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REVIEWARTICLE Ranganath et.al / IJIPSR / 5 (01), 2017, 38-49
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
DOI: 10.21276/IJIPSR.2017.05.01.183
Available online: www.ijipsr.com January Issue 38
AN OVERVIEW ON PYRIMIDINES AND THEIR BIOLOGICAL
SIGNIFICANCE
P L N Ranganath*, ND Nizamuddin
Department of pharmaceutical chemistry,
St.Johns college of Pharmaceutical sciences, Yerrakota, Yemmiganur-518360,
Andhra Pradesh, INDIA
Corresponding Author:
P L N Ranganath
Department of pharmaceutical chemistry,
St.Johns college of Pharmaceutical sciences,
Yerrakota, Yemmiganur-518360,
Andhra Pradesh, INDIA
E-mail: [email protected]
Phone: +91- 8985213402
International Journal of Innovative
Pharmaceutical Sciences and Research www.ijipsr.com
Abstract
The present article briefly outlines about the importance and pharmacological significance of
one of the most successful heterocyclic compound pyrimidine and its analogues which are
active as antitubercular, anticancer, antimalarial, anti-inflammatory, antioxidant, antithyroid,
antimicrobial, antiviral and in many other CVS and CNS active medicinal properties.
Keywords: Pyrimidines , Pharmacological activities.
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INTRODUCTION
Pyrimidine is an heterocyclic compound containg two nitrogen atoms at 1, 3 positions in a six
membered cyclic ring containing molecular formula C4H4N2 , mol.wt 82 , mp 250C and bp 124
0C.
Many of the biologically active compounds like alkaloids, aminoacids, vitamins, harmones
contains these heterocyclic ring systems [1]. The pyrimidine ring is present in uracil, thymine,
cytosine will form the building blocks of nucleic acids RNA and DNA [2]. In addition it is also
present in folic acid, riboflavin, thiamine, isoalloxazine like vitamins [3]. The well known
Sedatives and hypnotics like Barbiturates, Benzodiazepines also contains this pyrimidine ring in
their structures.
Fig.1: Nucleic acids and vitamin
Synthesis: Here are past reports for the synthesis of pyrimidines. Among them the most facile
and simple widely used method for the synthesis is Biginelli reaction.
1) Biginelli reaction Is the method of synthesis in which the ethylacetoacetate, aromatic
aldehydes and urea condensed to give pyrimidines [4].
2) Is the method in which the pyrimidine are synthesized from ketones using HMDS and
formamide [5].
3) 2- substituted pyrimidine 5-carboxylic esters are prepared by reacting amidinium salts
with 3,3-dimethoxy-2-methoxycarbonylpropen-1-ol [6].
REVIEWARTICLE Ranganath et.al / IJIPSR / 5 (01), 2017, 38-49
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
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4) in this method the pyrimidines are prepared by β-formyl enamide involving samarium
chloride mediated cyclization with urea in microwave [7].
5) Synthesis of pyrimidines from chalcones and amines using potassium hydroxide by
Kaswan et al (2014) [8].
6) Xavier et al (2013) has reported multiple component microwave assisted synthesis of
pyrimidines derivatives [9].
7) Goyan et al (2012) also reported synthesis of pyrimidines from β-enamines [10].
8) Pyrimidines 5-carbaldehydes are prepared from α-formylaroylketone dithioacetals by
Mathews and Asokan (2007) [11].
STRUCTURAL ACTIVITY RELATIONSHIP
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Presence of 5-memebered heterocyclic ring as substitutent on N1 position will gives
antiviral and anticancer property.
Presence of hetero cyclic ring on C2 will makes it active against GIT infections and also
antiparkinsonism agent.
Presence of Keto and amino groups on C2 and C4 will makes it antiviral, antimicrobial,
antifungal and anticancer agents.
Presence of halogens and substituted amines on C5 will give anticancer activity to the
pyrimidines.
Fusion of C5 and C6 postions with heterocyclic ring and ortho, meta and para substitution
leads to anticancer, antiviral, antibacterial and vasodilatory properties.
BIOLOGICAL ACTIVE COMPOUNDS
Table 1: Antineoplastic and Anticancer agents [12-17]
DRUG STRUCTURE IUPAC NAME
5-Flourouracil
5-fluoropyrimidine-2,4(1H,3H)-dione
5-Thiouracil
5-mercaptopyrimidine-2,4(1H,3H)-dione
Mercaptopurine
5,6-dihydro-1H-purine-6-thiol
Thioguanine
2-amino-5,6-dihydro-1H-purine-6-thiol
Tegafur
5-fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-
2,4(1H,3H)-dione
Gemcitabine
4-amino-1-(3,3-difluoro-4-hydroxy-5-
(hydroxymethyl)tetrahydrofuran-2-
yl)pyrimidin-2(1H)-one
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Table 2: Antithyroid agents [18]
DRUG STRUCTURE IUPAC NAME
2-Thiouracil
6-propyl-2-thioxotetrahydropyrimidin-
4(1H)-one
Propylthiouracil
5,5-diethyl-2-thioxodihydropyrimidine-
4,6(1H,5H)-dione
Thiobarbital
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-
diamine
Table 3: Antifolates [19-24]
DRUG STRUCTURE IUPAC NAME
Pyrimethamine
5-(3,4,5-
trimethoxybenzyl)pyrimidine-2,4-
diamine
Trimethoprim
5-(3,4,5-
trimethoxybenzyl)pyrimidine-2,4-
diamine
Methotrexate
2-(4-(((2,4-diaminopteridin-6-
yl)methyl)(methyl)amino)benzami
do)pentanedioic acid
Aminopterin
2-(4-(((2,4-diaminopteridin-6-
yl)methyl)amino)benzamido)penta
nedioic acid
Table 4: Sulfa Drugs [25-27]
DRUG STRUCTURE IUPAC NAME
sulfadoxine
N-(5,6-dimethoxypyrimidin-4-
yl)benzenesulfonamide
Sulfadiazine
4-((pyrimidin-2-ylmethyl)sulfonyl)aniline
Sulfamerazine
4-(((4-methylpyrimidin-2-
yl)methyl)sulfonyl)aniline
Sulfadimidine
4-(((4,6-dimethylpyrimidin-2-
yl)methyl)sulfonyl)aniline
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Table 5: Antiviral and Anti-AIDS [28-30]
DRUG STRUCTURE IUPAC NAME
Retrovir
4-(((5-methylpyrimidin-2-
yl)methyl)sulfonyl)aniline
Acyclovir
2-amino-9-((2-hydroxyethoxy)methyl)-1H-
purin-6(9H)-one
Ganciclovir
2-amino-9-(((1,3-dihydroxypropan-2-
yl)oxy)methyl)-1H-purin-6(9H)-one
Valaciclovir
2-((2-amino-6-oxo-1H-purin-9(6H)-
yl)methoxy)ethyl 2-amino-3-methylbutanoate
Lamivudine
1-(4-azido-5-(hydroxymethyl)-3-
methyltetrahydrofuran-2-yl)-5-
methyldihydropyrimidine-2,4(1H,3H)-dione
Table 6: Antihelmenthic agents [31]
DRUG STRUCTURE IUPAC NAME
Pyrantel pamoate
2-(2-(2,3-dihydrothiophen-2-yl)ethyl)-1-
methyl-1,4,5,6-tetrahydropyrimidine
Didanosine
9-(5-(hydroxymethyl)tetrahydrofuran-2-yl)-
1H-purin-6(9H)-one
Table 7: Antibiotics [32-34]
DRUG STRUCTURE IUPAC NAME
Bacimethrin
(4-amino-2-methylpyrimidin-5-yl)methanol
Tubercidine
2-(hydroxymethyl)-2,3,4-trimethyl-5-(7H-
pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-
3,4-diol
Amicetin
1-(3,4-dihydroxy-5-
(hydroxymethyl)tetrahydrofuran-2-yl)-4-((4-
methoxybenzyl)amino)-5,6-dihydropyrimidin-
2(1H)-one
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Table 8: Antifungal agents [35,36]
DRUG STRUCTURE IUPAC NAME
Flucytosine
4-amino-5-fluoropyrimidin-2(1H)-one
Flexitidine
1,3-bis(2-ethylhexyl)-5-
methylhexahydropyrimidin-5-amine
Table 9: Anxiolytic agents [37,38]
DRUG STRUCTURE IUPAC NAME
Buspirone
8-(5-(4-(pyridin-2-yl)piperazin-1-yl)pentyl)-
8-azaspiro[4.5]decane-7,9-dione
Ritanserin
6-[2-[4-[bis(4
fluorophenyl)methylidene]piperidn-1-
yl]ethyl]-7-methyl-[1,3]thiazolo[3,2-
a]pyrimidin-5-one
Table 10: Anaesthetic agents [39,40]
DRUG STRUCTURE IUPAC NAME
Thimylal
5-allyl-2-methylene-5-(pentan-2-
yl)dihydropyrimidine-4,6(1H,5H)-dione
Table 11: Anti-Hypertensive agents [41-44]
DRUG STRUCTURE IUPAC NAME
Prazosin
(4-(4-amino-6,7-dimethoxyquinazolin-2-
yl)piperazin-1-yl)(furan-3-yl)methanone
Terazosin
(4-(4-amino-6,7-dimethoxyquinazolin-2-
yl)piperazin-1-yl)(tetrahydrofuran-3-
yl)methanone
Minoxidil
5-(piperidin-1-yl)pyrimidine-2,4-diamine
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Table 12: Diuretic agents [45-49]
DRUG STRUCTURE IUPAC NAME
Caffiene
1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purin-
2(6H)-one
Lomiphylline
1,3-dimethyl-7-(5-oxohexyl)-3,4,5,7-
tetrahydro-1H-purin-2(6H)-one
Etophylline
7-(2-hydroxyethyl)-1,3-dimethyl-3,4,5,7-
tetrahydro-1H-purin-2(6H)-one
Theophylline
1,3-dimethyl-3,4,5,7-tetrahydro-1H-purin-
2(6H)-one
Triampterene
6-phenylpteridine-2,4,7-triamine
Table 13: Bronchodilators [50]
DRUG STRUCTURE IUPAC NAME
Aminophylline
1,3-dimethyl-1H-purine-2,6(3H,7H)-dione
Proxyphylline
7-(2-hydroxypropyl)-1,3-dimethyl-1H-purine-
2,6(3H,7H)-dione
Table 14: Anti-inflammatory agents [51-53]
DRUG STRUCTURE IUPAC NAME
Afloqualone
6-amino-2-(fluoromethyl)-3-(o-tolyl)-2,3-
dihydroquinazolin-4(1H)-one
Epirizole
4-methoxy-2-(5-methoxy-3-methyl-1H-
pyrazol-1-yl)-6-methylpyrimidine
Proquazone
1-isopropyl-7-methyl-4-phenylquinazolin-
2(1H)-one
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Table 15: Metabolic electrolytes [54]
DRUG STRUCTURE IUPAC NAME
Orotic acid
2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-
carboxylic acid
CONCLUSION
Pyrimidines among the heterocyclic compounds were occupied a perpetual and distinct role in the
field of medicinal chemistry as they possess multiple activities like anticancer, antibiotic,
antifungal, anti inflammatory, antihypertensive, anxiolytic and many other biological properties.
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