Polyethylene Glycol Modified PKG Inhibitor for Chronic Pain

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Solution Overview

Problem

Current compounds targeting protein kinase G (PKG) for pain relief have inadequate water solubility and PKG inhibitory activity, limiting their effectiveness in treating chronic pain.

Innovation Solution

Modification of compound 46 by incorporating a low-molecular polyethylene glycol fragment to enhance water solubility and PKG inhibitory activity, resulting in a new compound with improved analgesic effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current PKG-targeting compounds are used for pain relief, then they can provide some analgesic effect, but their water solubility is inadequate and PKG inhibitory activity is insufficient

Engineering Contradiction:

ImprovePKG inhibitory activityVSAvoidwater solubility

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent modifies the chemical structure of compound 46 by incorporating a low-molecular polyethylene glycol fragment, which changes the physical and chemical parameters of the molecule. This structural modification increases both water solubility and PKG inhibitory activity simultaneously, resolving the technical contradiction between these two properties.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite molecular structure by combining the parent compound 46 with a polyethylene glycol fragment. This composite structure integrates the pharmacological activity of the original compound with the hydrophilic properties of polyethylene glycol, achieving both high PKG inhibitory activity and improved water solubility.

Inventive Principle:

Principle #40Composite materials

2Reliability

If the structural modification with polyethylene glycol fragment is implemented, then water solubility and PKG inhibitory activity are significantly improved, but the molecular complexity increases

Engineering Contradiction:

Improveanalgesic effectivenessVSAvoidmolecular structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs parameter changes by modifying specific molecular parameters - adding a low-molecular polyethylene glycol fragment that increases hydrophilicity and solubility without excessively complicating the overall molecular architecture. The modification is targeted and controlled to balance complexity improvement with effectiveness enhancement.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS9567319B2Compound having higher inhibitory activity on protein kinase G and preparation method thereof

Publication Date: 2017.02.14 JENKEM TECH CO LTD TIANJIN

AI summary

Disclosed are a compound of Formula I,having higher inhibition of protein kinase G (PKG) activity and pharmaceutically acceptable salts thereof. In Formula I, R1 and R2 are the same or different, each being independently chosen from the halogens, the C1-C6 alkoxyl group, the C1-C6 alkyl group, the C2-C6 alkenyl group, and the C2-C6 alkynyl group; R3 is chosen from H, the halogens, the substituted or unsubstituted C1-C6 alkyl group, C3-C6 cycloalkyl group, C2-C6 alkenyl group, and C2-C6 alkynyl group, aryl group, and heteroaryl group; and n is an integer between 0 and 15. Also disclosed is a pharmaceutical composition comprising said compound, the use of the compound in treating pains, in particular chronic pain, a preparation method for the compound, and a new intermediate.