Background: Aldose reductase, the first enzyme of the polyol pathway, is the key determinant for the pathogenesis of long term diabetic complications. Accordingly, its inhibition represents the major therapeutic strategy to treat this kind of pathologies. Objectives: In this work we describe the synthesis and the functional evaluation of a number of spiro-oxazolidinone and spiro-morpholinone acetic acid derivatives, and their benzyloxy analogs, developed as aldose reductase inhibitors. Results: Most of them proved to inhibit the target enzyme, showing IC50 values in the micromolar/low micromolar range. SARs observed among the three different series allowed to highlight their key pharmacophoric elements, thus creating sound basis for the design of novel and more effective inhibitors. Conclusion: Although further substitution patterns are needed, the novel compounds here proposed represent a good starting point for the development of novel and effective ARIs.

Synthesis and functional evaluation of novel aldose reductase inhibitors bearing a spirobenzopyran scaffold / Digiacomo, Maria; Sartini, Stefania; Nesi, Giulia; Sestito, Simona; Coviello, Vito; La Motta, Concettina; Rapposelli, Simona. - In: THE OPEN MEDICINAL CHEMISTRY JOURNAL. - ISSN 1874-1045. - 11:(2017), pp. 9-23. [10.2174/1874104501711010009]

Synthesis and functional evaluation of novel aldose reductase inhibitors bearing a spirobenzopyran scaffold

Sestito, Simona;
2017

Abstract

Background: Aldose reductase, the first enzyme of the polyol pathway, is the key determinant for the pathogenesis of long term diabetic complications. Accordingly, its inhibition represents the major therapeutic strategy to treat this kind of pathologies. Objectives: In this work we describe the synthesis and the functional evaluation of a number of spiro-oxazolidinone and spiro-morpholinone acetic acid derivatives, and their benzyloxy analogs, developed as aldose reductase inhibitors. Results: Most of them proved to inhibit the target enzyme, showing IC50 values in the micromolar/low micromolar range. SARs observed among the three different series allowed to highlight their key pharmacophoric elements, thus creating sound basis for the design of novel and more effective inhibitors. Conclusion: Although further substitution patterns are needed, the novel compounds here proposed represent a good starting point for the development of novel and effective ARIs.
Synthesis and functional evaluation of novel aldose reductase inhibitors bearing a spirobenzopyran scaffold / Digiacomo, Maria; Sartini, Stefania; Nesi, Giulia; Sestito, Simona; Coviello, Vito; La Motta, Concettina; Rapposelli, Simona. - In: THE OPEN MEDICINAL CHEMISTRY JOURNAL. - ISSN 1874-1045. - 11:(2017), pp. 9-23. [10.2174/1874104501711010009]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11388/236167
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