Parallel Approach for Solution-Phase Synthesis of 2-Quinoxalinol Analogues and Their Inhibition of LPS-Induced TNF-α Release on Mouse Macrophages in Vitro

Abstract

A parallel solution-phase synthesis of 2-quinoxalinol analogues is described. The key step-simultaneous reductions of m-Ar(NO2)2 to m-Ar(NH2)2 was investigated extensively. We obtained preliminary pharmacological activity of those analogues for the inhibition of LPS-induced TNF-alpha release on mouse macrophage in vitro. Two compounds revealed inhibitory activity, with IC50 values of 0.40 microM (7-amino-6-[(3-methoxypropyl)amino]-3-methyl-2-quinoxalinol) and 2.2 microM (7-amino-6-[(3-butoxypropyl)amino]-3-methyl-2-quinoxalinol), respectively.

Multistep Microwave-Assisted Divergent Synthesis of Indolo-Fused Pyrazino-/Diazepinoquinoxalinones on PEG Support

“…DFDNB is preferred to construct the designed skeletons because of its easy accessibility for two directional elongations via utilization of two fluoro groups which could be successively substituted by different nucleophiles. This symmetric scaffold has been utilized for the construction of various bioactive-fused heterocycles . Previously, we demonstrated the use of this bifunctional cross-linker for the synthesis of imidazoquinoxalinones on PEG support .…”

Present status of quinoxaline motifs: Excellent pathfinders in therapeutic medicine

“…A reagent-based diversification approach coupled with the Pictet-Spengler type condensation used, was also reported to afford of 4,5-dihydroimidazo-and imidazo [1,5-a]quinoxalines in another study [57]. <<<<Scheme 10>>>> (e) Although, the solution-phase parallel synthesis of a series of diamino-2-quinoxalinol derivatives was previously reported [58,59]. However, Wu and Gorden had simplified further and optimized the method for the synthesis of diamino-2-quinoxalinols 34 [60] by replacing the scavenger resins used in the previous investigations with 2 equivalents of DIPEA (diisopropylethyl amine) to remove the produced HF and HCl in first step (Scheme 11).…”

Solution-Phase Parallel Synthesis of a 1,2,7-Trialkyl-1H-imidazo[4,5-g]quinoxalin-6-ol Library Scaffold

“…In response, combinatorial chemistry has made significant achievements in this area during the past decade. We recently launched a “scaffold-directed” project to make benzofused chemical libraries using 1,5-difluoro-2,4-dinitrobenzene (DFDNB) as a unique starting material, such as 2-hydroxyquinoxaline and benzimidazole libraries. , To extend the scope of our recent studies, we report herein the parallel synthesis of a novel 1,2,7-trialky-1 H -imidazo[4,5- g ]quinoxalin-6-ol library.…”