, succinate, sulfate, sulfosalicylate, tartrate, tosylate, and 25 trifluoroacetate. In some embodiments, the salt is a tartrate salt, a fumarate salt, a citrate salt, a benzoate salt, a succinate salt, a suberate salt, a lactate salt, an oxalate salt, a phthalate salt, a methanesulfonate salt, a benzenesulfonate salt, a maleate salt, a trifluoroacetate salt, a hydrochloride salt, or a tosylate salt. Also included are salts of amino acids such as arginate and the like, and salts of organic acids such as glucuronic or galactunoric acids and the like 30 (see, e.g., Berge et al, Journal of Pharmaceutical Science 66: 1-19 (1977)). Certain specific compounds of the present application contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts or exist in zwitterionic form. These salts may be prepared by methods known to those skilled in the art. Other 2026203365   02 May 2026 pharmaceutically acceptable carriers known to those of skill in the art are suitable for the inventive compositions disclosed herein. As used herein, the term "protecting group" or “PG” refers to a chemical group that is reacted with, and bound to (at least for some period of time), a functional group (e.g. -OH, -5 NH2 or -SH) in a molecule to prevent said functional group from participating in reactions of the molecule but which chemical group can subsequently be removed to thereby regenerate said functional group. Additional reference is made to: Oxford Dictionary of Biochemistry and Molecular Biology, Oxford University Press, Oxford, 1997 as evidence that protecting group is a term well-established in field of organic chemistry. Further reference is made to 0 Greene’s Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc. which is known as a primary reference for researching the suitability of various protecting groups (e.g., protecting groups (i.e., PG) for hydroxyl or amine groups) for in organic synthesis reactions. As used herein, the term "solvate" refers to forms of the compound that are associated with a 15 solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. As used herein, the term "tautomer" refers to compounds that are interchangeable forms of a particular compound structure, and that vary in the displacement of hydrogen atoms and 20 electrons. Thus, two structures may be in equilibrium through the movement of % electrons and an atom (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either acid or base. Tautomeric forms may be relevant to the attainment of the optimal chemical reactivity and biological activity of a compound of interest. 25 II. Other Definitions: It is to be appreciated that certain aspects, modes, embodiments, variations and features of the technology are described below in various levels of detail in order to provide a substantial understanding of the present application. The definitions of certain terms as used in this specification are provided below. Unless defined otherwise, all technical and scientific terms 30 used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. 2026203365   02 May 2026 As used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural references unless the content clearly dictates otherwise. For example, reference to “a cell” includes a combination of two or more cells, and the like. As used herein, the “administering” or the “administration” of an agent (i.e. therapeutic 5 agent) or drug to a subject includes any route of introducing or delivering to a subject a compound to perform its intended function. Administration can be carried out by any suitable route, such as oral administration. Administration may be carried out subcutaneously. Alternatively, administration may be carried out, topically, intranasally, systemically, intravenously, intraperitoneally, intradermally, intraocularly, ophthalmically, 0 intrathecally, intracerebroventricularly, iontophoretically, transmucosally, intravitreally, or intramuscularly. Administration includes self-administration and the administration by another. As used herein the terms “carrier” and “pharmaceutically acceptable carrier” refer to a diluent, adjuvant, excipient, or vehicle with which a compound is administered or formulated 15 for administration. Non-limiting examples of such pharmaceutically acceptable carriers include liquids, such as water, saline, and oils; and solids, such as gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like. In addition, auxiliary, stabilizing, thickening, lubricating, flavoring, and coloring agents may be used. Other examples of suitable pharmaceutical carriers are described in Remington’s Pharmaceutical Sciences by 20 E.W. Martin, herein incorporated by reference in its entirety. As used herein, the phrase “delaying the onset of’ refers to, in a statistical sample, postponing, hindering, or causing one or more symptoms of a disorder, symptom, condition or indication to occur more slowly than normal in a treated sample relative to an untreated control sample. 25 As used herein, the term “effective amount” refers to a quantity sufficient to achieve a desired therapeutic and / or prophylactic effect, e.g., an amount that reduces, ameliorates, prevents or delays the onset of the physiological symptoms of mitochondrial disease, such as Friedreich’s ataxia. In the context of therapeutic or prophylactic applications, in some embodiments, the amount of a composition administered to the subject will depend on the 30 type and severity of the disease and on the characteristics of the individual, such as general health, age, sex, body weight and tolerance to drugs. In some embodiments, it will also depend on the degree, severity and type of disease. The skilled artisan will be able to 2026203365   02 May 2026 determine appropriate dosages depending on these and other factors. The compositions can also be administered in combination with one or more additional therapeutic compounds. In the methods described herein, therapeutic compounds, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, may 5 be administered to a subject having one or more signs, symptoms, or risk factors of mitochondrial disease such as Friedreich’s ataxia; e.g., muscle weakness, especially in the arms and legs, loss of coordination, motor control impairment, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, heart and / or ophthalmic conditions or disorders. For example, a “therapeutically effective amount” of therapeutic 0 compound includes levels at which the presence, frequency, or severity of one or more signs, symptoms, or risk factors of mitochondrial disease, for example Friedreich’s ataxia, are reduced or eliminated. In some embodiments, a therapeutically effective amount reduces or ameliorates the physiological effects of a mitochondrial disease (e.g. Friedreich’s ataxia), and / or the risk factors of Friedreich’s ataxia, and / or delays the progression or onset of a 15 mitochondrial disease (e.g. Friedreich’s ataxia). As used herein, “inhibit” or “inhibiting” means reduce by an objectively measurable amount or degree compared to control. In one embodiment, inhibit or inhibiting means reduce by at least a statistically significant amount compared to control. In one embodiment, inhibit or inhibiting means reduce by at least 5 percent compared to control. In various 20 individual embodiments, inhibit or inhibiting means reduce by at least 2, 3, 4, 5, 10, 15, 20, 25, 30, 33, 40, 50, 60, 67, 70, 75, 80, 90, 95, or 99 percent compared to control. As used herein, the term “simultaneous” therapeutic use refers to the administration of at least two active ingredients by the same route and at the same time or at substantially the same time. 25 As used herein, the term “separate” therapeutic use refers to an administration of at least two active ingredients at the same time or at substantially the same time by different routes. As used herein, the term “sequential” therapeutic use refers to administration of at least two active ingredients at different times, the administration route being identical or different. More particularly, sequential use refers to the whole administration of one of the active 30 ingredients before administration of the other or others commences. It is thus possible to administer one of the active ingredients over several minutes, hours, or days before administering the other active ingredient or ingredients. There is no simultaneous treatment 2026203365   02 May 2026 in this definition. As used herein, a “subject” refers to a living animal. In various embodiments, a subject is a mammal. In various embodiments, a subject is a non-human mammal, including, without limitation, a mouse, rat, hamster, guinea pig, rabbit, sheep, goat, cat, dog, pig, horse, cow, or 5 non-human primate. In certain embodiments, the subject is a human. As used herein, the terms “treating” or “treatment” or “alleviation” refers to therapeutic treatment, wherein the object is to reduce, alleviate or slow down (lessen) the targeted pathologic condition or disorder. By way of example, but not by way of limitation, a subject is successfully “treated” for a mitochondrial disease (e.g. Friedreich’s ataxia) if, after 0 receiving an effective amount of the compounds of the present application (including a pharmaceutically acceptable salt (such as hydrochloride, acetate, citrate, trifluoroacetate, benzoate, oxalate or mesylate salt), stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof) according to the methods described herein, the subject shows observable and / or measurable reduction in or absence of one or more signs and 15 symptoms of a mitochondrial disease (e.g. Friedreich’s ataxia), such as but not limited to, e.g., muscle weakness, especially in the arms and legs, loss of coordination, motor control impairment, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, heart or ophthalmic conditions or disorders. It is also to be appreciated that the various modes of treatment of medical conditions as described are intended to mean 20 “substantial,” which includes total but also less than total treatment, and wherein some biologically or medically relevant result is achieved. Treating Friedreich’s ataxia, as used herein, also refers to treating the signs and symptoms related to reduced frataxin activity or frataxin expression levels characteristic of Friedreich’s ataxia. As used herein, “prevention” or “preventing” of a disease or condition, e.g., a mitochondrial 25 disease such as Friedreich’s ataxia refers to results that, in a statistical sample, exhibit a reduction in the occurrence of the disorder or condition in the treated sample relative to an untreated control sample, or exhibit a delay in the onset of one or more symptoms of the disorder or condition relative to the untreated control sample. Such prevention is sometimes referred to as a prophylactic treatment. As used herein, preventing mitochondrial disease 30   (e.g. Friedreich’s ataxia) includes preventing or delaying the onset of, preventing, delaying, or slowing the progression or advancement of mitochondrial disease (e.g. Friedreich’s ataxia). As used herein, prevention of Friedreich’s ataxia also includes preventing a 2026203365   02 May 2026 recurrence of one or more signs or symptoms of Friedreich’s ataxia. III. Chiral / Stereochemistry Considerations: Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various isomeric forms, e.g., enantiomers and / or diastereomers (i.e., stereoisomers). 5 Chiral centers in illustrated structures (including the claims) may be identified herein by use of an asterisk (*). For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in 0 the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques el al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of 15 Resolving Agents and Optical Resolutions p. 268 (E.L. Eliel, Ed., Univ, of Notre Dame Press, Notre Dame, IN 1972). The disclosure of the present application additionally encompasses compounds described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. As used herein, a pure enantiomeric compound is substantially free from other enantiomers or 20 stereoisomers of the compound (i.e., in enantiomeric excess); as purity is a relative term in the sense that it is exceedingly difficult to achieve 100% purity. In other words, an "S" form of the compound is substantially free from the "R" form of the compound and is, thus, in enantiomeric excess of the "R" form. With respect to amino acids (which are more commonly described in terms of “D” and “L” enantiomer, it is to be understood that for a 25 “D”-amino acid the configuration is “R” and for an “L”-amino acid, the configuration is “S”. In some embodiments, 'substantially free', refers to: (i) an aliquot of an "R" form compound that contains less than 2% "S" form; or (ii) an aliquot of an "S" form compound that contains less than 2% "R" form. The term "enantiomerically pure" or "pure enantiomer" denotes that the compound comprises more than 90% by weight, more than 91 % by weight, more 30 than 92% by weight, more than 93% by weight, more than 94% by weight, more than 95% by weight, more than 96% by weight, more than 97% by weight, more than 98% by weight, more than 99% by weight, more than 99.5% by weight, or more than 99.9% by weight, of the 2026203365   02 May 2026 particularly identified enantiomer (e.g. as compared with the other enantiomer). In certain embodiments, the weights are based upon total weight of all enantiomers or stereoisomers of the compound. In the compositions provided herein, an enantiomerically pure compound can be present with 5 other active or inactive ingredients. For example, a pharmaceutical composition comprising enantiomerically pure "R" form compound can comprise, for example, about 90% excipient and about 10% enantiomerically pure "R" form compound. In certain embodiments, the enantiomerically pure "R" form compound in such compositions can, for example, comprise, at least about 95% by weight "R" form compound and at most about 5% by weight "S" form 0 compound, by total weight of the compound. For example, a pharmaceutical composition comprising enantiomerically pure "S" form compound can comprise, for example, about 90% excipient and about 10% enantiomerically pure "S" form compound. In certain embodiments, the enantiomerically pure "S" form compound in such compositions can, for example, comprise, at least about 95% by weight "S" form compound and at most about 5% by weight 15   "R" form compound, by total weight of the enantiomers of the compound. In certain embodiments, the active ingredient can be formulated with little or no excipient or carrier. IV. Pharmaceutical Compositions, Routes of Administration, and Dosing: In certain embodiments, the present application is directed to a pharmaceutical composition. In some embodiments, the composition comprises a therapeutic compound (i.e. agent) and a 20 pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition comprises a plurality of compounds and a pharmaceutically acceptable carrier. The pharmaceutical composition can be a medicament. In certain embodiments, a pharmaceutical composition further comprises at least one additional therapeutic agent other than a compound of the present application. The at least 25 one additional therapeutic agent can be an agent useful in the treatment of mitochondrial disease, such as Friedreich’s ataxia. Pharmaceutical compositions can be prepared by combining one or more compounds of the present application with a pharmaceutically acceptable carrier and, optionally, one or more additional therapeutic agents. 30 As stated above, an “effective amount” refers to any amount that is sufficient to achieve a desired biological effect. Combined with the teachings provided herein, by choosing among 2026203365   02 May 2026 the various active compounds and weighing factors such as potency, relative bioavailability, patient body weight, severity of adverse side-effects and mode of administration, an effective prophylactic (i.e. preventative) or therapeutic treatment regimen can be planned which does not cause substantial unwanted toxicity and yet is effective to remedy the condition or disease 5 of a particular subject. The effective amount for any particular indication can vary depending on such factors as the disease or condition being treated, the particular compound of the present application being administered, the size of the subject, or the severity of the disease or condition. The effective amount may be determined during pre-clinical trials and clinical trials by methods familiar to physicians and clinicians. One of ordinary skill in the art can 0 empirically determine the effective amount of a particular compound of the present application and / or other therapeutic agent without necessitating undue experimentation. A maximum dose may be used, that is, the highest safe dose according to some medical judgment. Multiple doses per day may be contemplated to achieve appropriate systemic levels of compounds. Appropriate systemic levels can be determined by, for example, 15 measurement of the patient’s peak or sustained plasma level of the drug. “Dose” and “dosage” are used interchangeably herein. A dose can be administered by oneself, by another or by way of a device (e.g. a pump). Compounds for use in therapy or prevention can be tested in suitable animal model systems. Similarly, for in vivo testing, any of the animal model system known in the art can be used 20 prior to administration to human subjects. Suitable animal model systems include, but are not limited to, rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. A therapeutic compound and optionally other therapeutic agents may be administered per se (neat) or in the form of a pharmaceutically acceptable salt. When used in medicine, the salts 25 should be pharmaceutically acceptable, but non-pharmaceutically acceptable salts may conveniently be used to prepare pharmaceutically acceptable salts thereof. Pharmaceutical compositions of the present application contain an effective amount of a therapeutic compound as described herein and may optionally be disbursed in a pharmaceutically acceptable carrier. The components of the pharmaceutical compositions 30 also are capable of being commingled with the compounds of the present application, and with each other, in a manner such that there is no interaction which would substantially impair the desired pharmaceutical efficiency. 2026203365   02 May 2026 Dosage, toxicity and therapeutic efficacy of any therapeutic compounds, compositions (e.g. formulations or medicaments), other therapeutic agents, or mixtures thereof can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the 5 dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50 / ED50. Compounds that exhibit high therapeutic indices are advantageous. While compounds that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to 0 uninfected cells and, thereby, reduce side effects. The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds may be within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of 15 administration utilized. For any compound used in the methods, the therapeutically effective dose can be estimated initially from cell culture assays. A dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to determine useful doses in 20 humans accurately. Levels in plasma may be measured, for example, by high performance liquid chromatography. In some embodiments, an effective amount of a therapeutic compound disclosed herein sufficient for achieving a therapeutic or prophylactic effect, can range from about 0.000001 mg per kilogram body weight per day to about 10,000 mg per kilogram body weight per day. 25 Suitably, the dosage ranges are from about 0.0001 mg per kilogram body weight per day to about 100 mg per kilogram body weight per day. For example dosages can be 1 mg / kg body weight or 10 mg / kg body weight every day, every two days or every three days or within the range of 1-10 mg / kg every week, every two weeks or every three weeks. In some embodiments, a single dosage of a therapeutic compound disclosed herein ranges from 0.001 30   10,000 micrograms per kg body weight. In some embodiments, a therapeutic compound disclosed herein dissolved or suspended in a carrier range from 0.2 to 2000 micrograms per delivered milliliter. 2026203365   02 May 2026 An exemplary treatment regime can entail administration once per day or once a week. In therapeutic applications, a relatively high dosage at relatively short intervals is sometimes required until progression of the disease is reduced or terminated, or until the subject shows partial or complete amelioration of symptoms of disease. Thereafter, the patient can be 5 administered a prophylactic regimen. In some embodiments, a therapeutically effective amount of a therapeutic compound disclosed herein may be defined as a concentration of compound existing at the target tissue of 10'12 to 10'6 molar, e.g., approximately 10'7 molar. This concentration may be delivered by systemic doses of 0.001 to 100 mg / kg or equivalent dose by body surface area. The schedule 0 of doses would be optimized to maintain the therapeutic concentration at the target tissue, such as by single daily or weekly administration, but also including continuous administration (e.g., oral, systemic, topical, subcutaneous, parenteral infusion or transdermal application) In some embodiments, intravenous or subcutaneous administration of a therapeutic 15 compound may typically be from 0.01 pg / kg / day to 20 mg / kg / day. In some embodiments, intravenous or subcutaneous administration of a therapeutic compound may typically be from 0.01 pg / kg / day to 100 pg / kg / day. In some embodiments, intravenous or subcutaneous administration of a therapeutic compound may typically be from 0.1 pg / kg / day to 1 mg / kg / day. In some embodiments, intravenous or subcutaneous administration of a 20 therapeutic compound may typically be from 10 pg / kg / day to 2 mg / kg / day. In some embodiments, intravenous or subcutaneous administration of a therapeutic compound may typically be from 500 pg / kg / day to 5 mg / kg / day. In some embodiments, intravenous or subcutaneous administration of a therapeutic compound may typically be from 1 mg / kg / day to 20 mg / kg / day. In some embodiments, intravenous or subcutaneous administration of a 25 therapeutic compound may typically be from 1 mg / kg / day to 10 mg / kg / day. Generally, daily oral doses of a compound will be, for human subjects, from about 0.01 micrograms / kg per day to 100 milligrams / kg per day. It is expected that oral doses in the range of 0.01 to 50 milligrams / kg, in one or more administrations per day, will yield therapeutic results. Dosage may be adjusted appropriately to achieve desired drug levels, 30 local or systemic, depending upon the mode of administration. For example, it is expected that intravenous administration would be from one order to several orders of magnitude lower dose per day. In the event that the response in a subject is insufficient at such doses, even 2026203365   02 May 2026 higher doses (or effective higher doses by a different, more localized delivery route) may be employed to the extent that patient tolerance permits. Multiple doses per day are contemplated to achieve appropriate systemic levels of the compound. For use in therapy, an effective amount of the compound can be administered to a subject by 5 any mode that delivers the compound to the desired surface. Administering a pharmaceutical composition may be accomplished by any means known to the skilled artisan. Routes of administration include but are not limited to oral, topical, intranasal, systemic, intravenous, subcutaneous, intraperitoneal, intradermal, intraocular, ophthalmic, intrathecal, intracerebroventricular, iontophoretic, transmucosal, intravitreal, or intramuscular 0 administration. Administration includes self-administration, the administration by another and administration by a device. A therapeutic compound disclosed herein can be delivered to the subject in a formulation or medicament (i.e. a pharmaceutical composition). Formulations and medicaments can be prepared by, for example, dissolving or suspending a therapeutic compound disclosed herein 15 in water or a carrier (i.e. a pharmaceutically acceptable carrier). For example, the formulations and medicaments of the present application can be administered in pharmaceutically acceptable solutions, which may routinely contain pharmaceutically acceptable concentrations of salt, buffering agents, preservatives, compatible carriers, adjuvants, and optionally other therapeutic ingredients. 20 The pharmaceutical compositions (e.g. a formulation or medicament) can include a carrier, which can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and 25 by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thiomerasol, and the like. Glutathione and other antioxidants can be included to prevent oxidation. In many cases, it will be advantageous to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the 30 composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent that delays absorption, for example, aluminum monostearate or gelatin. 2026203365   02 May 2026 Solutions or suspensions (e.g. a formulation or medicament) used for parenteral, intradermal, subcutaneous or intraocular application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or 5 methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or 0 plastic. For convenience of the patient or treating physician, the dosing formulation can be provided alone or in a kit containing all necessary equipment (e.g., vials of drug, vials of diluent, syringes and needles) for a treatment course (e.g., 7 days or more of treatment). Systemic formulations include those designed for administration by injection, e.g., subcutaneous, intravenous, intramuscular, intrathecal or intraperitoneal injection, as well as 15 those designed for transdermal, transmucosal oral or pulmonary administration. For intravenous and other parenteral routes of administration, a compound or pharmaceutical composition of the present application can be formulated as a lyophilized preparation, as a lyophilized preparation of liposome-intercalated or -encapsulated active compound, as a lipid complex in aqueous suspension, or as a salt complex. Lyophilized formulations are generally 20 reconstituted in suitable aqueous solution, e.g., in sterile water or saline, shortly prior to administration. Pharmaceutical compositions (e.g. a formulation or medicament) suitable for injectable use can include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For 25 intravenous administration, suitable carriers include physiological saline, bacteriostatic water, CREMOPHOR EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). A composition for administration by injection will generally be sterile and should be fluid to the extent that easy syringability exists. It should be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such 30 as bacteria and fungi. Sterile injectable solutions (e.g. a formulation or medicament) can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one 59 2026203365   02 May 2026 or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle, which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile 5 injectable solutions, typical methods of preparation include vacuum drying and freeze drying, which can yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. The therapeutic compounds or pharmaceutical compositions, when it is desirable to deliver them systemically, may be formulated for parenteral administration by injection, e.g., by 0 bolus injection or continuous infusion (for example by IV injection or via a pump to meter the administration over a defined time). Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or 15    di spersing agents. Pharmaceutical compositions for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the therapeutic compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as 20 ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the therapeutic compounds to allow for the preparation of highly concentrated solutions. 25 For oral administration, the compounds can be formulated readily by combining the active compound(s) with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds of the present application to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a subject to be treated. The tablets, pills, capsules, troches and the like can contain any of the 30 following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel®, or corn starch; a lubricant such as magnesium stearate 2026203365   02 May 2026 or sterates; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring. Pharmaceutical preparations for oral use can be obtained as solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable 5 auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP). If desired, disintegrating agents 0 may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Optionally the oral formulations may also be formulated in saline or buffers, e.g., EDTA for neutralizing internal acid conditions or may be administered without any carriers. Also specifically contemplated are oral dosage forms of the above component or components. 15 The component or components may be chemically modified so that oral delivery of the derivative is efficacious. Generally, the chemical modification contemplated is the attachment of at least one moiety to the component molecule itself, where said moiety permits (a) inhibition of acid hydrolysis; and (b) uptake into the blood stream from the stomach or intestine. Also desired is the increase in overall stability of the component or 20 components and increase in circulation time in the body. Examples of such moieties include: polyethylene glycol, copolymers of ethylene glycol and propylene glycol, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone and polyproline. Abuchowski and Davis, “Soluble Polymer-Enzyme Adducts”, In: Enzymes as Drugs, Hocenberg and Roberts, eds., Wiley-Interscience, New York, N.Y., pp. 367-383 (1981); Newmark et al., J 25 ApplBiochem 4:185-9 (1982). Other polymers that could be used are poly-1,3-dioxolane and poly-1,3,6-tioxocane. For pharmaceutical usage, as indicated above, polyethylene glycol (PEG) moieties of various molecular weights are suitable. For a particular therapeutic compound or pharmaceutical composition the preferred location of release may be the stomach, the small intestine (the duodenum, the jejunum, or the ileum), 30 or the large intestine. One skilled in the art has available formulations which will not dissolve in the stomach yet will release the material in the duodenum or elsewhere in the intestine. Preferably, the release will avoid the deleterious effects of the stomach 2026203365   02 May 2026 environment, either by protection of the compound of the present application (or derivative) or by release of the biologically active material beyond the stomach environment, such as in the intestine. A coating or mixture of coatings can also be used on tablets, which are not intended for 5 protection against the stomach. This can include sugar coatings, or coatings which make the tablet easier to swallow. Capsules may consist of a hard shell (such as gelatin) for delivery of dry therapeutic (e.g., powder); for liquid forms, a soft gelatin shell may be used. The shell material of cachets could be thick starch or other edible paper. For pills, lozenges, molded tablets or tablet triturates, moist massing techniques can be used. 0 The therapeutic compound or pharmaceutical composition can be included in the formulation as fine multi-particulates in the form of granules or pellets of particle size about 1-2 mm. The formulation of the material for capsule administration could also be as a powder, lightly compressed plugs or even as tablets. The therapeutic compound or pharmaceutical composition could be prepared by compression. Colorants and flavoring agents may all be 15 included. For example, the therapeutic compound or pharmaceutical composition may be formulated and then further contained within an edible product, such as a refrigerated beverage containing colorants and flavoring agents. One may dilute or increase the volume of a formulation or medicament comprising a therapeutic compound, other therapeutic agent, or mixtures thereof with an inert material. 20 These diluents could include carbohydrates, especially mannitol, lactose, anhydrous lactose, cellulose, sucrose, modified dextrans and starch. Certain inorganic salts may be also be used as fillers including calcium triphosphate, magnesium carbonate and sodium chloride. Some commercially available diluents are Fast-Flo®, Emdex®, STARCH 1500®, Emcompress® and Avicel®. 25 Disintegrants may be included in the pharmaceutical composition to thereby provide a solid dosage form. Materials used as disintegrates include but are not limited to starch, including the commercial disintegrant based on starch, Explotab. Sodium starch glycolate, Amberlite®, sodium carboxymethylcellulose, ultramylopectin, sodium alginate, gelatin, orange peel, acid carboxymethyl cellulose, natural sponge and bentonite may all be used. 30 Another form of the disintegrants are the insoluble cationic exchange resins. Powdered gums may be used as disintegrants and as binders and these can include powdered gums such as agar, Karaya or tragacanth. Alginic acid and its sodium salt are also useful as disintegrants. 2026203365   02 May 2026 Binders may be used to hold the therapeutic agent together to form a hard tablet and include materials from natural products such as acacia, tragacanth, starch and gelatin. Others include methyl cellulose (MC), ethyl cellulose (EC) and carboxymethyl cellulose (CMC). Polyvinyl pyrrolidone (PVP) and hydroxypropylmethyl cellulose (HPMC) could both be used in 5 alcoholic solutions to granulate the therapeutic. An anti-frictional agent may be included in the formulation of the therapeutic to prevent sticking during the formulation process. Lubricants may be used as a layer between the therapeutic and the die wall, and these can include but are not limited to; stearic acid including its magnesium and calcium salts, polytetrafluoroethylene (PTFE), liquid paraffin, 0 vegetable oils and waxes. Soluble lubricants may also be used such as sodium lauryl sulfate, magnesium lauryl sulfate, polyethylene glycol (PEG) of various molecular weights, Carbowax™ 4000 and 6000. Glidants that might improve the flow properties of the drug during formulation and to aid rearrangement during compression might be added. The glidants may include starch, talc, 15 pyrogenic silica and hydrated silicoaluminate. To aid dissolution of the therapeutic compound or pharmaceutical composition into the aqueous environment a surfactant might be added as a wetting agent. Surfactants may include anionic detergents such as sodium lauryl sulfate, dioctyl sodium sulfosuccinate and dioctyl sodium sulfonate. Cationic detergents which can be used and can include 20 benzalkonium chloride and benzethonium chloride. Potential non-ionic detergents that could be included in the formulation as surfactants include lauromacrogol 400, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil 10, 50 and 60, glycerol monostearate, polysorbate 40, 60, 65 and 80, sucrose fatty acid ester, methyl cellulose and carboxymethyl cellulose. These surfactants could be present in the formulation of the compound of the 25 present application or derivative either alone or as a mixture in different ratios. Pharmaceutical compositions that can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and / or lubricants such as talc or magnesium stearate 30 and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. Microspheres formulated for oral 2026203365   02 May 2026 administration may also be used. Such microspheres have been well defined in the art. All formulations for oral administration should be in dosages suitable for such administration. For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner. 5 For topical administration, a therapeutic compound as disclosed herein may be formulated as solutions, gels, ointments, creams, suspensions, etc. as are well-known in the art. For administration of a therapeutic compound or pharmaceutical composition by inhalation for use according to the present application, it may be conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable 0 propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, di chlorotetrafluoroethane, carbon dioxide or other suitable gas. In some embodiments, the formulation, medicament or therapeutic compound can be delivered in the form of an aerosol spray from a pressurized container or dispenser, which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer. Such methods include those described in U.S. Pat. No. 6,468,798. In 15 the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the therapeutic compound and a suitable powder base such as lactose or starch. Nasal delivery of a therapeutic compound or pharmaceutical composition of the present 20 application is also contemplated. Nasal delivery allows the passage of a therapeutic compound or pharmaceutical composition of the present application to the blood stream directly after administering the therapeutic compound or pharmaceutical composition to the nose, without the necessity for deposition of the product in the lung. Formulations for nasal delivery include those with dextran or cyclodextran. 25 For nasal administration, a useful device is a small, hard bottle to which a metered dose sprayer is attached. In one embodiment, the metered dose is delivered by drawing the pharmaceutical composition of the present application solution into a chamber of defined volume, which chamber has an aperture dimensioned to aerosolize and aerosol formulation by forming a spray when a liquid in the chamber is compressed. The chamber is compressed 30 to administer the therapeutic compound or pharmaceutical composition. In a specific embodiment, the chamber is a piston arrangement. Such devices are commercially available. 2026203365   02 May 2026 Alternatively, a plastic squeeze bottle with an aperture or opening dimensioned to aerosolize an aerosol formulation by forming a spray when squeezed is used. The opening is usually found in the top of the bottle, and the top is generally tapered to partially fit in the nasal passages for efficient administration of the aerosol formulation. Preferably, the nasal inhaler 5 will provide a metered amount of the aerosol formulation, for administration of a measured dose of the therapeutic compound or pharmaceutical composition. Alternatively, the therapeutic compound or pharmaceutical composition may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. Also contemplated herein is pulmonary delivery of the therapeutic compound or 0 pharmaceutical composition disclosed herein. The compound, formulation or medicament can be delivered to the lungs of a mammal while inhaling and traverses across the lung epithelial lining to the blood stream. Other reports of inhaled molecules include Adjei et al., PharmRes 7:565-569 (1990); Adjei et al., Int J Pharmaceutics 63:135-144 (1990) (leuprolide acetate); Braquet et al., JCardiovasc Pharmacol 13(suppl. 5):143-146 (1989) (endothelin-1); 15 Hubbard et al., Annal IntMed 3.2Q6-2X2 (1989) (al-antitrypsin); Smith et al., 1989, J Clin Invest 84:1145-1146 (a-1-proteinase); Oswein et al., 1990, "Aerosolization of Proteins", Proceedings of Symposium on Respiratory Drug Delivery II, Keystone, Colorado, March, (recombinant human growth hormone); Debs et al., 1988, J Immunol 140:3482-3488 (interferon-gamma and tumor necrosis factor alpha) and Platz et al., U.S. Pat. No. 5,284,656 20 (granulocyte colony stimulating factor; incorporated by reference). A method and composition for pulmonary delivery of drugs for systemic effect is described in U.S. Pat. No. 5,451,569 (incorporated by reference), issued Sep. 19, 1995 to Wong et al. Contemplated for use in the practice of this technology are a wide range of mechanical devices designed for pulmonary delivery of therapeutic products, including but not limited to 25 nebulizers, metered dose inhalers, and powder inhalers, all of which are familiar to those skilled in the art. Some specific examples of commercially available devices suitable for the practice of this technology are the Ultravent™ nebulizer, manufactured by Mallinckrodt, Inc., St. Louis, Mo.; the Acorn II® nebulizer, manufactured by Marquest Medical Products, Englewood, 30 Colo.; the Ventolin® metered dose inhaler, manufactured by Glaxo Inc., Research Triangle Park, North Carolina; and the Spinhaler® powder inhaler, manufactured by Fisons Corp., Bedford, Mass. 2026203365   02 May 2026 All such devices require the use of formulations suitable for the dispensing of the therapeutic compounds, formulations and medicaments of the present application. Typically, each formulation is specific to the type of device employed and may involve the use of an appropriate propellant material, in addition to the usual diluents, adjuvants and / or carriers 5 useful in therapy. Also, the use of liposomes, microcapsules or microspheres, inclusion complexes, or other types of carriers is contemplated. Chemically modified compounds, of the present application may also be prepared in different formulations and medicaments depending on the type of chemical modification or the type of device employed. Formulations suitable for use with a nebulizer, either jet or ultrasonic, can comprise a 0 therapeutic compound of the present application (or derivative) dissolved in water at a concentration of about 0.1 to 25 mg of biologically active compound of the present application per mL of solution. The formulation may also include a buffer and a simple sugar (e.g., for inhibitor stabilization and regulation of osmotic pressure). The nebulizer formulation may also contain a surfactant, to reduce or prevent surface induced aggregation 15 of the compound of the present application caused by atomization of the solution in forming the aerosol. Formulations for use with a metered-dose inhaler device may generally comprise a finely divided powder containing the compound of the present application (or derivative) suspended in a propellant with the aid of a surfactant. The propellant may be any conventional material 20 employed for this purpose, such as a chlorofluorocarbon, a hydrochlorofluorocarbon, a hydrofluorocarbon, or a hydrocarbon, including trichlorofluoromethane, dichlorodifluoromethane, di chlorotetrafluoroethanol, and 1,1,1,2-tetrafluoroethane, or combinations thereof. Suitable surfactants include sorbitan trioleate and soya lecithin. Oleic acid may also be useful as a surfactant. 25 Formulations for dispensing from a powder inhaler device may comprise a finely divided dry powder containing therapeutic compound of the present application (or derivative) and may also include a bulking agent, such as lactose, sorbitol, sucrose, or mannitol in amounts which facilitate dispersal of the powder from the device, e.g., 50 to 90% by weight of the formulation. The therapeutic compound or pharmaceutical composition of the present 30 application (or derivative) can advantageously be prepared in particulate form with an average particle size of less than 10 micrometers (pm), most preferably 0.5 to 5 pm, for most effective delivery to the deep lung. 2026203365   02 May 2026 For ophthalmic or intraocular indications, any suitable mode of delivering the therapeutic compounds or pharmaceutical compositions to the eye or regions near the eye can be used. For ophthalmic formulations generally, see Mitra (ed.), Ophthalmic Drug Delivery Systems, Marcel Dekker, Inc., New York, N.Y. (1993) and also Havener, W. H., Ocular 5 Pharmacology, C.V. Mosby Co., St. Louis (1983). Nonlimiting examples of pharmaceutical compositions suitable for administration in or near the eye include, but are not limited to, ocular inserts, minitablets, and topical formulations such as eye drops, ointments, and in situ gels. In one embodiment, a contact lens is coated with a pharmaceutical composition comprising a therapeutic compound disclosed herein. In some embodiments, a single dose 0 comprises from between 0.1 ng to 5000 pg, 1 ng to 500 pg, or 10 ng to 100 pg of the therapeutic compounds or pharmaceutical compositions administered to the eye. Eye drops can comprise a sterile liquid formulation that can be administered directly to the eye. In some embodiments, eye drops comprise at least one therapeutic compound disclosed herein and may further comprise one or more preservatives. In some embodiments, the 15 optimum pH for eye drops equals that of tear fluid and is about 7.4. In situ gels are viscous liquids, showing the ability to undergo sol-to-gel transitions when influenced by external factors, such as appropriate pH, temperature, and the presence of electrolytes. This property causes slowing of drug drainage from the eyeball surface and increase of the active ingredient bioavailability. Polymers commonly used in in situ gel 20 formulations include, but are not limited to, gellan gum, poloxamer, silicone containing formulations and cellulose acetate phthalate. In some embodiments, the therapeutic compound is formulated into an in-situ gel (as the pharmaceutical composition). For topical ophthalmic administration, therapeutic compound or pharmaceutical composition may be formulated as solutions, gels, ointments, creams, suspensions, etc. as are well-known 25 in the art. Ointments are semisolid dosage forms for external use such as topical use for the eye or skin. In some embodiments, ointments comprise a solid or semisolid hydrocarbon base of melting or softening point close to human core temperature. In some embodiments, an ointment applied to the eye decomposes into small drops, which stay for a longer time period in conjunctival sac, thus increasing bioavailability. 30 Ocular inserts are solid or semisolid dosage forms without disadvantages of traditional ophthalmic drug forms. They are less susceptible to defense mechanisms like outflow through nasolacrimal duct, show the ability to stay in conjunctival sac for a longer period, 2026203365   02 May 2026 and are more stable than conventional dosage forms. They also offer advantages such as accurate dosing of one or more therapeutic compounds, slow release of one or more therapeutic compounds with constant speed and limiting of one or more therapeutic compounds’ systemic absorption. In some embodiments, an ocular insert comprises one or 5 more therapeutic compounds as disclosed herein and one or more polymeric materials. The polymeric materials can include, but are not limited to, methylcellulose and its derivatives (e.g., hydroxypropyl methylcellulose (HPMC)), ethylcellulose, polyvinylpyrrolidone (PVP K-90), polyvinyl alcohol, chitosan, carboxymethyl chitosan, gelatin, and various mixtures of the aforementioned polymers. An ocular insert can comprise silica. 0 Minitablets are biodegradable, solid drug forms, that transit into gels after application to the conjunctival sac, thereby extending the period of contact between active ingredient (i.e. the therapeutic compound disclosed herein) and the eyeball surface, which in turn increases a therapeutic compounds’ bioavailability. The advantages of minitablets include easy application to conjunctival sac, resistance to defense mechanisms like tearing or outflow 15 through nasolacrimal duct, longer contact with the cornea caused by presence of mucoadhesive polymers, and gradual release of the active ingredient from the formulation in the place of application due to the swelling of the outer carrier layers. Minitablets can comprise one or more of the therapeutic compounds disclosed herein and one or more polymers. Nonlimiting examples of polymers suitable for use in in a minitablet formulation 20 include cellulose derivatives, like hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), sodium carboxymethyl cellulose, ethyl cellulose, acrylates (e.g., polyacrylic acid and its cross-linked forms), Carbopol® or carbomer, chitosan, and starch (e.g., drum-dried waxy maize starch). In some embodiments, minitablets further comprise one or more excipients. Nonlimiting examples of excipients include mannitol and magnesium stearate. 25 The ophthalmic or intraocular formulations and medicaments may contain non-toxic auxiliary substances such as antibacterial components which are non-injurious in use, for example, thimerosal, benzalkonium chloride, methyl and propyl paraben, benzyldodecinium bromide, benzyl alcohol, or phenyl ethanol; buffering ingredients such as sodium chloride, sodium borate, sodium acetate, sodium citrate, or gluconate buffers; and other conventional 30 ingredients such as sorbitan monolaurate, triethanolamine, polyoxyethylene sorbitan monopalmitylate, ethylenediamine tetraacetic acid, and the like. In some embodiments, the viscosity of the ocular formulation comprising one or more 2026203365   02 May 2026 therapeutic compounds is increased to improve contact with the cornea and bioavailability in the eye. Viscosity can be increased by the addition of hydrophilic polymers of high molecular weight which do not diffuse through biological membranes and which form threedimensional networks in the water. Nonlimiting examples of such polymers include 5 polyvinyl alcohol, poloxamers, hyaluronic acid, carbomers, and polysaccharides, cellulose derivatives, gellan gum, and xanthan gum. In some embodiments, the ocular formulation can be injected into the eye, for example as a sol-gel. In some embodiments, the ocular formulation is a depot formulation such as a controlled release formulation. Such controlled release formulation may comprise particles, 0 such as microparticles or nanoparticles. The therapeutic compound or pharmaceutical composition may also be formulated in rectal or vaginal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides. In addition to the formulations described above, a therapeutic compound may also be 15 formulated as a depot preparation. Such long acting pharmaceutical compositions may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. Suitable liquid or solid pharmaceutical depot forms can be, for example, aqueous or saline 20 solutions for inhalation, microencapsulated, encochleated, coated onto microscopic gold particles, contained in liposomes, nebulized, aerosols, pellets for implantation into the skin, or dried onto a sharp object to be scratched into the skin. The pharmaceutical compositions also include granules, powders, tablets, coated tablets, (micro)capsules, suppositories, syrups, emulsions, suspensions, creams, drops or preparations with protracted release of active 25 compounds, in whose preparation excipients and additives and / or auxiliaries such as disintegrants, binders, coating agents, swelling agents, lubricants, flavorings, sweeteners or solubilizers are customarily used as described above. The pharmaceutical compositions can be suitable for use in a variety of drug delivery systems. For a brief review of methods for drug delivery, see Langer R, Science 249:1527-33 (1990). 30 The therapeutic compound or pharmaceutical composition may be provided in particles. Particles as used herein means nanoparticles or microparticles (or in some instances larger particles) which can consist in whole or in part of the compound of the present application or 69 2026203365   02 May 2026 the other therapeutic agent(s) as described herein. The particles may contain the therapeutic agent(s) in a core surrounded by a coating, including, but not limited to, an enteric coating. The therapeutic agent(s) also may be dispersed throughout the particles. The therapeutic agent(s) also may be adsorbed into the particles. The particles may be of any order release 5 kinetics, including zero-order release, first-order release, second-order release, delayed release, sustained release, immediate release, and any combination thereof. The particle may include, in addition to the therapeutic agent(s), any of those materials routinely used in the art of pharmacy and medicine, including, but not limited to, erodible, non-erodible, biodegradable, or nonbiodegradable material or combinations thereof. The particles may be 0 microcapsules which contain the compound of the present application in a solution or in a semi-solid state. The particles may be of virtually any shape. Both non-biodegradable and biodegradable polymeric materials can be used in the manufacture of particles for delivering the therapeutic agent(s). Such polymers may be natural or synthetic polymers. The polymer is selected based on the period of time over 15 which release is desired. Bioadhesive polymers of particular interest include bioerodible hydrogels described in Sawhney H S et al. (1993) Macromolecules 26:581-7, the teachings of which are incorporated herein. These include polyhyaluronic acids, casein, gelatin, glutin, polyanhydrides, polyacrylic acid, alginate, chitosan, polyethylene glycols (PEGs), polyvinylalcohols (PVAs), poly(methyl methacrylates), poly(ethyl methacrylates), 20 poly(butylmethacrylate), poly(isobutyl methacrylate), poly(lactic -co-glycolic) acid (PLGA), poly(hexylmethacrylate), poly(isodecyl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly(methyl acrylate), poly (isopropyl acrylate), poly(isobutyl acrylate), poly(octadecyl acrylate) and poly(s-caprolactone). A therapeutic compound or other therapeutic agent or mixtures thereof can be formulated in a 25 carrier system. The carrier can be a colloidal system. The colloidal system can be a liposome, a phospholipid bilayer vehicle. In one embodiment, therapeutic compound or other therapeutic agent or mixtures thereof can be encapsulated in a liposome while maintaining integrity of the therapeutic compound or other therapeutic agent or mixtures thereof. One skilled in the art would appreciate that there are a variety of methods to prepare liposomes. 30 (See Lichtenberg, et al.. Methods Biochem. Anal., 33:337-462 (1988); Anselem, et al, Liposome Technology, CRC Press (1993)). Liposomal formulations can delay clearance and increase cellular uptake (See Reddy, Ann. Pharmacother., 34(7-8):915-923 (2000)). For 2026203365   02 May 2026 example, an active agent can also be loaded into a particle prepared from pharmaceutically acceptable ingredients including, but not limited to, soluble, insoluble, permeable, impermeable, biodegradable or gastroretentive polymers or liposomes. Such particles include, but are not limited to, nanoparticles, biodegradable nanoparticles, microparticles, 5 biodegradable microparticles, nanospheres, biodegradable nanospheres, microspheres, biodegradable microspheres, capsules, emulsions, liposomes, micelles and viral vector systems. The carrier can also be a polymer, e.g., a biodegradable, biocompatible polymer matrix. In one embodiment, the therapeutic compound or other therapeutic agent or mixtures thereof 0 can be embedded in the polymer matrix, while maintaining integrity of the composition. The polymer can be a nanoparticle that encapsulates the therapeutic agent or agents. The polymer may be natural, such as polypeptides, proteins or polysaccharides, or synthetic, such as poly a-hydroxy acids. Examples include carriers made of, e.g., collagen, fibronectin, elastin, cellulose acetate, cellulose nitrate, polysaccharide, fibrin, gelatin, and combinations thereof. 15 In one embodiment, the polymer is poly-lactic acid (PLA) or poly lactic / glycolic acid (PLGA). The polymeric matrices can be prepared and isolated in a variety of forms and sizes, including microspheres and nanospheres. Polymer formulations can lead to prolonged duration of therapeutic effect. (See Reddy, Ann. Pharmacother., 34(7-8):915-923 (2000)). A polymer formulation for human growth hormone (hGH) has been used in clinical trials. (See 20 Kozarich and Rich, Chemical Biology, 2:548-552 (1998)). Examples of polymer microsphere sustained release formulations are described in PCT publication WO 99 / 15154 (Tracy, etal.), U.S. Pat. Nos. 5,674,534 and 5,716,644 (both to Zale, et al.), PCT publication WO 96 / 40073 (Zale, etal), and PCT publication WO 00 / 38651 (Shah, etal.). U.S. Pat. Nos. 5,674,534 and 5,716,644 and PCT publication WO 96 / 40073 25 describe a polymeric matrix containing particles of erythropoietin that are stabilized against aggregation with a salt. In some embodiments, the therapeutic compound or other therapeutic agent or mixtures thereof are prepared with carriers that will protect the therapeutic compound, other therapeutic agent or mixtures thereof against rapid elimination from the body, such as a 30 controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Such 2026203365   02 May 2026 formulations can be prepared using known techniques. The materials can also be obtained commercially, e.g., from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to specific cells with monoclonal antibodies to cell-specific antigens) can also be used as pharmaceutically acceptable carriers. These can be 5 prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811. The therapeutic compound(s) may be contained in controlled release systems. The term “controlled release” is intended to refer to any drug-containing formulation in which the manner and profile of drug release from the formulation are controlled. This refers to 0 immediate as well as non-immediate release formulations, with non-immediate release formulations including but not limited to sustained release and delayed release formulations. The term “sustained release” (also referred to as “extended release”) is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that preferably, although not necessarily, results in 15 substantially constant blood levels of a drug over an extended time period. The term “delayed release” is used in its conventional sense to refer to a drug formulation in which there is a time delay between administration of the formulation and the release of the drug there from. “Delayed release” may or may not involve gradual release of drug over an extended period of time, and thus may or may not be “sustained release.” 20 Use of a long-term sustained release implant may be particularly suitable for treatment of chronic conditions. The term “implant” is intended to include a single composition (such as a mesh) or composition comprising multiple components (e.g. a fibrous mesh constructed from several individual pieces of mesh material) or a plurality of individual compositions where the plurality remains localized and provide the long-term sustained release occurring 25 from the aggregate of the plurality of compositions. “Long-term” release, as used herein, means that the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for at least 2 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for at least 7 days. In some embodiments, the implant is constructed and arranged to deliver 30 therapeutic or prophylactic levels of the active ingredient for at least 14 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for at least 30 days. In some embodiments, the implant is 2026203365   02 May 2026 constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for at least 60 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for at least 90 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic 5 levels of the active ingredient for at least 180 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for at least one year. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for 15-30 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic 0 levels of the active ingredient for 30-60 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for 60-90 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic levels of the active ingredient for 90-120 days. In some embodiments, the implant is constructed and arranged to deliver therapeutic or prophylactic 15 levels of the active ingredient for 120-180 days. In some embodiments, the Long-term sustained release implants are well-known to those of ordinary skill in the art and include some of the release systems described above. In some embodiments, such implants can be administered surgically. In some embodiments, such implants can be administered topically or by injection. 20 It will be understood by one of ordinary skill in the relevant arts that other suitable modifications and adaptations to the compositions and methods described herein are readily apparent from the description of the present technology contained herein in view of information known to the ordinarily skilled artisan, and may be made without departing from the scope of the present application or any embodiment thereof. 25 V. Compounds & Compositions Useful For Treating Mitochondrial Disease (e.g., Friedreich’s Ataxia) and Intermediates Related Thereto (a) Therapeutic Compounds In some embodiments, the present application provides novel compounds and compositions useful for treating mitochondrial disease such as Friedreich’s ataxia in a mammalian subject. 30 Said compounds and compositions (e.g. formulations) can be formulated in any way suitable for administration to the subject. Said compounds and compositions can, for example, be formulated as a tablet, in solution for subcutaneous injection, in solution for intravenous 2026203365   02 May 2026 injection or in a gel, cream or drop for topical or intraocular application. In some embodiments, said compounds and compositions can be used to prepare medicaments. In some embodiments, the present application pertains to compounds represented by the formula E-F, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, 5 tautomers, hydrates, and / or solvates thereof, wherein E is 21 or 22: 21 22 and F is 13, 14, 15, 16, 17, 18, 19 or 20: 13 17 19 wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 10 independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 2026203365   02 May 2026 of R4, Rs, Re and R7 attached thereto is independently absent (if w=Wis a double bond) or selected from H, D and Ci-Ce alkyl (if w=wis a single bond); each X is independently a group of formula -(CR12R13)-; each Y is independently absent or a group of formula -(CR12R13)-; each Z is independently a group of formula -(CR14)-; each of Ri, R2 and R3 is 5 independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 5membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each Rs and R9 is independently H, D, F, Cl, Br, I or C1-C4 alkyl; or taken together Rs and R9 form a 3-, 4-, 5-, 6-, or 7-membered carbocyclic or heterocyclic ring; Rio is H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R11 is 0 H, D or Ci-Ce alkyl; each R12, R13 and Rm is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R20 is H, D, F or C1-C12 alkyl; each R21 is H, D, F, Cl, Br, I, or C1-C4 alkyl; n is an integer from 0 to 12 (i.e., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12); and *** indicates the point of attachment of E to F and ** indicates the point of attachment of F to E; and further provided that: (i) at least one group of formula Ri, R2, R3, R4, Rs, Re, R7, Rs, R9, Rio, R12, R13, 15 Rm, R20 or R21 comprises at least one fluorine atom; and / or (ii) Rs and R9 taken together form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring. In some embodiments, at least one of Rs and R9 is fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. In some embodiments, each of Rs and R9 is independently fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. In some embodiments, each of Rs and R9 20 is fluorine. In some embodiments, each of Rs, R9 and Rio is fluorine. In some embodiments, each of Rs, R9 and Rio is independently fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. As used herein, in compounds such as those of formula E-F, the aromatic group such as 21 and 22 are sometimes referred to the ‘head’ group and the aliphatic groups such as 13, 14, 15, 25    16, 17, 18, 19 and 20 are referred to as the ‘tail’ group. Thus, the therapeutic compounds disclosed herein (not just compounds of formula E-F) generally comprise an aromatic ‘head’ group covalently link to an aliphatic ‘tail’ group, wherein the aromatic head group is a quinone or hydroquinone. The quinone (or hydroquinone in reduced form) can be a substituted benzoquinone ring, naphthoquinone ring or other aromatic ring. 30 Any combination of 21 and 22 with 13, 14, 15, 16, 17, 18, 19 or 20 is permissible. In some embodiments, E is 21 and F is 13, 14, 19 or 20. In some embodiments, wherein E is 22 and F is 13, 14, 19 or 20. In some embodiments, E is 21 and F is 15, 16, 17 or 18, In some 2026203365   02 May 2026 embodiments, E is 22 and F is 15, 16, 17 or 18. In some embodiments, E is 21 and F is 13. In some embodiments, E is 21 and F is 14. In some embodiments, E is 21 and F is 15. In some embodiments, E is 21 and F is 16. In some embodiments, E is 21 and F is 17. In some embodiments, E is 21 and F is 18. In some embodiments, E is 21 and F is 19. In some 5 embodiments, E is 21 and F is 20. In some embodiments, E is 22 and F is 13. In some embodiments, E is 22 and F is 14. In some embodiments, E is 22 and F is 15. In some embodiments, E is 22 and F is 16. In some embodiments, E is 22 and F is 17. In some embodiments, E is 22 and F is 18. In some embodiments, E is 22 and F is 19. In some embodiments, E is 22 and F is 20. 0 The atom or group represented by J can be O, S or N-Rn. In some embodiments, J is O (oxygen). In some embodiments, J is S (sulfur). In some embodiment, J is N-Ru, wherein Rn is defined above. In some embodiments, J is O or N-Ru and K is absent. In some embodiments, the groups represented by K and L can each independently be: -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, 15   -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)-, 20   -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, 25   each of K and L is independently -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, each 30 of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some 2026203365   02 May 2026 embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-. In some embodiments, each of K and L are -(CH2)-. In some embodiments, K is absent and L is -(CH2)-. In some embodiments, each of K and L are -(CD2)-. In some embodiments, K is 5 absent and L is-(CD2)-. In some embodiments, each of K and L are -(CF2)-. In some embodiments, K is absent and L is -(CF2)-. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, 0   -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -och2cf3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, 15 -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, 20   -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In 25 some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CF3 or -OCF3. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3 or -CF3. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is -CH3. In some embodiments of the compound represented by 30 E-F, wherein E is 21, each of Ri, R2 and R3 is H. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H or -CH3. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri, R2 and R3 is independently H or -OCH3. In some embodiments of the compound represented by E-77 2026203365   02 May 2026 F, wherein E is 21, each of Ri, R2 and R3 is independently H, -CEE or -OCEE. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri and R2 is -OCEE and R3 is -CEE. In some embodiments of the compound represented by E-F, wherein E is 21, each of Ri and R2 is -CEE and R3 is H. In some embodiments of the compound 5 represented by E-F, wherein E is 21, each of Ri and R2 is -OCEE and R3 is H. In some embodiments of the compound represented by E-F, wherein E is 21, at least one of Ri, R2 and R3 is F. In some embodiments of the compound represented by E-F wherein E is 21, J is O, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, 0   -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -0CH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2. In some embodiments of the compound represented by E-F wherein E is 21, J is O, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In some 15 embodiments of the compound represented by E-F wherein E is 21, J is O, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CF3 or -OCF3. In some embodiments of the compound represented by E-F wherein E is 21, J is O; each of K and L is -(CH2)-; and each of Ri, R2 and R3 is -CH3. In some embodiments of the compound represented by E-F wherein E is 21, 20 J is O; each of K and L is -(CH2)-; and each of Ri, R2 and R3 is H. In some embodiments of the compound represented by E-F wherein E is 21, J is O; each of K and L is -(CH2)-; and each of Ri, R2 and R3 is CH3. In some embodiments of the compound represented by E-F wherein E is 21, J is O; each of K and L is -(CH2)-; each of Ri, R2 and R3 is independently H or -CH3. In some embodiments of the compound represented by E-F wherein E is 21, J is O; 25   each of K and L is -(CH2)-; each of Ri, R2 and R3 is independently H or -OCH3. In some embodiments of the compound represented by E-F wherein E is 21, J is O; each of K and L is -(CH2)-; each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some embodiments of the compound represented by E-F wherein E is 21, J is O; each of K and L is -(CH2)-; each of Ri and R2 is -OCH3 and R3 is -CH3. In some embodiments of the compound represented by 30 E-F wherein E is 21, J is O; each of K and L is -(CH2)-; each of Ri and R2 is -OCH3 and R3 is H. In some embodiments of the compound represented by E-F wherein E is 21, J is O; each of K and L is -(CH2)-; each of Ri and R2 is -CH3 and R3 is H. In some embodiments of the compound represented by E-F, wherein E is 21, J is O; each of K and L is -(CH2)-; each of Ri 2026203365   02 May 2026 and R2 is -OCH3 and R3 is H. In some embodiments of the compound represented by E-F, wherein E is 21, J is O; each of K and L is -(CH2)- and at least one of Ri, R2 and R3 is F. In some embodiments of the compound represented by E-F wherein E is 21, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CF3, -0CF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, 5   -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2 and Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by E-F wherein E is 21, (i) R3 is H, F, -CH3, or -OCH3, and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by E-F wherein E is 0   21, (i) R3 is H; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by E-F wherein E is 21, (i) R3 is -CH3; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by E-F wherein E is 21, (i) R3 is -OCH3; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic 15 or heterocyclic ring. In some embodiments of the compound represented by E-F wherein E is 21, (i) R3 is F; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of E-F, Ri and R2 of 21, taken together, form a heterocycle as represented in 21A, 21B, 21C, 21D, 21E or 21F: 20 wherein each of Rie and R17 are each independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, -CH(CH3)2, -OCH(CH3)2, -C(CH3)3 or -O(CH3)3; and J” is 2026203365   02 May 2026 O, S or N-Ris, wherein Ri8 is H, D, -CH3, -CH2F, -CHF2 or -CF3. In some embodiments, Rie and R17 are each independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, or -OCF3. In some embodiments, Rie and R17 are each independently H, D, F, or -CH3. In some embodiments, Rie and R17 are H. In some embodiments, Rie and R17 are F. In some 5 embodiments, Rie and R17 are -CH3. In some embodiments, Ris is H or -CH3. In some embodiments of the compound represented by E-F wherein E is 22, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, 0   -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, 15 -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently H, D, F, Cl, Br, I, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2, and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or selected from H, D, methyl, ethyl, isopropyl or t-butyl. In 20 some embodiments, for each instance of w=w, the bond between each W is a single bond. In some embodiments, for each instance of w=w, the bond between each W is a double bond. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, or -CH(CH3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached 25 thereto is independently H, D, F, Cl, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2, and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or selected from H, D, methyl and ethyl. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In some embodiments, each W is C (carbon) and each of R4, 30 Rs, Re and R7 is independently H, D, Cl, F, -CH3 or -OCH3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, -CH3 or -OCH3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is H. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is -CH3. 2026203365   02 May 2026 In some embodiments of the compound E-F, each of Rs and R9 can be independently H, D, F, Cl, Br, I, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, - CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, 5   -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In some embodiments of the compound E-F, each of Rs and R9 can be independently H, F, -CH3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CF2CH3, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CF3)3, - CH2CH2CH3, -CH(CH2CH3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In some embodiments of the compound E-F, each of Rs and 0 R9 can be independently H, F, -CH3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound E-F, each of Rs and R9 can be independently a C1-C4 alkyl group. Said alkyl group can be, for example, substituted with one or more fluorine atoms. For example, said alkyl group can be fluoromethyl, difluoromethyl or trifluoromethyl. In some embodiments of the compound E-F, Rs and R9, taken together, can form a 3-, 4-, 5-, 15   6- or 7-membered carbocyclic or heterocyclic ring. For example, the 3-, 4-, 5-, 6- or 7 membered carbocyclic or heterocyclic ring can be 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45,46 or 47: 31      32       33       34         35 36      37     38      39     40      41 42       43       44       45       46       47 20 wherein # indicates the point of attachment of the carbocycle or heterocycle to the remainder of the compound. In some embodiments, the 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring can comprise one or more fluorine substitutions. In some embodiments, the 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring can comprise one or more 25 deuterium substitutions. In some embodiments of the compound E-F, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, 2026203365   02 May 2026 -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CEECEE, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), 5   -OC(CH3)(CF3)2, -CEECEECEE, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CF2CF3, -CF(CF2CF3)2, -C(CH2CH3)3, -C(CD2CD3)3, -C(CF2CF3)3, -OCEECEECEE, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments of the compound E-F, Rio is H, D, F, -CEE, -OCEE, -CD3, -OCD3, -CEEF, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CEECEE or -CH(CH3)2. In some embodiments of 0 the compound E-F, Rio is H, D, F, -CEE, -CEEF, -CHF2, or -CF3. In some embodiments of the compound E-F, Rio is H, D or F. In some embodiments of the compound E-F, Rio is -CH3 or -CF3. In some embodiments of the compound E-F, Rio is -H or -CEE. In some embodiments of the compound E-F, Rio is H. In some embodiments of the compound E-F, Rio is -CEE. In some embodiments of the compound E-F, Rio is F. In some embodiments of 15 the compound E-F, Rio is absent. In some embodiments of the compound E-F, R11 is H, methyl or ethyl. In some embodiments of the compound E-F, R11 is H. In some embodiments of the compound E-F, R11 is methyl. In some embodiments of the compound E-F, R11 is ethyl. In some embodiments of the compound E-F, each instance of R12, R13 or Rm is independently 20 H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CEECEECEE, -CH(CH2CH3)2, -C(CH3)3, -OCH2CH3, -OCH(CH3)2, -OCEECEECEE, -OCH(CEECEE)2, or -OC(CEE)3. In some embodiments of the compound E-F, each instance of R12, R13 or Rm is independently H, D, F, -CEE, -OCH3, -CD3, -OCD3, -CEEF, -OCEEF, -CHF2, -OCHF2, -CF3 or -OCF3. In some embodiments of the compound E-25 F, each instance of R12, R13 or Rm is independently H, D, F, -CEE, -CD3 or -CF3. In some embodiments of the compound E-F, each instance of R12, R13 or Rm is independently H, D, or F. In some embodiments of the compound E-F, each instance of R12, R13 or Rm is independently H, F or -CEE. In some embodiments of the compound E-F, each instance of R12, R13 or Rm is H. In some embodiments of the compound E-F, each instance of R12, R13 or 30 Rm is D. In some embodiments of the compound E-F, each instance of R12, R13 or Rm is F. In some embodiments of the compound E-F, R20 is H, D, F, -CEE, -CD3, -CEEF, -CHF2, -CF3, -CH2CH3, -CEECEECEE, -CH(CH3)2, -C(CH3)3, -CEECEECEECEE, -CEECEECEECEECEE, 2026203365   02 May 2026 -CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH2CH3 or -CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3. In some embodiments of the compound E-F, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2 or 5   -C(CH3)3. In some embodiments of the compound E-F, R20 is H, D, F, -CEE, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound E-F, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound E-F, R20 is -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound E-F, R20 is H. In some embodiments of the compound E-F, R20 is -CH3. In some embodiments of the compound E- 0 F, R2ois-CF3. In some embodiments of the compound E-F, R20 is F. In some embodiments of the compound E-F, each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3 or -C(CH3)3. In some embodiments of the compound E-F, each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound E-F, each R21 is 15 independently H, -CH3 or -CF3. In some embodiments of the compound E-F, each R21 is -CH3. In some embodiments of the compound E-F, each R21 is H. In some embodiments of the compound E-F, each R21 is -CF3. In some embodiments of the compound E-F, n is 0, 1, 2, 3, 4, 5, 6, 7 or 8. In some embodiments of the compound E-F, n is 0, 1, 2, 3, 4, 5 or 6. In some embodiments of the 20 compound E-F, n is 0, 1, 2, 3 or 4. In some embodiments of the compound E-F, n is 0. In some embodiments of the compound E-F, n is 1. In some embodiments of the compound E-F, n is 2. In some embodiments of the compound E-F, n is 3. In some embodiments of the compound E-F, n is 4. In some embodiments of the compound E-F, n is 5. In some embodiments of the compound E-F, n is 6. In some embodiments of the compound E-F, n is 25   7. In some embodiments of the compound E-F, n is 8. In some embodiments of the compound E-F, n is 9. In some embodiments of the compound E-F, n is 10. In some embodiments of the compound E-F, n is 11. In some embodiments of the compound E-F, n is 12. In some embodiments of the compound E-F has the formula referred to herein as Compound 30 A: 2026203365   02 May 2026 In some embodiments of the compound E-F has the formula referred to herein as Compound B: 5 In some embodiments of the compound E-F has the formula referred to herein as Compound O In some embodiments of the compound E-F has the formula referred to herein as Compound D: io                         o In some embodiments of the compound E-F has the formula referred to herein as Compound E: O In some embodiments of the compound E-F has the formula referred to herein as Compound 15 F: 2026203365   02 May 2026 O In some embodiments of the compound E-F has the formula referred to herein as Compound 5 In some embodiments of the compound E-F has the formula referred to herein as Compound H: o Compound H In some embodiments of the compound E-F has the formula referred to herein as Compound I: Compound I In some embodiments of the compound E-F has the formula referred to herein as Compound J: Compound J In some embodiments of the compound E-F has the formula referred to herein as Compound 15 K: 2026203365   02 May 2026 Compound K In some embodiments of the compound E-F has the formula referred to herein as Compound L: 5 In some embodiments of the compound E-F has the formula referred to herein as Compound N: As illustrated in Examples 17 & 18, below, certain compounds disclosed herein exhibit a high degree of potency in the BSO Assay (Example 17) and in the Rotenone ATP Assay 10 (Example 18). More specifically, for several of the compounds disclosed herein the potency and efficacy is similar to or greater than that of vatiquinone with respect to ameliorating the effects of Friedreich’s ataxia in a cell-based assay (See: Example 17; BSO Assay). Similarly, several of the compounds disclosed herein are also effective in rescuing cells exhibiting an induced Complex I deficiency in the Rotenone ATP Assay (Example 18). In many cases, 15 compounds disclosed herein have fair to good activity in both the BSO Assay and the Rotenone ATP Assay (See: Examples 17 & 18 and Table 2). By comparison, while several currently available therapeutics such as vatiquinone, idebenone or omaveloxolone may exhibit good or fair activity in one or the other of the BSO Assay or the Rotenone ATP Assay (See: Table 2, below), none of them are active in both assays, thereby suggesting that 20 compounds disclosed herein may exhibit a unique mechanism of action and therefore be superior therapeutics as compared with compounds currently being evaluated as therapeutic agents for treatment of certain mitochondrial diseases (e.g. Friedreich’s ataxia) in clinical trials. Thus, it is believed that the therapeutic compounds disclosed herein will prove to be superior agents for the treatment of certain mitochondrial diseases, such as Friedreich’s 25 ataxia. The aforementioned compounds can be used in the preparation of compositions, such 86 2026203365   02 May 2026 as medicaments. Said compounds or compositions can thus be used in the treatment and / or prevention of mitochondrial disease, such as Friedreich’s ataxia. As further illustrated by Examples 19-22 (in combination with Examples 17 and 18), compounds disclosed herein exhibit the unique ability to protect cells from BSO induced 5 ferroptosis; protect cells from RSL3 induced ferroptosis; and exhibit Complex I by-pass activity. No prior art compounds appear to possess this unique combination of properties that are therapeutically valuable in treating mitochrial disease, such as Freidreich’s ataxia. (b) Intermediates to Therapeutic Agents In addition to the novel agents provided herein for the treatment of Friedreich’s ataxia, novel intermediates to said novel agents are provided. In some embodiments, those intermediates are compounds of formula A-B: or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein A is 1, 2, 3 or 4: and B is 5, 6, 7 or 8 R21           Rs 5 R21           Rs R2i           Rs 7 6 wherein, J is O, S orN-Rn, K is absent or -(CR12R13)-, L is -(CR12R13)-, each W is independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, 20 Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 2026203365   02 May 2026 of R4, Rs, Re and R7 attached thereto is independently absent (if w=Wis a double bond) or selected from H, D and Ci-Ce alkyl (if w=wis a single bond), each X is independently a group of formula -(CR12R13)-, each Y is independently absent or a group of formula -(CR12R13)-, each Z is independently a group of formula -(CRh)-, each of Ri, R2 and R3 is 5 independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 5membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or heteroaromatic ring or a 6-membered heterocyclic ring, each Rs and R9 is each independently H, D, F, Cl, Br, I or C1-C4 alkyl; or taken together Rs and R9 form a 3-, 4-, 5-, 6-, or 7membered carbocyclic or heterocyclic ring, Rio is H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce 0 alkoxy, R11 is H, D or Ci-Ce alkyl, each instance of R12, R13 and Rh is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy, Ris is H, -CH3, -CH2CH3 or PG, wherein PG is a phenol protecting group, R20 is H, D, F or C1-C12 alkyl, each R21 is independently H, D, F, Cl, Br, I, or C1-C4 alkyl, n is an integer from 0 to 12, inclusive, and *** indicates the point of attachment of A to B and ** indicates the point of attachment of C to D; and further provided 15 that: (i) at least one group of formula Ri, R2, R3, R4, Rs, Re, R7, Rs, R9, Rio, R12, R13, R14, R20 or R21 comprises at least one fluorine atom; and / or (ii) Rs and R9 taken together form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring. In some embodiments, at least one of Rs and R9 is fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. In some embodiments, each of Rs and R9 is independently fluorine or a substituted C1-C4 alkyl 20 group comprising at least one fluorine. In some embodiments, each of Rs and R9 is fluorine. In some embodiments, each of Rs, R9 and Rio is fluorine. In some embodiments, each of Rs, R9 and Rio is independently fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. In some embodiments of A-B, R15 is H. Any combination of 1, 2, 3 and 4 with 5, 6, 7 or 8 is permissible. In some embodiments, A is 25   1 and B is 5, 6, 7 or 8. In some embodiments, A is 2 and B is 5, 6, 7 or 8. In some embodiments, A is 3 and B is 5, 6, 7 or 8. In some embodiments, A is 4 and B is 5, 6, 7 or 8. In some embodiments, A is 1 and B is 5. In some embodiments, A is 1 and B is 6. In some embodiments, A is 1 and B is 7. In some embodiments, A is 2 and B is 5. In some 30 embodiments, A is 2 and B is 7. In some embodiments, A is 3 and B is 5. In some embodiments, A is 3 and B is 7. In some embodiments, A is 4 and B is 5. In some embodiments, A is 1 and B is 8. In some embodiments, A is 2 and B is 6. In some embodiments, A is 2 and B is 8. In some embodiments, A is 3 and B is 6. In some embodiments, A is 3 and B is 8. In some embodiments, A is 4 and B is 6. In some 2026203365   02 May 2026 embodiments, A is 4 and B is 7. In some embodiments, A is 4 and B is 8. The atom or group represented by J can be O, S or N-Rn. In some embodiments, J is O (oxygen). In some embodiments, J is S (sulfur). In some embodiment, J is N-Ru, wherein Rn is defined below. In some embodiments, J is O or N-Ru and K is absent. 5 In some embodiments, the groups represented by K and L can each independently be: -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, 0   -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))- 15   , -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, each of K and L is independently -CH2-, -CD2-,-CF2-, -CH(CH3)-, -CD(CD3)-, -CF(CF3)-, -C(CH3)2-, -C(CD3)2-, -C(CF3)2, -CH(OCH3)-, -CD(OCD3)-, -CF(OCF3)-, or -C(OCH3)2-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, 20   -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, each of K and 25 L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-. In some embodiments, each of K and L are -(CH2)-. In some embodiments, K is absent and L is -(CH2)-. In some embodiments, each of K and L are -(CD2)-. In some embodiments, K is absent and L is -(CD2)-. In some embodiments, each of K and L are -(CF2)-. In some embodiments, K is absent and L is 30   -(CF2)-. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, 2026203365   02 May 2026 -OCHF2, -CF3, -0CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), 5   -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments of the compound represented by A-0 B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3 15 or -CH(CH3)2. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently H, F, -CH3, -CF3, -OCH3 or -OCF3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently 20 H, F, -CH3, -OCH3 or -CF3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is -CH3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is H. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently H or -CH3. In some embodiments of the compound represented by A-B, 25 wherein A is 1 or 3, each of Ri, R2 and R3 is independently H or -OCH3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri and R2 is -OCH3 and R3 is -CH3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri and R2 is 30 -OCH3 and R3 is H. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri and R2 is -CH3 and R3 is H. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of Ri and R2 is -OCH3 and R3 is H. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, at least one of Ri, R2 2026203365   02 May 2026 and R3 is F. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, J is O, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, 5 -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, J is O, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, J is O, each of K and L is 0 independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CF3 or -OCF3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; and each of Ri, R2 and R3 is -CH3. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; and each of Ri, R2 and R3 is H. In some 15 embodiments of the compound represented by A-B, wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; each of Ri and R2 is -OCH3 and R3 is -CH3. In some embodiments of the compound represented by A-B wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; each of Ri, R2 and R3 is independently H or -OCH3. In some embodiments of the compound represented by A-B wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; each of Ri, R2 20 and R3 is independently H, -CH3 or -OCH3. In some embodiments of the compound represented by A-B wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; each of Ri and R2 is -OCH3 and R3 is -CH3. In some embodiments of the compound represented by A-B wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; each of Ri and R2 is -OCH3 and R3 is -CH3. In some embodiments of the compound represented by A-B wherein A is 1 or 3, J is 25   O; each of K and L is -(CH2)-; each of Ri and R2 is -CH3 and R3 is H. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, J is O; each of K and L is -(CH2)-; each of Ri and R2 is -OCH3 and R3 is H. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, each of K and L is -(CH2)- and at least one of Ri, R2 and R3 is F. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, R3 is H, D, 30 Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2 and Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the 2026203365   02 May 2026 compound represented by A-B, wherein A is 1 or 3, (i) Ra is H, F, -CHa, or -OCHa, and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, (i) R3 is H; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some 5 embodiments of the compound represented by A-B, wherein A is 1 or 3, (i) R3 is -CHa; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by A-B, wherein A is 1 or 3, (i) R3 is -OCH3; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by A-B, wherein A is 0   1 or 3, (i) R3 is F; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments, Ri and R2 of 1 or 3, taken together, form a heterocycle as represented in 1A, IB, IC, ID, IE, IF, 3A, 3B, 3C, 3D, 3E or 3F: 15 2026203365   02 May 2026 3D 3F wherein each of Rie and R17 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -0CF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, -CH(CH3)2, -OCH(CH3)2, -C(CH3)3 or -O(CH3)3; and J” is 5 O, S or N-Ris, wherein Ri8 is H, D, -CH3, -CH2F, -CHF2 or -CF3. In some embodiments, Rie and R17 are each independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, or -OCF3. In some embodiments, Rie and R17 are each independently H, D, F, or -CH3. In some embodiments, Rie and R17 are H. In some embodiments, Rie and R17 are F. In some embodiments, Rie and R17 are -CH3. In some embodiments, Ris is H or -CH3. 10   In some embodiments of the compound represented by A-B wherein A is 2 or 4, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, 15   -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2; and 20 where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently H, D, F, Cl, Br, I, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2; and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or selected from H, D, methyl, ethyl, isopropyl and t-butyl. In some embodiments, for each instance of w=w, the bond between each W is a single bond. 25 In some embodiments, for each instance of w=w, the bond between each W is a double bond. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached 2026203365   02 May 2026 thereto is independently H, D, F, Cl, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2; and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or selected from H, D, methyl and ethyl. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3, -OCH3, 5 -CH2F, -CHF2, -CF3 or -OCF3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3 or -OCH3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, -CH3 or -OCH3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is H. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is -CH3. 0 In some embodiments of the compound A-B, each of Rs and R9 can be independently H, D, F, Cl, Br, I, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, - CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3 or 15   -CF(CF2CF3)2. In some embodiments of the compound A-B, each of Rs and R9 can be independently H, F, -CH3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CF2CH3, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CF3)3, - CH2CH2CH3, -CH(CH2CH3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In some embodiments of the compound A-B, each of Rs and R9 can be independently H, F, -CH3, -CH2F, -CHF2, or -CF3. 20 In some embodiments of the compound A-B, each of Rs and R9 can be independently a C1-C4 alkyl group. Said alkyl group can be, for example, substituted with one or more fluorine atoms. For example, said alkyl group can be fluoromethyl, difluoromethyl or trifluoromethyl. In some embodiments of the compound A-B, Rs and R9, taken together, can form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring. For example, the 3-, 4-, 5-, 6- or 7 25 membered carbocyclic or heterocyclic ring can be 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 or 47: 36      37     38      39     40      41 2026203365   02 May 2026 42       43       44       45       46       47 wherein # indicates the point of attachment of the carbocycle or heterocycle to the remainder of the compound. In some embodiments, the 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring can comprise one or more fluorine substitutions. In some embodiments, the 5   3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring can comprise one or more deuterium substitutions. In some embodiments of the compound A-B, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, 0   -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CF2CF3, -CF(CF2CF3)2, -C(CH2CH3)3, -C(CD2CD3)3, -C(CF2CF3)3, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In 15 some embodiments of the compound A-B, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -CH(CH3)2. In some embodiments of the compound A-B, Rio is H, D, F, -CH3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound A-B, Rio is H, D or F. In some embodiments of the compound A-B, Rio is -CH3 or -CF3. In some embodiments of the compound A-B, Rio is H 20 or -CH3. In some embodiments of the compound A-B, Rio is H. In some embodiments of the compound A-B, Rio is -CH3. In some embodiments of the compound A-B, Rio is absent. In some embodiments of the compound A-B, R11 is H, methyl or ethyl. In some embodiments of the compound A-B, R11 is H. In some embodiments of the compound A-B, R11 is methyl. In some embodiments of the compound A-B, R11 is ethyl. 25   In some embodiments of the compound A-B, each instance of R12, R13 or Rm is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH(CH2CH3)2, -C(CH3)3, -OCH2CH3, -OCH(CH3)2, -OCH2CH2CH3, -OCH(CH2CH3)2 or -OC(CH3)3. In some embodiments of the compound A-B, each instance of R12, R13 or Rh is independently H, D, F, -CH3, -OCH3, 30   -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3 or -OCF3. In some embodiments of 2026203365   02 May 2026 the compound A-B, each instance of R12, R13 or Rm is independently H, D, F, -CH3, -CD3 or -CF3. In some embodiments of the compound A-B, each instance of R12, R13 or Rm is independently H, D, or F. In some embodiments of the compound A-B, each instance of R12, R13 or Rm is independently H, F or -CH3. In some embodiments of the compound A-B, each 5 instance of R12, R13 or Rm is H. In some embodiments of the compound A-B, each instance of R12, R13 or R14 is D. In some embodiments of the compound A-B, each instance of R12, R13 or Rm isF. The atom or group R15 can vary depending on the starting material and desired product. For example, if R15 is a C1-C4 alkyl group, that group is generally intended to remain in the final 0 product as such groups are not easily removed. In some embodiments, R15 is methyl, ethyl, isopropyl or t-butyl. In some embodiments, R15 is -CH3. Thus, if a product (intermediate or therapeutic agent) with an alkyl group is desired, the starting material will generally contain the alkyl group. In some embodiments, R15 is H (the unprotected phenol). 15 In some embodiments, R15 is a protecting group (PG) that transiently protects the phenol during chemical synthesis - but ultimately is removed to regenerate the unprotected phenol. For example, in some embodiments, the protecting group can be a triphenylmethyl-based protecting group. In some embodiments, a triphenylmethyl-based protecting group can include: triphenylmethyl-, 4-monomethyl-triphenylmethyl-, 4,4’-dimethyl-triphenylmethyl-, 20 4,4’,4”-trimethyl-triphenylmethyl, 4-monomethoxy-triphenylmethyl-, 4,4’-dimethoxy- triphenylmethyl-, or 4,4’,4”-trimethoxy-triphenylmethyl-. Triphenylmethyl-based protecting groups can generally be removed in the presence of medium to strong acid. In some embodiments, the protecting group can be a silyl-based protecting group. A silyl protecting group generally comprises a silicon atom to which is linked 2 to 3 (preferably 3) 25 alkyl groups. A few non-limiting examples of silyl protecting groups include: trimethyl silyl (TMS), Zert-butyldiphenylsilyl (TBDPS), Zert-butyldimethylsilyl (TBS / TBDMS) and triisopropyl silyl (TIPS). Silyl protecting groups can generally be removed in the presence of fluoride ion. In some embodiments, R15 is a substituted or unsubstituted benzyl group. In some 30 embodiments, the benzyl group can be left intact in the therapeutic agent. In some embodiments, the benzyl group is used as a protecting group and can be removed, for example, by hydrogenation or by treatment with strong acid. 2026203365   02 May 2026 In some embodiments of the compound A-B, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -CH2CH2CH2CH3, -CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH3, - CH2CH2CH2CH2CH2CH2CH2CH2CH3 or 5 -CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3. In some embodiments of the compound A-B, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2 or -C(CH3)3. In some embodiments of the compound A-B, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound A-B, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound A-B, R20 is -CH3, -CD3, 0 -CH2F, -CHF2 or -CF3. In some embodiments of the compound A-B, R20 is H. In some embodiments of the compound A-B, R20 is -CH3. In some embodiments of the compound A-B, R20 is -CF3. In some embodiments of the compound A-B, R20 is F. In some embodiments of the compound A-B, each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3 or -C(CH3)3. 15 In some embodiments of the compound A-B, each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound A-B, each R21 is independently H, -CH3 or -CF3. In some embodiments of the compound A-B, each R21 is -CH3. In some embodiments of the compound A-B, each R21 is H. In some embodiments of the compound A-B, each R21 is -CF3. 20 In some embodiments of the compound A-B, n is 0, 1, 2, 3, 4, 5, 6, 7 or 8. In some embodiments of the compound A-B, n is 0, 1, 2, 3, 4, 5 or 6. In some embodiments of the compound A-B, n is 0, 1, 2, 3 or 4. In some embodiments of the compound A-B, n is 0. In some embodiments of the compound A-B, n is 1. In some embodiments of the compound A-B, n is 2. In some embodiments of the compound A-B, n is 3. In some embodiments of the 25 compound A-B, n is 4. In some embodiments of the compound A-B, n is 5. In some embodiments of the compound A-B, n is 6. In some embodiments of the compound A-B, n is 7. In some embodiments of the compound A-B, n is 8. In some embodiments of the compound A-B, n is 9. In some embodiments of the compound A-B, n is 10. In some embodiments of the compound A-B, n is 11. In some embodiments of the compound A-B, n 30 is 12. In some embodiments of the compound A-B has the formula: 26 2026203365   02 May 2026 In some embodiments of the compound A-B has the formula: 29 In some embodiments of the compound A-B has the formula: 5                                                                  32                . In some embodiments of the compound A-B has the formula: 35 In some embodiments of the compound A-B has the formula: 38 10 In some embodiments of the compound A-B has the formula: 41 In some embodiments of the compound A-B has the formula: 44 In some embodiments of the compound A-B has the formula: 2026203365   02 May 2026 56 In some embodiments of the compound A-B has the formula: 67 In some embodiments of the compound A-B has the formula: 78 In some embodiments of the compound A-B has the formula: 87 In some embodiments of the compound A-B has the formula: 96 10 In some embodiments of the compound A-B has the formula: 104 (c) Other Derivatives / Therapeutic Agents In some embodiments, this application further provides therapeutic compounds of formula C- 15 D (defined below), that can be prepared by reduction of the therapeutic compounds of formula E-F. Such reduced versions of compounds of formula E-F are believed to also be 2026203365   02 May 2026 suitable for use in the treatment of mitochondrial disease, such as Friedreich’s ataxia or other ataxia’s (such as Ataxia with vitamin E deficiency (AVED)) because other compounds that have a hydroquinone structure, such are vitamin E, have also been shown to be clinically linked with ataxia (See: Imounan et al., Clinical and Genetic Study of Friedreich’s ataxia and 5 Ataxia with Vitamin E Deficiency in 44 Moroccan Families, World Journal of Neuroscience, 2014, 4, 299-305; and Abeti et al., Calcium Deregulation: Novel Insights to Understand Friedreich’s ataxia Pathophysiology, Frontiers in Cellular Neuroscience: doi: 10.3398 / fncel.2018.00264). For example, it is believed that the therapeutic compounds of formula C-D (below) can themselves be considered therapeutic agents or alternatively as 0 prodrug forms of the therapeutic agents of formula E-F. Specifically, therapeutic compounds of formula E-F are believed to be active in the processes affecting the in vivo concentration (e.g., the internal and external mitochondrial concentration) of reactive oxygen species (ROS) and indeed may actively cycle, in vivo, between the reduced form (compounds of formula CD) and oxidized form (compounds of formula E-F). Compounds of the formula E-F can, for 15 example, be converted to compounds of the formula C-D as described below in Examples 8 and 9, below. Furthermore, compounds of formula C-D were shown to be effective as lipoxygenase-15 (LO-15) inhibitors in Example 22. Thus, in some embodiments, this application further provides novel compounds of formula C-D, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, 20 tautomers, hydrates, and / or solvates thereof, wherein C is 11 or 12: and D is 13, 14, 15, 16, 17, 18, 19 or 20: 2026203365   02 May 2026 19 wherein, J’ is OH, SH or NH-Rn, K is absent or -(CR12R13)-, L is -(CR12R13)-, each W is independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single 5 bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if w=w is a single bond), each X is independently a 10 group of formula -(CR12R13)-, each Y is independently absent or a group of formula -(CR12R13)-, each Z is independently a group of formula -(CR14)-, each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; or Ri and R2 together form a 5membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or heteroaromatic ring or a 6-membered heterocyclic ring, each Rs and R9 is each independently 15 H, D, F, Cl, Br, I or C1-C4 alkyl; or taken together Rs and R9 form a 3-, 4-, 5-, 6-, or 7membered carbocyclic or heterocyclic ring, Rio is H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy, R11 is H, D or Ci-Ce alkyl, each instance of R12, R13 and R14 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy, R19 is H, C1-C4 alkyl or benzyl (substituted or unsubstituted), R20 is H, D, F or C1-C12 alkyl, each R21 is independently H, D, F, Cl, Br, I, or 20   C1-C4 alkyl, n is an integer from 0 to 12, inclusive, and *** indicates the point of attachment of C to D and ** indicates the point of attachment of C to D; and further provided that: (i) at 101 2026203365   02 May 2026 least one group of formula Ri, R2, R3, R4, R5, Re, R7, Rs, R9, Rio, R12, Ri3, R14, R20 or R21 comprises at least one fluorine atom; and / or (ii) Rs and R9 taken together form a 3-, 4-, 5-, 6-or 7-membered carbocyclic or heterocyclic ring. In some embodiments, at least one of Rs and R9 is fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. In 5 some embodiments, each of Rs and R9 is independently fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. In some embodiments, each of Rs and R9 is fluorine. In some embodiments, each of Rs, R9 and Rio is fluorine. In some embodiments, each of Rs, R9 and Rio is independently fluorine or a substituted C1-C4 alkyl group comprising at least one fluorine. In some embodiments of E-F, R19 is H. Any combination of 11 and 12 with 13, 14, 15, 16, 17, 18, 19 or 20 is permissible. In some embodiments, C is 12 and D is 13, 14, 15, 16, 17, 18, 19 or 20. In some embodiments, C is 11 and D is 13, 14, 19 or 20. In some embodiments, C is 12 and D is 13, 14, 19 or 20. In some embodiments, C is 11 and D is 15, 16, 17 or 18. In some embodiments, C is 12 and D is 13, 14, 19 or 20. In some embodiments, C is 12 and D is 15, 16, 17 or 18. In some 15   embodiments, C is 11 and D is 13. In some embodiments, C is 11 and D is 14. In some embodiments, C is 11 and D is 15. In some embodiments, C is 11 and D is 16. In some embodiments, C is 11 and D is 17. In some embodiments, C is 11 and D is 18. In some embodiments, C is 11 and D is 19. In some embodiments, C is 11 and D is 20. In some embodiments, C is 12 and D is 13. In some embodiments, C is 12 and D is 14. In some 20   embodiments, C is 12 and D is 15. In some embodiments, C is 12 and D is 16. In some embodiments, C is 12 and D is 17. In some embodiments, C is 12 and D is 18. In some embodiments, C is 12 and D is 19. In some embodiments, C is 12 and D is 20. The atom or group represented by J’ can be OH, SH or NH-R11. In some embodiments, J’ is OH. In some embodiments, J’ is S. In some embodiment, J’ is NH-R11, wherein R11 is 25 defined below. In some embodiments, J’ is OH or NH-R11 and K is absent. In some embodiments, the groups represented by K and L can each independently be: -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, 30   -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)-, 2026203365   02 May 2026 -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, 5   -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, 0   -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-. In some embodiments, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-. In 15 some embodiments, K is absent and L is -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-. In some embodiments, each of K and L are -(CH2)-. In some embodiments, K is absent and L is -(CH2)-. In some embodiments, each of K and L are -(CD2)-. In some embodiments, K is absent and L is -(CD2)-. In some embodiments, each of K and L are -(CF2)-. In some embodiments, K is absent and L is -(CF2)-. 20 In some embodiments of the compound represented by C-D, wherein C is 11, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, 25   -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, 30 -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments of the compound represented by CD, wherein C is 11, each of Ri, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2. In some embodiments of the compound 2026203365   02 May 2026 represented by C-D, wherein C is 11, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2. In some embodiments of the compound represented by C-D, wherein C is 11, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In 5 some embodiments of the compound represented by C-D, wherein C is 11, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CF3 or -OCF3. In some embodiments of the compound represented by C-D, wherein C is 11, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3 or -CF3. In some embodiments of the compound represented by C-D, wherein C is 11, each of Ri, R2 and R3 is -CH3. In some embodiments of the compound represented 0 C-D, wherein C is 11, each of Ri, R2 and R3 is H. In some embodiments of the compound represented C-D, wherein C is 11, each of Ri, R2 and R3 is independently H or -CH3. In some embodiments of the compound represented C-D, wherein C is 11, each of Ri, R2 and R3 is independently H or -OCH3. In some embodiments of the compound represented C-D, wherein C is 11, each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some 15 embodiments of the compound represented by C-D, wherein C is 11, each of Ri and R2 is -OCH3 and R3 is -CH3. In some embodiments of the compound represented by C-D, wherein C is 11, each of Ri and R2 is -CH3 and R3 is H. In some embodiments of the compound represented by C-D, wherein C is 11, each of Ri and R2 is -OCH3 and R3 is H. In some embodiments of the compound represented by C-D, wherein C is 11, at least one of Ri, R2 20 and R3 is F. In some embodiments of the compound represented by C-D, wherein C is 11, J’ is OH, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2. In 25 some embodiments of the compound represented by C-D, wherein C is 11, J’ is OH, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-; and each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In some embodiments of the compound represented by C-D, wherein C is 11, J’ is OH, each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)- or -(CF2)-; and each of Ri, R2 and R3 is 30 independently H, F, -CH3, -OCH3, -CF3 or -OCF3. In some embodiments of the compound represented by C-D, wherein C is 11, J’ is OH; each of K and L is -(CH2)-; and each of Ri, R2 and R3 is -CH3. In some embodiments of the compound represented by C-D wherein C is 11, J’ is OH; each of K and L is -(CH2)-; and each of Ri, R2 and R3 is independently H or -CH3. 2026203365   02 May 2026 In some embodiments of the compound represented by C-D wherein C is 11, J is O; each of K and L is -(CH2)-; each of Ri, R2 and R3 is independently H or -OCH3. In some embodiments of the compound represented by C-D wherein C is 11, J’ is OH; each of K and L is -(CH2)- and each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some 5 embodiments of the compound represented by C-D wherein C is 11, J’ is OH; each of K and L is -(CH2)- and each of Ri and R2 is -OCH3 and R3 is -CH3. In some embodiments of the compound represented by C-D wherein C is 11, J’ is OH; each of K and L is -(CH2)- and each of Ri and R2 is -OCH3 and R3 is H. In some embodiments of the compound represented by C-D wherein C is 11, J’ is OH; each of K and L is -(CH2)- and each of Ri and R2 is -CH3 0 and R3 is H. In some embodiments of the compound represented by C-D wherein C is 11, J’ is OH; each of K and L is -(CH2)- and each of Ri and R2 is -OCH3 and R3 is H. In some embodiments of the compound represented by C-D, wherein C is 11, J’ is OH; each of K and L is -(CH2)- and at least one of Ri, R2 and R3 is F. In some embodiments of the compound represented by C-D, wherein C is 11, R3 is H, D, Cl, 15 F, -CH3, -OCH3, -CD3, -OCD3, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2 and Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by C-D, wherein C is 11, (i) R3 is H, F, -CH3, or -OCH3, and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some 20 embodiments of the compound represented by C-D, wherein C is 11, (i) R3 is H; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by C-D, wherein C is 11, (i) R3 is -CH3; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by C-D, wherein C is 11, (i) R3 is -OCH3; and (ii) 25 Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments of the compound represented by C-D, wherein C is 11, (i) R3 is F; and (ii) Ri and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring. In some embodiments, Ri and R2 of 11, taken together, form a heterocycle as represented in 11 A, 11B, 11C, 11D, 1 IE or 1 IF: 2026203365   02 May 2026 wherein each of Rie and R17 are each independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -0CF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, 5   -OC(CF3)3, -CH2CH3, -OCH2CH3, -CH(CH3)2, -OCH(CH3)2, -C(CH3)3 or -O(CH3)3; and J” is OH, SH or NH-Ris, wherein Ris is H, D, -CH3, -CH2F, -CHF2 or -CF3. In some embodiments, Rie and R17 are each independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, or -OCF3. In some embodiments, Rie and R17 are each independently H, D, F, or -CH3. In some embodiments, Rie and R17 are H. In some embodiments, Rie and 10 RnareF. In some embodiments, Rie and R17 are-CH3. In some embodiments, Ris is H or -CH3. In some embodiments of the compound represented by C-D, wherein C is 12, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, 15   -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2, -OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, 20 -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently H, D, F, Cl, Br, I, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2; and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached 2026203365   02 May 2026 thereto is independently absent or selected from H, D, methyl, ethyl, isopropyl and t-butyl. In some embodiments, for each instance of w=w, the bond between each W is a single bond. In some embodiments, for each instance of w=w, the bond between each W is a double bond. In some embodiments, R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, 5   -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, or -CH(CH3)2; and where if W is C (carbon), each of R4, Rs, Re and R7 attached thereto is independently H, D, F, Cl, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -CH2CH3, or -CH(CH3)2; and where if W is N (nitrogen), each of R4, Rs, Re and R7 attached thereto is independently absent or selected from H, D, methyl and ethyl. In some embodiments, each 0 W is C (carbon) and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3 or -OCF3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, D, Cl, F, -CH3 or -OCH3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is independently H, -CH3 or -OCH3. In some embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is H. In some 15 embodiments, each W is C (carbon) and each of R4, Rs, Re and R7 is -CH3. In some embodiments of the compound C-D, each of Rs and R9 can be independently H, D, F, Cl, Br, I, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, - CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, 20   -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In some embodiments of the compound C-D, each of Rs and R9 can be independently H, F, -CH3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CF2CH3, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CF3)3, -CH2CH2CH3, -CH(CH2CH3)2, -CF2CF2CF3 or -CF(CF2CF3)2. In some embodiments of the compound C-D, each of Rs and 25 R9 can be independently H, F, -CH3, -CH2F, -CHF2, or -CF3. In some embodiments of the compound C-D, each of Rs and R9 can be independently a C1-C4 alkyl group. Said alkyl group can be, for example, substituted with one or more fluorine atoms. For example, said alkyl group can be fluoromethyl, difluoromethyl or trifluoromethyl. In some embodiments of the compound C-D, Rs and R9, taken together, can form a 3-, 4-, 5-, 30   6- or 7-membered carbocyclic or heterocyclic ring. For example, the 3-, 4-, 5-, 6- or 7 membered carbocyclic or heterocyclic ring can be 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 or 47: 2026203365   02 May 2026 wherein # indicates the point of attachment of the carbocycle or heterocycle to the remainder 5   of the compound. In some embodiments, the 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring can comprise one or more fluorine substitutions. In some embodiments, the 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring can comprise one or more deuterium substitutions. In some embodiments of the compound C-D, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, 10 -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, 15 -CF2CF2CF3, -CF(CF2CF3)2, -C(CH2CH3)3, -C(CD2CD3)3, -C(CF2CF3)3, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2. In some embodiments of the compound C-D, Rio is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -CH(CH3)2. In some embodiments of the compound C-D, Rio is H, D, F, -CH3, -CH2F, -CHF2 or -CF3. In some 20   embodiments of the compound C-D, Rio is H, D or F. In some embodiments of the compound C-D, Rio is -CH3 or -CF3. In some embodiments of the compound C-D, Rio is H or -CH3. In some embodiments of the compound C-D, Rio is H. In some embodiments of the compound E-F, Rio is -CH3. In some embodiments of the compound C-D, Rio is absent. In some embodiments of the compound C-D, R11 is H, methyl or ethyl. In some 25 embodiments of the compound C-D, R11 is H. In some embodiments of the compound C-D, R11 is methyl. In some embodiments of the compound C-D, R11 is ethyl. 2026203365   02 May 2026 In some embodiments of the compound C-D, each instance of R12, Ri3 or Rm is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH(CH2CH3)2, -C(CH3)3, -OCH2CH3, -OCH(CH3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, or -OC(CH3)3. In some embodiments of the 5 compound C-D, each instance of R12, Ri3 or Rh is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3 or -OCF3. In some embodiments of the compound C-D, each instance of R12, Ri3 or Rm is independently H, D, F, -CH3, -CD3 or -CF3. In some embodiments of the compound C-D, each instance of R12, Ri3 or Rm is independently H, D, or F. In some embodiments of the compound C-D, each instance of R12, 0 Ri3 or Rm is independently H, F or -CH3. In some embodiments of the compound C-D, each instance of R12, Ri3 or Rm is H. In some embodiments of the compound C-D, each instance of R12, Ri3 or R14 is D. In some embodiments of the compound C-D, each instance of R12, Ri3 or Rm isF. In some embodiments, R19 is H. In some embodiments, R19 is C1-C4 alkyl. For example, R19 15   can be methyl, or R19 can be ethyl, or R19 can be isopropyl or R19 can be tert-butyl. In some embodiments, R19 can be benzyl (substituted or unsubstituted). For example, in some embodiments, R19 is a group of formula: wherein each Ai is independently H, D, F, Cl, Br, I, -CH3, -OCH3, CH2CH3, -OCH2CH3, 20 tri chloromethyl or trifluoromethyl. In some embodiments of the compound C-D, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -CH2CH2CH2CH3, -CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH3, - CH2CH2CH2CH2CH2CH2CH2CH2CH3 or 25 -CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3. In some embodiments of the compound C-D, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2 or -C(CH3)3. In some embodiments of the compound C-D, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound C-D, R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound C-D, R20 is -CH3, -CD3, 2026203365   02 May 2026 -CH2F, -CHF2 or -CF3. In some embodiments of the compound C-D, R20 is H. In some embodiments of the compound C-D, R20 is -CH3. In some embodiments of the compound E-F, R20 is -CF3. In some embodiments of the compound C-D, R20 is F. In some embodiments of the compound C-D, each R21 is independently H, D, F, -CH3, -CD3, 5 -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3 or -C(CH3)3. In some embodiments of the compound C-D, each R21 is independently H, D, F, -CH3, -CD3, -CH2F, -CHF2 or -CF3. In some embodiments of the compound C-D, each R21 is independently H, -CH3 or -CF3. In some embodiments of the compound C-D, each R21 is -CH3. In some embodiments of the compound C-D, each R21 is H. In some embodiments of 0 the compound C-D, each R21 is -CF3. In some embodiments of the compound C-D, n is 0, 1, 2, 3, 4, 5, 6, 7 or 8. In some embodiments of the compound C-D, n is 0, 1, 2, 3, 4, 5 or 6. n some embodiments of the compound C-D, n is 0, 1, 2, 3 or 4. In some embodiments of the compound C-D, n is 0. In some embodiments of the compound C-D, n is 1. In some embodiments of the compound C-15 D, n is 2. In some embodiments of the compound C-D, n is 3. In some embodiments of the compound C-D, n is 4. In some embodiments of the compound C-D, n is 5. In some embodiments of the compound C-D, n is 6. In some embodiments of the compound C-D, n is 7. In some embodiments of the compound C-D, n is 8. In some embodiments of the compound C-D, n is 9. In some embodiments of the compound C-D, n is 10. In some 20   embodiments of the compound C-D, n is 11. In some embodiments of the compound C-D, n is 12. In some embodiments of the compound C-D has the formula referred to herein as Compound A-2: OH 25 In some embodiments of the compound C-D has the formula referred to herein as Compound B-2: 2026203365   02 May 2026 OH In some embodiments of the compound C-D has the formula referred to herein as Compound C-2: OH 5 In some embodiments of the compound C-D has the formula referred to herein as Compound D-2: OH In some embodiments of the compound C-D has the formula referred to herein as Compound E-2: OH 10 In some embodiments of the compound C-D has the formula referred to herein as Compound F-2: 2026203365   02 May 2026 OH In some embodiments of the compound C-D has the formula referred to herein as Compound G-2: OH 5 In some embodiments of the compound C-D has the formula referred to herein as Compound H-2: In some embodiments of the compound C-D has the formula referred to herein as Compound 1-2: 0H Compound 1-2 In some embodiments of the compound C-D has the formula referred to herein as Compound J-2: 2026203365   02 May 2026 Compound J-2 In some embodiments of the compound C-D has the formula referred to herein as Compound K-2: Compound K-2 5 In some embodiments of the compound C-D has the formula referred to herein as Compound L-2: 0H Compound L-2 In some embodiments of the compound C-D has the formula referred to herein as Compound N-2: In some embodiments, this application further provides therapeutic compounds comprising a substituted quinone head group to which is covalently linked an aliphatic tail group that comprises at least one chiral center, at least one hydroxyl group and at least one silicon atom. In some embodiments, such compounds can have the formula E-G, or pharmaceutically 15 acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein E is 21 or 22: 2026203365   02 May 2026 and Gis 23 or 24: 22 wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 5 independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 10 of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if W=w is a single bond); each Q is independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered 15 heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each of Rs’, R9’ and Rio’ is independently a C1-C4 alkyl, or taken together Rs’ and R9’ form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; R11 is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R20 is H, D, F or C1-C12 alkyl; p is an integer from 0 to 20, inclusive; and *** 20 indicates the point of attachment of E to G and ** indicates the point of attachment of G to E. In some embodiments, each of Rs’, R9’ and Rio’ is independently methyl or ethyl. In some embodiments, E is 21, J is O, K is -(CH2)-, L is -(CH2)-, each of Ri, R2 and R3 is independently selected from: H, D, F, -CH3, -OCH3 and -OCF3, each Rs’, R9’ and Rio’ is 2026203365   02 May 2026 independently methyl or ethyl and R20 is C1-C4 alkyl. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each Q is -(CH2)-. In some embodiments, at least one Q is O and each 5 other Q is -(CH2)-. In some embodiments, at least one Q is Si and each other Q is -(CH2)-. In some embodiments, only one Q is O. In some embodiments, only one Q is O and the remaining Q’s are -(CH2)-. In some embodiments, E-G is Compound M-0 or M-0’: R2'Tf R3                 R2'1T R3 Compound M-0                  Compound M-0' 10   wherein, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2CH3, -OCH2CH3, or -OCF3, p’ is an integer from 1 to 9, inclusive and p” is an integer from 1 to 9, inclusive. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each of p’ and p” in independently an 15 integer from 1-4, inclusive. In some embodiments, E-G is Compound M or Compound M’: In some embodiments, this application further provides therapeutic compounds comprising a substituted hydroquinone head group to which is covalently linked an aliphatic tail group that 20 comprises at least one chiral center, at least one hydroxyl group and at least one silicon atom. Thus, in some embodiments, this application further provides therapeutic compounds or intermediates of formula C-G, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein C is 11 or 12: 2026203365   02 May 2026 and Gis 23 or 24: 24 wherein, J’ is OH, SH or NH-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 5 independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 10 of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if W=w is a single bond); each Q is independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy, or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered 15 heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each of Rs’, R9’ and Rio’ is independently a C1-C4 alkyl, or taken together Rs’ and R9’ form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; R11 is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R19 is H, C1-C4 alkyl or benzyl (substituted or unsubstituted); R20 is H, D, F or C1-C12 20 alkyl; p is an integer from 0 to 20, inclusive; and *** indicates the point of attachment of C to G and ** indicates the point of attachment of G to C. In some embodiments, each of Rs’, R9’ and Rio’ is independently methyl or ethyl. In some embodiments, C is 11, J’ is OH, K is -(CH2)-, L is -(CH2)-, each of Ri, R2 and R3 is independently selected from: H, D, F, -CH3, -OCH3 and -OCF3, each of Rs’, R9’ and Rio’ is 116 2026203365   02 May 2026 independently methyl or ethyl, R19 is H and R20 is C1-C4 alkyl. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each Q is -(CH2)-. In some embodiments, at least one Q is O and each 5 other Q is -(CH2)-. In some embodiments, at least one Q is Si and each other Q is -(CH2)-. In some embodiments, only one Q is O. In some embodiments, only one Q is O and the remaining Q’s are -(CH2)-. In some embodiments, C-G is a Compound M-3 or Compound M-3’: OH HO                     OH < OH R2 r R3                         R2 C R3 । J. Compound M-3               । Compound M-3' Un                         Un 10 wherein, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2CH3, -OCH2CH3, or OCF3, p’ is an integer from 1 to 9, inclusive and p” is an integer from 1 to 9, inclusive. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each of p’ and p” in independently an 15 integer from 1-4, inclusive. In some embodiments, C-G is Compound M-2 or M-2’: In some embodiments, this application further provides therapeutic compounds or intermediates to therapeutic compounds comprising a precursor to an aromatic quinone or 20 hydroquinone head group to which is linked a precursor to an aliphatic tail group that comprises at least one chiral center, at least one hydroxyl group and at least one silicon atom. In some embodiments, this application pertains to compounds of formula A-H, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein A is 1, 2, 3, or 4: 2026203365   02 May 2026 25 wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 5 independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 10 of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if w=wis a single bond); each Q is independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy, or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered 15 heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each of Rs’, R9’ and Rio’ is independently a C1-C4 alkyl, or taken together Rs’ and R9’ form a 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring; R11 is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R15 is H, C1-C4 alkyl or PG, wherein PG is a phenol protecting group; R20 is H, D, F 20 or C1-C12 alkyl; p is an integer from 0 to 20, inclusive; and *** indicates the point of attachment of A to H and ** indicates the point of attachment of H to A. In some embodiments, each of Rs’, R9’ and Rio’ is independently methyl or ethyl. 2026203365   02 May 2026 In some embodiments, A is 1 or 3, J is O, K is -(CH2)-, L is -(CH2)- and each of Ri, R2 and R3 is independently selected from: H, D, F, -CH3, -OCH3 and -OCF3, each Rs’, R9’ and Rio’ is independently methyl or ethyl, and R15 is H or PG. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some embodiments, each of Ri, R2 and R3 is 5 independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each Q is -(CH2)-. In some embodiments, at least one Q is O and each other Q is -(CH2)-. In some embodiments, at least one Q is Si and each other Q is -(CH2)-. In some embodiments, only one Q is O. In some embodiments, only one Q is O and the remaining Q’s are -(CH2)-. 0 In some embodiments, A-H is Compound M-4 or M-4’: r3                                   r3 Compound M-4                   Compound M-4' wherein, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2CH3, -OCH2CH3, or OCF3, p’ is an integer from 1 to 9, inclusive and p” is an integer from 1 to 9, inclusive. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some 15 embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each of p’ and p” in independently an integer from 1-4, inclusive. In some embodiments, A-H is Compound M-5 or M-5’: R3        Compound M-5              R3        Compound M-5' 20 In some embodiments, this application further provides therapeutic compounds of formula EI, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein E is 21 or 22: 2026203365   02 May 2026 wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 5 independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 10 of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if w=w is a single bond); each Q is independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered 15 heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each Rs”, R9” and Rio” is independently H, F, or C1-C4 alkyl provided however that at least one of Rs”, R9” and Rio” is F; R11 is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R20 is H, D, F or Ci-C12 alkyl; p is an integer from 0 to 20, inclusive; and *** indicates the point of attachment of 20 E to I and ** indicates the point of attachment of I to E. In some embodiments, at least one of Rs”, R9” and Rio” is F. In some embodiments, each of Rs”, R9” and Rio” is independently H or F. In some embodiments, each of Rs”, R9” and Rio” is F. In some embodiments, E is 21, J is O, K is -(CH2)-, L is -(CH2)-, each of Ri, R2 and R3 is independently selected from: H, D, F, -CH3, -OCH3 and -OCF3, each Rs”, R9” and Rio” is 120 2026203365   02 May 2026 independently H or F and R20 is C1-C4 alkyl. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each Q is -(CH2)-. In some embodiments, at least one Q is O and each 5 other Q is -(CH2)-. In some embodiments, at least one Q is Si and each other Q is -(CH2)-. In some embodiments, only one Q is O. In some embodiments, only one Q is O and the remaining Q’s are -(CH2)-. In some embodiments, E-I is Compound N-0 orN-0’: 10   wherein, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2CH3, -OCH2CH3, or -OCF3, Q is -(CH2)-, O or Si, p’ is an integer from 0 to 9, inclusive and p” is an integer from 0 to 9, inclusive. In some embodiments, Q is -(CH2)-. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In 15 some embodiments, each of p’ and p” is independently an integer from 0-4, inclusive. In some embodiments, E-I is Compound N or Compound N’: In some embodiments, this application further provides therapeutic compounds or intermediates of formula C-I, or pharmaceutically acceptable salts, stereoisomers, mixtures of 20 stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein C is 11 or 12: 2026203365   02 May 2026 and I is 26 or 27: 26 wherein, J’ is OH, SH or NH-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 5 independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 10 of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if w=w is a single bond); each Q is independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy, or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered 15 heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each Rs”, R9” and Rio” is independently H, F, or C1-C4 alkyl provided however that at least one of Rs”, R9” and Rio” is F; R11 is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R19 is H, C1-C4 alkyl or benzyl (substituted or unsubstituted); R20 is H, D, F or C1-C12 alkyl; p is an integer from 0 20 to 20, inclusive; and *** indicates the point of attachment of C to I and ** indicates the point of attachment of I to C. In some embodiments, each of Rs”, R9” and Rio” is independently H or F. In some embodiments, at least one of Rs”, R9” and Rio” is F. In some embodiments, each of Rs”, R9” and Rio” is F. 2026203365   02 May 2026 In some embodiments, C is 11, J’ is OH, K is -(CH2)-, L is -(CH2)-, each of Ri, R2 and R3 is independently selected from: H, D, F, -CH3, -OCH3 and -OCF3, each Rs”, R9” and Rio” is independently H or F, R19 is H and R20 is C1-C4 alkyl. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some embodiments, each of Ri, R2 and R3 is 5 independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each Q is -(CH2)-. In some embodiments, at least one Q is O and each other Q is -(CH2)-. In some embodiments, at least one Q is Si and each other Q is -(CH2)-. In some embodiments, only one Q is O. In some embodiments, only one Q is O and the remaining Q’s are -(CH2)-. 0 In some embodiments, C-I is Compound N-3 or N-3’: wherein, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2CH3, -OCH2CH3, or OCF3, Q is -(CH2)-, O or Si, p’ is an integer from 0 to 9, inclusive and p” is an integer from 0 to 9, inclusive. In some embodiments, Q is -(CH2)-. In some embodiments, each of 15 Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each of p’ and p” is independently an integer from 0-4, inclusive. In some embodiments, C-G is Compound N-2 or N-2’: 20 In some embodiments, this application further provides therapeutic compounds or intermediates of formula A-U, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein A is 1, 2, 3, or 4: 2026203365   02 May 2026 and U is 28: wherein, J is O, S orN-Rn; K is absent or -(CR12R13)-; L is -(CR12R13)-; each W is 5 independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a hydrogen atom linked hereto in addition to one of R4, Rs, Re or R7 and in either case each of R4, Rs, Re and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, Ci-Ce alkyl and Ci-Ce alkoxy, and if W is N (nitrogen), each 10 of R4, Rs, Re and R7 attached thereto is independently absent (if w=w is a double bond) or selected from H, D and Ci-Ce alkyl (if W=w is a single bond); each Q is independently a group of formula -(CR12R13)-, O or Si provided that each O and each Si is not directly bonded to O or Si; each of Ri, R2 and R3 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy, or Ri and R2 together form a 5-membered carbocyclic ring, a 5-membered 15 heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6-membered heterocyclic ring; each Rs”, R9” and Rio” is independently H, F, or C1-C4 alkyl provided however that at least one of Rs”, R9” and Rio” is F; R11 is H, D or Ci-Ce alkyl; each of R12 and R13 is independently H, D, F, Cl, Br, I, Ci-Ce alkyl or Ci-Ce alkoxy; R15 is H, C1-C4 alkyl or PG, wherein PG is a phenol protecting group; R20 is H, D, F or C1-C12 alkyl; p is an integer 20 from 0 to 20, inclusive; and *** indicates the point of attachment of A to U and ** indicates the point of attachment of U to A. In some embodiments, each of Rs”, R9” and Rio” is independently H or F. In some embodiments, at least one of Rs”, R9” and Rio” is F. In some embodiments, each of Rs”, R9” and Rio” is F. 2026203365   02 May 2026 In some embodiments, A is 1 or 3, J is O, K is -(CH2)-, L is -(CH2)- and each of Ri, R2 and R3 is independently selected from: H, D, F, -CH3, -OCH3 and -OCF3, each Rs”, R9” and Rio” is independently H or F and R15 is H or PG. In some embodiments, each of Ri, R2 and R3 is independently H, -CH3 or -OCH3. In some embodiments, each of Ri, R2 and R3 is 5 independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each Q is -(CH2)-. In some embodiments, at least one Q is O and each other Q is -(CH2)-. In some embodiments, at least one Q is Si and each other Q is -(CH2)-. In some embodiments, only one Q is O. In some embodiments, only one Q is O and the remaining Q’s are -(CH2)-. 0 In some embodiments, A-H is Compound N-4 or Compound N-4’: Compound N-4                   Compound N-4' wherein, each of Ri, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2CH3, -OCH2CH3, or OCF3, Q is -(CH2)-, O or Si, p’ is an integer from 0 to 9, inclusive and p” is an integer from 0 to 9, inclusive. In some embodiments, Q is -(CH2)-. In some embodiments, each of 15 Ri, R2 and R3 is independently H, -CH3, or -OCH3. In some embodiments, each of Ri, R2 and R3 is independently H, or -CH3. In some embodiments, each of Ri, R2 and R3 is -CH3. In some embodiments, each of p’ and p” is independently an integer from 0-4, inclusive. In some embodiments, A-U is Compound 104 or Compound 104’: 20 VI. Methods For Making Therapeutic Compounds And Related Intermediates In some embodiments, the present application pertains to methods for the production of the novel compositions disclosed herein. Suitable methods are generically illustrated in Figs. 1 A, IB, IC, ID, 2A, 2B, 2C, 2D and 3. Specific examples of the use of the generic methodology for the production of certain of the novel compounds can be found in Examples 1-7, and 9-10 125 2026203365   02 May 2026 below. The generic illustrations found in Figs. 1 A, IB, IC, ID, 2A, 2B, 2C and 2D and the following description is in close alignment with Scheme 2 (below), and the associated description in Example 1. The generic illustrations found in Fig. 3 and following description for producing compound of formula 203 is in close alignment with Scheme 1 (below), and 5 the associated description in Example 1. A general method for reducing therapeutic compounds of general Formula 1-0 to other therapeutic compounds of general Formula I-OR can be found in Fig. 4, and in Examples 9 and 10. With reference to Fig. 1 A, a compound of formula 204 is provided. Representative known compounds of formula 204 can be found in Figs. 6A, 6B and 6C (the Chemical Abstracts 0 Service (CAS) registration number is provided for each known composition that is illustrated). The asterisk shown in the compound of formula 204 (and for all other compounds illustrated in the Figs.) identifies a chiral center. If available, stereochemically pure compounds of formula 204 (i.e., pure enantiomers of 204 or 205 if that is the starting material as mentioned below) can be used in the processes described herein - but that is not a 15 requirement or limitation. Racemic mixtures of 204 (or 205) can be used as the process produces diastereomers at step d, e. (discussed below) that can be separated by chromatographic (or other) techniques, including in the examples discussed herein. In the compounds of formula 204, J, K, L, Ri, R2, R3 and R20 are as defined above. In some embodiments, R30 is H. In some embodiments, the phenol is already protected (either 20 transiently (in which case R30 is a protecting group PG) or with a more permanent group such as a methyl, ethyl, isopropyl or tert-butyl ether (in which case R30 can be a Ci-Ce alkyl group). In those cases, R30 represents the phenolic protecting group. For those cases wherein the phenol is already protected, performing step b. (below) need not be performed to obtain compound of formula 206. 25 The carboxylic acid compounds of formula 204 can be converted to esters of formula 205 under suitable conditions. The conversion of a carboxylic acid to an ester is well-known chemistry. Any suitable method known in the art may be used to effect this conversion of a carboxylic acid to an ester but in particular the methodology discussed in step a. under Scheme 2 in Example 1 is illustrative. As discussed in step a. under Scheme 2 in Example 1, 30 the methyl ester (5) is produced by heating (4) in methanol in the presence of p-toluenesulfonic acid (PTSA) to thereby yield (5). Higher order esters can be prepared by using the appropriate alternative alcohol or by application of other processes well-known in 2026203365   02 May 2026 the art. Alternatively, with reference to Fig. 1 A, an ester compound of formula 205 is provided. As can be seen from Figs. 6A, 6B and 6C, various esters of formula 205 are commercially known and / or available. In the compounds of formula 205, J, K, L, Ri, R2, R3, R20 and R30 are as defined above. The 5 group R31 represents any Ci-Ce alkyl or benzyl group, but typically will be methyl, ethyl or benzyl. If R30 is not H, then the compound of formula 205 is synonymous with the compound of formula 206, discussed below. With reference to Fig. 1 A, it can be seen that compounds of formula 205 (where R30 is H) can be converted to compounds of formula 206 by protection of the exocyclic phenol. Any 0 suitable method known in the art may be used to effect this conversion of a phenol to a protected phenol but in particular the methodology discussed in step b. under Scheme 2 in Example 1 is illustrative. In Example 1 step b., benzyl bromide in DMF (as solvent) in the presence of K2CO3 (as a base) was used at room temperature to alkylate the phenol of (5) and thereby produce the benzyl ether (6). Any benzyl halide could be used to produce a 15 substituted or unsubstituted benzyl protecting group linked to the phenol. Generally, the protection reaction will proceed in a dry, aprotic solvent in the presence of a (inorganic or organic) base. However, any suitable protecting group and any suitable conditions can be used. For example, the phenol could be protected with a triphenylmethyl-based protecting group by use of, for example, triphenylmethyl chloride and similar conditions. Alternatively, 20 the phenol could be protected with a silyl-based protecting group by use of, for example, tertbutyldimethylsilyl chloride and similar conditions. In some embodiments, the phenol can optionally be reacted with a reagent that produces a more permanent modification, such as for example, methyl iodide, ethyl iodide or isopropyl iodide to thereby produce the methyl ether, ethyl ether or isopropyl ether, respectively. 25 In the compounds of formula 206, J, K, L, Ri, R2, R3, R20 and R31 are as defined above. The group R32 represents any phenol protecting group (e.g., a C1-C4 alkyl group, a triphenylmethyl-based protecting group, a silyl protecting group or a benzyl protecting group), but R32 is not hydrogen (H). With reference to Fig. 1 A, it can be seen that compounds of formula 206 can be converted to 30 compounds of formula 207 by conversion of the ester group back to a carboxylic acid (the process being known as saponification of an ester). Saponification of an ester is well-known chemistry. Any suitable method known in the art may be used to effect this conversion of an 127 2026203365   02 May 2026 ester to a carboxylic acid but in particular the methodology discussed in step c. under Scheme 2 in Example 1 is illustrative. Generally this process involves treatment of the ester in a mixture of water or water and water miscible organic solvent (e.g., methanol, ethanol, tetrahydrofuran and / or acetonitrile) with a strong base such as sodium hydroxide, potassium 5 hydroxide or lithium hydroxide for a period necessary to saponify the ester, followed by neutralization with an acid (generally a strong acid such as hydrochloric acid) to generate the carboxylic acid from the carboxylate anion. Depending on the nature of the starting material, the reaction can be carried out at reduced temperature, room temperature or at elevated temperature. In the compounds of formula 207, J, K, L, Ri, R2, R3, R20 and R32 are as defined 0 above. With reference to Fig. 1 A, it can be seen that compounds of formula 207 can be converted to compounds of formula 209 by, for example, conversion of the acid group to a mixed anhydride. Formation of mixed anhydrides is well-known chemistry. Any suitable method known in the art may be used to effect this conversion of the carboxylic acid to a mixed 15   anhydride but in particular the methodology discussed in step d„ under Scheme 2 in Example 1 is illustrative. Generally, this conversion can be effected by treatment of the carboxylic acid (7) an dry, aprotic solvent (e.g., THF) in the presence of a (inorganic or organic) base and an acid chloride (illustrated as a compound of formula 208 (in Fig. 1 A), wherein R33 is any alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, cycloheteroalkyl, 20 heteroalkyl, or heteroaryl group known in the art; and illustrated as 8 in Scheme 2). The reaction can be carried out at reduced temperature (e.g., -30°C). In the compounds of formula 209, J, K, L, Ri, R2, R3, R20 and R32 are as defined above. Generally, R33 is a bulky group such as t-butyl or adamantyl. As mixed anhydrides tend to be unstable (especially prone to hydrolysis in the presence of any water), the mixed anhydride is typically (but not 25 necessarily) used directly in the subsequent reaction without isolation or purification. With reference to Fig. 1 A, it can be seen that compounds of formula 209 can be converted to diastereomers of formula 211a or 211b by reaction with an appropriate chiral oxazolidine-2-one (in Fig. 1 A, the compound of formula 210 is illustrative). Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in 30 step d, e. under Scheme 2 in Example 1 is illustrative. Generally, as provided in Example 1, the mixed anhydride is further reacted with the oxazolidine-2-one in the presence of n-butyl lithium (nBuLi) in an aprotic solvent under anhydrous conditions and at reduced temperature 2026203365   02 May 2026 (e.g. -78°C). In the compounds of formula 211a and 211b, J, K, L, Ri, R2, R3, R20 and R32 are as defined above. While it is possible to proceed to the subsequent steps with the mixture of stereoisomers, use of the chiral compound 210 produces diastereoisomers that can be chromatographically (or otherwise) separated. As therapeutic agents are generally 5 stereochemically pure, the mixture will most often be chromatographically separated to produce an isolated compound of formula 211a and an isolated compound of formula 211b, but that is not a requirement or limitation. The process may proceed with stereochemically pure compounds or stereochemical mixtures. The products of subsequent reactions will thus be stereochemically pure or stereochemical mixtures based on the nature of the starting 0 materials (unless purified in subsequent reactions). If stereochemical mixtures are obtained, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. With reference to Fig. 1 A, it can be seen that compounds of formula 211a and / or 211b can be converted to compounds of formula 212 by conversion of the amide to an alcohol. Any 15   suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step f. under Scheme 2 in Example 1 is illustrative. Generally, as seen in Example 1, a stereochemically pure 11b can be treated with lithium aluminum hydride (LiH) in an aprotic solvent under anhydrous conditions and at reduced temperature to produce the alcohol (12). In the compounds of formula 212, J, K, L, Ri, R2, R3, R20 and R32 20 are as defined above. Compounds of formula 212 can be stereochemically pure or stereochemical mixtures. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. With reference to Fig. 1 A, it can be seen that compounds of formula 212 can be converted to 25 compounds of formula 213 by reaction of the alcohol group with trifluoromethane sulfonic anhydride (or other group (e.g., tosyl) that renders the alcohol derivative subject to nucleophilic attach). Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step g. under Scheme 2 in Example 1 is illustrative. Generally, as seen in Example 1, (12) can be converted to (13) by 30 treatment with trifluoromethanesulfonic anhydride and pyridine in DCM at reduced temperature (e.g., 0°C). In the compounds of formula 213, J, K, L, Ri, R2, R3, R20 and R32 are as defined above and “OTf” refers to the trifluoromethanesulfonyl protected hydroxyl group. 2026203365   02 May 2026 Compounds of formula 213 can be stereochemically pure or stereochemical mixtures. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. 5 With reference to Fig. 1 A, it can be seen that compounds of formula 213 can be converted to compounds of formula 214 by reaction with a compound of formula 203. Compounds of formula 203 can be purchased from available sources or otherwise produced as described below with reference to Fig. 3, and Scheme 1 and the associated discussion in Example 1. Any suitable method known in the art may be used to effect this conversion but in particular 0 the methodology discussed in step h. under Scheme 2 in Example 1 is illustrative. Generally as seen in Example 1, the reaction is performed by dissolving or suspending (3) and hexamethylphosphoramide in an aprotic solvent (e.g. THF) at reduced temperature (e.g, -78°C) and then adding "BuLi dropwise followed by the trifluoromethane sulfonate (13). In the compounds of formula 214, J, K, L, Ri, R2, R3, R20 and R32 are as defined above. In the 15 compounds of formula 214, the group B’ has the formula: R21                Rg SO2Ph wherein, X, Y, Rs, R9, R21 are as defined above, n’ is 0-11, inclusive, and # indicates the point of attachment. Each bond represented as = is either a single bond or a double bond. If = is a double bond, then each Z’ is Z as defined above and Rio’ is absent. If = is a 20 single bond, then each Z’ is X as defined above and Rio’ is Rio as defined above. The abbreviation Ph refers to a phenyl group (full structure of 203 is illustrated in Fig. 3). Compounds of formula 214 can be stereochemically pure or stereochemical mixtures. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure 25 product is desired. With reference to Fig. 1 A, it can be seen that compounds of formula 214 can be converted to compounds of formula 215. Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step i. under Scheme 2 in Example 1 is illustrative. Generally, as seen in Example 1, (14) is treated, in the presence of a 2026203365   02 May 2026 palladium catalyst (e.g., bis[(diphenylphosphino)ferrocene]palladium(II) chloride, with lithium triethylborohydride to thereby yield (15). The reaction can be performed in an aprotic solvent (e.g. THF) at reduced temperature (e.g., 0°C). In the compounds of formula 215, each bond represented as =, n, J, K, L, X, Y, Z’, Ri, R2, R3, Rs, R9, Rio’, R20, R21 and 5   R32 are as defined above. Compounds of formula 215 can be stereochemically pure or contain stereochemical mixtures. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. With reference to Fig. 1 A, it can be seen that compounds of formula 215 can be converted to 0 compounds of formula 216 by removal of the group R32 to thereby regenerate the unprotected phenol (-OH). The exact conditions used to remove R32 will depend on the nature of R32. If R32 is alkyl, generally it is not removed and hence, the compound of formula 215 is not converted to a compound of formula 216. If R32 is a silyl-based protecting group, it generally can be removed by treatment in the presence of fluoride ion, such as by treatment with tetra-15 n-butyl ammonium fluoride (TBAF). If R32 is a triphenylmethyl-based protecting group, it generally can be removed by treatment with an acid, such as dichloroacetic acid, trichloroacetic acid or trifluoroacetic acid (neat or diluted in a compatible organic solvent such as DCM). Other phenol protecting groups, methods for their production (i.e. protection of a phenol) and deprotection (regeneration of the phenol from the protected phenol) are well-20 known to those of ordinary skill in the art. In the compounds illustrated in Example 1, the group R32 is benzyl. Any suitable method known in the art may be used to effect removal of the benzyl group but in particular the methodology discussed in step i. under Scheme 2 in Example 1 is illustrative. Generally, (15) is treated with a suspension of lithium (metal) in n-propylamine in an aprotic solvent 25 such as diethyl ether to give (16). The reaction can be quenched by the addition of sat. aq. ammonium chloride and alcohol (e.g., methanol). In the compounds of formula 216, each bond represented as =, n, J, K, L, X, Y, Z’, Ri, R2, R3, Rs, R9, Rio’, R20 and R21 are as defined above. Compounds of formula 216 can be stereochemically pure or stereochemical mixtures. If stereochemical mixtures, the compounds can optionally be purified by 30 appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In some embodiments, in compounds of formula 216, Rs and R9 are H and Rio’ is absent. 2026203365   02 May 2026 Preparation of compounds of this structure will typically result from the availability of suitable alcohols of formula 201 as illustrated in Fig. 3 and discussed in more detail below with respect to the production of compounds of formula 203 (as discussed above in the production of compounds of formula 214). Species of compounds of formula 216, where Rs 5 and R9 are H and Rio’ is absent are illustrated in Fig. IB and identified as compounds of formula 216a. Because the availability of compounds of formula 201 may be limited, the process described in Fig. IB illustrates an alternative approach to the production of compounds having desired groups Rs an R9 (that are not H) from starting material where Rs and R9 are H. 0 With reference to Fig. IB, a compound of formula 216a is provided. Compounds of this formula can be prepared as described above, and as illustrated in Fig. 1 A. The asterisk shown in the compound of formula 216a (and for all other compounds illustrated in Fig IB) identifies a chiral center. If available, stereochemically pure compounds of formula 216a (i.e., pure enantiomers of 216a) can be used in the processes described herein - but that is not 15 a requirement or limitation. Racemic mixtures of 216a can be used but generally the products will also be a mixture of stereochemically impure compounds. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the compounds of formula 216a, each bond represented as =, n, J, K, L, X, Y, 20 Z, Z’, Ri, R2, R3, R20 and R21 are as defined above. With reference to Fig. IB, it can be seen that compounds of formula 216a can be converted to compounds of formula 217a by protection of the exocyclic phenol. Any suitable method known in the art may be used to effect this conversion of a phenol to a protected phenol but in particular the methodology discussed in step k. under Scheme 2 in Example 1 is 25 illustrative. In Example 1 step k„ tert-butyldimethylsilyl chloride in DMF (as solvent) in the presence of imidazole (as a base) was used to protect the phenol of (16) and thereby produce the tert-butyldimethylsilyl protected product (17). Generally, the protection reaction will proceed in a dry, aprotic (e.g. DMF) solvent in the presence of a (inorganic or organic) base. However, any suitable protecting group and any suitable conditions can be used. For 30 example, the phenol could be protected with a (substituted or unsubstituted) benzyl protecting group by use of, for example, (substituted or unsubstituted) benzyl chloride and similar conditions (such as described above for producing compound 206). Alternatively, the phenol 2026203365   02 May 2026 could be protected with a triphenylmethyl-based protecting group by use of, for example, triphenylmethyl chloride and similar conditions. In some embodiments, the phenol can optionally (but not preferably) be reacted with a reagent that produces a more permanent modification, such as methyl iodide, ethyl iodide or isopropyl iodide to thereby produce the 5 methyl ether, ethyl ether or isopropyl ether, respectively. If available, stereochemically pure compounds of formula 216a (i.e., pure enantiomers of 216a) can be used in the processes described herein - but that is not a requirement or limitation). Racemic mixtures of 216a can be used but generally the products (i.e., 217a) will also be a mixture of stereochemically impure compounds. If stereochemical mixtures, the 0 compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the compounds of formula 217a, each bond represented as =, n, J, K, L, X, Y, Z, Z’, Ri, R2, R3, R20 and R21 are as defined above. In the compounds of formula 217a, the group R34 represents any phenol protecting group (e.g., a C1-C4 alkyl group, a triphenylmethyl-based 15 protecting group, a silyl protecting group or a benzyl protecting group), but R34 is not hydrogen (H)). For example, R34 can be a silyl-based protecting group such as tertbutyldimethylsilyl. With reference to Fig. IB, it can be seen that compounds of formula 217a can be converted to compounds of formula 218a. Any suitable method known in the art may be used to effect 20 this conversion but in particular the methodology discussed in step 1. under Scheme 2 in Example 1 is illustrative. Generally as seen in Example 1, compound (17) can be treated with N-bromosuccinimide in a mixture of organic solvent (e.g., THF) and water at reduced temperature (e.g, 0°C) to yield (18). However, any suitable conditions can be used. If available, stereochemically pure compounds of formula 217a (i.e., pure enantiomers of 217a) 25 can be used in the processes described herein - but that is not a requirement or limitation. Racemic mixtures of 217a can be used but generally the products (218a) will also be a mixture of stereochemically impure compounds. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the 30 compounds of formula 218a, each bond represented as =, n, J, K, L, X, Y, Z, Z’, Ri, R2, R3, R20, R21 and R34 are as defined above. With reference to Fig. IB, it can be seen that compounds of formula 218a can be converted to 2026203365   02 May 2026 epoxide compounds of formula 219a by treatment with a base. Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step m. under Scheme 2 in Example 1 is illustrative. Generally as seen in Example 1, compound (18) can be reacted in an alcohol such as methanol or ethanol (or an aqueous 5 mixture of alcohol) in the presence of an inorganic base such as sodium carbonate, potassium carbonate or cesium carbonate at reduced temperature (e.g., 0°C) to give the epoxide (19). However, any suitable conditions can be used. If available, stereochemically pure compounds of formula 218a (i.e., pure enantiomers of 218a) can be used in the processes described herein - but that is not a requirement or limitation. Racemic mixtures of 218a can 0 be used but generally the products (219a) will also be a mixture of stereochemically impure compounds. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the compounds of formula 219a, each bond represented as =, n, J, K, L, X, Y, Z, Z’, Ri, R2, R3, R20, R21 and R34 are as defined above. 15 With reference to Fig. IB, it can be seen that compounds of formula 219a can be converted to an aldehyde of formula 220a by treatment an oxidizing agent such as sodium periodate. Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step n. under Scheme 2 in Example 1 is illustrative. Generally and shown in Example 1, the epoxide (19) is treated in water or a mixture of water and organic 20 solvent at reduced temperature (e.g., 0°C) with sodium periodate and periodic acid to give (20). However, any suitable conditions can be used. If available, stereochemically pure compounds of formula 219a (i.e., pure enantiomers of 219a) can be used in the processes described herein - but that is not a requirement or limitation. Racemic mixtures of 219a can be used but generally the products (220a) will also be a mixture of stereochemically impure 25 compounds. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the compounds of formula 220a, each bond represented as =, n, J, K, L, X, Y, Z, Z’, Ri, R2, R3, R20, R21 and R34 are as defined above. With reference to Fig. IB, it can be seen that aldehydes of formula 220a can be converted to 30 an alcohol of formula 221a by treatment with a reducing agent such as sodium borohydride. Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step 0. under Scheme 2 in Example 1 is illustrative. Generally 2026203365   02 May 2026 as shown in Example 1, the aldehyde (20) is treated with sodium borohydride in alcohol (e.g. ethanol) or a mixture of water and alcohol at reduced temperature (e.g., 0°C) to give the alcohol (21). However, any suitable conditions can be used. If available, stereochemically pure compounds of formula 220a (i.e., pure enantiomers of 220a) can be used in the 5 processes described herein - but that is not a requirement or limitation. Racemic mixtures of 220a can be used but generally the products (221a) will also be a mixture of stereochemically impure compounds. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the compounds of formula 221a, each bond 0 represented as =, n, J, K, L, X, Y, Z’, Ri, R2, R3, R20, R21 and R34 are as defined above. With reference to Fig. IB, it can be seen that alcohols of formula 221a can be converted to an iodide of formula 222a by treatment with imidazole and iodine. Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step p. under Scheme 2 in Example 1 is illustrative. Generally as illustrated in Example 1 the 15 alcohol (21), can be treated with triphenylphosphine, imidazole and iodine in an aprotic solvent (e.g., DCM) at room temperature to give the iodide (22). However, any suitable conditions can be used. If available, stereochemically pure compounds of formula 221a (i.e., pure enantiomers of 221a) can be used in the processes described herein - but that is not a requirement or limitation. Racemic mixtures of 221a can be used but generally the products 20   (222a) will also be a mixture of stereochemically impure compounds. If stereochemical mixtures, the compounds can optionally be purified by appropriate means (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the compounds of formula 222a, each bond represented as =, n, J, K, L, X, Y, Z’, Ri, R2, R3, R20, R21 and R34 are as defined above. 25 With reference to Fig. IB, it can be seen that iodides of formula 222a can be converted to a triphenylphosphonium iodide salt of formula 223a by treatment with a large excess of triphenylphosphine. Any suitable method known in the art may be used to effect this conversion but in particular the methodology discussed in step q. under Scheme 2 in Example 1 is illustrative. Generally as illustrated in Example 1, the iodide (22) can be treated 30 with a large excess of triphenylphosphine in an aprotic solvent (e.g., ACN) at elevated temperature (e.g., 85°C) to give the triphenylphosphonium iodide salt (23). However, any suitable conditions can be used. If available, stereochemically pure compounds of formula 2026203365   02 May 2026 222a (i.e., pure enantiomers of 222a) can be used in the processes described herein - but that is not a requirement or limitation. Racemic mixtures of 222a can be used but generally the products (223a) will also be a mixture of stereochemically impure compounds. If stereochemical mixtures, the compounds can optionally be purified by appropriate means 5   (e.g., chromatography or chiral chromatography, as appropriate) if stereochemically pure product is desired. In the compounds of formula 223a, each bond represented as =, n, J, K, L, X, Y, Z’, Ri, R2, R3, R20, R21 and R34 are as defined above. With reference to Fig. IB, it can be seen that triphenylphosphonium iodide salts of formula 223a can be converted to a compounds of formula 225a by treatment with 0 hexamethyldisilazide followed by addition of a compound of formula 224. In the compounds of formula 224, Rs’ embodies any definition of Rs set forth above and R9’ embodies any definition of R9 set forth above, provided however that both of Rs and R9 cannot be H (because that would regenerate compound 216a; the starting material of the process illustrated in Fig. IB). Any suitable method known in the art may be used to effect this 15 conversion but in particular the methodology discussed in (i) step r. under Scheme 2 in Example 1 is illustrative, or (ii) step a. under Scheme 3 in Example 2 is illustrative. Generally as illustrated in Example 1, step r„ the triphenylphosphonium iodide salt (23) is treated with hexamethyldisilazide and the ketone (24) an aprotic solvent (e.g., THF) at reduced (e.g., -78°C) temperature to give the compound (25). However, any suitable 20 conditions can be used. If available, stereochemically pure compounds ...

Claims

1. A compound of formula C-D, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, wherein C is 11 or 12:and D is 13, 14, 15, 16, 17, 18, 19 or 20:LH^R**^ k rxxL HO** / "k'R21 AX^Z 13R21R8R9** / X nR21R814L HO** / ^k'L HO** / '''k'x")X''Y^z'' R915 n**-"xR2116R21X^X n 17R8R10R9R21X n18R21x / Y^x n19R8 R10R9R21R'4 >OH / L^ JXE / Y\**^ K I X XX^X n20R9, Y-XnR8R10R9wherein,J’ is OH, SH or NH-R11;K is absent or -(CR12R13)-;L is -(CR12R13)-;each W is independently C (carbon) or N (nitrogen) and wherein for each use of w = w, the bond between each W can be a single bond or double bond and further provided that if a single bond, each C (carbon) atom will have a2026203365   02 May 2026hydrogen atom linked hereto in addition to one of R4, R5, R6 or R7 and in either case each of R4, R5, R6 and R7 attached thereto is independently selected from H, D, F, Cl, Br, I, C1-C6 alkyl and C1-C6 alkoxy, and if W is N (nitrogen), each of R4, R5, R6 and R7 attached thereto is independently absent (if w = wis a double bond) or selected from H, D and C1-C6 alkyl (if W-Wis a single bond);each X is independently a group of formula -(CR12R13)-;each Y is independently absent or a group of formula -(CR12R13)-;each Z is independently a group of formula -(CR14)-;each of R1, R2 and R3 is independently H, D, F, Cl, Br, I, C1-C6 alkyl or C1-C6 alkoxy; or R1 and R2 together form a 5-membered carbocyclic ring, a 5-membered heterocyclic ring, a 5-membered aromatic or heteroaromatic ring, or a 6membered heterocyclic ring;each R8 and R9 is each independently H, D, F, Cl, Br, I, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, -CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, - CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3 or -CF(CF2CF3)2;R10 is H, D, F, Cl, Br, I, C1-C6 alkyl or C1-C6 alkoxy;R11 is H, D or C1-C6 alkyl;each of R12, R13 and R14 is independently H, D, F, Cl, Br, I, C1-C6 alkyl or C1-C6 alkoxy;R20 is H, D, F or C1-C12 alkyl;each R21 is independently H, D, F, Cl, Br, I, or C1-C4 alkyl;n is an integer from 0 to 12; and*** indicates the point of attachment of E to F and ** indicates the point of attachment of F to E;and further provided that at least one group of formula R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R20 or R21 comprises at least one fluorine atom.

2. The compound of claim 1, wherein C is 11 and D is 13, 14, 19 or 20; or C is 12 and D is 13, 14, 19 or 20, or C is 11 and D is 15, 16, 17 or 18; or C is 12 and D is 15, 16, 17 or 18.2026203365   02 May 20263. The compound of claims 1 or 2, wherein J’ is OH or SH or wherein J’ is OH or NH-R11 and K is absent.

4. The compound of any one of claims 1-3, wherein each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2), -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-; or each of K and L is independently -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-; or each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-.

5. The compound of claim 3, wherein J’ is OH or NH-R11 and K is absent and wherein L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-,-(CH(CH3))-, -(CD(CD3))-, -(CF(CH3))-, -(CH(CF3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCH3))-, -(CH(OCF3))-, -(CF(OCF3))-, -(C(OCH3)2)-, -(C(OCD3)2)-, -(C(OCF3)2)-, -(C(CH3)(CF3))-, -(C(CD3)(CF3))-, -(CH(CH2CH3))-, -(CD(CD2CD3))-, -(CF(CH2CH3))-, -(CH(CH2CF3))-, -(CH(CF2CF3))-, -(CF(CF2CF3))-, -(C(CH2CH3)2)-, -(C(CD2CD3)2)- or -(C(CF2CF3)2)-; or L is -(CH2)-, -(CD2)-, -(CF2)-, -(CH(CH3))-, -(CD(CD3))-, -(CF(CF3))-, -(C(CH3)2)-, -(C(CD3)2)-, -(C(CF3)2)-, -(CH(OCH3))-, -(CD(OCD3))-, -(CF(OCF3))- or -(C(OCH3)2)-; or L is -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-.

6. The compound of any one of claims 1-5, wherein C is 11 and each of R1, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2CH3, -OCF(CH3)2,2026203365   02 May 2026-OCH2CF3, -OCH(CF3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CH2CH3, -CF(CH2CH3)2, -CH2CF2CF3, -CH(CF2CF3)2, -CF2CF2CF3, -CF(CF2CF3)2, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CH2CH3, -OCF(CH2CH3)2, -OCH2CF2CF3, -OCH(CF2CF3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2; or each of R1, R2 and R3 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2; or each of R1, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, -OCH2CH3 or -CH(CH3)2.

7. The compound of any one of claims 1-6, wherein J’ is OH; each of K and L is independently -(CH2)-, -(CD2)-, -(CHF)-, -(CF2)-, -(CH(CH3))-, -(CF(CF3))-, -(C(CH3)2)- or -(C(CF3)2)-; and each of R1, R2 and R3 is independently H, F, -CH3, -OCH3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CF3)3, -CH2CH3, - OCH2CH3 or -CH(CH3)2; or wherein R3 is H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, - OCH2CH3, or -CH(CH3)2 and R1 and R2 taken together form a 5-, or 6-membered carbocyclic or heterocyclic ring.

8. The compound of claim 7, wherein C is 11A, 11B, 11C, 11D, 11E or 11F:2026203365   02 May 2026wherein each of R16 and R17 is independently H, D, Cl, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -CHF2, -CF3, -OCF3, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -CH2CH3, -OCH2CH3, -CH(CH3)2, -OCH(CH3)2, -C(CH3)3 or -O(CH3)3; and J” is OH, SH or NH-R18, wherein R18 is H, D, -CH3, -CH2F, -CHF2 or -CF3.

9. The compound of any one of claims 1-8, wherein R10 is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CD2CD3, -CD(CD3)2, -CF2CH3, CF(CH3)2, -CH2CF3, -CH(CF3)2, -CF2CF3, -CF(CF3)2, -C(CH3)3, -C(CD3)3, -C(CF3)3, -OCH2CH3, -OCH(CH3)2, -OCD2CD3, -OCD(CD3)2, -OCF2(CF3), -OCF(CF3)2, -OC(CH3)3, -OC(CD3)3, -OC(CF3)3, -C(CH3)2(CF3), -C(CH3)(CF3)2, -OC(CH3)2(CF3), -OC(CH3)(CF3)2, -CH2CH2CH3, -CH(CH2CH3)2, -CD2CD2CD3, -CD(CD2CD3)2, -CF2CF2CF3, -CF(CF2CF3)2, -C(CH2CH3)3, -C(CD2CD3)3, -C(CF2CF3)3, -OCH2CH2CH3, -OCH(CH2CH3)2, -OCD2CD2CD3, -OCD(CD2CD3)2, -OCF2CF2CF3 or -OCF(CF2CF3)2; or wherein R10 is H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3, -CH2CH3 or -CH(CH3)2.

10. The compound of any one of claims 1-9, wherein R11 is H, methyl or ethyl.

11. The compound of any one of claims 1-10, wherein each of R12, R13 or R14 is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2,-OCHF2, -CF3, -OCF3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH(CH2CH3)2, -C(CH3)3, -OCH2CH3, -OCH(CH3)2, -OCH2CH2CH3, -OCH(CH2CH3)2 or -OC(CH3)3; or wherein each of R12, R13 or R14 is independently H, D, F, -CH3, -OCH3, -CD3, -OCD3, -CH2F, -OCH2F, -CHF2, -OCHF2, -CF3, -OCF3,-CH2CH3 or -OCH2CH3.

12. The compound of any one of claims 1-11, wherein R20 is H, D, F, -CH3, -CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -CH2CH2CH2CH3, -CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH3, -CH2CH2CH2CH2CH2CH2CH2CH3,2026203365   02 May 2026-CH2CH2CH2CH2CH2CH2CH2CH2CH3 or-CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3.

13. The compound of any one of claims 1-12, wherein each R21 is independently H, D, F, -CH3,-CD3, -CH2F, -CHF2, -CF3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2,-CH2CH2CH2CH3 or -C(CH3)3.

14. The compound of any one of claims 1-14, wherein n is 0, 1, 2, 3 or 4.

15. The compound of claim 1, wherein the compound isOHor a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, atautomer, a hydrate, and / or a solvate thereof; or wherein the compound isOHor a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof; or wherein the compound isOHor a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof; or wherein the compound is2026203365   02 May 2026or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof; or wherein the compound isor a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof; or wherein the compound isor a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof; or wherein the compound isor a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof; or wherein the compound isor a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof; or wherein the compound is2026203365   02 May 2026or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, a tautomer, a hydrate, and / or a solvate thereof.

16. A compound of any one of claims 1-15, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, when used in treating or preventing Friedreich’s ataxia in a subject in need thereof, wherein the compound is effective to increase or maintain frataxin levels in a subject suspected of having Friedreich’s ataxia; or wherein the compound is effective to inhibit the reduction in frataxin levels in a subject suspected of having Friedreich’s ataxia or wherein the compound is effective to treat one or more symptoms of Friedreich’s ataxia selected from the group consisting of: muscle weakness, loss of coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders.

17. A compound of any one of claims 1-15, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, when used in increasing the levels of frataxin expression in a subject in need thereof.

18. A compound of any one of claims 1-15, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, when used in treating Complex I deficiency in a subject in need thereof, wherein the compound is optionally effective to increase intracellular adenosine triphosphate (ATP) levels in tissue in a subject diagnosed as having Friedreich’s ataxia.

19. A compound of any one of claims 1-15, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, when used in reducing or inhibiting lipoxygenase-15 activity in a mammalian subject having or suspected of having Friedreich’s ataxia.2026203365   02 May 202620. A compound of any one of claims 1-15, or pharmaceutically acceptable salts, stereoisomers, mixtures of stereoisomers, tautomers, hydrates, and / or solvates thereof, when used in reducing or inhibiting ferroptosis in a mammalian subject having or suspected of having Friedreich’s ataxia.

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