Novel Steroidal Esters for Prostate Disorder Treatment
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Solution Overview
Problem
Current treatments for benign prostatic hyperplasia, such as Finasteride and Dutasteride, have side effects like decreased libido and erectile dysfunction, and there is a need for compounds that can effectively inhibit 5α-reductase activity and promote antiproliferative activity to reduce prostate size without these issues.
Innovation Solution
Development of novel steroidal esters of 17-oximino-5-androsten-3β-ol, synthesized from Dehydroandrosterone acetate, which exhibit high 5α-reductase inhibitory activity and antiproliferative effects, potentially offering a safer alternative for treating benign prostatic hyperplasia by decreasing androgen levels and inhibiting prostate cell growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Finasteride and Dutasteride are used to treat benign prostatic hyperplasia, then 5α-reductase activity is inhibited and prostate size is reduced, but side effects such as decreased libido and erectile dysfunction occur
Solution Approach 1:
The patent modifies the chemical structure of known 5α-reductase inhibitors by changing molecular parameters - specifically introducing oximino groups at position 17 and ester groups with various aromatic and aliphatic chains. These parameter changes in the molecular structure aim to alter the drug's interaction with the enzyme and/or androgen receptors, potentially improving the therapeutic index by reducing side effects while maintaining inhibitory efficacy.
Solution Approach 2:
The invention creates composite molecular structures by combining the steroidal core with oximino and ester functional groups. These composite structures integrate multiple pharmacophoric elements that work synergistically - the steroidal framework provides 5α-reductase binding, while the oximino-ester moieties may contribute to antiproliferative activity and reduced androgenic side effects, creating a multi-functional inhibitor.
2Reliability
If current 5α-reductase inhibitors are used, then prostate growth is suppressed, but antiproliferative activity is insufficient
Solution Approach 1:
The patent designs compounds that perform multiple functions simultaneously - acting as both 5α-reductase inhibitors (to suppress prostate growth) and antiproliferative agents (to directly inhibit prostate cell proliferation). The oximino-ester modified steroidal compounds are envisioned to have dual mechanisms of action, making them universal agents that address both the hormonal drive and the proliferative activity in BPH.
3Object-affected harmful factors
If novel steroidal esters are developed to reduce side effects, then compound complexity increases, but clinical applicability is improved
Solution Approach 1:
The patent segments the molecular structure into distinct functional modules - the steroidal core (providing 5α-reductase inhibition), the oximino group at position 17 (contributing to antiproliferative activity), and various ester groups (modulating pharmacokinetics and reducing androgenic side effects). This segmentation allows each component to be optimized independently for its specific function, managing overall molecular complexity through modular design.
Data Source
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AI summary
The present invention relates to steroidal esters of 17-oximino -5-androsten-3-ol,of compound of general formula A wherein R is selected form a group consisting of arylalkyl, aryl, substituted aryl. The ester derivatives are synthesized starting from Dehydroandrosterone acetate. The compounds were tested for their antiproliferative activity and 5a-reductase inhibitory activity in comparison to Finasteride. Decreased androgen level have been found in serum of animal treated with newly synthesized compounds. These compounds have also shown better cytotoxicity in comparison to reference drug Finasteride. Thus such compounds can be useful in treatment of androgen dependent disorder of prostate alone or by synergistic effect they can decrease the size of prostate due to their antiproliferative activity.