Naphthylamine Mitophagy Salt Forms for Stable Bioavailability
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Solution Overview
Problem
Existing technologies lack effective mitophagy inducers that can selectively induce autophagy in damaged mitochondria, leading to accumulation of dysfunctional mitochondria and associated pathological consequences.
Innovation Solution
Development of various solid forms of naphthylamine-type compounds, including pharmaceutically usable salts such as sodium, potassium, calcium, tromethamine, lysine, tert-butylammonium, diisopropylammonium, ethanolammonium, and diethanolammonium salts, with specific X-ray diffraction and calorimetry patterns, to enhance mitophagy and address mitochondrial dysfunction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mitophagy inducers are developed to remove damaged mitochondria, then cellular function is maintained, but selective induction of autophagy in damaged mitochondria is difficult to achieve
Solution Approach 1:
The patent modifies the chemical structure of naphthylamine compounds by changing parameters such as introducing different side chains (e.g., -CH2OH, -COOH, -NH2 groups) and adjusting molecular weight and lipophilicity to achieve selective induction of autophagy in damaged mitochondria while maintaining crystalline stability and bioavailability
Solution Approach 2:
The patent creates composite salt forms by combining naphthylamine compounds with various counterions (sodium, potassium, calcium salts and amino acid salts) to enhance the selective mitophagy induction capability while improving pharmacological properties
2Reliability
If solid forms of naphthylamine compounds are prepared with specific crystalline structures, then bioavailability is improved, but preparation complexity increases
Solution Approach 1:
The patent utilizes phase transition processes including crystallization from solvent systems (acetone, ethanol, methanol) and control of cooling rates to obtain solid forms with specific crystalline structures that enhance bioavailability while maintaining preparation feasibility
Solution Approach 2:
The patent optimizes preparation parameters such as solvent selection, temperature control, pH adjustment, and concentration levels to achieve desired crystalline forms with improved bioavailability without excessive preparation complexity
3Reliability
If multiple salt forms are synthesized to improve pharmacological properties, then bioavailability increases, but manufacturing cost increases
Solution Approach 1:
The patent systematically evaluates different salt forms (sodium, potassium, calcium salts and amino acid salts) by modifying chemical parameters to identify the most cost-effective formulation that achieves improved bioavailability, avoiding unnecessary synthesis of all possible salt forms
Data Source
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AI summary
The present application discloses solid form of naphthylamine-type mitochondrial autophagy inducer, and preparation method therefor, pharmaceutical composition and use thereof. Various solid forms of the compound of formula (I) are prepared and obtained in the present application, such as sodium salt, potassium salt, calcium salt, tromethamine salt, lysine salt, tert-butylammonium salt, diisopropylammonium salt, ethanolammonium salt, and diethanolammonium salt of the compound of formula (I).