Bicyclic Thrombin Receptor Antagonists for Multi-Receptor Inhibition
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for thrombosis, atherosclerosis, and inflammatory disorders lack effective thrombin receptor antagonists and cannabinoid receptor inhibitors that can address a wide range of diseases including thrombotic, inflammatory, and fibroproliferative disorders, with existing compounds having limitations in specificity and efficacy.
Innovation Solution
Development of novel compounds represented by structural formulas Ik and IIk, which act as thrombin receptor antagonists or cannabinoid CB2 receptor inhibitors, offering anti-thrombotic, anti-inflammatory, and anti-atherosclerotic activities, and are useful in treating various cardiovascular, inflammatory, and cancer-related conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing thrombin receptor antagonist compounds are used, then some therapeutic effect is achieved, but specificity and efficacy are limited
Solution Approach 1:
The patent develops compounds that can act on multiple target receptors including thrombin receptors (PAR-1), cannabinoid receptors (CB2), and other G-protein coupled receptors, enabling a single compound to treat multiple disease conditions including thrombotic disorders, inflammatory conditions, and fibroproliferative disorders
Solution Approach 2:
The patent employs systematic modification of molecular parameters including substitution patterns on the bicyclic and tricyclic rings, variation of side chain lengths and functional groups, and adjustment of stereochemistry to optimize both binding affinity (specificity) and pharmacological activity (efficacy) across different disease models
2Adaptability or versatility
If broad-spectrum therapeutic compounds are developed, then more diseases can be treated, but compound complexity increases
Solution Approach 1:
The compounds achieve multi-functionality through a modular molecular architecture where a core bicyclic or tricyclic structure serves as a common scaffold that can interact with multiple receptor types, reducing the need for entirely separate complex molecules for each therapeutic indication
Solution Approach 2:
The molecular structure is divided into distinct functional segments including the core ring system, side chains with specific functional groups, and substituent patterns that can be independently optimized for different receptor interactions, allowing systematic development of multi-target compounds
Data Source
AI summary
Substituted bicyclic and tricyclic modified himbacine derivative of the formula (I) : or a pharmaceutically acceptable salt or solvate of said compound wherein (DU) represents an optional double bond and wherein En, Fn, Gn, Zn, Jn, X, R3, R9, R10, R11, R32, R33, B and Het are herein defined 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 agents is also claimed.