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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Review Article

Medicinal Chemistry of Pyrazolopyrimidine Scaffolds Substituted with Different Heterocyclic Nuclei

Author(s): Galal H. Elgemeie*, Rasha A. Azzam, Wafaa A. Zaghary, Mohammed A. Khedr and Gihad E. Elsherif

Volume 28, Issue 41, 2022

Published on: 21 November, 2022

Page: [3374 - 3403] Pages: 30

DOI: 10.2174/1381612829666221102162000

Price: $65

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.

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[1]
Lunagariya MV, Thakor KP, Waghela BN, Pathak C, Patel MN. Design, synthesis, pharmacological evaluation and DNA interaction stud-ies of binuclear Pt(II) complexes with pyrazolo[1,5-a]pyrimidine scaffold. Appl Organomet Chem 2018; 32(4): e4222.
[http://dx.doi.org/10.1002/aoc.4222]
[2]
Rahmouni A, Souiei S, Belkacem MA, Romdhane A, Bouajila J, Ben Jannet H. Synthesis and biological evaluation of novel pyrazolopy-rimidines derivatives as anticancer and anti-5-lipoxygenase agents. Bioorg Chem 2016; 66: 160-8.
[http://dx.doi.org/10.1016/j.bioorg.2016.05.001] [PMID: 27179178]
[3]
Shaaban MR, Saleh TS, Mayhoub AS, Mansour A, Farag AM. Synthesis and analgesic/anti-inflammatory evaluation of fused heterocy-clic ring systems incorporating phenylsulfonyl moiety. Bioorg Med Chem 2008; 16(12): 6344-52.
[http://dx.doi.org/10.1016/j.bmc.2008.05.011] [PMID: 18502132]
[4]
Shiota T, Yamamori T, Sakai K, et al. Synthesis and structure-activity relationship of a new series of potent angiotensin II receptor an-tagonists: Pyrazolo[1,5-a]pyrimidine derivatives. Chem Pharm Bull (Tokyo) 1999; 47(7): 928-38.
[http://dx.doi.org/10.1248/cpb.47.928] [PMID: 10434395]
[5]
Modi P, Patel S, Chhabria M. Structure-based design, synthesis and biological evaluation of a newer series of pyrazolo[1,5-a]pyrimidine analogues as potential anti-tubercular agents. Bioorg Chem 2019; 87: 240-51.
[http://dx.doi.org/10.1016/j.bioorg.2019.02.044] [PMID: 30908967]
[6]
Soares de Melo C, Feng TS, van der Westhuyzen R, et al. Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization. Bioorg Med Chem 2015; 23(22): 7240-50.
[http://dx.doi.org/10.1016/j.bmc.2015.10.021] [PMID: 26522089]
[7]
Petek N, Štefane B, Novinec M, Svete J. Synthesis and biological evaluation of 7-(aminoalkyl)pyrazolo[1,5-a]pyrimidine derivatives as cathepsin K inhibitors. Bioorg Chem 2019; 84: 226-38.
[http://dx.doi.org/10.1016/j.bioorg.2018.11.029] [PMID: 30502634]
[8]
Griffith DA, Hargrove DM, Maurer TS, et al. Discovery and evaluation of pyrazolo[1,5-a]pyrimidines as neuropeptide Y1 receptor an-tagonists. Bioorg Med Chem Lett 2011; 21(9): 2641-5.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.116] [PMID: 21295475]
[9]
Al-Etaibi AM, Al-Awadi NA, El-Apasery MA, Ibrahim MR. Synthesis of some novel pyrazolo[1,5-a]pyrimidine derivatives and their application as disperse dyes. Molecules 2011; 16(6): 5182-93.
[http://dx.doi.org/10.3390/molecules16065182] [PMID: 21697775]
[10]
Xu J, Liu H, Li G, et al. 18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: Synthesis from 2,4-dinitrobenzamide and tosylate precursors and comparative biological evaluation for tumor imaging with positron emission tomography. Molecules 2012; 17(4): 3774-93.
[http://dx.doi.org/10.3390/molecules17043774] [PMID: 22453929]
[11]
Gogula T, Zhang JQ, Zou HB. Rhodium(III)-catalyzed regioselective C(sp2)-H functionalization of 7-arylpyrazolo[1,5-a]pyrimidines with dioxazolones as amidating agents. Org Lett 2019; 21(15): 5933-7.
[http://dx.doi.org/10.1021/acs.orglett.9b02059] [PMID: 31328523]
[12]
Buriol L, München TS, Frizzo CP, et al. Resourceful synthesis of pyrazolo[1,5-a]pyrimidines under ultrasound irradiation. Ultrason Sonochem 2013; 20(5): 1139-43.
[http://dx.doi.org/10.1016/j.ultsonch.2013.02.006] [PMID: 23545105]
[13]
Dalinger IL, Vatsadse IA, Shevelev SA, Ivachtchenko AV. Liquid-phase synthesis of combinatorial libraries based on 7-trifluoromethyl-substituted pyrazolo[1,5-a]pyrimidine scaffold. J Comb Chem 2005; 7(2): 236-45.
[http://dx.doi.org/10.1021/cc049855o] [PMID: 15762751]
[14]
Jismy B, Tikad A, Akssira M, Guillaumet G, Abarbri M. Efficient access to 3,5-disubstituted 7-(trifluoromethyl)pyrazolo[1,5-a]] pyrimidines involving SNAr and suzuki cross-coupling reactions. Molecules 2020; 25(9): 2062.
[http://dx.doi.org/10.3390/molecules25092062] [PMID: 32354132]
[15]
Mehranpour A, Hashemnia S, Bornak M. Synthesis and characterization of new pyrido- and pyrazolopyrimidine derivatives using 2-substituted vinamidinium salts. Chem Heterocycl Compd 2019; 55(11): 1087-91.
[http://dx.doi.org/10.1007/s10593-019-02582-7]
[16]
Abdelriheem NA, Zaki YH, Abdelhamid AO. 2017.
[17]
Gambouz K, Driowya M, Loubidi M, et al. Unusual rearrangement of imidazo[1,5- a]imidazoles and imidazo[1,2- b]pyrazoles into imidazo[1,5- a]pyrimidines and pyrazolo[1,5- a]pyrimidines. RSC Advances 2019; 9(50): 29051-5.
[http://dx.doi.org/10.1039/C9RA04609G] [PMID: 35528450]
[18]
Shkineva TK, Vatsadze IA, Dalinger IL. A new general synthesis of functionally substituted pyrazolo[1,5-a]pyrimidines. Mendeleev Commun 2019; 29(4): 429-31.
[http://dx.doi.org/10.1016/j.mencom.2019.07.025]
[19]
Salem ME, Ahmed AA, Shaaban MR, Shibl MF, Farag AM. Regioselective synthesis and abinitio calculations of fused heterocycles thermally and under microwave irradiation. Spectrochim Acta A Mol Biomol Spectrosc 2015; 148: 175-83.
[http://dx.doi.org/10.1016/j.saa.2015.03.102] [PMID: 25879987]
[20]
Kamal A, Tamboli JR, Nayak VL, Adil SF, Vishnuvardhan MVPS, Ramakrishna S. Synthesis of pyrazolo[1,5-a]pyrimidine linked ami-nobenzothiazole conjugates as potential anticancer agents. Bioorg Med Chem Lett 2013; 23(11): 3208-15.
[http://dx.doi.org/10.1016/j.bmcl.2013.03.129] [PMID: 23623491]
[21]
Elgemeie GEH, Riad BY, Nawwar GA, Elgamal S. Nitriles in Heterocyclic synthesis: Synthesis of new pyrazolo [1,5-a]pyrimidines, pyrano[2,3-c]pyrazoles and pyrano[3,4-c] pyrazoles. Arch Pharm (Weinheim) 1987; 320(3): 223-8.
[http://dx.doi.org/10.1002/ardp.19873200307]
[22]
Elnagdi MH, Elmoghayar MRH, Elgemeie GEH. Chemistry of Pyrazolopyrimidines. Adv Heterocycl Chem 1987; 41: 319-76.
[http://dx.doi.org/10.1016/S0065-2725(08)60164-6]
[23]
Elgemeie GH, Elfahham HA, Ibraheim YR, Elnagdi MH. Studies on 3,5-diaminopyrazoles: New routes for the synthesis of new pyrazo-loazines and pyrazoloazoles. Liebigs Ann Chem 1988; 819-22.
[24]
Elgemeie GH, Elghandour AH, Elshimy HM. Studies on aminoazoles: Synthesis of pyrazolo[1,5-a]-pyrimidines and their aza deriva-tives. J Prakt Chem 1989; 331(3): 466-74.
[http://dx.doi.org/10.1002/prac.19893310318]
[25]
Elgemeie GEH, Fathy NM, Faddah LM, Ebeid MY, Elsaid MK. Reactions with 3,5-diaminopyrazoles: New routes to pyrazolo[1,5-a]pyrimidines. Arch Pharm (Weinheim) 1991; 324(3): 149-52.
[http://dx.doi.org/10.1002/ardp.19913240304]
[26]
Elgemeie GEH, El-Ezbawy SE, Ali HA, Mansour AK. Novel synthesis of mercaptopurine and pentaaza-as-indacene analogues: Reaction of [bis(methylthio)methylene]malononitrile and ethyl 2-cyano-3,3-bis(methylthio)acrylate with 5-aminopyrazoles. Bull Chem Soc Jpn 1994; 67(3): 738-41.
[http://dx.doi.org/10.1246/bcsj.67.738]
[27]
Elgemeie GEH, Ali HA, Mansour AK. Antimetabolites: A convenient synthesis of mercaptopurine and thioguanine analogues. Phosphorus Sulfur Silicon Relat Elem 1994; 90(1-4): 143-6.
[http://dx.doi.org/10.1080/10426509408016395]
[28]
Elgemeie GEH, Elghandour AH, Elzanate AM, Hussein AM. Synthetic strategies to novel condensed methylsulfanylazoles: Reaction of ketene dithioacetals with amino- and oxo-azoles. J Chem Res Synop 1997; (7): 256-7.
[http://dx.doi.org/10.1039/a700128b]
[29]
Elgemeie GH, Fathy NM, Farag DS. Antimetabolites: A novel synthesis of nonclassical condensed carbocyclic purine analogues. Egypt J Pharm Sci 1997; 38: 351-61.
[30]
Elgemeie GH, Elghandour AH, Elzanate AM, Ahmed SA. Novel synthesis of thioguanine and sulfanylpurine analogues: Reaction of heterocyclic ketene dithio-acetals with nucleophiles. J Chem Res Synop 1998; (3): 162-3.
[http://dx.doi.org/10.1039/a704612j]
[31]
Elgemeie GH, Metwally NH. Synthesis of structurally related purines: Benzimidazo[1,2-a]pyridines, Benzimidazo-[1,2-c]pyrimidines, and pyrazolo-[1,5-a]pyrimidines. Monatsh Chem 2000; 131(7): 779-85.
[http://dx.doi.org/10.1007/s007060050025]
[32]
Elgemeie GH, El-Ezbawy SR, Ali HA. Reactions of chlorocarbonyl isocyanate with 5-aminopyrazoles and active methylene nitriles: A novel synthesis of pyrazolo[1,5-a]-1,3,5-triazines and barbiturates. Synth Commun 2001; 31(22): 3459-67.
[http://dx.doi.org/10.1081/SCC-100106205]
[33]
Elgemeie GH, El-Ezbawy SR, El-Aziz HA. The design and synthesis of structurally related mercaptopurine analogues: Reaction of dime-thyl N-cyano-dithioiminocarbonate with 5-aminopyrazoles. Synth Commun 2001; 31(22): 3453-8.
[http://dx.doi.org/10.1081/SCC-100106204]
[34]
Elgemeie GH, Sood SA. The reaction of dimethyl N-cyanodithioiminocarbonate with amino- and oxo-azoles: A new general synthesis of methylsulfanylazoloazines. J Chem Res 2001; 2001(10): 439-41.
[http://dx.doi.org/10.3184/030823401103168398]
[35]
Elgemeie GH, Ali HA. Potential purine analogue antagonists: Synthesis of novel cycloalkane ring-fused pyrazolo[1,5-a]pyrimidines. Synth Commun 2002; 32(2): 253-64.
[http://dx.doi.org/10.1081/SCC-120002010]
[36]
Elgemeie GH, Zahran MK, Abbas EM, Abdel Mowla EA. Preparation and characterization of novel methylsulfanylpyrazolopyrimidine and methylsulfanylpyrazolotriazine azo dyes. Pigm Resin Technol 2002; 31(5): 297-309.
[http://dx.doi.org/10.1108/03699420210442338]
[37]
Elgemeie GH, Ali HA, Jones PG. 2-Phenyl-7,8-dihydro-6H-cyclopenta[e]pyrazolo [1,5-a]pyrimidine. Acta Crystallogr 2002; 58: 1247-9.
[38]
Elgemeie GH, Helal MH, Ahmed KA. Synthesis and dyeing properties of a new class of condensed carbocyclic arylazopyrazolo[1,5‐a] pyrimidines. Pigm Resin Technol 2003; 32(1): 10-23.
[http://dx.doi.org/10.1108/03699420310454893]
[39]
Elgemeie GH, Helal MH, El-Sayed HM. Synthesis of and dyeing characteristics of novel pyrazolo[1,5‐a]pyrimidine derivatives contain-ing two arylazo functions. Pigm Resin Technol 2003; 32(2): 100-6.
[http://dx.doi.org/10.1108/03699420310464801]
[40]
Elgemeie GH, Helal MH, El-Sayed HM. Novel arylazopyrazolo[1,5‐a]pyrimidine derivatives: Synthesis, properties and dyeing charac-teristics. Pigm Resin Technol 2004; 33(2): 91-8.
[http://dx.doi.org/10.1108/03699420410524902]
[41]
Elgemeie GH, Sood SA. First synthesis of N-substituted Amino and N-sulfonyl-aminated methylthiopyrimidines: Reaction of dimethyl N-cyanodithio-iminocarbonate with substituted hydrazides. Synth Commun 2006; 36(6): 743-53.
[http://dx.doi.org/10.1080/00397910500449427]
[42]
Helal MH, Elgemeie GH, Masoud DM. Preparation and characterisation of novel methylsulfanylpyrazolopyrimidines as heterocyclic dyes from ketene dithioacetals. Pigm Resin Technol 2007; 36(5): 306-11.
[http://dx.doi.org/10.1108/03699420710820423]
[43]
Elgemeie G, Abu-Zaied M, Hebishy A, Abbas N, Hamed M. First microwave-assisted synthesis of a new class of purine and guanine thioglycoside analogs. Nucleosides Nucleotides Nucleic Acids 2016; 35(9): 459-78.
[http://dx.doi.org/10.1080/15257770.2016.1202964] [PMID: 27556784]
[44]
Elgemeie GH, Salah AM, Abbas NS, Hussein HA, Mohamed RA. Pyrimidine non-nucleoside analogs: A direct synthesis of a novel class of N -substituted amino and N -sulfonamide derivatives of pyrimidines. Nucleosides Nucleotides Nucleic Acids 2017; 36(3): 213-23.
[http://dx.doi.org/10.1080/15257770.2016.1257808] [PMID: 28102765]
[45]
Elgemeie GH, Abu-Zaied MA, Loutfy SA. 4-Aminoantipyrine in carbohydrate research: Design, synthesis and anticancer activity of a novel class of derivatives of 4-aminoantipyrine thioglycosides and their corresponding pyrazolopyrimidine and pyrazolopyridine thio-glycosides. Tetrahedron 2017; 73: 5853-61.
[http://dx.doi.org/10.1016/j.tet.2017.08.024]
[46]
Abu-Zaied MA, Elgemeie GH. A facile synthesis of novel pyrazolopyrimidine thioglycosides as purine thioglycoside analogues. Nucleosides Nucleotides Nucleic Acids 2018; 37(1): 67-77.
[http://dx.doi.org/10.1080/15257770.2017.1419254] [PMID: 29336674]
[47]
Asati V, Anant A, Patel P, Kaur K, Gupta GD. Pyrazolopyrimidines as anticancer agents: A review on structural and target-based ap-proaches. Eur J Med Chem 2021; 225: 113781.
[http://dx.doi.org/10.1016/j.ejmech.2021.113781] [PMID: 34438126]
[48]
Abu-Zaied MA, Loutfy SA, Hassan AE, Elgemeie GH. Novel purine thioglycoside analogs: Synthesis, nanoformulation and biological evaluation in in vitro human liver and breast cancer models. Drug Des Devel Ther 2019; 13: 2437-57.
[http://dx.doi.org/10.2147/DDDT.S201249] [PMID: 31440030]
[49]
Hebishy AMS, Salama HT, Elgemeie GH. New route to the synthesis of benzamide-based 5-aminopyrazoles and their fused heterocycles showing remarkable antiavian influenza virus activity. ACS Omega 2020; 5(39): 25104-12.
[http://dx.doi.org/10.1021/acsomega.0c02675] [PMID: 33043189]
[50]
Elgemeie GH, Elghandour AH, Elzanate AM, Ahmed SA. Synthesis of some novel α-cyanoketene S,S-acetals and their use in heterocy-clic synthesis. J Chem Soc, Perkin Trans 1 1997; 21(21): 3285-90.
[http://dx.doi.org/10.1039/a702343j]
[51]
Shaaban MR, Saleh TS, Mayhoub AS, Farag AM. Single step synthesis of new fused pyrimidine derivatives and their evaluation as po-tent Aurora-A kinase inhibitors. Eur J Med Chem 2011; 46(9): 3690-5.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.033] [PMID: 21664013]
[52]
Heathcote DA, Patel H, Kroll SHB, et al. A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J Med Chem 2010; 53(24): 8508-22.
[http://dx.doi.org/10.1021/jm100732t] [PMID: 21080703]
[53]
Ali S, Heathcote DA, Kroll SHB, et al. The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res 2009; 69(15): 6208-15.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-0301] [PMID: 19638587]
[54]
Ali GME, Ibrahim DA, Elmetwali AM, Ismail NSM. Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity. Bioorg Chem 2019; 86: 1-14.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.008] [PMID: 30682722]
[55]
El Sayed MT, Hussein HAR, Elebiary NM, et al. Tyrosine kinase inhibition effects of novel pyrazolo[1,5-a]pyrimidines and Pyrido[2,3-d]pyrimidines ligand: Synthesis, biological screening and molecular modeling studies. Bioorg Chem 2018; 78: 312-23.
[http://dx.doi.org/10.1016/j.bioorg.2018.03.009] [PMID: 29625271]
[56]
Frey RR, Curtin ML, Albert DH, et al. 7-Aminopyrazolo[1,5-a]pyrimidines as potent multitargeted receptor tyrosine kinase inhibitors. J Med Chem 2008; 51(13): 3777-87.
[http://dx.doi.org/10.1021/jm701397k] [PMID: 18557606]
[57]
Liu Y, Laufer R, Patel NK, et al. Discovery of pyrazolo[1,5-a]pyrimidine TTK inhibitors: CFI-402257 is a potent, selective, bioavailable anticancer agent. ACS Med Chem Lett 2016; 7(7): 671-5.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00485] [PMID: 27437075]
[58]
Salem MA, Helal MH, Gouda MA. Abd EL-Gawad HH, Shehab MAM, El-Khalafawy A. Recent synthetic methodologies for pyrazo-lo[1,5- a]pyrimidine. Synth Commun 2019; 49(14): 1750-76.
[http://dx.doi.org/10.1080/00397911.2019.1604967]
[59]
Kamal A, Faazil S, Hussaini SMA, et al. Synthesis and mechanistic aspects of 2-anilinonicotinyl-pyrazolo[1,5-a]pyrimidine conjugates that regulate cell proliferation in MCF-7 cells via estrogen signaling. Bioorg Med Chem Lett 2016; 26(8): 2077-83.
[http://dx.doi.org/10.1016/j.bmcl.2016.02.072] [PMID: 26948540]
[60]
Kamal A, Tamboli JR, Ramaiah MJ, et al. Anthranilamide-pyrazolo[1,5-a]pyrimidine conjugates as p53 activators in cervical cancer cells. ChemMedChem 2012; 7(8): 1453-64.
[http://dx.doi.org/10.1002/cmdc.201200205] [PMID: 22700474]
[61]
Kim DC, Lee YR, Yang BS, et al. synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidines as CDK2 inhibitors. Eur J Med Chem 2003; 38: 525-32.
[http://dx.doi.org/10.1016/S0223-5234(03)00065-5] [PMID: 12767603]
[62]
Alexander A, Karakas C, Chen X, et al. Cyclin E overexpression as a biomarker for combination treatment strategies in inflammatory breast cancer. Oncotarget 2017; 8(9): 14897-911.
[http://dx.doi.org/10.18632/oncotarget.14689] [PMID: 28107181]
[63]
Janetka JW, Ashwell S. Checkpoint kinase inhibitors: A review of the patent literature. Expert Opin Ther Pat 2009; 19(2): 165-97.
[http://dx.doi.org/10.1517/13543770802653622] [PMID: 19441917]
[64]
Paruch K, Dwyer MP, Alvarez C, et al. Discovery of dinaciclib (SCH 727965): A potent and selective inhibitor of cyclin-dependent ki-nases. ACS Med Chem Lett 2010; 1(5): 204-8.
[http://dx.doi.org/10.1021/ml100051d] [PMID: 24900195]
[65]
Li Y, Gao W, Li F, et al. An in silico exploration of the interaction mechanism of pyrazolo[1,5-a]pyrimidine type CDK2 inhibitors. Mol Biosyst 2013; 9(9): 2266-81.
[http://dx.doi.org/10.1039/c3mb70186g] [PMID: 23864105]
[66]
Labroli M, Paruch K, Dwyer MP, et al. Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach-Part 2. Bioorg Med Chem Lett 2011; 21(1): 471-4.
[http://dx.doi.org/10.1016/j.bmcl.2010.10.114] [PMID: 21094607]
[67]
Chen J, Zhang M, Ma Q, Qin D, Zhang L, Lu X. QSAR study of pyrazolo[1,5-a]pyrimidine derivative inhibitors of Chk1. Chemom Intell Lab Syst 2016; 150: 23-8.
[http://dx.doi.org/10.1016/j.chemolab.2015.10.014]
[68]
Ding M, Wang H, Qu C, et al. Pyrazolo[1,5-a]pyrimidine TRPC6 antagonists for the treatment of gastric cancer. Cancer Lett 2018; 432: 47-55.
[http://dx.doi.org/10.1016/j.canlet.2018.05.041] [PMID: 29859875]
[69]
Cherukupalli S, Karpoormath R, Chandrasekaran B, Hampannavar GA, Thapliyal N, Palakollu VN. An insight on synthetic and medicinal aspects of pyrazolo[1,5-a]pyrimidine scaffold. Eur J Med Chem 2017; 126: 298-352.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.019] [PMID: 27894044]
[70]
McCoull W, Abrams RD, Anderson E, et al. Discovery of pyrazolo[1,5-a]pyrimidine B-Cell Lymphoma 6 (BCL6) binders and optimiza-tion to high affinity macrocyclic inhibitors. J Med Chem 2017; 60(10): 4386-402.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00359] [PMID: 28485934]
[71]
Attia MH, Elrazaz EZ, El-Emam SZ, Taher AT, Abdel-Aziz HA, Abouzid KAM. Synthesis and in-vitro anti-proliferative evaluation of some pyrazolo[1,5-a]pyrimidines as novel larotrectinib analogs. Bioorg Chem 2020; 94: 103458.
[http://dx.doi.org/10.1016/j.bioorg.2019.103458] [PMID: 31785854]
[72]
Bussenius J, Anand NK, Blazey CM, et al. Design and evaluation of a series of pyrazolopyrimidines as p70S6K inhibitors. Bioorg Med Chem Lett 2012; 22(6): 2283-6.
[http://dx.doi.org/10.1016/j.bmcl.2012.01.105] [PMID: 22342124]
[73]
Abdel-Aziz HA, Saleh TS, El-Zahabi HS. Facile synthesis and in-vitro antitumor activity of some pyrazolo[3,4-b]pyridines and pyrazo-lo[1,5-a]pyrimidines linked to a thiazolo[3,2-a]benzimidazole moiety. Arch Pharm (Weinheim) 2010; 343(1): 24-30.
[PMID: 19921685]
[74]
Kiessling A, Wiesinger R, Sperl B, Berg T. Selective inhibition of c-Myc/Max dimerization by a pyrazolo[1,5-a]pyrimidine. ChemMedChem 2007; 2(5): 627-30.
[http://dx.doi.org/10.1002/cmdc.200600294] [PMID: 17315254]
[75]
Fraley ME, Rubino RS, Hoffman WF, et al. Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: Improvements in physical properties enhance cellular activity and pharmacokinetics. Bioorg Med Chem Lett 2002; 12(24): 3537-41.
[http://dx.doi.org/10.1016/S0960-894X(02)00827-2] [PMID: 12443771]
[76]
Hassan AS, Moustafa GO, Awad HM. Synthesis and in vitro anticancer activity of pyrazolo[1,5- a]pyrimidines and pyrazolo[3,4- d][1,2,3]triazines. Synth Commun 2017; 47(21): 1963-72.
[http://dx.doi.org/10.1080/00397911.2017.1358368]
[77]
Gomha SM, Eldebss TMA, Abdulla MM, Mayhoub AS. Diphenylpyrroles: Novel p53 activators. Eur J Med Chem 2014; 82: 472-9.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.082] [PMID: 24934571]
[78]
Phillipson LJ, Segal DH, Nero TL, et al. Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9. Bioorg Med Chem 2015; 23(19): 6280-96.
[http://dx.doi.org/10.1016/j.bmc.2015.08.035] [PMID: 26349627]
[79]
Zhang J, Peng JF, Bai YB, et al. Synthesis of pyrazolo[1,5-a]pyrimidine derivatives and their antifungal activities against phytopathogenic fungi in vitro. Mol Divers 2016; 20(4): 887-96.
[http://dx.doi.org/10.1007/s11030-016-9690-y] [PMID: 27599494]
[80]
Fouda A, Abbas HA, Ahmed E, Shati A, Alfaifi M, Elbehairi S. Synthesis, in vitro antimicrobial and cytotoxic activities of some new pyrazolo[1,5-a]pyrimidine derivatives. Molecules 2019; 24(6): 1080.
[http://dx.doi.org/10.3390/molecules24061080] [PMID: 30893820]
[81]
Zaki YH, Sayed AR, Elroby SA. Regioselectivity of 1,3-dipolar cycloadditions and antimicrobial activity of isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-diones, pyrazolo[3,4-d]pyridazines and pyrazolo[1,5-a]pyrimidines. Chem Cent J 2016; 10(1): 17.
[http://dx.doi.org/10.1186/s13065-016-0163-2] [PMID: 27042207]
[82]
He LL, Qi Q, Wang X, et al. Synthesis of two novel pyrazolo[1,5-a]pyrimidine compounds with antibacterial activity and biophysical insights into their interactions with plasma protein. Bioorg Chem 2020; 99: 103833.
[http://dx.doi.org/10.1016/j.bioorg.2020.103833] [PMID: 32305694]
[83]
Deshmukh S, Dingore K, Gaikwad V, Jachak M. An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicro-bial activity. J Chem Sci 2016; 128(9): 1459-68.
[http://dx.doi.org/10.1007/s12039-016-1141-x]
[84]
Dawane BS, Konda SG, Zangade SB. Design, synthesis, and characterization of some novel pyrazolo [1,5-a] pyrimidines as potent anti-microbial agents. J Heterocycl Chem 2010; 47(5): 1250-4.
[http://dx.doi.org/10.1002/jhet.413]
[85]
Kaping S, Boiss I, Singha LI, Helissey P, Vishwakarma JN. A facile, regioselective synthesis of novel 3-(N-phenylcarboxamide)] pyrazolo[1,5-a]pyrimidine analogs in the presence of KHSO4 in aqueous media assisted by ultrasound and their antibacterial activities. Mol Divers 2016; 20(2): 379-90.
[http://dx.doi.org/10.1007/s11030-015-9639-6] [PMID: 26511367]
[86]
Behbehani H, Ibrahim HM, Makhseed S, Mahmoud H. Applications of 2-arylhydrazononitriles in synthesis: Preparation of new indole containing 1,2,3-triazole, pyrazole and pyrazolo[1,5-a]pyrimidine derivatives and evaluation of their antimicrobial activities. Eur J Med Chem 2011; 46(5): 1813-20.
[http://dx.doi.org/10.1016/j.ejmech.2011.02.040] [PMID: 21397366]
[87]
Abdallah AEM, Elgemeie GH, Elgemeie GH. Design, synthesis, docking, and antimicrobial evaluation of some novel pyrazolo[1,5-a]pyrimidines and their corresponding cycloalkane ring-fused derivatives as purine analogs. Drug Des Devel Ther 2018; 12: 1785-98.
[http://dx.doi.org/10.2147/DDDT.S159310] [PMID: 29950813]
[88]
Gudmundsson KS, Johns BA, Weatherhead J. Pyrazolopyrimidines and pyrazolotriazines with potent activity against herpesviruses. Bioorg Med Chem Lett 2009; 19(19): 5689-92.
[http://dx.doi.org/10.1016/j.bmcl.2009.08.009] [PMID: 19700316]
[89]
Delang L, Neyts J, Vliegen I, Abrignani S, Neddermann P, De Francesco R. Hepatitis C virus-specific directly acting antiviral drugs Hepa-titis C virus: From Molecular Virology to Antiviral Therapy. Berlin, Heidelberg: Springer Berlin Heidelberg 2013; pp. 289-320.
[http://dx.doi.org/10.1007/978-3-642-27340-7_12]
[90]
Sun L, Gao P, Zhan P, Liu X. Pyrazolo[1,5-a]pyrimidine-based macrocycles as novel HIV-1 inhibitors: A patent evaluation of WO2015123182. Expert Opin Ther Pat 2016; 26(9): 979-86.
[http://dx.doi.org/10.1080/13543776.2016.1210127] [PMID: 27398994]
[91]
Hwang JY, Windisch MP, Jo S, et al. Discovery and characterization of a novel 7-aminopyrazolo[1,5-a]pyrimidine analog as a potent hepatitis C virus inhibitor. Bioorg Med Chem Lett 2012; 22(24): 7297-301.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.123] [PMID: 23159569]
[92]
Yamaguchi-Sasaki T, Tokura S, Ogata Y, et al. Discovery of a potent dual inhibitor of wild-type and mutant respiratory syncytial virus fusion proteins. ACS Med Chem Lett 2020; 11(6): 1145-51.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00008] [PMID: 32550994]
[93]
Kosugi T, Mitchell DR, Fujino A, et al. Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) as an antiinflammato-ry target: Discovery and in vivo activity of selective pyrazolo[1,5-a]pyrimidine inhibitors using a focused library and structure-based op-timization approach. J Med Chem 2012; 55(15): 6700-15.
[http://dx.doi.org/10.1021/jm300411k] [PMID: 22746295]
[94]
Lim J, Altman MD, Baker J, et al. Discovery of 5-Amino- N -(1 H -pyrazol-4-yl)pyrazolo[1,5- a]pyrimidine-3-carboxamide Inhibitors of IRAK4. ACS Med Chem Lett 2015; 6(6): 683-8.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00107] [PMID: 26101574]
[95]
Almansa C, de Arriba AF, Cavalcanti FL, et al. Synthesis and SAR of a new series of COX-2-selective inhibitors: Pyrazolo[1,5-a]pyrimidines. J Med Chem 2001; 44(3): 350-61.
[http://dx.doi.org/10.1021/jm0009383] [PMID: 11462976]
[96]
Kaping S, Kalita U, Sunn M, Singha LI, Vishwakarma JN. A facile, regioselective synthesis of pyrazolo[1, 5-a]pyrimidine analogs in the presence of KHSO4 in aqueous media assisted by ultrasound and their anti-inflammatory and anti-cancer activities. Monatsh Chem 2016; 147(7): 1257-76.
[http://dx.doi.org/10.1007/s00706-015-1638-x]
[97]
Nassar E, El-Badry YAM, El Kazaz H. Synthesis, in vivo anti-inflammatory, and in vitro antimicrobial activity of new 5-benzofuranyl fused pyrimidines. Chem Pharm Bull (Tokyo) 2016; 64(6): 558-63.
[http://dx.doi.org/10.1248/cpb.c15-00922] [PMID: 27250790]
[98]
Peytam F, Adib M, Shourgeshty R, et al. An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity. Sci Rep 2020; 10(1): 2595.
[http://dx.doi.org/10.1038/s41598-020-59079-z] [PMID: 32054916]
[99]
Abe M, Seto M, Gogliotti RG, et al. Discovery of VU6005649, a CNS penetrant mGlu7/8 receptor PAM derived from a series of pyrazo-lo[1,5-a]pyrimidines. ACS Med Chem Lett 2017; 8(10): 1110-5.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00317] [PMID: 29057060]
[100]
Lelas S, Wong H, Li YW, et al. Anxiolytic-like effects of the corticotropin-releasing factor1 (CRF1) antagonist DMP904 [4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo- [1,5-a]-pyrimidine] administered acutely or chronically at doses occupying central CRF1 receptors in rats. J Pharmacol Exp Ther 2004; 309(1): 293-302.
[http://dx.doi.org/10.1124/jpet.103.058784] [PMID: 14742750]
[101]
Chen C, Wilcoxen KM, Huang CQ, et al. Design of 2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1, 5-a]pyrimidine (NBI 30775/R121919) and structure-activity relationships of a series of potent and orally active corticotropin-releasing fac-tor receptor antagonists. J Med Chem 2004; 47(19): 4787-98.
[http://dx.doi.org/10.1021/jm040058e] [PMID: 15341493]
[102]
Wegner F, Deuther-Conrad W, Scheunemann M, et al. GABAA receptor pharmacology of fluorinated derivatives of the novel sedative-hypnotic pyrazolopyrimidine indiplon. Eur J Pharmacol 2008; 580(1-2): 1-11.
[http://dx.doi.org/10.1016/j.ejphar.2007.10.016] [PMID: 18035350]
[103]
Zhang F, Mi Y, Qi JL, et al. Modulation of Kv7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58. Br J Pharmacol 2013; 168(4): 1030-42.
[http://dx.doi.org/10.1111/j.1476-5381.2012.02232.x] [PMID: 23013484]
[104]
Koizumi Y, Tanaka Y, Matsumura T, et al. Discovery of a pyrazolo[1,5-a]pyrimidine derivative (MT-3014) as a highly selective PDE10A inhibitor via core structure transformation from the stilbene moiety. Bioorg Med Chem 2019; 27(15): 3440-50.
[http://dx.doi.org/10.1016/j.bmc.2019.06.021] [PMID: 31235264]
[105]
Ivachtchenko AV, Golovina ES, Kadieva MG, Kysil’ VM, Mitkin OD. Antagonists of serotonin 5-HT6 receptors. iv. synthesis and structure-activity interactions in amines containing the 3-(arylsulfonyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidine fragment. Pharm Chem J 2013; 46(10): 595-602.
[http://dx.doi.org/10.1007/s11094-013-0853-1]
[106]
Berezhnoy D, Gravielle MC, Downing S, et al. Pharmacological properties of DOV 315,090, an ocinaplon metabolite. BMC Pharmacol 2008; 8(1): 11.
[http://dx.doi.org/10.1186/1471-2210-8-11] [PMID: 18554397]
[107]
Mikami S, Kawasaki M, Ikeda S, et al. Discovery of a novel series of pyrazolo[1,5-a]pyrimidine-based phosphodiesterase 2a inhibitors structurally different from n-((1s)-1-(3-fluoro-4-(trifluoromethoxy)] phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1h)-carboxamide (tak-915), for the treatment of cogni-tive disorders. Chem Pharm Bull (Tokyo) 2017; 65(11): 1058-77.
[http://dx.doi.org/10.1248/cpb.c17-00564] [PMID: 29093293]
[108]
Selleri S, Bruni F, Costagli C, et al. Synthesis and benzodiazepine receptor affinity of pyrazolo[1,5-a]pyrimidine derivatives. 3. New 6-(3-thienyl) series as α 1 selective ligands. J Med Chem 2003; 46(2): 310-3.
[http://dx.doi.org/10.1021/jm020999w] [PMID: 12519068]
[109]
Selleri S, Bruni F, Costagli C, et al. Synthesis and BZR affinity of pyrazolo[1,5- a]pyrimidine derivatives. part 1: Study of the structural features for BZR recognition. Bioorg Med Chem 1999; 7(12): 2705-11.
[http://dx.doi.org/10.1016/S0968-0896(99)00232-1] [PMID: 10658575]
[110]
Wustrow DJ, Capiris T, Rubin R, et al. Pyrazolo[1,5-a]pyrimidine CRF-1 receptor antagonists. Bioorg Med Chem Lett 1998; 8(16): 2067-70.
[http://dx.doi.org/10.1016/S0960-894X(98)00372-2] [PMID: 9873487]
[111]
Guerrini G, Ciciani G, Daniele S, et al. A new class of pyrazolo[5,1-c][1,2,4]triazines as γ-aminobutyric type A (GABAA) receptor sub-type ligand: Synthesis and pharmacological evaluation. Bioorg Med Chem 2018; 26(9): 2475-87.
[http://dx.doi.org/10.1016/j.bmc.2018.04.011] [PMID: 29650463]

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