Crystalline AR Modulator Forms for Agonist-Free Prostate Cancer Control
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Solution Overview
Problem
Current treatments for prostate cancer, particularly hormone refractory prostate cancer, are limited in efficacy due to the continued dependence of cancer cells on androgen receptor (AR) signaling, and existing anti-androgens can exhibit agonist activity, leading to resistance and recurrence.
Innovation Solution
The development of 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide, which inhibits AR nuclear translocation and binding to DNA, providing a novel approach to target AR activity without agonist activity, suitable for various prostate cancer stages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-androgens are used to treat prostate cancer, then androgen receptor signaling is blocked, but agonist activity occurs leading to resistance and recurrence
Solution Approach 1:
The patent modifies the chemical structure of anti-androgen compounds by introducing specific substituents (e.g., fluorine atoms at positions 2 and 4 of the benzamide ring, cyano and trifluoromethyl groups on the pyridine ring) to alter the molecular properties. These parameter changes in the chemical structure eliminate agonist activity while maintaining antagonist efficacy against androgen receptor signaling in prostate cancer treatment
2Reliability
If conventional treatments are used for hormone refractory prostate cancer, then some androgen receptor blocking is achieved, but continued dependence on AR signaling persists
Solution Approach 1:
The invention employs parameter changes in the molecular structure of the androgen receptor modulator, specifically the spiro[3.4]octane core with diazaspiro structure combined with substituted pyridine and benzamide groups. These structural parameter changes enable the compound to effectively block AR signaling even in hormone refractory prostate cancer where conventional treatments fail to eliminate AR dependence
Data Source
AI summary
Described herein are amorphous and crystalline forms of the androgen receptor modulator 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide. Also described are pharmaceutical compositions suitable for administration to a mammal that include the androgen receptor modulator, and methods of using the androgen receptor modulator, alone and in combination with other compounds, for treating diseases or conditions that are associated with androgen receptor activity.