IDO Inhibitor Compounds Modulating Enzymatic Activity

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Solution Overview

Problem

Current IDO inhibitors have limitations in efficacy for treating proliferative disorders, cancer, viral infections, and autoimmune diseases, necessitating the development of new IDO modulators and compositions.

Innovation Solution

Development of specific compounds of formulas I and II, which are designed to modulate or inhibit indoleamine 2,3-dioxygenase (IDO) activity, including pharmaceutical compositions and methods for treating various diseases associated with IDO enzymatic activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing IDO inhibitors are used to treat proliferative disorders and cancer, then immune suppression is reduced and T cell activation is enhanced, but efficacy is limited and treatment success is highly variable

Engineering Contradiction:

Improvetreatment efficacyVSAvoidtumor cell escape mechanisms

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs parameter changes by developing new chemical compounds with modified molecular structures (formulas I and II) that exhibit improved IDO inhibitory activity. The compounds feature specific structural parameters including heterocyclic rings, substituent groups, and molecular weight ranges optimized to enhance binding affinity to IDO enzyme, thereby improving treatment efficacy and reliability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite therapeutic approaches by combining novel IDO inhibitor compounds with specific pharmacophore elements and structural motifs. The composite molecular structures integrate multiple functional groups that work synergistically to achieve potent and selective IDO inhibition, overcoming limitations of single-structure inhibitors

Inventive Principle:

Principle #40Composite materials

2Productivity

If IDO activity is inhibited to enhance T cell activation, then immune response is improved, but current inhibitors show highly variable long-term success due to tumor cell regeneration and metastasis

Engineering Contradiction:

ImproveT cell activationVSAvoidlong-term treatment success

Core Design Contradiction:

ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by developing compounds designed to prevent tumor cell escape mechanisms before they occur. The novel IDO inhibitors are structured to maintain sustained inhibition of IDO activity, preventing tumor cell regeneration and metastasis by continuously enhancing T cell activation and immune surveillance over the long term

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent ensures continuity of useful action through compounds formulated for sustained release and prolonged IDO inhibition. The molecular structures are designed to maintain therapeutic concentrations and continuous immune system activation, preventing tumor cell adaptation and ensuring long-term treatment success

Inventive Principle:

Principle #20Continuity of useful action

3Object-affected harmful factors

If immunotherapy is used to treat cancer, then toxicity is reduced compared to traditional chemotherapy, but efficacy is limited by tumor manipulation of immune function through IDO upregulation

Engineering Contradiction:

ImprovetoxicityVSAvoidtherapeutic impact

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent converts the harmful effect of IDO upregulation by tumors into a beneficial therapeutic target. By designing specific IDO inhibitors that selectively block IDO activity, the patent transforms the tumor's immune suppression mechanism into a validated drug target, enhancing immune response while maintaining the low toxicity profile of immunotherapy

Inventive Principle:

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

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 compounds effectively modulate IDO activity, providing therapeutic benefits in treating cancer, viral infections, and autoimmune diseases by altering tryptophan levels and immunosuppression, offering improved treatment options compared to existing IDO inhibitors.

Implementation Method 1

compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO)... IDO is an oxidoreductase and one of two enzymes that catalyze the first and rate-limiting step in the conversion of tryptophan to N-formylkynurenine

Methodology Applied

Scientific EffectEnzyme inhibition: Enzyme

Data Source

PatentUS10323004B2Inhibitors of indoleamine 2,3-dioxygenase and methods of their use

Publication Date: 2019.06.18 BRISTOL MYERS SQUIBB CO

AI summary

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.