Therapeutic compounds
Inventors
Hecht, Sidney • KHDOUR, Omar • Chowdhury, Sandipan Roy • VISAVADIYA, Nishant P
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Assignees
Arizona State University ASU • Arizona State University Downtown Phoenix campus
Member
Arizona State UniversityArizona State University (ASU) is a comprehensive public research university known for its commitment to inclusivity, excellence, and societal impact. ASU is dedicated to advancing research-based solutions for global challenges, fostering strong leadership, and providing quality education accessible to all learners. The university is recognized for its innovative approach to education and its efforts in sustainability, research, and community service. ASU exemplifies a new prototype for the American public research university, focusing on excellence, broad access to quality education, and meaningful societal impact.
Arizona State University (ASU) is a comprehensive public research university known for its commitment to inclusivity, excellence, and societal impact. ASU is dedicated to advancing research-based solutions for global challenges, fostering strong leadership, and providing quality education accessible to all learners. The university is recognized for its innovative approach to education and its efforts in sustainability, research, and community service. ASU exemplifies a new prototype for the American public research university, focusing on excellence, broad access to quality education, and meaningful societal impact.
Publication Number
US-10745366-B2
Publication Date
2020-08-18
Expiration Date
2037-08-24
Abstract
The invention provides compounds having the general formula I: and pharmaceutically acceptable salts thereof, wherein the variables R1, R2, R3, R4, subscipt m and n, have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
Core Innovation
The invention provides new antioxidant compounds of formula I and pharmaceutically acceptable salts thereof, where the structure incorporates specific alkyl, alkenyl, alkynyl, and heterocyclic substituents as described. These compounds are characterized by their potential to reduce cytotoxicity and side effects compared to related molecules, such as methylene blue and methylene violet, and are formulated for pharmaceutical compositions and therapeutic applications.
A central problem addressed is the limitation of existing antioxidants like methylene blue, which suffer from poor bioavailability, reduced cellular uptake due to hydrophilicity, and intolerability at high dosages. Additionally, there is a need for alternatives with reduced pro-oxidant effects and improved mitochondrial targeting for diseases linked to mitochondrial dysfunction, such as neurodegenerative disorders, cardiovascular diseases, cancer, and diabetes.
The core innovation is the design, synthesis, and therapeutic application of phenothiazine derivatives with tailored side chains that enhance hydrophobicity, enabling better cellular uptake and mitochondrial protection. The invention describes pharmaceutical compositions containing these compounds and methods for using them to treat mitochondrial, neurodegenerative, cardiovascular diseases, cancer, and diabetes by preserving mitochondrial function, protecting against oxidative stress, and maintaining ATP production and mitochondrial membrane potential.
Claims Coverage
The patent includes multiple independent claims, each focusing on core inventive features such as the novel compound structures, pharmaceutical compositions, and methods of synthesis.
Novel phenothiazine derivative compounds of formula I
The invention encompasses compounds of formula I, where: - R1 and R2 are C1-20 alkyl, C2-20 alkenyl, or C2-20 alkynyl, optionally substituted as specified, or together with nitrogen form a 3-12 membered heterocycle. - R3 and R4 are independently selected from defined substituents, such as —F, —Cl, —Br, —I, —OH, —ORa, —SRa, —NRaRb, —CN, C1-4 alkyl, and others as detailed in the claim. - Ra and Rb are hydrogen or C1-4 alkyl; m and n are 0–3. - The compounds also include their pharmaceutically acceptable salts. This inventive feature covers the structural definition and scope of the new compounds.
Pharmaceutical composition containing a compound of formula I
This feature includes a pharmaceutical composition comprising: - A compound of formula I (or its pharmaceutically acceptable salt). - A pharmaceutically acceptable carrier. The claim covers the formulation aspect of the invention, enabling therapeutic use.
Process for preparing a compound of formula I
The inventive feature provides a method for preparing the compounds of formula I by: 1. Converting a corresponding compound of formula II (with specified structural parameters) or its salt. 2. Obtaining the compound of formula I or its pharmaceutically acceptable salt. Details of structural variables and intermediates are explicitly covered.
The claims cover the novel phenothiazine antioxidant compounds defined by precise structural attributes, pharmaceutical formulations containing these, and methods for their chemical synthesis.
Stated Advantages
The compounds offer reduced cytotoxicity and side effects compared to existing antioxidants such as methylene blue and methylene violet.
The compounds enable improved bioavailability and cellular uptake due to their enhanced hydrophobicity.
They are capable of preserving mitochondrial function, protecting cells from oxidative stress, maintaining mitochondrial membrane potential, and augmenting ATP production.
Documented Applications
Therapeutic and prophylactic treatment of mitochondrial disease, neurodegenerative disease, cardiovascular disease, cancer, and diabetes.
Protecting cells from oxidative stress in animals and in vitro.
Preserving mitochondrial membrane potential and/or augmenting ATP production in animals and in vitro.
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