Main Article Content
In recent years, the resistance of organisms toward drugs has accelerated at an alarming rate. Hence, the search for newer drugs is incessant. Pyrimidines, six-membered heterocyclic compounds, form the basis of our DNA and RNA. This pharmacophore possesses an extensive array of biological activities, namely antimicrobial, anti-cancer, anticonvulsant, anthelmintic, etc. This review aims at describing recent reports in the field of pyrimidine synthesis along with the pyrimidine-based drugs employed to treat numerous disorders. A detailed summary of the pyrimidine moiety, including its structure, various reactions it undergoes, numerous substituted and fused pyrimidines, along with their biological significance, etc., has been reported. This panoramic study has been undertaken to facilitate a scaffold for discovering newer drugs.
Sharma V, Chitranshi N, Agarwal AK. Significance and biological importance of pyrimidine in the microbial world. International journal of medicinal chemistry. 2014;2014:1-31.
Schwarz S, Loeffler A, Kadlec K. Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine. Advances in Veterinary Dermatology. 2017;8:95-110.
Panlilio A, Culver D, Gaynes R et al. Methicillin-resistant Staphylococcus aureus in U.S. hospitals, 1975–1991. Infection Control and Hospital Epidemiology.1992;13(10) : 582–586.
Levy SB, Marshall B. Anti-bacterial resistance worldwide: causes, challenges and responses. Nature medicine. 2004;10(12s):S122.
Coates A and Hu Y. Novel approaches to developing new antibiotics for bacterial infections.The British Journal of Pharmacology.2007; 152(8):1147–1154.
Ju Y and Varma R. Aqueous N-heterocyclization of primary amines and hydrazines with dihalides: microwave-assisted syntheses of N-azacycloalkanes, isoindole, pyrazole, pyrazolidine, and phthalazine derivatives. Journal of Organic Chemistry.2006;71(1):135–141.
Eswara R G, Srinivasa BP, Sai K O., Sharmila R and MaruthiK.International Journal of Recent Scientific Research .2016; 7(4) :10238-10241.
Al-Mulla A. A review: biological importance of heterocyclic compounds. Der PharmaChemica. 2017;9(13):141-72.
Nirwan N, Pareek C, Chohadia A. Role of Nitrogen-Containing Natural Heterocyclic Compounds in Medical Science: A Mini Review .IJSRST. 2015;1(1):76-84.
Rakesh N. M and Desai K.Studies on Synthesis of Some Novel Heterocyclic Chalcone, Pyrazoline, Pyrimidine - 2 - One, Pyrimidine -2- Thione, para-Acetanilide Sulphonyl,and Benzoyl Derivatives and their Antimicrobial Activity.E-Journal of Chemistry .2005; 2(6): 30-41.
Bagul C, Rao GK, Makani VK, Tamboli JR, Pal-Bhadra M, Kamal A. Synthesis and biological evaluation of chalcone-linked pyrazolo [1, 5-a] pyrimidines as potential anti-cancer agents. MedChemComm. 2017; 8(9):1810-6.
Sharma V, Chitranshi N, Agarwal AK. Significance and biological importance of pyrimidine in the microbial world. International journal of medicinal chemistry. 2014;2014.
Bhat KI, Kumar A, Nisar M, Kumar P. Synthesis, pharmacological and biological screening of some novel pyrimidine derivatives. Medicinal Chemistry Research. 2014; 23(7):3458-67.
Rani J, Kumar S, Saini M, Mundlia J, Verma PK. Biological potential of pyrimidine derivatives in a new era. Research on Chemical Intermediates. 2016;42(9):6777-804.
Bazgir A, Khanaposhtani MM, Soorki AA. One-pot synthesis and anti-bacterial activities of pyrazolo [4′, 3′: 5, 6] pyrido [2, 3-d] pyrimidine-dione derivatives. Bioorganic & medicinal chemistry letters. 2008 Nov 1;18(21):5800-3.
Mohana S, Sompalle R. Synthetic chemistry of pyrimidines and fused pyrimidines: a review. Synthetic Communications. 2016 Apr 17;46(8):645-72.
Henderson, J.F, and Paterson, A.R.P., "Nucleotide Metabolism – An Introduction" Academic Press, New York (1973) 1–304.
Kogon, Irving C.; Minin, Ronald; Overberger, C. G. "2-Chloropyrimidine". Organic Syntheses. 35( 4):182
Yerragunta V, Patil P, Anusha V, Swamy TK, Suman A, Samhitha T. Pyrimidine and its biological activity: a review. PharmaTutor. 2013; 1(2):39-44.
Mohana Roopan S, Sompalle R. Synthetic chemistry of pyrimidines and fused pyrimidines: a review. Synthetic Communications. 2016 Apr 17;46(8):645-72.
Lagoja IM. Pyrimidine as constituent of natural biologically active compounds. Chemistry & Biodiversity. 2005 ;2(1):1-50.
Dinakaran VS, Bomma B, Srinivasan KK. Fused pyrimidines: The heterocycle of diverse biological and pharmacological significance. Der Pharma Chemica. 2012;4(1):255-65.
Hausen A, Fuchs D, Reibnegger G, Wachter H. Urinary pteridines on patients suffering from cancer. A comment on the method and results of rao and associates and of trehan and associates. Cancer. 1984 Apr 1;53(7):1634-6.
Comprehensive Heterocyclic Chemistry Volume 3, 1984, Pages 263-327
Forrest HS, Hanly EW, Lagowski JM. Biochemical differences between the mutants rosy-2 and maroon-like of Drosophila melanogaster. Genetics. 1961 Nov;46(11):1455.
Albert A. Progress in the Chemistry of Organic Natural Products. Journal of soil science and plant nutrition. 1954: 350-403.
Gready, J. E.; McKinlay, C.; Gebauer, M. G. Synthesis of quaternised 2-aminopyrimido[4,5-d] pyrimidin-4(3H)-ones and their biological activity with dihydrofolate reductase. Eur. J. Med. Chem. 2003, 38, 719–728
Sahu ME, Siddiqui NA. A review on biological importance of pyrimidines in the new era. Int J Pharm Pharm Sci. 2016;8(5):8-21.
Jhansi K, Vanita P, Lavanya S and Satya V. A Review on Antidepressant Drugs. Adv Pharmacoepidemiol Drug Saf. 2014;3(1):1-2.
Sindhu T, Mamatha A, Sahith K, Venkateshwarlu K. Anti-depressant activity of Pyrimidine derivatives in mice. J Drug Med. 2013; 5:129-34.
Imperiale BR, Cataldi ÁA, Morcillo NS. In vitro anti-tuberculosis activity of azole drugs against Mycobacterium tuberculosis clinical isolates. Revista Argentina de microbiologia. 2017;49(4):332-8.
Peloquin CA. Pharmacology of the antimycobacterial drugs. The Medical clinics of North America. 1993;77(6):1253-62.
Trivedi AR, Dodiya DK, Ravat NR, Shah VH. Synthesis and biological evaluation of some new pyrimidines via a novel chalcone series. Arkivoc. 2008; 11:131-41.
Umaa K, Ramanathan M, Krishnakumar K, Kannan K. Elucidation and evaluation of substituted pyrimidines. Asian Journal of Chemistry. 2009; 21(9):6674.
Leelaprakash G, Mohan D S. Invitro Anti-Inflammatory Activity of Methanol Extract of EnicostemmaAxillare. Int. J. Drug Dev. & Res., July-Sept 2011, 3 (3): 189-196.
Amri et al. Anti-inflammatory activity of P. Atlantica Pharmacogn J. 2018; 10(1): 71-76
Vishal DJ, Mahendra DK, Sarita S. Synthesis and pharmacological study of some novel pyrimidines. Pelagia Research Library. 2012; 3(3):343-8.
Kachroo M, Panda R, Yadav Y. Synthesis and biological activities of some new pyrimidine derivatives from chalcones. Pharm Chem. 2014; 6(2):352.
Shehab WS, Abdellattif MH, Mouneir SM. Heterocyclization of polarized system: synthesis, antioxidant and anti-inflammatory 4-(pyridin-3-yl)-6-(thiophen-2-yl) pyrimidine-2-thiol derivatives. Chemistry Central Journal. 2018;12(1):68.
Caulfield MP, Birdsall NJ. International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacological reviews. 1998;50(2):279-90.
Wonderlin WF. Muscarinic Blocking Drugs. Craig CR and Stitzel RE. Modern Pharmacology with Clinical Applications. 6th ed. Baltimore, MD: Lippincott Williams & Wilkins. 2004.
Bender AM, Weiner RL, Luscombe VB, Cho HP, Niswender CM, Engers DW, Bridges TM, Conn PJ, Lindsley CW. Synthesis and evaluation of 4, 6-disubstituted pyrimidines as CNS penetrant pan-muscarinic antagonists with a novel chemotype. Bioorganic & medicinal chemistry letters. 2017;27(11):2479-83.
Becker DE. Antimicrobial drugs. Anesthesia progress. 2013 Aug;60(3):111-23.
Waheed A, Alorainy MS, Alghasham AA, Khan SA, Raza M. Synthesis of a new series of substituted pyrimidines and its evaluation for anti-bacterial and antinociceptive effects. International journal of health sciences. 2008;2(1):39.
Eswara Rao G, SrinivasaBabu P, SaiKoushik O, Sharmila R, SSS MK. Synthesis, characterization and biological evaluation of pyrimidines from chalcones.2016;7(4):10238-41.
Mistry RN, Desai KR. Studies on synthesis of some novel heterocyclic chalcone, pyrazoline, pyrimidine-2-one, pyrimidine-2-thione, para-acetanilide sulphonyl and benzoyl derivatives and their antimicrobial activity. Journal of Chemistry. 2005;2(1):30-41.
Kidwai M, Mishra AD. An expeditious synthesis of 3, 4-dihydro-benzo [2.3-d] pyrimidines using inorganic solid supports. Journal-Serbian Chemical Society. 2004;69(4):247-54.
Naik TA, Chikhalia KH. Studies on synthesis of pyrimidine derivatives and their pharmacological evaluation. Journal of Chemistry. 2007;4(1):60-6.
Misra A, Sharma S, Sharma D, Dubey S, Mishra A, Kishore D, Dwivedi J. Synthesis and molecular docking of pyrimidine incorporated novel analogue of 1, 5-benzodiazepine as anti-bacterial agent. Journal of Chemical Sciences. 2018;130(3):31.
Fang Y, Xia W, Cheng B, Hua P, Zhou H, Gu Q, Xu J. Design, synthesis, and biological evaluation of compounds with a new scaffold as anti-neuroinflammatory agents for the treatment of Alzheimer's disease. European journal of medicinal chemistry. 2018;149:129-38.
Gant J, Blalock EM, Chen KC. FK506-Binding Protein 12.6/1b, a negative regulator of [Ca(2þ) ], rescues memory and restores genomic regulation in the hippocampus of aging rats. J. Neurosci.2018; 38 (4) : 1030-1041.
Heneka MT, M.J. Carson MJ. Neuroinflammation in Alzheimer's disease.Lancet Neurol. 2015;14 :388-405.
Hsieh CJ, Xu K, Lee I, Graham TJ, Tu Z, Dhavale D, Kotzbauer P, Mach RH. Chalcones and five-membered heterocyclic isosteres bind to alpha synuclein fibrils in vitro. ACS Omega. 2018;3(4):4486-93.
Kaur R, Kaur P, Sharma S, Singh G, Mehndiratta S, MS Bedi P, Nepali K. Anti-cancer pyrimidines in diverse scaffolds: a review of patent literature. Recent patents on anti-cancer drug discovery. 2015 Jan 1;10(1):23-71.
Bagul C, Rao GK, Makani VK, Tamboli JR, Pal-Bhadra M, Kamal A. Synthesis and biological evaluation of chalcone-linked pyrazolo [1, 5-a] pyrimidines as potential anti-cancer agents. MedChemComm. 2017;8(9):1810-6.
Napoleon AA, Angajala G, Chetry P. Synthesis of new pyrimidine derivatives via 1, 3 dipolar cycloaddition and their in-silico molecular docking studies as thymidylate synthase inhibitors. Der Pharmacia Lettre.2015; 7(6):45-52.
Kumar S, Lim SM, Ramasamy K, Vasudevan M, Shah SA, Selvaraj M, Narasimhan B. Synthesis, molecular docking and biological evaluation of bis-pyrimidine Schiff base derivatives. Chemistry Central Journal. 2017;11(1):89.
Matias M, Campos G, Santos AO, Falcão A, Silvestre S, Alves G. Synthesis, in vitro evaluation and QSAR modeling of potential antitumoral 3, 4-dihydropyrimidin-2-(1H)-thiones. Arabian Journal of Chemistry. 2017.
C Danta C, B Sahu S, R Swain T. 2D Pharmacophoric Design and Synthesis of Novel Pyrimidine Derivatives as Anticonvulsants. Current Bioactive Compounds. 2017 Jun 1;13(2):130-6.
Ulloora S, Shabaraya R, Aamir S, Adhikari AV. New imidazo[1,2-a]pyridines carrying active pharmacophores: Synthesis and anticonvulsant studies. Bioorg. Med. Chem. Lett. 2013;23(5):1502-6.
Ulloora S, Adhikari AV, Shabaraya R. Synthesis and antiepileptic studies of new imidazo[1,2-a]pyridine derivatives. Chin. Chem. Lett. 2013;24(9):853-6.
Li H, Kang DZ, Wang SB, et al. Synthesis and evaluation of the anticonvulsant activity of 9-alkyl-2,9-dihydro-3H-1,2,4- triazolo[4,3-a]benzimidazole-3-one derivatives. Lat Am J Pharm 2015;34:5–12.
Zhang HJ, Shen QK, Jin CM, et al. Synthesis and pharmacological evaluation of new 3,4-dihydroisoquinolin derivatives containing heterocycle as potential anticonvulsant agents.Molecules 2016;21:e1635.
Mohana KN, Kumar BN, Mallesha L. Synthesis and biological activity of some pyrimidine derivatives. Drug invention today. 2013;5(3):216-22.
Kamiński K, Zagaja M, Łuszczki JJ, Rapacz A, Andres-Mach M, Latacz G, Kieć-Kononowicz K. Design, synthesis, and anticonvulsant activity of new hybrid compounds derived from 2-(2, 5-dioxopyrrolidin-1-yl) propanamides and 2-(2, 5-dioxopyrrolidin-1-yl) butanamides. Journal of medicinal chemistry. 2015;58(13):5274-86.
Ugwu DI, Okoro UC, Mishra NK. Synthesis, characterization and anthelmintic activity evaluation of pyrimidine derivatives bearing carboxamide and sulphonamide moieties. J. Serb. Chem. Soc. 2018;83(4):401-9.
Guan LP, Sui X, Chang Y, Yan ZS, Tong GZ, Qu YL. Design, Synthesis and Anticonvulsant Activity Evaluation of 7-Substituted–[1, 2, 4]-Triazolo [4, 3-f] Pyrimidine Derivatives. Medicinal Chemistry. 2012 Nov 1;8(6):1076-83.
Jiang N, Deng XQ, Li FN, Quan ZS. Synthesis of novel 7-substituted-5-phenyl-[1, 2, 4] triazolo [1, 5-a] pyrimidines with anticonvulsant activity. Iranian journal of pharmaceutical research: IJPR. 2012;11(3):799.
Amir M, Ali I, Hassan MZ. Design and synthesis of some new quinazolin-4-(3H)-ones as anticonvulsant and antidepressant agents. Archives of pharmacal research. 2013;36(1):61-8.
Anisuzzaman M, Rahman AHMM, Harun‐or‐Rashid M, Naderuzzaman ATM, Islam. An Ethnobotanical Study of Mdahupur, Tangail. J App Sci Research 2007; 3: 519‐530.
Partridge FA, Murphy EA, Willis NJ, Bataille CJR, Forman R, Heyer-Chauhan N, et al. Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilizing whipworm and reducing infectivity in vivo. PLoS Negl Trop Dis. 2017;11: e0005359.
Silbereisen A, Tritten L, Keiser J. Exploration of novel in vitro assays to study drugs against Trichuris spp. J Microbiol Methods. 2011;87: 169–175.
Hayes KS, Bancroft AJ, Goldrick M, Portsmouth C, Roberts IS, Grencis RK. Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris. Science. 2010;328: 1391–1394.
Vijayan A, Liju VB, Reena John JV, Parthipan B, Renekac. Traditional remedies of kani tribes of kotor reserve forest, Agasthyavanam, Thiruvanathapuram kerala. Ind. J Trad Know 2007; 6 : 589‐594.
Yadav P, Singh R. A review on anthelmintic drugs and their future scope. Int J Pharm Pharm Sci. 2011;3(3):17-21.
Geary TG, Sangster, NC, Thompson, DP. Frontiers in anthelmintic pharmacology. Vet Parasitol 1999; 84: 275–295.
Greenberg RM. Ca2+ signaling, voltage‐gated Ca2+ channels and praziquantel in flatworm neuromusculature. Parasitol 2005; 131: S97–S108.
Ali MR, Verma G, Shaquiquzzaman M, Akhter M, Alam MM. Synthesis and anticonvulsant activity of some newer dihydro-pyrimidine-5-carbonitrile derivatives: Part II. Journal of Taibah University Medical Sciences. 2015 Dec 1;10(4):437-43.
Partridge FA, Forman R, Willis NJ, Bataille CJ, Murphy EA, Brown AE, Heyer-Chauhan N, Marinič B, Sowood DJ, Wynne GM, Else KJ. 2, 4-Diaminothieno [3, 2-d] pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm. PLoS neglected tropical diseases. 2018;12(7):0006487.