NAD-Modulating Compounds for Selective Tissue Intervention

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Solution Overview

Problem

There is a need for improved compositions and methods for pharmacologic intervention and controlled modulation of the NAD pathway in living cells and tissues, as existing naturally-occurring compounds are insufficient for certain modulations.

Innovation Solution

Development of compounds and compositions that modulate nicotinamide adenine dinucleotide (NAD) levels in cells, including pharmaceutical compositions containing NAD-modulating compounds, to increase or maintain intracellular NAD levels for therapeutic purposes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If naturally-occurring compounds are used to modulate NAD levels, then the modulation is limited to natural pathways, but the ability to achieve controlled pharmacologic intervention and specific modulations is insufficient

Engineering Contradiction:
Improvemodulation capabilityVSAvoidcontrolled intervention
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of NAD-related compounds through synthetic chemistry. Specific parameters changed include: adding functional groups (hydroxyl, carboxyl, amino groups), modifying ring structures (pyridine, pyrimidine rings), changing chain lengths and positions of substituents. These structural parameter changes enable the compounds to selectively modulate NAD pathways with controlled pharmacologic intervention, achieving both adaptability and reliability.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If NAD levels are increased in all cells, then healthy cell survival is improved, but unhealthy cells are not selectively targeted

Engineering Contradiction:
Improvehealthy cell protectionVSAvoidselective targeting
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by designing compounds with specific structural features that enable selective interaction with NAD pathways in different cell types. The compounds contain localized functional groups (such as specific hydroxyl positions, carboxyl groups at defined positions) that confer selectivity. This allows the same compound to be taken up by cells and modulate NAD levels locally in a cell-type-specific manner, achieving both healthy cell protection and selective targeting of unhealthy cells.

Inventive Principle:
Principle #3Local quality

3Ease of manufacture

If existing NAD compounds are used, then the synthesis follows natural pathways, but the manufacturing precision and structural diversity are limited

Engineering Contradiction:
Improvesynthesis feasibilityVSAvoidstructural control
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent applies segmentation by dividing the synthesis of complex NAD-modulating compounds into separate modular steps. The synthesis is segmented into: (1) preparation of substituted pyridine or pyrimidine ring structures, (2) attachment of ribose or deoxyribose moieties, (3) addition of functional groups at specific positions, (4) final coupling to form the complete NAD analog. This segmented approach enables precise structural control at each stage while maintaining overall synthesis feasibility.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP4013766B1Compounds and compositions for differential modulation of nicotinamide adenine dinucleotide
Publication Date: 2025.01.22 METRO INTERNATIONAL BIOTECH LLC
  • EP4013766B1 patent drawingFigure 1A~1B
  • EP4013766B1 patent drawingFigure 2A~2C
  • EP4013766B1 patent drawingFigure 3A~3D

AI summary

The invention relates to compounds and compositions for differential modulation of nicotinamide adenine dinucleotide (NAD) in various tissues or cell types. Further, the invention relates to pharmaceutical compositions containing one or more NAD-modulating compounds as an active pharmaceutical ingredient. The invention also relates to methods of making such compounds and compositions. Methods of using such compounds or compositions include administration of such compounds and compositions to promote the increase or maintenance of intracellular levels of nicotinamide adenine dinucleotide (NAD) in healthy cells and tissues thus improving healthy cell and tissue survival. Also included are methods of increasing or maintaining intracellular levels of NAD in selected cells or tissues while simultaneously reducing NAD levels in unhealthy tissue or cells thus reducing the survival of unhealthy cells and tissue.