Synthesis and in-vitro anti-proliferative evaluation of some pyrazolo[1,5-a]pyrimidines as novel larotrectinib analogs

Attia, Mahmoud; Elrazaz, Eman Z.; El-Emam, Soad Z.; Taher, Azza T.; Abdel‐Aziz, Hatem A.; Abouzid, Khaled A.M.

doi:10.1016/j.bioorg.2019.103458

Cited by 23 publications

(14 citation statements)

References 25 publications

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“…However, it was also found that changing the salt concentration was sufficient to invert the inhibitor's binding pose such that N1 no longer interacted with the hinge. 40 Thus, while not all thieno [2,3-d]pyrimidines are devoid of kinase activity, 39 in the case of STK17B it appears that the more basic thieno [3,2-d]pyrimidine regioisomers are much more active as inhibitors.…”

Section: Discussionmentioning

confidence: 99%

A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation

et al. 2020

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We present the discovery of thieno[3,2-d]pyrimidine SGC-STK17B-1 (11s), a high-quality chemical probe for this understudied "dark" kinase. 11s is an ATP-competitive inhibitor that showed remarkable selectivity over other kinases including the closely related STK17A. X-ray crystallography of 11s and related thieno[3,2-d]pyrimidines bound to STK17B revealed a unique P-loop conformation characterized by a salt bridge between R41 and the carboxylic acid of the inhibitor. File list (9) download file view on ChemRxiv STK17B chemical probe final.pdf (4.28 MiB) download file view on ChemRxiv SI File 2.pdf (2.81 MiB) download file view on ChemRxiv SI combined final.pdf (1.64 MiB) download file view on ChemRxiv SI File 1.xlsx (32.16 KiB) download file view on ChemRxiv SI Movie 1.mp4 (36.75 MiB) download file view on ChemRxiv SI Movie 2.mp4 (32.23 MiB) download file view on ChemRxiv SI Movie 3.mp4 (56.17 MiB) download file view on ChemRxiv SI Movie 4.mp4 (58.45 MiB) download file view on ChemRxiv SI Movie 5.mp4 (62.15 MiB)

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Section: Discussionmentioning

confidence: 99%

A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation

et al. 2020

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“…In other studies, the N -heterocyclic core has been synthetized from β-enaminone derivatives bearing aryl groups substituted with halogen atoms or methoxy groups. Additionally, carboxamides, aryl groups, nitriles, and esters have been employed as substituents on the starting NH -3-aminopyrazole [ 40 , 41 , 42 ].…”

Section: Synthesis and Functionalizationmentioning

confidence: 99%

“…In 2020, Abouzidb et al [ 40 ] published the synthesis of some pyrazolo[1,5- a ]pyrimidines as novel larotrectinib analogs using a reaction between β-enaminones 19 and the 4,5-disubstituted 3-aminopyrazole 169 ( Scheme 48 ). The antiproliferative activity of compounds 170e , 170j , and 170k stand out as the most active against three cancer cell lines: hepatocellular carcinoma Huh-7 , cervical adenocarcinoma HeLa and breast adenocarcinoma MCF-7 .…”

Section: Antitumor Activitymentioning

confidence: 99%

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold

2021

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Pyrazolo[1,5-a]pyrimidine (PP) derivatives are an enormous family of N-heterocyclic compounds that possess a high impact in medicinal chemistry and have attracted a great deal of attention in material science recently due to their significant photophysical properties. Consequently, various researchers have developed different synthesis pathways for the preparation and post-functionalization of this functional scaffold. These transformations improve the structural diversity and allow a synergic effect between new synthetic routes and the possible applications of these compounds. This contribution focuses on an overview of the current advances (2015–2021) in the synthesis and functionalization of diverse pyrazolo[1,5-a]pyrimidines. Moreover, the discussion highlights their anticancer potential and enzymatic inhibitory activity, which hopefully could lead to new rational and efficient designs of drugs bearing the pyrazolo[1,5-a]pyrimidine core.

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“…Compound C, 4-(6-(4-(1-(pyrrolidin-1yl)ethyl)phenyl)pyrazolo [1,5-a]pyrimidin-3-yl)naphthalene-1-sulfonamide, act as a potent and selective ALK2 inhibitor [15]. Recently, Attia et al have synthesized the two derivatives, 7-(4methoxyphenyl)-pyrazolo [1,5-a]pyrimidine-3,6-dicarbonitrile (D) and 7-(naphthalen-2-yl)pyrazolo [1,5-a]pyrimidine-3-carbonitrile (E), which have a potent anti-proliferative activity [16]. Also, Singleton et al [1,5a]pyrimidine (F) which act as a selective inhibitor of JAK1 JH2 pseudokinase [17].…”

Section: Introductionmentioning

confidence: 99%

Copper-based glass-ceramic as an efficient catalyst in the synthesis of pyrazolo[1,5-a] pyrimidineunder solvent-free condition with docking validation as Covid-19 main protease (Mpro) inhibitor

Abdelghany¹,

Khatab²,

Hassan³

2021

Bull. Chem. Soc. Eth.

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Copper-based oxide glass-ceramic was successfully synthesized through the single-step melt annealing technique. Synthesized glass-ceramics was characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM) supported with energy dispersive X-ray (EDX) and mapping. Pyrazolo[1,5-a]pyrimidines 5a-f were synthesized via the reaction of 5-amino-1H-pyrazole-4-carboxamide (1) with enaminones 2a-f in the presence of synthesized oxide glass-ceramic catalyst powder under solvent-free condition. The molecular docking study demonstrated that the COVID-19 main protease (MPro) inhibitor. KEY WORDS: Pyrazolopyrimidine, Enaminones, Copper-based catalysis, Solvent-free, COVID-19 Bull. Chem. Soc. Ethiop. 2021, 35(1), 185-196. DOI: https://dx.doi.org/10.4314/bcse.v35i1.16

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Synthesis and in-vitro anti-proliferative evaluation of some pyrazolo[1,5-a]pyrimidines as novel larotrectinib analogs

Cited by 23 publications

References 25 publications

A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation

A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold

Copper-based glass-ceramic as an efficient catalyst in the synthesis of pyrazolo[1,5-a] pyrimidineunder solvent-free condition with docking validation as Covid-19 main protease (Mpro) inhibitor

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