Spirolactone Compounds Inhibit ACC1 and ACC2 Enzymes
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Solution Overview
Problem
Current treatments for conditions associated with aberrant ACC1 and ACC2 activities, such as non-alcoholic steatohepatitis, acne, obesity, and cancer, lack effective inhibitors to modulate these enzymes, leading to inadequate therapeutic options.
Innovation Solution
Development of spirolactone compounds that act as inhibitors of ACC1 and ACC2, which can be administered alone or in combination with other therapies, formulated for various routes of administration including topical and oral, to inhibit ACC activities and treat related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for conditions associated with aberrant ACC1 and ACC2 activities, then existing therapeutic options are maintained, but effective inhibition of ACC activities is not achieved
Solution Approach 1:
The patent employs structure-activity relationship analysis to optimize the chemical structure of spirolactone compounds, systematically varying molecular parameters (substituents at positions R1-R6) to enhance ACC inhibitory activity. This includes modifying the core spirolactone structure with different aromatic rings, heterocycles, and substituent patterns to achieve potent and selective ACC inhibition for treating metabolic disorders
Solution Approach 2:
The invention creates composite pharmaceutical formulations combining spirolactone compounds with excipients and delivery systems. The compounds are formulated as pharmaceutical compositions that may include multiple components working synergistically to achieve effective drug delivery, stability, and therapeutic effect while minimizing side effects
2Reliability
If spirolactone compounds are developed as ACC inhibitors, then effective therapeutic options are created, but synthesis complexity increases
Solution Approach 1:
The synthesis of spirolactone compounds is divided into modular stages: preparation of substituted phenol or phenyl ether starting materials, formation of the spirolactone core structure through cyclization, and subsequent functional group transformations. This segmented approach allows for systematic optimization of each synthetic step and facilitates parallel synthesis of analogs
Solution Approach 2:
The patent employs preliminary protection of functional groups (such as silyl protection of hydroxyl groups) during synthesis to prevent unwanted side reactions. Protecting groups are strategically applied before key cyclization steps and removed in controlled sequences to ensure high yields and purity of the final spirolactone compounds
Data Source
AI summary
Provided herein are spirolactone compounds of Formula I that are useful as inhibitors of ACC1 and/or ACC2. The spirolactone compounds described herein can be used for treating a disease or disorder associated with aberrant ACC1 and/or ACC2 activities, for example, non-alcoholic steatohepatitis (NASH), acne, obesity, diabetes, and cancer. Also provided herein are pharmaceutical compositions comprising the spirolactone compound of Formula I, or pharmaceutically acceptable salt thereof.