Pyrrolidine Compounds Restore Gap Junction Integrity
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Solution Overview
Problem
Current peptides that influence gap junction intercellular communication (GJIC) for treating heart diseases, such as antiarrhythmic peptides AAP and AAP10, exhibit low stability, short half-life, and lack oral bioavailability, making them ineffective for maintaining gap junction integrity.
Innovation Solution
The development of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid and its salts, which are synthesized through specific chemical processes involving conversion and reaction with metal hydroxides, to restore and maintain gap junction integrity between cell membranes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides such as AAP and AAP10 are used to influence GJIC, then gap junction integrity can be restored, but stability and half-life are reduced
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of peptides to create small molecule compounds with improved stability. Specifically, compounds of formula (I) and (II) are designed with modified molecular parameters including specific substituent groups (R1-R7) and structural features that enhance metabolic stability while preserving gap junction restoring activity, thereby resolving the contradiction between therapeutic efficacy and stability.
Solution Approach 2:
The patent employs composite materials by creating hybrid molecular structures that combine the therapeutic functionality of peptides with the stability characteristics of small molecules. The compounds feature composite structural elements including pyrrolidine rings, amide bonds, and various substituent groups that work together to provide both GJIC restoration capability and enhanced stability profile.
2Reliability
If peptides such as AAP and AAP10 are used to influence GJIC, then gap junction integrity can be restored, but oral bioavailability is lacking
Solution Approach 1:
The patent applies parameter changes by optimizing molecular properties such as lipophilicity, molecular weight, and hydrogen bonding capacity of the compounds. The specific structural parameters (substituent groups R1-R7, molecular formula constraints) are tuned to improve membrane permeability and metabolic stability, enabling oral bioavailability while maintaining therapeutic efficacy for gap junction restoration.
3Reliability
If peptides are used for treating heart diseases, then therapeutic effect is achieved, but half-life is short
Solution Approach 1:
The patent applies parameter changes by modifying molecular characteristics including resistance to enzymatic degradation, plasma protein binding affinity, and metabolic stability. The compounds of formula (I) and (II) are designed with structural parameters that extend half-life through reduced clearance rates while preserving the therapeutic effect of gap junction restoration in cardiac tissues.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compound effectively restores and maintains gap junction integrity, providing a therapeutic solution for diseases associated with abnormal GJIC, including heart diseases, with improved stability and bioavailability compared to existing peptides.
Implementation Method 1
The compound (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid: restores and maintains the gap junction integrity between cell membranes
Data Source
AI summary
Provided are methods for the preparation of certain substituted pyrrolidine compounds, forms of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride, and methods for preparing and using these forms.