A REVIEW ON BIOLOGICAL IMPORTANCE OF PYRIMIDINES IN THE NEW ERA


Meeta Sahu, Nadeem Siddiqui

Abstract


Pyrimidines occupy an important position in the medicinal world as it has a number of diverse biological properties. Their related fused heterocycles are of interest as potential bioactive molecules. Pyrimidine derivatives are reported to have diverse pharmacological activities such as anticonvulsant, analgesic, sedative, anti-depressive, antipyretic, anti-inflammatory, antiviral, anti-HIV, antimicrobial and anti-tumor activities. Therefore, the study in this review has been emphasized on the research work reported in the recent scientific literature on different biological activities of pyrimidine analogs.

Keywords: Pyrimidine, Biological activity, Anti-cancer, Anti-microbial, Anti-convulsant, Anti-diabetic


Keywords


Pyrimidine; Biological activity; Anti-cancer; Anti-microbial; Anti-convulsant; Anti-diabetic

| PDF | HTML |

References


Al-Harbi NO, Bahashwan SA, Fayed AA, Aboonq MS, Amr AEE. Anti-parkinsonism, hypoglycemic and anti-microbial activities of new poly fused ring heterocyclic candidates. Int J Biol Macromol 2013;57:165–73.

Sukach VA, Tkachuk VM, Rusanov EB, Roschenthaler GV, Vovk MV. Heterocyclization of N-(1-chloro-2,2,2-trifluoro ethylidene)carbamates with β-enamino esters-a novel synthetic strategy to functionalized trifluoromethylated pyrimidines. Tetrahedron 2012;68:8408-15.

Gondkar AS, Deshmukh VK, Chaudhari SR. Synthesis, characterization and in vitro antiinflammatory activity of some substituted 1,2,3,4 tetrahydropyrimidine derivatives. Drug Invention Today 2013;5:175-81.

Elmegeed GA, Ahmed HH, Hashash MA, Abd-Elhalim MM, El-kady DS. Synthesis of novel steroidal curcumin derivatives as anti-Alzheimer’s disease candidates: evidences-based on in vivo study. Steroids 2015;101:78–89.

Loidreau Y, Marchand P, Dubouilh-Benard C, Nourrisson M, Duflos M, Loaec N, et al. Synthesis and biological evaluation of N-aryl-7-methoxybenzo[b]furo[3,2-d]pyrimidin-4-amines and their N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amine analogues as dual inhibitors of CLK1 and DYRK1A kinases. Eur J Med Chem 2013;59:283-95.

Loidreau Y, Marchand P, Dubouilh-Benard C, Nourrisson M, Duflos M, Lozach O, et al. Synthesis and biological evaluation of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amines and their pyrido and pyrazino analogues as Ser/Thr kinase inhibitors. Eur J Med Chem 2012;58:171-83.

Perspicace E, Jouan-Hureaux V, Ragno R, Ballante F, Sartini S, Motta CL, et al. Design, synthesis and biological evaluation of new classes of thieno [3,2-d] pyrimidinone and thieno[1,2,3]triazine as an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2). Eur J Med Chem 2013;63:765-81.

Madadi NR, Penthala NR, Janganati V, Crooks PA. Synthesis and antiproliferative activity of aromatic substituted 5-((1-benzyl-1H-indol-3-yl)methylene)-1,3-dimethyl pyrimidine-2,4,6(1H,3H,5H)-trione analogs against human tumor cell lines. Bioorg Med Chem Lett 2014;24:601–3.

Ma L, Wang B, Pang L, Zhang M, Wang S, Zheng Y, et al. Design and synthesis of novel 1,2,3-triazole–pyrimidine–urea hybrids as potential anticancer agents. Bioorg Med Chem Lett 2015;25:1124–8.

Qin W, Sang C, Zhang L, Wei W, Tian H, Liu H, et al. Synthesis and biological evaluation of 2,4-diaminopyrimidines as selective aurora kinase inhibitors. Eur J Med Chem 2015;95:174-84.

Jin C, Jun K, Le E, Kim S, Kwon Y, Kim K, et al. Ethyl 2-(benzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate analogues as a new scaffold for protein kinase casein kinase 2 inhibitor. Bioorg Med Chem 2014;22:4553–65.

Ma L, Pang L, Wang B, Zhang M, Hu B, Xue D, et al. Design and synthesis of novel 1,2,3-triazole-pyrimidine hybrids as potential anticancer agents. Eur J Med Chem 2014;86:368-80.

Temburnikar KW, Zimmermann SC, Kim NT, Ross CR, Gelbmann C, Salomon CE, et al. Antiproliferative activities of halogenated thieno[3,2-d]pyrimidines. Bioorg Med Chem 2014;22:2113–22.

Abbas SE, Gawad NMA, George RF, Akar YA. Synthesis, antitumor and antibacterial activities of some novel tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives. Eur J Med Chem 2013;65:195-204.

Cheng H, Hoffman JE, Le PT, Pairish M, Kania R, Farrell W, et al. Structure-based design, SAR analysis and antitumor activity of PI3K/mTOR dual inhibitors from 4-methylpyridopyrimidinone series. Bioorg Med Chem Lett 2013;23:2787–92.

Fargualy AM, Habib NS, Ismail KA, Hassan AMM, Sarg MTM. Synthesis, biological evaluation and molecular docking studies of some pyrimidine derivatives. Eur J Med Chem 2013;66,276-95.

Lee W, Ortwine DF, Bergeron P, Lau K, Lin L, Malek S, et al. A hit to lead discovery of novel N-methylated imidazolo-, pyrrolo, and pyrazolopyrimidines as potent and selective mTOR inhibitors. Bioorg Med Chem Lett 2013;23:5097–104.

Xu Y, Foulks JM, Clifford A, Brenning B, Lai S, Luo B, et al. Synthesis and structure–activity relationship of 2-arylamino-4-aryl-pyrimidines as potent PAK1 inhibitors. Bioorg Med Chem Lett 2013;23:4072–5.

Wu K, Ai J, Liu Q, Chen T, Zhao A, Peng X, et al. Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: synthesis and SAR study as tyrosine kinase c-Met inhibitors. Bioorg Med Chem Lett 2012;22:6368–72.

Jiao XY, Kopecky DJ, Liu JS, Liu JQ, Jaen JC, Cardozo MG, et al. Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors. Bioorg Med Chem Lett 2012;22:6212–7.

Amr AEE, Sayed HH, Abdulla MM. Synthesis and reactionsof some newsubstituted pyridine and pyrimidine derivatives as analgesic, anticovulsant and antiparkinsonian agents. Arch Pharm Chem Life Sci 2005;338:433-40.

Wang S, Deng X, Zheng Y, Yuan Y, Quan Z, Guan L. Synthesis and evaluation of anticonvulsant and antidepressant activities of 5-alkoxy tetrazolo[1,5-c]thieno[2,3-e]pyrimidine derivatives. Eur J Med Chem 2012;56:139-44.

Yang Z, Fang Y, Pham TN, Lee J, Park H. Synthesis and biological evaluation of 5-nitropyrimidine analogs with azabicyclic substituents as GPR119 agonists. Bioorg Med Chem Lett 2013;23:1519–21.

Koga Y, Sakamaki S, Hongu M, Kawanishi E, Sakamoto T, Yamamoto Y, et al. C-Glucosides with heteroaryl thiophene as novel sodium-dependent glucose cotransporter 2 inhibitors. Bioorg Med Chem 2013;21:5561–72.

Toobaei Z, Yousefi R, Panahi F, Shahidpour S, Nourisefat M, Doroodmand MM, et al. Synthesis of novel poly-hydroxyl functionalized acridine derivatives as inhibitors of α-Glucosidase and α–Amylase. Carbohydr Res 2015;411:22-32.

Negoro K, Yonetoku Y, Moritomo A, Hayakawa M, Iikubo K, Yoshida S, et al. Synthesis and structure–activity relationship of fused pyrimidine derivatives as a series of novel GPR119 agonists. Bioorg Med Chem 2012;20:6442–51.

Lee HW, Kim BK, Ahn JB, Kang SK, Lee JH, Shin JS, et al. Molecular design, synthesis, and hypoglycemic and hypolipidemic activities of novel pyrimidine derivatives having thiazolidinedione. Eur J Med Chem 2005;40:862–74.

Shakya N, Vedi S, Liang C, Yang F, Agrawal B, Kumar R, et al. 4’-Substituted pyrimidine nucleosides lacking 5’-hydroxyl function as potential anti-HCV agents. Bioorg Med Chem Lett 2014;24:1407–9.

Hwang JY, Windisch MP, Jo S, Kim K, Kong S, Kim HC, 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;22:7297–301.

Shakya N, Vedi S, Liang C, Aggrawal B, Tyrrell DL, Kumar R. A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses. Bioorg Med Chem Lett 2012;22:6475–80.

Hua J, Wang Y, Wei X, Wu X, Chen G, Cao G, et al. Synthesis and biological evaluation of novel thiazolidinone derivatives as potential anti-inflammatory agents. Eur J Med Chem 2013;64:292-301.

Townes JA, Golebiowski A, Clark MP, Laufersweiler MJ, Brugel TA, et al. The development of new bicyclic pyrazole-based cytokine synthesis inhibitors. Bioorg Med Chem Lett 2004;14:4945–8.

McIver EG, Bryans J, Birchall K, Chugh J, Drake J, Lewis SJ, et al. Synthesis and structure–activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases. Bioorg Med Chem Lett 2012;22:7169–73.

Keche AP, Hatnapure GD, Tale RH, Rodge AH, Birajdar SS, Kamble M. A novel pyrimidine derivatives with aryl urea, thiourea and sulfonamide moieties: Synthesis, anti-inflammatory and antimicrobial evaluation. Bioorg Med Chem Lett 2012;22:3445–8.

Mane UR, Li H, Huang J, Gupta RC, Nadkarni SS, Giridha R, et al. Pyrido[1,2-a]pyrimidin-4-ones as antiplasmodial falcipain-2 inhibitors. Bioorg Med Chem Lett 2012;20:6296–304.

Singh K, Kaur H, Chibale K, Balzarini J. Synthesis of 4-amino quinoline-pyrimidine hybrids as potent antimalarials and their mode of action studies. Eur J Med Chem 2013;66:314-23.

Thumar NJ, Patel MP. Synthesis, characterization, and antimicrobial evaluation of carbostyril derivatives of 1H-pyrazole. Saudi Pharm J 2011;19:75–83.

Ramiz MMM, El-Sayed WA, El-Tantawy AI, Abdel-Rahman AAH. Antimicrobial activity of new 4,6-disubstituted pyrimidine, pyrazoline, and pyran derivatives. Arch Pharm Res 2010;33:647-54.

Desai NC, Makwana AH, Senta RD. Synthesis, characterization and antimicrobial activity of some novel 4-(4-(arylamino)-6-(piperidin-1-yl)-1,3,5-triazine-2-ylamino)-N-(pyrimidin-2-yl)benzenesulfonamides. J Saudi Chem Soc 2015. Doi:10.1016/J.Jscs.2015.01.004. [Article in Press]

Kanawade SB, Toche RB, Rajani DP. Synthetic tactics of new class of 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile derivatives acting as antimicrobial agents. Eur J Med Chem 2013;64:314-20.

Luo Y, Zhang S, Liu Z, Chen W, Fu J, Zeng Q, et al. Synthesis and antimicrobial evaluation of a novel class of 1,3,4-thiadiazole: derivatives are bearing 1,2,4-triazolo[1,5-a]pyrimidine moiety. Eur J Med Chem 2013;64:54-61.

Yousefia A, Yousefia R, Panahi F, Sarikhani S, Zolghadr AR, Bahaoddini A, et al. Novel curcumin-based pyrano[2,3-d] pyrimidine anti-oxidant inhibitors for-amylase and-glucosidase: implications for their pleiotropic effects against diabetes complications. Int J Biol Macromol 2015;78:46–55.

Vartale SP, Halikar NK, Pawar YD, Tawde KV. Synthesis and evaluation of 3-cyano-4-imino-2-methylthio-4H-pyrido[1,2-a] pyrimidine derivatives as potent antioxidant agents. Arab J Chem 2012. Doi:10.1016/j.arabjc.2011.12.007.

Attri P, Bhatia R, Gaur J, Arora B, Gupta A, Kumar N, et al. Triethylammonium acetate ionic liquid assisted one-pot synthesis of dihydropyrimidinones and evaluation of their antioxidant and antibacterial activities. Arab J Chem 2014. Doi.org/10.1016/j.arabjc.2014.05.007. [Article in Press]

Kotaiah Y, Nagaraju K, Harikrishna N, Rao CV, Yamini L, Vijjulatha M. Synthesis, docking and evaluation of antioxidant and antimicrobial activities of novel 1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-6-yl)selenopheno[2,3-d]pyrimidines. Eur J Med Chem 2014;75:195-202.

Shook BC, Chakravarty D, Barbay JK, Wang A, Leonard K, Alford V, et al. Substituted thieno[2,3-d]pyrimidines as adenosine A2A receptor antagonists. Bioorg Med Chem Lett 2013;23:2688–91.

Kaspersen SJ, Sundby E, Charnock C, Hoff BH. Activity of 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines to Tetrahymena. Bioorg Chem 2012;44:35–41.

Suryawanshi SN, Kumar S, Shivahare R, Pandey S, Tiwari A, Gupta S. Design, synthesis and biological evaluation of aryl pyrimidine derivatives as potential leishmanicidal agents. Bioorg Med Chem Lett 2013;23:5235–8.

Kumar VP, Frey KM, Wang Y, Jain HK, Gangjee A, Anderson KS. Substituted pyrrolo[2,3-d]pyrimidines as Cryptosporidium hominis thymidylate synthase inhibitors. Bioorg Med Chem Lett 2013;23:5426–8.

Lacotte P, Buisson D, Ambroise Y. Synthesis, evaluation and absolute configuration assignment of novel dihydropyrimidin-2-ones as picomolar sodium iodide symporter inhibitors. Eur J Med Chem 2013;62:722-7.

Manikannan R, Venkatesan R, Muthusubramanian S, Yogeeswari P, Sriram D. Pyrazole derivatives from azines of substituted phenacyl aryl/cyclohexyl sulfides and their antimycobacterial activity. Bioorg Med Chem Lett 2010;20:6920–4.

Chikhale R, Menghani S, Babu R, Bansode R, Bhargavi G, Karodia N, et al. Development of selective DprE1 inhibitors: design, synthesis, crystal structure and antitubercular activity of benzothiazolylpyrimidine-5-carboxamides. Eur J Med Chem 2015;96:30-46.

Matyugina E, Khandazhinskaya A, Chernousova L, Andreevskaya S, Smirnova T, Chizhov A, et al. The synthesis and antituberculosis activity of 5’-nor carbocyclic uracil derivatives. Bioorg Med Chem 2012;20:6680–6.

Toti KS, Verbeke F, Risseeuw MDP, Frecer V, Munier-Lehmann H, Calenbergh SV. Synthesis and evaluation of 5’-modified thymidines and 5-hydroxymethyl-2’-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors. Bioorg Med Chem 2013;21:257–68.

Shmalenyuk ER, Chernousova LN, Karpenko IL, Kochetkov SN, Smirnova TG, Andreevskaya SN, et al. Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides. Bioorg Med Chem 2013;21:4874–84.

Guo D, Zhang X, Wang R, Zhou Y, Li Z, Xu J, et al. Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity. Bioorg Med Chem Lett 2012;22:7114–8.

Tremblay M, Bethell RC, Cordingley MG, DeRoy P, Duan J, Duplessis M, et al. Identification of benzofurano[3,2-d]pyrimidin-2-ones, a new series of HIV-1 nucleotide-competing reverse transcriptase inhibitors. Bioorg Med Chem Lett 2013;23:2775–80.

Tichy M, Pohl R, Xu HY, Chen Y, Yokokawa F, Shi P, et al. Synthesis and antiviral activity of 4,6-disubstituted pyrimido[4,5-b]indole ribonucleosides. Bioorg Med Chem 2012;20:6123–33.

Mizuhara T, Oishi S, Ohno H, Shimura K, Matsuoka M, Fujii N. Structure–activity relationship study of pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives for potent anti-HIV agents. Bioorg Med Chem 2012;20:6434–41.

Martínez-Montero S, Fernandez S, Sanghvi YS, Theodorakis EA, Detorio MA, Mcbrayer TR, et al. Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2’,3’-dideoxy-2’,2’-difluoro-4’-azanucleosides. Bioorg Med Chem 2012;20:6885–93.

Tichy M, Pohl R, Tloustova E, Weber J, Bahador G, Lee Y, et al. Synthesis and biological activity of benzo-fused 7-deazaadenosine analogues. 5-and 6-substituted 4-amino-or 4-alkylpyrimido [4,5-b]indole ribonucleosides. Bioorg Med Chem 2013;21:5362–72.

Sakakibara N, Hamasaki T, Baba M, Demizu Y, Kurihara M, Irie K, et al. Synthesis and evaluation of novel 3-(3,5-dimethyl benzyl)uracil analogs as potential anti-HIV-1 agents. Bioorg Med Chem 2013;21:5900–6.

Rai D, Chen W, Tian Y, Chen X, Zhan P, Clercq ED, et al. Design, synthesis and biological evaluation of 3-benzyloxy-linked pyrimidine phenylamine derivatives as potent HIV-1 NNRTIs. Bioorg Med Chem 2013;21:7398–405.

Sakakibara N, Hamasaki T, Baba M, Demizu Y, Kurihara M, Irie K, et al. Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents. Bioorg Med Chem 2013;21:5900–6.

Kim J, Kwon J, Lee D, Jo S, Park D, Choi J, et al. Synthesis and biological evaluation of triazolothieno pyrimidine derivatives as novel HIV-1 replication inhibitors. Bioorg Med Chem Lett 2013;23:153–7.

Mohamed SF, Flefel EM, Amra AEE, El-Shafy DNA. Anti-HSV-1 activity and mechanism of action of some new synthesized substituted pyrimidine, thiopyrimidine and thiazolopyrimidine derivatives. Eur J Med Chem 2010;45:1494–501.

Stella A, Belle KV, Jonghe SD, Louat T, Herman J, Rozenski J, et al. Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a mixed lymphocyte reaction assay. Bioorg Med Chem Lett 2013;21:1209–18.




About this article

Title

A REVIEW ON BIOLOGICAL IMPORTANCE OF PYRIMIDINES IN THE NEW ERA

Keywords

Pyrimidine; Biological activity; Anti-cancer; Anti-microbial; Anti-convulsant; Anti-diabetic

Date

30-03-2016

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 8, Issue 5, 2016 Page: 8-21

Online ISSN

0975-1491

Statistics

398 Views | 1691 Downloads

Authors & Affiliations

Meeta Sahu

Nadeem Siddiqui
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi-110062, India
India


Article Tools



Refbacks

  • There are currently no refbacks.