N-Substituted Phthalamic Acids as Sortilin Inhibitors

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Solution Overview

Problem

Current therapies lack specific small molecule modulators to target Sortilin, a receptor implicated in various neurodegenerative and inflammatory disorders, despite its role in mediating pro-apoptotic effects and protein trafficking.

Innovation Solution

Development of N-substituted-5-substituted phthalamic acid compounds that act as Sortilin inhibitors, which can be used in pharmaceutical compositions to treat neurodegenerative diseases, psychiatric disorders, and inflammatory conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies are used to treat neurodegenerative disorders, then treatment is provided, but specific small molecule modulators targeting Sortilin are lacking

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidtarget specificity
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically varying molecular parameters of phthalamic acid derivatives, including substituent types at different positions, stereochemistry, and molecular size, to optimize Sortilin binding affinity and selectivity. This approach transforms a general therapeutic approach into a targeted therapy with specific molecular parameters tuned for Sortilin inhibition.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements local quality by introducing specific substituents at defined positions on the phthalamic acid core structure. Different substituents (R1-R6 groups) provide localized interactions with specific regions of the Sortilin binding site, enabling selective targeting while maintaining overall molecular framework.

Inventive Principle:
Principle #3Local quality

2Object-affected harmful factors

If Sortilin-mediated interactions are blocked to treat neurodegenerative diseases, then neurodegenerative processes are alleviated, but potential side effects on other Vps10p family receptors may occur

Engineering Contradiction:
Improveneurodegenerative damageVSAvoidoff-target effects
Core Design Contradiction:
Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent uses local quality to achieve selective Sortilin targeting by placing specific functional groups at precise positions on the phthalamic acid core. This localized functional differentiation enables the molecule to distinguish Sortilin from other Vps10p family members (SorLA, SorCS1-3) by forming specific local interactions with Sortilin's unique binding site features.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent applies segmentation by dividing the molecular structure into distinct functional segments (core phthalamic acid, N-substituents, 5-substituents) that can independently contribute to Sortilin binding. This modular design allows optimization of Sortilin specificity while minimizing cross-reactivity with other receptors through selective segment configuration.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP2948147B1N-substituted-5-substituted phthalamic acids as sortilin inhibitors
Publication Date: 2019.03.13 H LUNDBECK AS
  • EP2948147B1 patent drawingFigure 1
  • EP2948147B1 patent drawingFigure 2
  • EP2948147B1 patent drawing

AI summary

The present invention is directed to N-substituted-5-substituted phthalamic acids which of formula (A). The compounds are considered useful for the treatment of diseases treatment of a neurodegenerative disease, psychiatric disease, motorneuron disease, peripheral neuropathies, pain, neuroinflammation or atherosclerosis such as Alzheimer's disease and Parkinson's disease.