Design and Synthesis of New Biprivileged Molecular Scaffolds: Indolo‐Fused Benzodiazepinyl/quinoxalinyl benzimidazoles

Abstract

The present article describes the design and synthesis of new biprivileged molecular scaffolds with diverse structural features. Commercially available, simple heterocyclic building blocks such as 4-fluoro-3-nitrobenzoic acid, 2-chloro-3-nitrobenzoic acid, and indoline were utilized for the synthesis of the novel heterocycles. Pictet-Spengler-type condensation was used as a key step to construct tetracyclic indolo-benzodiazepines and indolo-quinoxalines linked with substituted benzimidazoles. Analysis of single crystals of representative compounds showed that these molecular skeletons have the potential to present various substituents with distinct three-dimensional orientations.

Microwave‐Assisted Synthesis of Benzimidazole‐Linked Indoline and Indole Hybrids from C‐2 Linked (o‐Aminobenzyl)benzimidazoles

“…Our planned synthesis started with the preparation of various C‐2‐linked ( o ‐aminobenzyl)benzimidazoles 5 . We first performed esterification of 4‐fluoro‐3‐nitrobenzoic acid and the resulting 4‐fluoro‐3‐nitrobenzoates were reacted with different amines followed by reduction of the nitro group to afford the corresponding 3,4‐diaminobenzoates 1 . In the next step, aminobenzoates 1 were coupled with 2‐(2‐nitrophenyl)acetic acid 2 in the presence of DCC and DMAP in dichloromethane at room temperature to obtain amides 3 in 75–95% yields.…”

Synthesis and structure elucidation using 2D NMR and thermal coefficient investigation on amino acid tethered quinoxalines

“…Methyl‐4‐fluoro‐3‐nitrobenzoate ( 1 ) was prepared according to a known procedure, and 0.5 g (2.34 mmol) of 1 , the amino acid esters 2a–n (3.51 mmol) and NaHCO 3 (0.005 g, 4.68 mmol) were mixed in tetrahydrofuran (THF) (10 ml). The reaction mixture was stirred overnight at room temperature.…”

Regioselective synthesis of densely functionalized, enantiopure, sugar–pyrazole hybrids as potential scaffolds for drug discovery

“…Thus, in the one pot process, DMP seems to be playing a dual role; first oxidising the allylic hydroxy group of the MBH adduct and then promoting the oxidative aromatization step. 17 The non-flat skeleton 18 of these sugar-pyrazole hybrid molecules as revealed by X-ray diffraction analysis and the presence of multiple points for diversification (Fig. 4) further highlight their suitability as scaffolds for drug discovery.…”