2-Pyridyloxy-3-Ester-4-Ether Orexin Antagonists

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Solution Overview

Problem

Current treatments for neurological and psychiatric disorders associated with orexin receptors lack effective antagonists, which are essential for managing sleep disorders, insomnia, and other related conditions.

Innovation Solution

Development of 2-pyridyloxy-3-ester-4-ether compounds that act as antagonists for orexin receptors, potentially treating or preventing neurological and psychiatric disorders by inhibiting orexin receptor activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for neurological and psychiatric disorders are used, then existing therapeutic options are available, but effective orexin receptor antagonists are lacking

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidavailability of antagonist compounds

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs parameter changes by systematically varying molecular structures of compounds to optimize their binding affinity and selectivity for orexin receptors. By modifying chemical parameters such as substituent groups, molecular weight, and structural configuration, the invention develops compounds with improved therapeutic effectiveness and receptor specificity, directly addressing the lack of effective antagonists

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies segmentation by dividing the orexin receptor antagonist development into distinct molecular components and subclasses. The compounds are structured with specific functional groups and structural elements that can be independently optimized, allowing systematic development of multiple antagonist variants with different profiles for treating various neurological and psychiatric conditions

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If orexin receptor antagonists are developed, then sleep disorders and insomnia can be treated, but the compounds must achieve high selectivity and affinity for orexin receptors

Engineering Contradiction:

Improvetherapeutic application rangeVSAvoidcompound selectivity and affinity

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by optimizing specific regions of the molecular structure to enhance binding to particular orexin receptor subtypes. By modifying local chemical properties such as hydrogen bonding capabilities, hydrophobic regions, and electrostatic interactions at specific molecular locations, the compounds achieve high selectivity for orexin receptors while maintaining broader therapeutic applicability across different neurological and psychiatric disorders

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS9975876B22-pyridyloxy-3-ester-4-ether orexin receptor antagonists

Publication Date: 2018.05.22 MERCK SHARP & DOHME LLC

AI summary

The present invention is directed to 2-pyridyloxy-3-ester-4-ether compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyloxy-4-ether compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.