Fused Ring Thrombin Receptor Antagonists for Dual-Action Therapy
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Solution Overview
Problem
Current treatments for thrombosis, atherosclerosis, and inflammatory disorders lack effective thrombin receptor antagonists and cannabinoid CB2 receptor inhibitors that can address a wide range of diseases including cardiovascular issues, inflammatory conditions, and cancer, with existing compounds often having limited efficacy and specificity.
Innovation Solution
Development of novel compounds represented by structural formula I, which act as both thrombin receptor antagonists and cannabinoid CB2 receptor inhibitors, offering anti-thrombotic, anti-inflammatory, and anti-atherosclerotic activities, and can be used in combination with other agents for enhanced therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing thrombin receptor antagonist peptides are used, then some thrombotic activity is achieved, but the efficacy and specificity are limited
Solution Approach 1:
The patent combines two distinct pharmacological activities into a single molecular structure: thrombin receptor antagonism and cannabinoid CB2 receptor inhibition. This merging approach allows the compound to address multiple disease mechanisms simultaneously, improving therapeutic efficacy while managing structural complexity through rational drug design
Solution Approach 2:
The compounds of formula I are designed to function as dual-action agents, acting as both thrombin receptor antagonists and cannabinoid CB2 receptor inhibitors. This multi-functionality enables a single compound to treat diverse conditions including thrombotic disorders, inflammatory diseases, and neurodegenerative conditions, thereby improving reliability across multiple therapeutic indications
2Adaptability or versatility
If current treatments are used for multiple diseases, then broad coverage is attempted, but the specificity and effectiveness for each condition are insufficient
Solution Approach 1:
The dual-action compounds provide versatile therapeutic coverage by targeting two different receptor systems (thrombin receptor and CB2 receptor) with a single molecule, enabling treatment of cardiovascular, inflammatory, and neurological conditions while maintaining condition-specific effectiveness through mechanism-based action
Solution Approach 2:
The compounds exhibit different pharmacological activities at different target sites: thrombin receptor antagonism in platelets and vascular cells for thrombotic protection, and CB2 receptor inhibition in peripheral tissues for anti-inflammatory effects. This local quality differentiation allows broad adaptability while maintaining specific effectiveness for each condition
Data Source
AI summary
Fused-ring, heterocyclic-substituted tricyclics of the formula (I) or a pharmaceutically acceptable salt or solvate of said compound, isomer or racemic mixture wherein (II) represents an optional double bond, and wherein An, En, Mn, Gn, Jn, R3, n7, R8, R9, R10, R11, R32, R33, X, Y, B and Het are herein defined and the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.