50427-77-5Relevant articles and documents
The new green procedure for pyrazolopyrimidinone based dihydropyrimidinones and their antibacterial screening
Allam, Muralidhar,Bhavani,Vodnala, Sumathi
, p. 2712 - 2718 (2017)
A series of novel hybrid aza heterocycles containing pyrazolopyrimidinone and dihydropyrimidinone scaffolds was developed using Cu(II) catalyzed Biginelli condensation as an efficient, new green synthetic method under mild and solvent free conditions. Pyr
Design, synthesis and anticancer evaluation of 1H-pyrazolo[3,4-d]pyrimidine derivatives as potent EGFRWT and EGFRT790M inhibitors and apoptosis inducers
Gaber, Ahmed A.,Bayoumi, Ashraf H.,El-morsy, Ahmed M.,Sherbiny, Farag F.,Mehany, Ahmed B.M.,Eissa, Ibrahim H.
, p. 375 - 395 (2018)
In our attempt to develop effective EGFR-TKIs, two series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized. All the newly synthesized compounds were evaluated in vitro for their inhibitory activities against EGFRWT. Compounds 15b, 15j, and 18d potently inhibited EGFRWT at sub-micro molar IC50 values comparable to that of erlotinib. Moreover, thirteen compounds that showed promising IC50 values against EGFRWT were tested in vitro for their inhibitory activities against mutant EGFRT790M. Compounds 17d and 17f exhibited potent inhibitory activities towards EGFRT790M comparable to osimertinib. Compounds that showed promising IC50 values against EGFRWT were further tested for their anti-proliferative activities against three cancer cell lines bearing EGFRWT (MCF-7, HepG2, A549), and two cancer cell lines bearing EGFRT790M (H1975 and HCC827). Compounds 15g, 15j, 15n, 18d and 18e were the most potent anticancer agents against the EGFRWT containing cells, while compounds 15e, 17d and 17f showed promising anti-proliferative activities against EGFRT790M containing cells. Furthermore, the most active compound 18d was selected for further studies regarding to its effects on cell cycle progression and induction of apoptosis in the HepG2 cell line. The results indicated that this compound is good apoptotic agent and arrests G0/G1and G2/M phases of cell cycle. Finally, molecular docking studies were performed to investigate binding pattern of the synthesized compounds with the prospective targets, EGFRWT (PDB: 4HJO) and EGFRT790M (PDB: 3W2O).
COMBINATION THERAPY FOR TREATING MPS1
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, (2021/08/14)
The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3', R4, R4', and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with α-L-iduronidase or an analog or variant thereof, e.g., laronidase.
Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies
Abulkhair, Hamada S.,Al-Karmalawy, Ahmed A.,Bayoumi, Ashraf H.,El-Adl, Khaled,El-Gamal, Kamal M.,El-Morsy, Ahmed M.,Ezz Eldin, Rogy R.,Gaber, Ahmed A.,Saleh, Marwa A.,Sherbiny, Farag F.
, (2021/09/02)
Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential. These fragments include hydrazone, indoline-2-one, phthalimide, thiourea, oxadiazole, pyrazole, and dihydropyrazole. The synthesized molecules were evaluated for their anticancer activity against the human breast cancer cell line, MCF-7. The obtained results revealed comparable antitumor activity with that of the reference drugs doxorubicin and toceranib. Docking studies were performed along with EGFR-TK and ADMET profiling studies. The results of the docking studies showed the ability of the designed compounds to interact with key residues of the EGFR-TK through a number of covalent and noncovalent interactions. The obtained activity of compound 25 (IC50 = 2.89 μM) suggested that it may serve as a lead for further optimization and drug development.
