Urea Derivatives Modulating FPRL-1 Receptor Signaling
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Solution Overview
Problem
Current treatments for disorders associated with excessive inflammatory responses lack effective modulators for the N-formyl peptide receptor like-1 (FPRL-1) receptor, which plays a critical role in inflammation and leukocyte trafficking, and existing therapies fail to adequately address the receptor's dual pro-inflammatory and anti-inflammatory signaling.
Innovation Solution
Development of novel 1-(1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)urea derivatives that act as potent and selective modulators of the FPRL-1 receptor, including agonists, antagonists, inverse agonists, partial agonists, and partial antagonists, to treat various inflammatory disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used to treat inflammatory disorders, then treatment is provided, but the therapies fail to adequately address the receptor's dual pro-inflammatory and anti-inflammatory signaling
Solution Approach 1:
The patent modifies the chemical structure of FPRL-1 modulators by changing parameters such as introducing specific functional groups (carboxylic acid, ester, amide, urea, carbamate, or hydroxyl at positions 6, 7, or 8 of the isoquinoline ring) and adjusting substituents (R1-R16, X, Y, n, m values) to achieve selective modulation of the receptor's dual signaling pathways, thereby resolving the contradiction between treatment effectiveness and adaptability to dual signaling
2Ease of operation
If non-specific FPRL-1 modulators are used, then the receptor is activated, but pro-inflammatory and anti-inflammatory effects cannot be selectively controlled
Solution Approach 1:
The patent applies local quality by introducing specific functional groups at specific positions (6, 7, or 8) of the isoquinoline ring system, allowing selective modulation of particular signaling pathways. The substitution patterns (R1-R16, X, Y, n, m) enable localized chemical modifications that confer selective pro-inflammatory or anti-inflammatory activity, thereby achieving precision in signaling control while maintaining ease of receptor modulation
3Productivity
If current FPRL-1 modulators are used, then inflammation is addressed, but the compounds lack potent and selective modulation capability
Solution Approach 1:
The patent creates composite molecular structures by combining the core 1,2,3,4-tetrahydroisoquinoline-1,7-dione scaffold with various functional groups (carboxylic acid, ester, amide, urea, carbamate, hydroxyl) and substituents (R1-R16, X, Y, n, m). This composite approach enables the development of potent and selective FPRL-1 modulators that achieve reliable inflammation resolution, resolving the contradiction between productivity and reliability
Data Source
AI summary
The present invention relates to novel 1-(1-Oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)urea derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.