@article{3061755,
    title = "Structure-activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H- pyrrol-3-yl]phenylmethanone. the effect of methoxy substitution on aldose reductase inhibitory activity and selectivity",
    author = "Chatzopoulou, M. and Mamadou, E. and Juskova, M. and Koukoulitsa, C. and Nicolaou, I. and Stefek, M. and Demopoulos, V.J.",
    journal = "BIOORGANIC AND MEDICINAL CHEMISTRY",
    year = "2011",
    volume = "19",
    number = "4",
    pages = "1426-1433",
    issn = "0968-0896",
    doi = "10.1016/j.bmc.2011.01.009",
    keywords = "1 (3,5 difluoro 4 hydroxyphenyl) 1H pyrrol 2 yl] 3 methoxyphenylmethanone;  1 (3,5 difluoro 4 hydroxyphenyl) 1H pyrrol 2 yl] 4 methoxyphenylmethanone;  1 (3,5 difluoro 4 hydroxyphenyl) 1H pyrrol 2 yl]phenylmethanone;  1 (3,5 difluoro 4 hydroxyphenyl) 1H pyrrol 3 yl] 3 methoxyphenylmethanone;  1 (3,5 difluoro 4 hydroxyphenyl) 1H pyrrol 3 yl] 4 methoxyphenylmethanone;  1 (3,5 difluoro 4 hydroxyphenyl) 1H pyrrol 3 yl]phenylmethanone;  aldehyde reductase;  aldose reductase inhibitor;  sorbitol;  unclassified drug, animal experiment;  animal tissue;  antioxidant activity;  article;  drug potency;  drug selectivity;  drug synthesis;  enzyme inhibition;  male;  nonhuman;  rat;  simulation;  structure activity relation, Aldehyde Reductase;  Animals;  Enzyme Inhibitors;  Models, Molecular;  Phenols;  Pyrroles;  Rats;  Rats, Inbred F344;  Structure-Activity Relationship, Rattus",
    abstract = "Based on our previous work, we studied the effect of methoxy-substitution as well as the regioposition of the benzoyl-moiety of 4a [(1-(3,5-difluoro-4- hydroxyphenyl)-1H-pyrrol-3-yl)(phenyl)methanone]. On this basis, compounds 4b-c and 5a-c were synthesized and assayed for aldose and aldehyde reductase inhibitory activity. Furthermore, a 4,6-difluoro-5-hydroxyphenyl pattern (9) was studied, in order to verify the optimum position of the phenol-moiety. Compound 5b emerged as the most potent and selective inhibitor. Moreover, further assays proved 5b as a potent antioxidant and an inhibitor of sorbitol accumulation in isolated rat lenses. Combining the above attributes, 5b could serve as a lead compound targeted at long-term diabetes complications. © 2011 Elsevier Ltd. All rights reserved."
}