US 2026/0021068 A1 · METHODS AND COMPOSITIONS FOR INHIBITION OF TYROSINE AND PHENYLALANINE-MEDIATED DNA DAMAGE AND REPAIR

Abstract

Disclosed are compounds, compositions, and methods for inhibiting tyrosine-mediated DNA repair in a neuroprotective manner and/or activating transcription and/or protein synthesis. Compositions include a resveratrol, such as cis-resveratrol, or a compound of Formula I or Formula II. Compounds of Formula I and Formula II have the following structures where the variables, e.g., Y1, Y2, Y3, R1, R2, R3 the A-ring, and W are defined herein. Said compound and compositions may be utilized in treating aging and age-associated neurocognitive and metabolic disorders including various types of cancer. In particular, compositions disclosed herein are neuroprotective against tyrosine/phenylalanine or their metabolites-mediated neurodegeneration and neurocognitive disorders. The disclosure also includes combination pharmaceutical compositions and methods of treatment in which cis-resveratrol, a compound of Formula I, a compound of Formula II, or a pharmaceutically acceptable salt thereof is used in combination with a GLP-1 receptor agonist for treating a traumatic brain injury or a neurodegenerative disorder.

Claims32

Dependent claims

A compound of Formula II:

or a pharmaceutically acceptable salt thereof, wherein:
the bond is a double or single bond;
the A ring
is phenyl, C3-C6cycloalkyl, or a 4- to 6-membered heterocyclic group;
W is
R1 is absent or is 1 to 5 substituents independently selected from halogen, hydroxyl, amino, cyano, C1-C4alkyl, C1-C4alkoxy, (C3-C6cycloalkyl)C0-C2alkyl, C1-C2haloalkyl, and C1-C2haloalkoxy;
R2 is absent or is 1 to 5 substituents independently selected from halogen, hydroxyl, amino, cyano, C1-C4alkyl, C1-C4alkoxy, (C3-C6cycloalkyl)C0-C2alkyl, C1-C2haloalkyl, and C1-C2haloalkoxy;
R3 is absent or is 1 to 4 substituents independently selected from halogen, C1-C2alkyl, C1-C2alkoxy, cyclopropyl, C1-C2haloalkyl, and C1-C2haloalkoxy;
Y is NH or O;
Z is H, hydroxyl, methyl, proline where the proline pyrrolidine ring is formed by Z and the nearest NH being joined by a —CH2CH2CH2— chain, or Z is a group —CH2X;
X is an amino acid side chain selected from H, —CH3, —CH2SH, —CH2CO2H, 2OH, —CH(CH3)OH, —CH2CH2CO2H, —CH2CH2CONH2,
where a dash (—) indicates the point of attachment in Formula II.

9 more elements

Dependencies are inferred from the claim text.

Methods and compositions for inhibition of tyrosine and phenylalanine-mediated dna damage and repair

Life of this patent

Methods and compositions for inhibition of tyrosine and phenylalanine-mediated dna damage and repair

Life of this patent

Abstract

Claims32