[1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a bioisostere of a carboxylic acid aldose reductase inhibitor.
Published Apr 9, 2004 · I. Nicolaou, C. Zika, V. Demopoulos
Journal of medicinal chemistry
Q1 SJR score
46
Citations
0
Influential Citations
Abstract
[1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) was synthesized as a putative bioisostere of the known aldose reductase (AR) inhibitor (3-benzoylpyrrol-1-yl)acetic acid (I). It was found that 6 is approximately 5 times more potent as an in vitro inhibitor of AR than I, with an IC(50) value in the submicromolar range. Furthermore, 6 showed considerable activity in an in vitro experimental glycation model of diabetes mellitus. Our results support the notion that 6 might become a useful lead structure.
Study Snapshot
Key takeaway[1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) is a potent aldose reductase inhibitor with potential as a useful lead structure for treating diabetes mellitus.
PopulationOlder adults (50-71 years)
Sample size24
MethodsObservational
OutcomesBody Mass Index projections
ResultsSocial networks mitigate obesity in older groups.
Aldose reductase and protein tyrosine phosphatase 1B inhibitors as a promising therapeutic approach for diabetes mellitus.
Dual inhibitors of aldose reductase and protein tyrosine phosphatase 1B show promise for treating insulin-resistant type II diabetes mellitus and related comorbidities.
2020·39citations·Antonios Kousaxidis et al.·European journal of medicinal chemistry
European journal of medicinal chemistry
Enhancing activity and selectivity in a series of pyrrol-1-yl-1-hydroxypyrazole-based aldose reductase inhibitors: The case of trifluoroacetylation.
Adding a trifluoroacetyl group to pyrrol-1-yl-1-hydroxypyrazole-based aldose reductase inhibitors enhances their activity and selectivity, potentially benefiting therapeutic interventions in diabetes, inflammation, and cancer.
2017·12citations·N. Papastavrou et al.·European journal of medicinal chemistry
European journal of medicinal chemistry
Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts
Tephrosia humilis aerial parts exhibit significant antioxidant capacity and strong inhibitory capacities against aldose reductase enzymes, potentially acting against long-term diabetic complications.
2016·7citations·Michael Plioukas et al.·Natural Product Research
Natural Product Research
Applications of Fluorine in Medicinal Chemistry.
Fluorine's strategic incorporation in drug molecules can influence conformation, pKa, intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties, with potential applications in positron emission tomography.
2015·2,135citations·E. Gillis et al.·Journal of medicinal chemistry
Journal of medicinal chemistry
Benzothiazolyl substituted iminothiazolidinones and benzamido-oxothiazolidines as potent and partly selective aldose reductase inhibitors
New oxothiazolidine benzoate and acetate derivatives show potent and partly selective inhibition of aldose reductase, potentially targeting long-term diabetic complications.
2014·19citations·A. Saeed et al.·MedChemComm
MedChemComm
Decreasing acidity in a series of aldose reductase inhibitors: 2-Fluoro-4-(1H-pyrrol-1-yl)phenol as a scaffold for improved membrane permeation.
The most active aldose reductase inhibitor, 31 (31F), shows promising membrane permeation and selective activity against aldehyde reductase, potentially benefiting diabetic complications and inflammation.
2014·18citations·M. Chatzopoulou et al.·Bioorganic & medicinal chemistry
Bioorganic & medicinal chemistry