About This Special Issue
The synthetic route to synthesize desired benzopyrazines has been present in Scheme-1. In the first step, the α-methyl group of acetophenone was oxidized to carbonyl group by using selenium dioxide. The dicarbonyl intermediate 4 was then reacted without purification with 4-methylbenzene-1,2-diamine at room temperature to afford corresponding benzopyrazine (Scheme-1). Following the optimized method, a range of novel benzopyrazines has been prepared (Shah, et al., 2010, Wang, et al., 2009). 1H NMR spectra of the resulting products showed two regio-isomers in 1:1 to 1:0.5 ratio due to difference in reactivity of C-2 keto and C-3 aldehyde moieties in intermediate 4. The structure of two regio-isomers were fully characterize by 1H and 13C NMR two dimensional NMR techniques including COSY, NOESY, HSQC, and HMBC. Regio-isomers separation was proved to be difficult in different solvent systems. Only an isomer of 3'-bromo benzopyrazine 6i' was isolated that help to assign the structure of regioisomers from NMR data.
In this study, we synthesized sixteen benzopyrazine derivatives and screen evaluated them against ARL2 as well as ALR1 for selectivity purpose.
Aims and Scope:
- Role of aldose reductase (ALR2) in diabetic complications
- (16) methyl benzopyrazines were screened against aldose reductase
- 3'-hydroxyphenyl benzopyrazine 6l was found most active (IC50 = 1.34 ± 0.07 µM)
- 3'-bromophenyl analogue 6i showed comparable activity for ALR2
- Polyol pathway
- Benzopyrazines as aldose inhibitors