C07C50/02

Side-chain variants of redox-active therapeutics for treatment of mitochondrial diseases and other conditions and modulation of energy biomarkers

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), or Kearns-Sayre Syndrome (KSS) are disclosed, as well as compounds useful in the methods of the invention. Methods and compounds useful in treating other disorders are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

Side-chain variants of redox-active therapeutics for treatment of mitochondrial diseases and other conditions and modulation of energy biomarkers

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), or Kearns-Sayre Syndrome (KSS) are disclosed, as well as compounds useful in the methods of the invention. Methods and compounds useful in treating other disorders are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

Quinone compounds for inhibiting monomer polymerization

The polymerization of monomers may be at least partially reduced or inhibited by introducing an effective amount of an additive. The additive may be or include a first compound: ##STR00001## where: R1 and R2 may be or include an alkyl group, an aryl group, an alkyl group having a heteroatom, an aryl group having a heteroatom, and combinations thereof. The hetero atom may be or include sulfur, nitrogen and/or oxygen. R1 may be the same or different from R2. The polymerizable monomers may be or include, but are not limited to styrene, butadiene, isoprene, acrylic acid, acrylonitrile, vinyl acetate, and combinations thereof.

Method for producing an arene with an aromatic C—N bond ortho to an aromatic C—O bond

A method for producing an arene with an aromatic CN bond ortho to an aromatic CO bond from a hydroxy arene comprising said aromatic CO bond is provided. This method comprising the steps a) ortho-oxygenating the hydroxy arene to produce an ortho-quinone, b) condensating the ortho-quinone with a nitrogen nucleophile to generate a compound of Formula (IVa) or (IVb), and c) allowing 1,5-hydrogen atom shift of the compound of Formula (IVa) or (IVb), thereby producing arenes with a CN bond ortho to a CO bond of Formula (Va) and (Vb), respectively: ##STR00001##

Method for producing an arene with an aromatic C—N bond ortho to an aromatic C—O bond

A method for producing an arene with an aromatic CN bond ortho to an aromatic CO bond from a hydroxy arene comprising said aromatic CO bond is provided. This method comprising the steps a) ortho-oxygenating the hydroxy arene to produce an ortho-quinone, b) condensating the ortho-quinone with a nitrogen nucleophile to generate a compound of Formula (IVa) or (IVb), and c) allowing 1,5-hydrogen atom shift of the compound of Formula (IVa) or (IVb), thereby producing arenes with a CN bond ortho to a CO bond of Formula (Va) and (Vb), respectively: ##STR00001##

Efficient scalable syntheses of abscisic acid, 8′-acetylene abscisic acid and 8′-cyclopropyl abscisic acid

Methods are provided for synthesis of abscisic acid and 8 analogues thereof (including an enantiopure 8-acetylene analogue) including methods wherein the previously reported first step of oxidation of 2,6-dimethylphenol (VI) to 2,6-dimethylbenzoquinone, mono ketal (VII) is replaced by a novel two step process comprising (i) oxidation of 2,6-dimethylphenol (VI) using potassium peroxymonosulfate with a catalytic amount of iodobenzene to produce 2,6-dimethylbenzoquinone (XVI) and (ii) ketalization of 2,6-dimethylbenzoquinone (XVI) using ethylene glycol, trimethylorthoformate with a catalytic amount of p-toluenesulfonic acid to produce 2,6-dimethylbenzoquinone, mono ketal (VII).

Efficient scalable syntheses of abscisic acid, 8′-acetylene abscisic acid and 8′-cyclopropyl abscisic acid

Methods are provided for synthesis of abscisic acid and 8 analogues thereof (including an enantiopure 8-acetylene analogue) including methods wherein the previously reported first step of oxidation of 2,6-dimethylphenol (VI) to 2,6-dimethylbenzoquinone, mono ketal (VII) is replaced by a novel two step process comprising (i) oxidation of 2,6-dimethylphenol (VI) using potassium peroxymonosulfate with a catalytic amount of iodobenzene to produce 2,6-dimethylbenzoquinone (XVI) and (ii) ketalization of 2,6-dimethylbenzoquinone (XVI) using ethylene glycol, trimethylorthoformate with a catalytic amount of p-toluenesulfonic acid to produce 2,6-dimethylbenzoquinone, mono ketal (VII).

TREATMENT OF PERVASIVE DEVELOPMENTAL DISORDERS WITH REDOX-ACTIVE THERAPEUTICS
20170157065 · 2017-06-08 ·

Methods of treating or suppressing pervasive developmental disorders (PDDs) including; autistic disorder, Asperger's syndrome, childhood disintegrative disorder (CDD), Rett's disorder, and PDD-not otherwise specified (PDD-NOS) or attention deficit/hyperactivity disorder (ADHD) comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds as disclosed herein.

Tocopherol and tocopheryl quinone derivatives as correctors of Lysosomal Storage Disorders

The subject invention relates to improved tocopheryl quinone derivatives and tocopherol derivatives having improved pharmacokinetics in vivo that can, in some embodiments, be useful in the treatment of Lysosomal Storage Disorders, restoration of normal mitochondrial ATP production, modulation of intracellular calcium ion concentration and other treatments or therapies. The tocopheryl quinone derivatives and tocopherol derivatives have side chains that have terminally halogenated carbon atoms.

Tocopherol and tocopheryl quinone derivatives as correctors of Lysosomal Storage Disorders

The subject invention relates to improved tocopheryl quinone derivatives and tocopherol derivatives having improved pharmacokinetics in vivo that can, in some embodiments, be useful in the treatment of Lysosomal Storage Disorders, restoration of normal mitochondrial ATP production, modulation of intracellular calcium ion concentration and other treatments or therapies. The tocopheryl quinone derivatives and tocopherol derivatives have side chains that have terminally halogenated carbon atoms.