ER Modulator Scaffold for Metastatic and Resistant Disease
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Solution Overview
Problem
There is a need for new ER-α targeting agents that exhibit activity in the setting of metastatic disease and acquired resistance, particularly in conditions mediated by estrogen receptors.
Innovation Solution
Development of tetrahydro-pyrido[3,4-b]indol-1-yl compounds with estrogen receptor modulation activity, including Formula Ib or Ie structures, their stereoisomers, tautomers, and pharmaceutically acceptable salts, formulated into pharmaceutical compositions for treating ER-related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing estrogen receptor targeting agents are used, then treatment of early-stage disease is effective, but activity in metastatic disease and acquired resistance is insufficient
Solution Approach 1:
The patent applies parameter changes by developing novel chemical compounds with modified molecular structures (Formula Ib and Ie) that differ from existing ER targeting agents. These structural parameter changes enable the compounds to maintain efficacy in early-stage disease while also demonstrating activity in metastatic disease and acquired resistance settings, thus resolving the contradiction between reliable treatment and adaptability to resistant conditions
2Adaptability or versatility
If new ER-α targeting agents are developed for metastatic disease and acquired resistance, then activity in resistant conditions improves, but development complexity and validation requirements increase
Solution Approach 1:
The patent employs segmentation by dividing the development into distinct compound series (Formula Ib and Ie) with systematic variations in molecular substituents. This segmented approach allows for methodical optimization of activity in metastatic disease and acquired resistance while managing structural complexity through modular chemical design rather than creating entirely complex novel structures
Data Source
AI summary
Described herein are tetrahydro-pyrido[3,4-b]indol-1-yl compounds with estrogen receptor modulation activity or function having the Formula I structure: and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such estrogen receptor modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.