International Journal of Innovative Pharmaceutical … [email protected] Phone: +91- 8985213402 International Journal of Innovative Pharmaceutical Sciences and Research Abstract

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.

mailto:[email protected]



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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].



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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]


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]


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]


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-




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Table 5: Antiviral and Anti-AIDS [28-30]


Retrovir

4-(((5-methylpyrimidin-2-


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]


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]


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]


Flucytosine

4-amino-5-fluoropyrimidin-2(1H)-one

Flexitidine

1,3-bis(2-ethylhexyl)-5-

methylhexahydropyrimidin-5-amine

Table 9: Anxiolytic agents [37,38]


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]


Thimylal

5-allyl-2-methylene-5-(pentan-2-

yl)dihydropyrimidine-4,6(1H,5H)-dione

Table 11: Anti-Hypertensive agents [41-44]


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]


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]


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]


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]


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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International Journal of Innovative Pharmaceutical … [email protected] Phone: +91- 8985213402 International Journal of Innovative Pharmaceutical Sciences and Research Abstract