251649-37-3

Upstream product

• 696-59-3 cis,trans-2,5-dimethoxytetrahydrofuran 
• 6972-71-0 4,5-dimethyl-2-nitrobenzenamine 

Downstream Products

• 251649-42-0 2–(1H–pyrrol–1–yl)–4,5-dimethylaniline 

Relevant academic research and scientific papers

Simple and green synthesis of benzimidazoles and pyrrolo[1,2-: A] quinoxalines via Mamedov heterocycle rearrangement

A method for the synthesis of coupling compounds of benzimidazoles and pyrrolo[1,2-a]quinoxalines via Mamedov Heterocycle Rearrangement is reported here. This method was conducted at room temperature and only solvent (HOAc) was required. A series of 4-(1H-benzo[d]imidazol-2-yl)pyrrolo[1,2-a]quinoxaline derivatives were obtained in moderate to good yields.

Pyrrolo[1,2-a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B

PTP1B dephosphorylates insulin receptor and substrates to modulate glucose metabolism. This enzyme is a validated therapeutic target for type 2 diabetes, but no current drug candidates have completed clinical trials. Pyrrolo[1,2-a]quinoxalines substituted at positions C1–C4 and/or C7–C8 were found to be nontoxic to cells and good inhibitors in the low- to sub-micromolar range, with the 4-benzyl derivative being the most potent inhibitor (0.24 μm). Some analogues bearing chlorine atoms at C7 and/or C8 kept potency and showed good selectivity compared to TCPTP (selectivity index '40). The most potent inhibitors behaved as insulin mimetics by increasing glucose uptake. The 4-benzyl derivative inhibited insulin receptor substrate 1 and AKT phosphorylation. Molecular docking and molecular dynamics simulations supported a putative binding mode for these compounds to the allosteric α3/α6/α7 pocket, but inconsistent results in enzyme inhibition kinetics were obtained due to the high tendency of these inhibitors to form stable aggregates. Computational calculations supported the druggability of inhibitors.

Copper-Catalyzed Synthesis of Alkyl-Substituted Pyrrolo[1,2- a ]quinoxalines from 2-(1 H -Pyrrol-1-yl)anilines and Alkylboronic Acids

A radical pathway for the construction of pyrrolo[1,2- a ]quinoxalines by using 2-(1 H -pyrrol-1-yl)anilines and alkylboronic acids has been developed. Features of this process include Cu catalysis, readily accessible starting materials, and simple operat

Ruthenium-Catalyzed Synthesis of Pyrrolo[1,2- A [quinoxaline Derivatives from 1-(2-Aminophenyl)pyrroles and Sulfoxonium Ylides

A ruthenium-catalyzed [5+1] annulation of 1-(2-aminophenyl)pyrroles with α-carbonyl sulfoxonium ylides is reported. This reaction provides a one-step method for synthesizing pyrrolo[1,2- A [quinoxaline derivatives under ambient conditions. The system proceeds with a short reaction time and a high functional-group tolerance. Notably, this divergent protocol tolerates β-keto sulfoxonium ylides and can be applied to α-ester sulfoxonium ylides. A preliminary study was made of the mechanism of the reaction, and a reaction pathway is proposed.

TFAA-Catalyzed Annulation Synthesis of Spiro Pyrrolo[1,2-a]quinoxaline Derivatives from 1-(2-Aminophenyl)pyrroles and Benzoquinones/Ketones

A metal-free trifluorosulfonate anhydride (TFAA)-catalyzed strategy for the synthesis of spiro pyrrolo[1,2-a]quinoxalines from 1-(2-aminophenyl)pyrroles and benzoquinones/ketones has been developed. With this general method, spiro pyrrolo[1,2-a]quinoxalin

Copper-catalyzed tandem aerobic oxidative cyclization for the synthesis of 4-cyanoalkylpyrrolo[1,2-a]quinoxalines from 1-(2-aminophenyl)pyrroles and cyclobutanone oxime esters

A copper-catalyzed tandem ring-opening/cyclization reaction for the synthesis of 4-cyanoalkylpyrrolo[1,2-a]quinoxalines from 1-(2-aminophenyl)pyrroles and cyclobutanone oxime esters has been developed. This reaction involves C-C bond cleavage and C-C and C-N bond constructions with good functional group tolerance. A wide range of products are obtained in moderate to good yields under mild conditions.

Harnessing the pyrroloquinoxaline scaffold for FAAH and MAGL interaction: Definition of the structural determinants for enzyme inhibition

This paper describes the development of piperazine and 4-aminopiperidine carboxamides/carbamates supported on a pharmacogenic pyrroloquinoxaline scaffold as inhibitors of the endocannabinoid catabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Structure-activity relationships and molecular modelling studies allowed the definition of the structural requirements for dual FAAH/MAGL inhibition and led to the identification of a small set of derivatives (compounds 5e, i, k, m) displaying a balanced inhibitory profile against both enzymes, with compound 5m being the frontrunner of the subset. Favorable calculated physico-chemical properties suggest further investigation for specific analogues.

Gold(I)/chiral br??nsted acid catalyzed enantioselective hydroamination-hydroarylation of alkynes: The effect of a remote hydroxyl group on the reactivity and enantioselectivity

The catalytic enantioselective hydroamination-hydroarylation of alkynes under the catalysis of (R3P)AuMe/(S)-3,3a?2-bis(2,4,6-triisopropylphenyl)-1,1a?2-bi-naphthyl-2,2a?2-diyl hydrogenphosphate ((S)-TRIP) is reported. The alkyne was reacted with a range of pyrrole-based aromatic amines to give pyrrole-embedded aza-heterocyclic scaffolds bearing a quaternary carbon center. The presence of a hydroxyl group in the alkyne tether turned out to be very crucial for obtaining products in high yields and enantioselectivities. The mechanism of enantioinduction was established by carefully performing experimental and computational studies.

Pyrroloquinoxaline derivatives as high-affinity and selective 5-HT3 receptor agonists: Synthesis, further structure-activity relationships, and biological studies

The synthesis, pharmacological evaluation, and structure-activity relationships (SARs) of a series of novel pyrroloquinoxalines and heteroaromatic-related derivatives are described. The new pyrroloquinoxaline- related ligands were tested in rat cortex, a tissue expressing high density of 5-HT3 receptors, and on NG108-15 cells and exhibited IC50 values in the low nanomolar or subnanomolar range, as measured by the inhibition of [3H]zacopride binding. The SAR studies detailed herein delineated a number of structural features required for improving affinity. Some of the ligands were employed as 'molecular yardsticks' to probe the spatial dimensions of the lipophilic pockets L1, L2, and L3 in the 5-HT3 receptor cleft, while the 7-OH pyrroloquinoxaline analogue was designed to investigate hydrogen bonding with a putative receptor site H1 possibly interacting with the serotonin hydroxy group. The most active pyrroloquinoxaline derivatives showed subnanomolar affinity for the 5-HT3 receptor. In functional studies ([14C]guanidinium accumulation test in NG108-15 hybrid cells, in vitro) most of the tested compounds showed clear-cut 5-HT3 agonist properties, while some others were found to be partial agonists. Several heteroaromatic systems, bearing N-substituted piperazine moieties, have been explored with respect to 5-HT3 affinity, and novel structural leads for the development of potent and selective central 5-HT3 receptor agonists have been identified. Preliminary pharmacokinetic studies indicate that these compounds easily cross the blood brain barrier (BBB) after systemic administration with a brain/plasma ratio between 2 and 20, unless they bear a highly hydrophilic group on the piperazine ring. None of the tested compounds showed in vivo anxiolytic-like activity, but potential analgesic-like properties have been possibly disclosed for this new class of 5-HT3 receptor agonists.