PARP Inhibitor Compounds Selective Binding

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Solution Overview

Problem

Current therapeutic options for treating various disorders, including cancer, inflammatory diseases, and toxicities, lack effective PARP inhibitors that can selectively target and inhibit poly(ADP-ribose) polymerase activity without causing significant side effects.

Innovation Solution

Development of specific compounds, such as those with formula I, which inhibit PARP activity by administering therapeutically acceptable amounts to mammals, thereby treating cancer, inflammatory conditions, and toxicities while minimizing side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing PARP inhibitors are used to treat cancer and other disorders, then PARP activity is inhibited, but significant side effects occur and selectivity is insufficient

Engineering Contradiction:

Improveselectivity of PARP inhibitionVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing compounds with specific structural features at particular positions of the phthalazinone core. Different substituents (R1-R10) are strategically placed to optimize binding affinity for PARP enzymes while minimizing off-target effects, thereby achieving selective inhibition with reduced side effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by systematically varying chemical parameters such as substituent types, positions, and configurations on the phthalazinone scaffold. This includes exploring different aromatic rings, heterocycles, and functional groups to fine-tune the balance between PARP inhibition potency and selectivity, ultimately reducing harmful side effects

Inventive Principle:

Principle #35Parameter changes

2Productivity

If current therapeutic options are used, then treatment is provided, but effective PARP inhibition without significant side effects is not achieved

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidside effects

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the potential harm of non-selective PARP inhibition into benefit by designing compounds that specifically target pathological PARP activity in cancer and inflammatory conditions while sparing normal physiological functions. The selective compounds inhibit PARP in diseased tissues where it contributes to pathology, while minimizing side effects from inhibition in healthy tissues

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent optimizes treatment effectiveness while reducing side effects by systematically modifying chemical parameters of the phthalazinone compounds. This includes varying substituent patterns, molecular weight, lipophilicity, and other physicochemical properties to achieve the desired therapeutic window where effective disease treatment occurs with minimal adverse effects

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP2698062B1Inhibitors of poly(adp-ribose)polymerase

Publication Date: 2015.06.24 ABBVIE INC

AI summary

A compound selected from the group consisting of 1-(2-fluoro-5-((4-oxo-3,4,5,6,7,8-hexahydrophthalazin-1-yl)methyl)phenyl)pyrrolidine-2,5-dione and 4-(3-(1,4-diazepan-1-ylcarbonyl)-4-fluorobenzyl)-5,6,7,8-tetrahydrophthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof, for use in treating leukemia, colon cancer, glioblastomas, lymphomas, melanomas, carcinomas of the breast or cervical carcinomas in a mammal by administering thereto a therapeutically acceptable amount of said compound.