Medicinal Chemistry of Pyrazolopyrimidine Scaffolds Substituted with Different Heterocyclic Nuclei

Affiliations


Abstract

Background: Medicinal chemistry of pyrazolopyrimidine scaffolds substituted with different heterocyclic nuclei has attracted great attention due to their wide range of biological activities that have been reported. Pyrazolopyrimidine scaffold is an important privileged heterocycle nucleus in drug discovery.

Methods: All pharmacological activities of pyrazolopyrimidine scaffold have been mentioned, such as anticancer, anti-inflammatory, antihypertensive, antitubercular, antiviral, antibacterial, antifungal, antidiabetic, and anti-obesity agents. In addition, it was used in both osteoporosis and neurological disorders. The difference in potency and bioavailability of pyrazolopyrimidine derivatives refers to the substituent groups that can increase the activity against specific targets and enhance their selectivity.

Results: This review provides an overview of different synthetic pathways, structure activity relationships, and preclinical studies of pyrazolopyrimidine scaffolds substituted with a variety of heterocyclic nuclei, as well as it provides a discussion on the significant biological findings of these important scaffolds. In addition, it provides some insights on the different macromolecular targets that pyrazolopyrimidine scaffold can effectively work on, such as; cyclin dependent kinases; CDK2, CDK7, and CDK9, checkpoint kinases; CHK1 and CHK2 and their correlation with the anticancer activity, PI3Kα, transient receptor potential canonical 6, B-Raf kinase, Interleukin- 1 receptor-associated kinase 4, B-cell lymphoma 6, TRKA-C kinase, potent kDa ribosomal protein S6 kinase, colon cancer cell line (CaCo-2), domain receptor kinase (KDR), HepG-2 carcinoma cell, FLT3. The antibacterial activity against B. subtilis and E. coli and antifungal activity against C. albicans, C. tropicalis, A. niger, and A. clavatus are discussed.

Conclusion: This review provides an overview of the different pharmacological activities of the pyrazolopyrimidine scaffold and its correlation with chemical structure. Some exciting new developments in pyrazolopyrimidine scaffolds are also presented in this review.

Keywords: Pyrazolopyrimidine scaffolds; anti-inflammatory; anticancer; antimicrobial; antiviral; kinase inhibitors; structure activity relationship.


Similar articles

An assessment study of known pyrazolopyrimidines: Chemical methodology and cellular activity.

Rao RN, Chanda K.Bioorg Chem. 2020 Jun;99:103801. doi: 10.1016/j.bioorg.2020.103801. Epub 2020 Apr 1.PMID: 32278206 Review.

Biological Activity, Apoptotic Induction and Cell Cycle Arrest of New Hydrazonoyl Halides Derivatives.

Mohamed MF, Hassaneen HM, Elzayat EM, El-Hallouty SM, El-Manawaty M, Saleh FM, Mohamed Y, El-Zohiry D, Fahmy G, Abdelaal N, Hassanin N, Hossam N.Anticancer Agents Med Chem. 2019;19(9):1141-1149. doi: 10.2174/1871520619666190306123658.PMID: 30843494

Pyrazolopyrimidines as anticancer agents: A review on structural and target-based approaches.

Asati V, Anant A, Patel P, Kaur K, Gupta GD.Eur J Med Chem. 2021 Dec 5;225:113781. doi: 10.1016/j.ejmech.2021.113781. Epub 2021 Aug 18.PMID: 34438126 Review.

Synthesis, Characterization, Antimicrobial Activity and Anticancer of Some New Pyrazolo[1,5-a]pyrimidines and Pyrazolo[5,1-c]1,2,4-triazines.

Hosny MA, Zaki YH, Mokbel WA, Abdelhamid AO.Med Chem. 2020;16(6):750-760. doi: 10.2174/1573406415666190620144404.PMID: 31218963

Design, synthesis and biological evaluation of novel 3-substituted pyrazolopyrimidine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors.

Zheng N, Pan J, Hao Q, Li Y, Zhou W.Bioorg Med Chem. 2018 May 1;26(8):2165-2172. doi: 10.1016/j.bmc.2018.03.017. Epub 2018 Mar 12.PMID: 29567295


KMEL References