Annelation of pyrrolo[1,2-a]pyrimidine and pyrido[1,2-a]pyrimidine systems to a pyrazolopyridine framework by a cascade of two cyclization reactions

Acosta, Paola; Insuasty, Braulio; Abonı́a, Rodrigo; Quiroga, Jairo

doi:10.1016/j.tetlet.2015.04.068

Cited by 9 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The action of the agonist may be stimulatory or inhibitory [ 26 ]). As a starting point, we used as a reference these pharmacophoric features previously described and the structural similarity between the TASK-3 blocker GW2974 benzopyrazole [ 15 ] and pyrazolo [3,4- b ]pyridine compounds, which has been one of the most well studied scaffolds in our laboratory in the last years [ 27 ] ( Figure 2 H). Our pharmacophore-based preliminary design (upon reagent availability) resulted in nine compound candidates ( Figure 2 I–L).…”

Section: Resultsmentioning

confidence: 99%

5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis

et al. 2021

Self Cite

View full text Add to dashboard Cite

TASK channels belong to the two-pore-domain potassium (K2P) channels subfamily. These channels modulate cellular excitability, input resistance, and response to synaptic stimulation. TASK-channel inhibition led to membrane depolarization. TASK-3 is expressed in different cancer cell types and neurons. Thus, the discovery of novel TASK-3 inhibitors makes these bioactive compounds very appealing to explore new cancer and neurological therapies. TASK-3 channel blockers are very limited to date, and only a few heterofused compounds have been reported in the literature. In this article, we combined a pharmacophore hypothesis with molecular docking to address for the first time the rational design, synthesis, and evaluation of 5-(indol-2-yl)pyrazolo[3,4-b]pyridines as a novel family of human TASK-3 channel blockers. Representative compounds of the synthesized library were assessed against TASK-3 using Fluorometric imaging plate reader—Membrane Potential assay (FMP). Inhibitory properties were validated using two-electrode voltage-clamp (TEVC) methods. We identified one active hit compound (MM-3b) with our systematic pipeline, exhibiting an IC50 ≈ 30 μM. Molecular docking models suggest that compound MM-3b binds to TASK-3 at the bottom of the selectivity filter in the central cavity, similar to other described TASK-3 blockers such as A1899 and PK-THPP. Our in silico and experimental studies provide a new tool to predict and design novel TASK-3 channel blockers.

show abstract

Section: Resultsmentioning

confidence: 99%

5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The pyrrolopyrimidine is an important class of N ‐heterocyclic compounds which has displayed various biological activities such as antibacterial, anti‐HIV type, anti‐microbial, anti‐fungal, anti‐viral, antitumor, and antiinflammatory, properties. In addition, pyrrolo[1,2‐ a ]pyrimidine framework is an important structural part of some pigments and dyes for plastics .…”

Section: Introductionmentioning

confidence: 99%

A Highly Efficient Synthesis of Pyrrolo[1,2‐a]pyrimidine Derivatives Containing 1,3‐Indandione Skeleton

2019

View full text Add to dashboard Cite

The pyrimidines fused with pyrrole ring, pyrrolopyrimidines, showed broad applicability in medicinal chemistry. Herein, we synthesized the new derivatives (8 examples) of pyrrolo[1,2-a] pyrimidine containing 1,3-indandione skeleton by the use of triethylammonium thiolates, methyl iodide, and ketene aminals via a one-pot three-component reaction. Scheme 1. Synthesis of pyrrolo[1,2-a]pyrimidine containing 1,3-indandione skeleton.

show abstract

“…Pyrrolopyrimidines display a broad applicability in medicinal chemistry exhibiting antimicrobial [ 39 , 40 , 41 , 42 , 43 ], antitumour [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ], antiasthmatic [ 59 ], antihypertensive [ 60 ], and anti-inflammatory [ 61 ] activities. Several method have been developed for synthesizing pyrrolopyrimidines in the last few years [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure followed by Retro Diels-Alder Protocol

et al. 2017

View full text Add to dashboard Cite

From 2-aminonorbornene hydroxamic acids, a simple and efficient method for the preparation of pyrrolo[1,2-a]pyrimidine enantiomers is reported. The synthesis is based on domino ring-closure followed by microwave-induced retro Diels-Alder (RDA) protocols, where the chirality of the desired products is transferred from norbornene derivatives. The stereochemistry of the synthesized compounds was proven by X-ray crystallography. The absolute configuration of the product is determined by the configuration of the starting amino hydroxamic acid.

show abstract

Annelation of pyrrolo[1,2-a]pyrimidine and pyrido[1,2-a]pyrimidine systems to a pyrazolopyridine framework by a cascade of two cyclization reactions

Cited by 9 publications

References 23 publications

5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis

5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis

A Highly Efficient Synthesis of Pyrrolo[1,2‐a]pyrimidine Derivatives Containing 1,3‐Indandione Skeleton

Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure followed by Retro Diels-Alder Protocol

Contact Info

Product

Resources

About