Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Chatzopoulou, M.
Mamadou, E.
Juskova, M.
Koukoulitsa, C.
Nicolaou, I.
Stefek, M.
Demopoulos, V.J.
Περιοδικό:
BIOORGANIC AND MEDICINAL CHEMISTRY
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.bmc.2011.01.009
