Oxetanyl Sulfoxide Compounds for Fibrosis Treatment
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Solution Overview
Problem
Current therapies for fibrosis, such as idiopathic pulmonary fibrosis, are ineffective in reversing lung damage, and there is a need for alternative treatments beyond lung transplantation, as existing treatments like monoclonal anti-TGF-β antibodies have shown no efficacy.
Innovation Solution
Development of specific compounds, such as MMS-350 and its analogs, which are administered to subjects to inhibit fibrosis by reducing the deposition of extracellular matrix proteins and mitigating the effects of TGF-β, thereby treating fibrosis and providing radioprotection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal anti-TGF-β antibody is administered, then TGF-β signaling is blocked, but clinical efficacy is not achieved
Solution Approach 1:
The patent transitions from using monoclonal antibodies (large molecular weight, complex administration) to small molecule compounds (lower molecular weight, simpler administration) that target the same TGF-β pathway. This parameter change in molecular size and chemical structure maintains therapeutic efficacy while simplifying the treatment approach.
Solution Approach 2:
The invention employs small molecule compounds that can be administered orally or via simpler routes compared to monoclonal antibodies requiring intravenous infusion. These small molecules represent a more accessible, potentially cheaper alternative with easier logistics and administration.
2Ease of operation
If existing fibrosis therapies are administered, then treatment is provided, but reversal of lung damage is not achieved
Solution Approach 1:
The small molecule compounds act as intermediaries that block TGF-β signaling downstream of the receptor, preventing the fibrotic cascade without requiring neutralization of TGF-β itself. This intermediary approach provides therapeutic effectiveness where direct TGF-β neutralization failed.
Solution Approach 2:
The patent changes the therapeutic parameter from protein-based biologics to small molecule chemistry, enabling oral administration and potentially better tissue penetration while achieving the desired anti-fibrotic effect that previous therapies未能 accomplish.
Data Source
AI summary
A compound, or a pharmaceutically acceptable salt thereof, having a structure ofwherein Z is aryl or substituted aryl, heteroaryl, or substituted heteroaryl;X is —S—, —S(O)—, or S(O)2—;R20 and R21 are each independently H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, or halogenated alkyl;one of R22, R23, and R24 is —O— and the others of R22, R23 and R24 are independently —CH2—, or —C(R13)— wherein R13 is alkyl, alkenyl, alkynyl, trialkylsilyl group, or —(CH2)mOR15, wherein R15 is alkyl or an aryl and m is an integer in the range of 1 to 10; andR25 is H, alkyl, substituted alkyl, halogen, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C1-C3 alkoxy, aryloxy, or —(CH2)qOR17, wherein R17 is alkyl an aryl and q is an integer in the range of 1 to 10.