Beta-2 Adrenergic Agonist Compounds for Pulmonary Disease Treatment
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Solution Overview
Problem
Current β2 adrenergic receptor agonists have limitations in potency, selectivity, onset, and duration of action, as well as safety margins, necessitating the development of compounds with improved properties for treating pulmonary diseases, pre-term labor, glaucoma, and other disorders.
Innovation Solution
Development of novel β2 adrenergic receptor agonist compounds of formula (I) with specific structural features, including various substituents and functional groups, which are used in pharmaceutical compositions and processes to enhance therapeutic efficacy and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current β2 adrenergic receptor agonists are used, then therapeutic effects are achieved, but potency, selectivity, onset, and duration of action are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically modifying molecular structure parameters including substituent types (R1-R6 groups), their positions on the phenyl ring, and the nature of X and Y linkers. These structural parameter variations enable optimization of receptor binding affinity and selectivity while maintaining therapeutic efficacy, directly addressing the contradiction between improved potency and structural complexity
Solution Approach 2:
The invention employs local quality by introducing specific functional groups at targeted positions on the molecular structure. Different substituents (alkoxy, halo, alkyl groups) are placed at specific R positions to locally enhance interactions with the β2 adrenergic receptor, improving selectivity and potency without requiring complete restructuring of the entire molecule
2Ease of manufacture
If molecular structure is simplified, then ease of manufacture improves, but potency and selectivity may be reduced
Solution Approach 1:
The patent applies segmentation by dividing the molecule into distinct functional segments: a core phenylpropanolamine structure with separable substituent regions (R1-R6). This modular approach allows independent optimization of each segment for both synthetic accessibility and pharmacological activity, enabling simplified manufacturing while maintaining potency through careful design of individual segments rather than requiring complex integrated structures
Solution Approach 2:
The invention uses parameter changes to balance manufacturability and activity by selecting substituents with varying degrees of complexity. By adjusting parameters such as substituent size, electronic properties, and steric demands, the patent achieves optimal compounds that are sufficiently complex for high affinity binding but not so complex as to prohibit scalable synthesis
3Reliability
If therapeutic window is expanded, then safety margin improves, but may require increased molecular complexity
Solution Approach 1:
The patent applies local quality by introducing specific substituents at strategic positions to enhance β2 receptor selectivity over other adrenergic receptors. By locally modifying the molecule to preferentially bind β2 receptors, the invention expands the therapeutic window and improves safety margins without requiring global structural complexity, as the selectivity is achieved through targeted local interactions
Data Source
AI summary
The present invention provides a Compound of formula (I), wherein: R1 is a group selected from -CH2OH,-NH(CO)H; and R2 is a hydrogen atom; or R1 together with R2 form the group -NH-C(O)-CH=CH-, wherein the nitrogen atom is bound to the carbon atom in the phenyl ring holding R1 and the carbon atom is bound to the carbon atom in the phenyl ring holding R2;R3a and R3b are independently selected from the group consisting of hydrogen atoms and C1-4 alkyl groups; X and Y are independently selected from the group consisting of direct bond and oxygen atom; n, m and q each independently has a value selected from 0, 1, 2 and 3; p has a value selected from 1, 2 and 3; R4 and R5 are independently selected from hydrogen atoms, halogen atoms, C1-4 alkyl, C1-4 alkoxy, -CONH2, -NHCONH2, -SR7, -SOR7, -SO2R7, -SO2NHR8 and the groups (a) and (b), wherein R7 is selected from C1-4alkyl and C3-8 cycloalkyl and R8 is selected from hydrogen atoms and C1-4alkyl groups; R6 is selected from the group consisting of hydrogen atoms, halogen atoms, C1-4 alkyl and C1-4 alkoxy or a pharmaceutically-acceptable salt, solvate or stereoisomer thereof.