Synthesis and Structure–Activity Relationship Studies of Quinoxaline Derivatives as Aldose Reductase Inhibitors

Abstract

ARIs for diabetes: A series of 2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetic acid derivatives were designed and synthesized as inhibitors of aldose reductase (AR), a novel target for the treatment of diabetes complications. Most of the derivatives proved to be potent and selective, with IC50 values in the low nanomolar to micromolar range.

Phenolic compounds inhibit the aldose reductase enzyme from the sheep kidney

“…They examined its inhibitory effects on AR and determined that 3,6,7,4’,5’‐pentamethoxy‐5,3’‐dihydroxyflavone has significant inhibition on AR of rat's retina. Recently, researchers found various classes of ARIs, in which quinoxaline derivatives having a substituted phenoxyl or benzyl group as C3 side chain showed distinguished activity . Hussain et al .…”

Recent Advances in Photocatalytic Functionalization of Quinoxalin‐2‐ones

“…CPCC 200497, has shown moderate cytotoxicity against cancer cell line HepG2, [3] Caroverine has shown muscle relaxant activity, [4] and other derivatives have shown different pharmaceutical properties. Several quinoxalin-2-ones have been reported as antitumor agents, [5] antimicrobial compound, [6] angiotensin II receptor antagonist, [7] aldolase reductase inhibitor, [8] cannabinoid CB2 receptor agonist, [9] histamine-4 receptor antagonist, [10] epsteine-Barr virus inhibitor [11] among others. [12] Additionally, 3-arylquinoxalin-2-(1H)one derived polymers have been described as semiconductors having applications for material science.…”

Aromatic Heterobicyclics-Based Design of Aldose Reductase Inhibitors as Drug Candidates for the Treatment of Diabetic Complications

“…In the recent few years, the aromatic heterbiocyclic structures including benzothiadiazine, pyridythiadiazine, benzothiazine, and quinoxalinone have been found to be excellent framework for the ARI drug design, which led to a number of novel and potent series 1-7 ( Figure 2) [2,[8][9][10][11][12][13][14][15][16] as promising drug candidates for the treatment of diabetic complications. ( Figure 2) Table 1 shows the specific structure and inhibitory activity data of representative samples of each heterocyclic scaffold.…”

“…Benzyl groups as the side chains in the case of quinoxalinone series seem to have more impact on the inhibitory activity against ALR2 than phenoxyl groups as comparing the compounds 5c (IC 50 =6.4 nM) and 6b (IC 50 =23 nM) as shown in Table 1, but this effect is depending on substituents both at aromatic rings of the side chain and scaffold. Moreover, longer length of carbon chain spacer of the side chain leads to increase in the potency of quinoxalinone ARIs [8,13].…”