Benzothiazole Salt Polymorphs for Neurodegenerative Disease Treatment
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Solution Overview
Problem
Current treatments for neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are limited, and there is a need for effective inhibitors of the tyrosine kinase c-abl to block disease progression.
Innovation Solution
Development of novel salts and polymorphs of benzothiazole compounds that act as c-abl inhibitors, including hydrochloride, sulfate, and other acid salts, which improve the physicochemical properties and solubility of the compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for neurodegenerative diseases, then current standard therapy is maintained, but therapeutic effectiveness is limited and disease progression cannot be blocked
Solution Approach 1:
The patent modifies the chemical structure of benzothiazole compounds by creating novel salts with different counterions (e.g., hydrochloride, sulfate, phosphate, L-aspartate, maleate, fumarate, citrate, L-malate, and methane sulfate). These parameter changes in chemical formulation improve solubility and bioavailability, thereby enhancing therapeutic effectiveness and enabling better disease progression blockage compared to conventional treatments
Solution Approach 2:
The invention creates composite salt structures by combining the benzothiazole compound with various acid counterions. This composite approach allows the development of multiple salt forms (e.g., hydrochloride salt, sulfate salt, phosphate salt) that collectively provide improved pharmacological properties and broader therapeutic effectiveness for neurodegenerative diseases
2Reliability
If benzothiazole compounds are used as c-abl inhibitors, then c-abl activity is inhibited, but physicochemical properties and solubility need improvement
Solution Approach 1:
The patent systematically varies the counterion parameter in the salt structure to optimize solubility and physicochemical properties. By selecting different acids (hydrochloric, sulfuric, phosphoric, L-aspartic, maleic, fumaric, citric, L-malic, and methanesulfonic), the invention adjusts the salt's solubility characteristics while maintaining c-abl inhibition activity, making the compound more suitable for pharmaceutical development
Solution Approach 2:
The salt counterions act as intermediaries that facilitate the dissolution and absorption of the benzothiazole compound. These intermediary substances (e.g., hydrochloride, sulfate, phosphate) improve the physicochemical properties by enhancing solubility in biological fluids, thereby enabling better bioavailability and maintaining effective c-abl inhibition without compromising the compound's inhibitory activity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The novel salts and polymorphs of benzothiazole compounds effectively inhibit c-abl activity, offering potential therapeutic benefits for neurodegenerative diseases by ameliorating autophagic clearance of α-synuclein and reducing neurodegeneration.
Implementation Method 1
The compounds are c-abl inhibitors that are useful for the treatment of a disease or disorders such as α-synucleinopathy, Parkinson disease, Alzheimer disease, ALS, Dementia with Lewy body and MSA
Implementation Method 2
The present disclosure provides the hydrochloride, sulfate, L-aspartate, maleate, phosphate, L-(+)-tartrate, fumarate, citrate, L-malate and methane sulfate salts of the compound of Formula (I)
Data Source
AI summary
The present disclosure provides polymorphic forms and salts of (1S,2S)-2-fluoro-N-(6-(4-methylpyridin-3-yl)benzo[d]thiazol-2-yl)cyclopropane-1-carboxamide, pharmaceutical compositions comprising the compounds, processes for preparation of the compounds, and methods for treating neurodegenerative disorders.