Synthesis of novel pyrazolo[3,4-b]pyridine derivatives in aqueous medium

Baradarani, Mehdi M.; Fazlelahi, Hadi Zare; Rashidi, Ahmad Ramli; Joule, J. A.

doi:10.24820/ark.5550190.p010.389

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…5-(indol-2-yl)pyrazolo [3,4-b]pyridines derivatives MM-3a-i and intermediate 6. MM-3a [31] 180 15 In all cases, the regioisomers MM-3a-i were selectively obtained as unique products, and their structures were confirmed by 1 H and 13 C NMR (mono (1D) and two-dimensional (2D)) and mass spectrometry (see Section 4.1). Particularly, the 1 H NMR analysis confirms obtaining the desired compounds.…”

Section: Product R 1 Rmentioning

confidence: 82%

“…A a B b C c A a B b C c MM-3a [31] Scheme 1. Synthesis of new 5-(indol-2-yl)pyrazolo [3,4-b]pyridines MM-3a-i.…”

Section: Methods Methodsmentioning

confidence: 99%

“…5-(indol-2-yl)pyrazolo [3,4-b]pyridines derivatives MM-3a-i and intermediate 6. MM-3a [31] Molecules 2021, 26, 0 5 of 16 Table 1. 5-(indol-2-yl)pyrazolo [3,4-b]pyridines derivatives MM-3a-i and intermediate 6.…”

Section: Synthesis Of Designed Task-3 Blockersmentioning

confidence: 99%

“…5-(indol-2-yl)pyrazolo [3,4-b]pyridines derivatives MM-3a-i and intermediate 6. MM-3a [31] Scheme 1. Synthesis of new 5-(indol-2-yl)pyrazolo [3,4-b]pyridines MM-3a-i.…”

Section: Product R 1 Rmentioning

confidence: 99%

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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

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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.

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Section: Product R 1 Rmentioning

confidence: 82%

“…A a B b C c A a B b C c MM-3a [31] Scheme 1. Synthesis of new 5-(indol-2-yl)pyrazolo [3,4-b]pyridines MM-3a-i.…”

Section: Methods Methodsmentioning

confidence: 99%

Section: Synthesis Of Designed Task-3 Blockersmentioning

confidence: 99%

“…5-(indol-2-yl)pyrazolo [3,4-b]pyridines derivatives MM-3a-i and intermediate 6. MM-3a [31] Scheme 1. Synthesis of new 5-(indol-2-yl)pyrazolo [3,4-b]pyridines MM-3a-i.…”

Section: Product R 1 Rmentioning

confidence: 99%

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