One‐pot Synthesis of 2,4‐Diamino‐substituted Thieno[3,2‐<i>d</i>]pyrimidines

Lü, Xiaoying; Zhang, Yangming; Tang, Jie; Yang, Fan

doi:10.1002/cjoc.201090245

“…Palladium is the most frequently used metal in catalysis, and heterogeneous palladium catalysts are most commonly used as efficient catalysts. They have indeed been largely applied to redox reactions including oxidation and hydrogenation, alkenylation, C−H bond functionalization, asymmetric synthesis and carbon‐carbon coupling reactions . In addition, they are of interest in the synthesis of natural products (such as γ‐lactams and γ‐lactones) and often employed in total syntheses .…”

Section: Introductionmentioning

confidence: 99%

Development of the Applications of Palladium on Charcoal in Organic Synthesis

Liu

¹

,

Astruc

²

2018

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Palladium on charcoal( Pd/C)h as lots of salient merits:( i) it is ac heap andc ommercial source of palladium, (ii)i ts hows efficientc atalytic activity even without ligands,( iii)a saheterogeneous catalyst it is easily recycledm any times by simple filtration,a nd (iv) it is applicablet oag reat number of reactions and substrates,a lthough it is eventually less efficient than homogeneous Pd catalysts containing some sophisticated ligands.T hisr eview recalls the main background ands ummarizes the progress made essentially during the last twelve years in Pd/C-catalyzed organic synthesis since the reviews by Felpins group andSekiin2 006.

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Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Kremer

¹

,

Hennes

²

,

Brause

³

et al. 2019

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The Hedgehog (Hh) signaling pathway is crucial for vertebrate embryonic development, tissue homeostasis and regeneration. Hh signaling is upregulated in basal cell carcinoma and medulloblastoma and Hh pathway inhibitors targeting the Smoothened (SMO) protein are in clinical use. However, the signaling cascade is incompletely understood and novel druggable proteins in the pathway are in high demand. We describe the discovery of the Hh‐pathway modulator Pipinib by means of cell‐based screening. Target identification and validation revealed that Pipinib selectively inhibits phosphatidylinositol 4‐kinase IIIβ (PI4KB) and suppresses GLI‐mediated transcription and Hh target gene expression by impairing SMO translocation to the cilium. Therefore, inhibition of PI4KB and, consequently, reduction in phosphatidyl‐4‐phosphate levels may be considered an alternative approach to inhibit SMO function and thus, Hedgehog signaling.

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Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Kremer

¹

,

Hennes

²

,

Brause

³

et al. 2019

View full text Add to dashboard Cite

The Hedgehog (Hh) signaling pathway is crucial for vertebrate embryonic development, tissue homeostasis and regeneration. Hh signaling is upregulated in basal cell carcinoma and medulloblastoma and Hh pathway inhibitors targeting the Smoothened (SMO) protein are in clinical use. However, the signaling cascade is incompletely understood and novel druggable proteins in the pathway are in high demand. We describe the discovery of the Hh‐pathway modulator Pipinib by means of cell‐based screening. Target identification and validation revealed that Pipinib selectively inhibits phosphatidylinositol 4‐kinase IIIβ (PI4KB) and suppresses GLI‐mediated transcription and Hh target gene expression by impairing SMO translocation to the cilium. Therefore, inhibition of PI4KB and, consequently, reduction in phosphatidyl‐4‐phosphate levels may be considered an alternative approach to inhibit SMO function and thus, Hedgehog signaling.

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One‐pot Synthesis of 2,4‐Diamino‐substituted Thieno[3,2‐d]pyrimidines

Abstract: An efficient one-pot synthetic approach to 2,4-diamino-substituted thieno[3,2-d]pyrimidines from 2,4-dichlorothieno[3,2-d]pyrimidine was described.

Cited by 5 publications

References 6 publications

Development of the Applications of Palladium on Charcoal in Organic Synthesis

Development of the Applications of Palladium on Charcoal in Organic Synthesis

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

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