Pentafluorophosphate Derivatives for Protein Tyrosine Phosphatase Inhibition
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Solution Overview
Problem
Current protein tyrosine phosphatase inhibitors lack effective binding and stability, limiting their clinical use and cellular penetration, necessitating the development of novel inhibitors with improved properties.
Innovation Solution
The development of pentafluorophosphate derivatives with specific structural features, such as alkyl and aryl chains interrupted by oxygen, sulfur, and nitrogen atoms, which exhibit enhanced binding and inhibition properties, including increased stability and cell penetration, enabling better interaction with protein tyrosine phosphatases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional phosphatase inhibitors are used, then binding to the active site is achieved, but stability and cellular penetration are insufficient
Solution Approach 1:
The patent changes the chemical parameters of the phosphatase inhibitor by introducing a pentafluorophosphate group instead of conventional phosphate or phosphonate groups. This parameter change results in enhanced binding stability and compound stability while maintaining phosphotyrosine mimicry. The specific chemical modification (PF5 group) directly addresses the stability issues of conventional inhibitors.
2Reliability
If conventional phosphatase inhibitors are used, then enzyme inhibition is achieved, but cell penetration ability is limited
Solution Approach 1:
The patent modifies the physical-chemical parameters of the inhibitor compound by incorporating the pentafluorophosphate group, which changes the hydrophilicity and membrane permeability characteristics. This parameter change enables the inhibitor to penetrate cell membranes effectively while maintaining its phosphatase inhibition capability.
3Reliability
If existing phosphatase inhibitors are used, then therapeutic effect is achieved, but delivery to site of action is insufficient
Solution Approach 1:
The patent changes the pharmacokinetic parameters of the inhibitor by introducing the pentafluorophosphate group, which improves membrane permeability and cellular uptake. This parameter change enhances the delivery efficiency of the inhibitor to the site of action within cells, thereby improving therapeutic efficacy.
Data Source
AI summary
It is provided a pentafluorophosphate derivative according to general formula (I):or a pharmaceutically acceptable salt or solvate thereof. Thereby, R1 and R2 denote independently from each other H or F; R3 denotes H, a C1-C10 alkyl optionally substituted by a hydrocarbon chain comprising an amide function and/or a carboxyl function, or by a substituent chosen from the group consisting of alkyl, alkylamino, alkylaminocarboxy, carboxy, alkoxycarbonyl, hydroxy, N-morpholino, N-morpholinoalkyl, N-morpholinocarbonyl, N-methyl-N-piperazinyl, N-methyl-N-piperazinylalkyl, N-methyl-N-piperazinylcarbonyl, and sulfo, an optionally substituted C3-C10 cycloalkyl, or an optionally substituted C6-C20 aryl, wherein a hydrocarbon chain of the alkyl, the cycloalkyl or the aryl can be interrupted by one or more oxygen, sulfur and/or nitrogen atoms; and M denotes any cation; with the proviso that at least one of R1 and R2 denotes F, if R3 denotes H.