Retinoid Derivatives Modifying Metabolic Stability and Selectivity
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Solution Overview
Problem
Despite decades of research, there is a strong medical need for more potent retinoid derivatives with antiangiogenic, antitumoral, and pro-apoptotic activities to effectively treat various cancers and related diseases.
Innovation Solution
Development of compounds of formula (I) with specific structural features, including various substituents and functional groups, which exhibit antiangiogenic, antitumoral, and pro-apoptotic activities, useful for treating neoplasms, arthritic conditions, and other pathological states, through their cytotoxic and apoptotic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If retinoid derivatives are developed to enhance cytotoxic and antiangiogenic activities, then therapeutic efficacy against cancer is improved, but metabolic elimination through glucuronidation increases leading to reduced drug stability
Solution Approach 1:
The patent modifies the chemical structure of retinoid derivatives by introducing specific substituents at the 4' position (adamantyl, hydroxyphenyl, cinnamic acid groups) to alter metabolic parameters. These structural changes reduce glucuronidation rates while preserving or enhancing cytotoxic and antiangiogenic activities, thereby improving drug stability without sacrificing therapeutic efficacy.
2Reliability
If retinoid derivatives with enhanced potency are designed, then cancer treatment effectiveness is improved, but selectivity between tumor cells and normal cells deteriorates
Solution Approach 1:
The patent introduces specific functional groups at particular positions of the retinoid molecule (e.g., 4'-hydroxyphenyl, cinnamic acid moieties) to create localized regions of enhanced interaction with tumor-specific targets. This local modification approach improves potency against cancer cells while maintaining selectivity by targeting specific molecular pathways preferentially expressed or activated in tumor cells.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These compounds demonstrate significant therapeutic potential by inhibiting cancer cell proliferation and metastasis, offering effective treatment options for a range of cancers and conditions, including malignant neoplasms, sarcomas, carcinomas, and other pediatric and adult cancers.
Implementation Method 1
retinoid derivatives that bind to nuclear retinoid receptors; retinoic acid receptors (RAR) and retinoid X receptors (RXR). Once the retinoid derivative is coupled to the receptors, the latter form homo- or heterodimers, and through binding to the response element (RARE or RXRE) upstream of the target gene, regulates the gene expression as a transcriptional factor
Implementation Method 2
retinoid derivatives endowed with antiangiogenic, antitumoral and pro-apoptotic activities
Implementation Method 3
potent pro-apoptotic agent for the treatment of neoplastic diseases
Implementation Method 4
retinoid derivatives endowed with antiangiogenic, antitumoral and pro-apoptotic activities
Data Source
AI summary
The present invention relates to new retinoid derivatives of Formula (I), and to pharmaceutical compositions containing them for the treatment of patients affected by pathologies such as arthritic conditions, tumours, metastatic cancer, diabetic retinopathy, psoriasis, chronic inflammatory diseases or atherosclerosis.