Design and synthesis of novel series of pyrrole based chemotypes and their evaluation as selective aldose reductase inhibitors. A case of bioisosterism between a carboxylic acid moiety and that of a tetrazole

作者：Pegklidou Kyriaki; Koukoulitsa Catherine; Nicolaou Ioannis^*; Demopoulos Vassilis J

来源：Bioorganic & Medicinal Chemistry, 2010, 18(6): 2107-2114.

DOI：10.1016/j.bmc.2010.02.010

• Antidiabetic aldose reductase inhibitors
• Antioxidant activity
• Nonclassical bioisosterism
• Selectivity

Pyrrolyl-propionic and butyric-acid derivatives 1 and 2 were synthesized in order to study the effect of the variation of the methylene chain in comparison to the previously reported pyrrolyl-acetic acid compound I, which was found as potent aldose reductase inhibitor, while the pyrrolyl-tetrazole derivatives 3-5 were prepared as a non-classical bioisosteres of a carboxylic acid moiety. Also, pyrrolyl-tetrazole isomers 6 and 7 without an alkyl chain between the two aromatic rings were synthesized. The in vitro aldose reductase inhibitory activity of the prepared 1-7 compounds were estimated and compared with that of the initial compound ( I). Overall, the data indicate that the presented chemotypes 6 and 7 are a promising lead compounds for the development of selective aldose reductase inhibitors, aiming to the long-term complications of diabetes mellitus.

• 出版日期2010-3-15