2-(2,2-diarylethyl)-cyclic amine derivatives for M-receptor antagonism
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Solution Overview
Problem
Current drug compounds for treating diseases related to M-receptor antagonism, such as asthma, COPD, and OAB, do not have effective alternatives with novel structures that offer enhanced antagonistic activity and diastolic effects on tracheal smooth muscle.
Innovation Solution
Development of 2-(2,2-diarylethyl)-cyclic amine derivatives with a novel structure, featuring a propyl group connected to form a ring, exhibiting excellent M-receptor antagonistic activity, particularly with ortho hydroxyl groups enhancing this activity, and showing diastolic effects comparable to or better than tiotropium bromide.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If 3,3-diarylpropylamine derivatives are used for M-receptor antagonism, then therapeutic effects on asthma, COPD, and OAB are achieved, but structural novelty and enhanced antagonistic activity are limited
Solution Approach 1:
The invention segments the traditional 3,3-diarylpropylamine structure by separating the propyl chain into an ethyl group attached to a cyclic amine ring system. This segmentation creates a novel 2-(2,2-diarylethyl)-cyclic amine structure that maintains the pharmacophore elements while achieving structural innovation and enhanced M-receptor antagonistic activity
Solution Approach 2:
The invention changes the structural parameters by replacing the terminal amino group of 3,3-diarylpropylamine with a cyclic amine system containing nitrogen heteroatoms. This parameter change in the molecular structure leads to improved M-receptor binding affinity and antagonistic activity while maintaining the therapeutic effects for respiratory and urological conditions
2Reliability
If existing M-receptor antagonists are used, then treatment of respiratory and urological diseases is achieved, but diastolic effects on tracheal smooth muscle are insufficient
Solution Approach 1:
The invention applies local quality enhancement by introducing ortho hydroxyl groups on the aromatic rings of the 2-(2,2-diarylethyl)-cyclic amine structure. This localized functional group addition significantly enhances the diastolic effect on tracheal smooth muscle by improving receptor binding interactions, while the core molecular framework remains synthesizable from available precursors
3Reliability
If novel structural alternatives are developed, then enhanced antagonistic activity and diastolic effects are achieved, but synthesis complexity may increase
Solution Approach 1:
The invention achieves universality by designing a 2-(2,2-diarylethyl)-cyclic amine core structure that serves multiple therapeutic functions: M-receptor antagonism for respiratory diseases (asthma, COPD), urological conditions (OAB), and other M-receptor mediated disorders. This multi-functional structure can be synthesized from common cyclic amine precursors through established chemical transformations, balancing novelty with manufacturability
Data Source
AI summary
The disclosure relates to a 2-(2,2-diarylethyl)-cyclic amine derivative or salt, a synthesis method, an application and a composition thereof. Biological activity test shows that this kind of 2-(2,2-diarylethyl)-cyclic amine derivative has good M-receptor antagonistic activity; and can be used as an active component of drugs for the treatment of the diseases mediated or regulated by muscarinic receptors, such as asthma, chronic obstructive pulmonary disease (COPD), overactive bladder (OAB), bronchospasm with chronic obstructive pulmonary disease, visceral spasm, irritable bowel syndrome, Parkinson's disease, depression or anxiety, schizophrenia and related mental diseases.