Aromatic Ring Antagonist Salt Crystal Form for Dual Kidney Pathway Blockade
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Solution Overview
Problem
Current drug treatments for focal segmental glomerulosclerosis (FSGS) and other kidney diseases like IgA nephropathy and idiopathic membranous nephropathy have poor efficacy and significant side effects, with no approved treatments available, leading to progression to chronic renal failure and high economic burden.
Innovation Solution
Development of an acid salt of a compound with a specific aromatic ring derivative, formulated as a crystal form to target both angiotensin and endothelin pathways, providing a dual antagonistic mechanism to treat kidney diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucocorticoids and immunosuppressants are used to treat FSGS, then some therapeutic effect is achieved, but side effects are significant and complete response rate is less than 30%
Solution Approach 1:
The patent changes the therapeutic parameter from single-pathway inhibition (RAAS or endothelin alone) to dual-pathway inhibition (AT1 receptor and ETA receptor simultaneously). This parameter change in the mechanism of action enables better control of glomerular hypertension and proteinuria while reducing the need for high-dose immunosuppressants, thereby improving efficacy while reducing side effects
Solution Approach 2:
The invention develops a compound that combines dual antagonistic activities (AT1 and ETA receptor blockade) in a single molecule, analogous to composite materials. This composite pharmacological action allows simultaneous inhibition of both angiotensin II and endothelin-1 pathways, achieving synergistic therapeutic effects with reduced individual drug doses and fewer side effects
2Reliability
If dual antagonists (ARB and ERA) are used together, then synergistic effect is achieved, but device complexity increases
Solution Approach 1:
The patent merges the functions of two separate drugs (ARB and ERA) into a single compound that possesses both AT1 receptor blocking and ETA receptor blocking activities. This merging eliminates the need for combination therapy, simplifying the treatment regimen while maintaining the synergistic therapeutic effect of dual pathway inhibition
Solution Approach 2:
The invention creates a universal compound that performs multiple functions: it blocks both AT1 and ETA receptors, inhibits two different vasoconstrictor pathways (angiotensin II and endothelin-1), and treats multiple kidney diseases (FSGS, IgA nephropathy, IMN) with a single agent, thereby reducing treatment complexity
Data Source
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AI summary
The present application relates to a salt of an aromatic ring-containing derivative antagonist, a crystal form thereof, a preparation method therefor, and an application thereof. Specifically, the present application relates to a compound salt of formula (I), a crystal form, a preparation method, and a pharmaceutical composition containing a therapeutically effective amount of the salt or crystal form, and the use thereof as a protease inhibitor in the preparation of a medicament for treating or preventing a disease with dual angiotensin-dependent and endothelin-dependent mechanisms.