Selective EP2 Agonist Compound Design for Reduced Side Effects

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Solution Overview

Problem

Current therapies lack a selective EP2 agonist that effectively targets EP2 receptors without causing undesirable side effects, which are essential for treating various diseases such as autoimmune diseases, allergic diseases, and ocular disorders.

Innovation Solution

A compound represented by general formula (I) is developed, which acts as a selective EP2 agonist, specifically designed to target EP2 receptors, thereby minimizing unwanted actions and maximizing therapeutic benefits.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If PGE2 is used as a drug to achieve wide variety of physiological activities, then multiple therapeutic effects are obtained, but undesirable side effects occur due to lack of subtype specificity

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidside effects
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the broad PGE2 receptor activity into subtype-specific actions by designing compounds that selectively target EP2 receptors. The compound structure (formula I) with specific substituents (R1-R6, ring 1 being 5- or 6-membered aromatic ring) enables selective binding to EP2 receptors while avoiding other PGE2 receptor subtypes, thus achieving therapeutic effects without the side effects associated with non-selective PGE2 activation.

Inventive Principle:
Principle #1Segmentation

2Object-affected harmful factors

If selective EP2 agonists are developed to target specific subtype, then side effects are reduced, but such compounds were not previously available in prior art

Engineering Contradiction:
Improveside effectsVSAvoidavailability of effective compound
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The invention changes the chemical parameters of the prostaglandin structure by introducing specific substituents at defined positions (R1-R6 on the cyclopentane ring and aromatic ring system) to create compounds with enhanced EP2 selectivity. The compound in formula I represents a novel chemical space not previously explored in prior art documents, providing reliable selective EP2 agonist activity for treating diseases such as autoimmune disorders, allergic diseases, and ocular conditions.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3112362B1Compound exhibiting selective EP2 agonist activity
Publication Date: 2018.09.26 ONO PHARMA CO LTD

AI summary

To provide an excellent selective EP2 agonist in a safe manner. A compound represented by general formula (I): (wherein all symbols are as defined in the specification), a salt or N-oxide of the compound, or a solvate or prodrug of the compound or the salt or N-oxide has a selective EP2 agonist activity and is highly safe, and is therefore useful as a drug, especially as a therapeutic agent for EP2 receptor-related diseases including immune diseases, allergic diseases, neuronal death, dysmenorrhea, premature birth, miscarriage, baldness, ocular diseases, erectile dysfunction, arthritis, lung injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, bone diseases, cartilage injury and others.