INTRODUCTION:

Heterocyclic chemistry is one of the most interesting, applied branches of organic chemistry and of almost practical and theoretical importance. As a result, a great deal of research carried out in chemistry is devoted to heterocyclic chemistry. It is vast and expanding area of chemistry because of obvious application of compounds derived from heterocyclic rings in pharmacy, medicine, agriculture, plastic, polymer and other fields. Heterocyclic compounds are widely distributed in nature. By virtue of their therapeutic properties, they could be employed in the treatment of infectious diseases. Many heterocyclic compounds synthesized in laboratories have been successfully used as clinical agents. Heterocycles form by far the largest of classical organic divisions of organic chemistry and are of immense importance biologically and industrially.

The majority of pharmaceuticals and biologically active agrochemicals are heterocycles while countless additives and modifiers used in industrial applications ranging from cosmetics reprography, information storage and plastics are heterocycles in nature. One striking structural features inherent to heterocycles, which continue to be to great advantage by the drug industry, lies in their ability to manifest substituents around a core scaffold in defined three dimensional representations. For more than a century, heterocycles have constituted one of the largest areas of research in organic chemistry. They have contributed to the development of society from a biological and industrial point of view as well as to the understanding of life processes and to the efforts to improve the quality of life. Among the approximately 20 million chemical compounds identified by the end of the second millennium, more than two-thirds are fully or partially aromatic and Approximately half are heterocycles. The presence of heterocycles in all kinds of organic compounds of Interest in electronics, biology, optics, pharmacology, material sciences and so on is very well known. Among heterocycles; nitrogen-containing heterocyclic compounds have maintained the interest of researchers through decades of historical development of organic synthesis. The simple doubly unsaturated compound containing two nitrogen and three carbon atoms in the ring, with the nitrogen atoms neighboring, is known as pyrazole. For a long time no pyrazole derivative had been found in nature, but in 1959 β-(1-pyrazolyl) alanine was isolated from the seeds of water melons (Citurllus lanatus) (L. Fowden). Pyrazole is a tautomeric substance; the existence of tautomerism cannot be demonstrated in pyrazole itself, but it can be inferred by the consideration of pyrazole derivatives. Amongst the various heterocycles, pyrazole classes of compounds play an important role in medicinal chemistry.

Pyrazole and its derivatives, a class of well known nitrogen containing heterocyclic compounds, occupy an important position in medicinal and pesticide chemistry with having a wide range of bioactivities. Nitrogen heterocycles, those containing the pyrazole nucleus have been shown to possess high biological activities as herbicides, fungicides, analgesics, etc. Owing to the widespread applications, synthesis and biological activity evaluation of pyrazoles and their derivatives has been a subject of intensive investigational compounds for centuries.

Objectives:

1) An overview of different pharmacological activities of pyrazole moiety.

2) To co-relate the structural modifications with medicinal activities of pyrazole compounds.

3) This review unveils recent success in design and development of pyrazole derivatives.

4) This review also has revealed a systematic investigation of this class of heterocyclic lead , playing a important role in medicinal chemistry being a pharmacoactive agent.

History

· The term Pyrazole was given by Ludwig Knorr in 1883.

· Pyrazole refers to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions.

· Being so composed a pyrazole having pharmacological effects on humans, they are

· Classified as alkaloids, although they are rare in nature.

· Pyrazoles have illustrious history; in 1883, a German chemist Ludwig Knorr was the first to discover antipyretic action of pyrazole derivative in man, he named the compound antipyrine.

· When he attempted to synthesize quinoline derivatives with antipyretic activity, accidentally obtained antipyrine (2,3- dimethyl-1- henyl-3-pyrazolin-5-one) which has analgesic, antipyretic and antirheumatic activity; which stimulated interest in pyrazole chemistry.

· The first natural pyrazole derivative was isolated by Japanese workers Kosuge and Okeda in the year 1954, till their discovery it was thought that pyrazoles could not be obtained naturally.

· They isolated 3-ylpyrazole from Houttuynia Cordata, a plant of the “piperaceae” family from tropical Asia; which showed antimicrobial activity. They also isolated levo-β-(1-pyrazolyl) alanine an amino acid from watermelon seeds (Citrullus Vulgaris).

Chemistry of pyrazole:

· Replacing a CH group in the pyrrole ring with a nitrogen atom can give rise to two compounds: pyrazole and imidazole.

· Only one nitrogen atom can contribute two electrons to the aromatic sextet. It is the nitrogen with the hydrogen (black in color) and it is described ags pyrrole-like nitrogen. While the second nitrogen which has no hydrogen (green) is described as pyridine-like. The lone pair on pyrrole-like nitrogen is delocalized round the ring while that on the pyridine-like nitrogen is localized in sp2 orbital on nitrogen. Thus these compounds have properties intermediate between those of pyrrole and pyridine Pyrazole is water soluble solid and insoluble in aprotic solvents. They have higher boiling point: 187°C.Pyrazole molecules can form dimers only thus lesser energy is required to break these molecules.

Basicity of pyrazole:

Basicity order: Imidazole > Pyrazole > Pyridine > pyrrole:

· This can be explained as follows: i) Pyrrole is not basic because the lone pair on the only nitrogen is needed to complete the aromatic pi system and protonation if occurs at all occurs at carbon rather than on nitrogen and the resulting cation is not aromatic.

· Pyrazole have two nitrogen atoms and on protonation the positive charge can be

delocalized over them. However, pyrazoles are much weaker bases than Imidazole.

Effect of substitution on basicity:

· Generally E.D.G groups on the ring increase the basicity while E.W.G. decreases it.

· N-methyl imidazole is more basic than imidazole itself.

· However, N-methylpyrazole is less basic than pyrazole which can be attributed to steric hindrance effect which cause difficulty in accessing the lone pair of electron by the proton.

Electrophilic Aromatic Substitution:

· Diazoles are less reactive than 5-membered heterocycles with one heteroatom (pyrrole and its analogs) in electrophilic aromatic substitution due to the inductive electron-withdrawing effect of the second heteroatom.

· However, they are more reactive than pyridine due to delocalization of the lone pair of electrons on the N-atom make the C- atoms bear negative charges while in pyridine the N- atom exerts inductive electron withdrawing effect only.

· The orientation in pyrazole, is at the 4-position due to the deactivation effect of the pyridine-like nitrogen.

Diazocoupling

Since it occurs with electron rich aromatic compounds it occurs only with imidazole and ctivated pyrazole (with EDG) in alkaline medium

Pharmacological spectrum of pyrazole derivatives:

This review highlighted recent reports of antimicrobial, anticancer, ACE inhibitor, antiviral as well as anti-inflammatory activities of pyrazole. The purpose of this review was to collate literature work reported by researchers on Pyrazole for their various pharmacological activities and also reported recent efforts made on this moiety. A systematic investigation of this class of heterocyclic lead revealed that pyrazole containing pharmacoactive agents play important role in medicinal chemistry.

1) Antioxidants

2) Anti-inflammatory

3) Antimicrobial

4) Antitumor

5) Anti-convulsant

6) Anti-depressant

7) Antimycobacterial

8) Antiamoebic

9) Insecticidal

10) MAO-inhibitor

11) Hypotensive

12) Cholesterol-lowering agents

13) Photoluminescence activity

Reported antioxidant activities of pyrazole derivatives

The structures of newly synthesized compounds were elucidated by spectroscopic methods such as IR, 1H NMR, 13C NMR, mass, 1H NMR spectra and elemental analysis by Sharath et al. Antioxidant assays like 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azinobis (3ethylbenzothiazoline-6-sulfonic acid) (ABTS_þ) radical ion decolorization assay and lipid peroxidation activity (LPO) were performed. Among the synthesized analogues compound revealed broad spectrum of antioxidant activity.

Babu et al [63] synthesized a series of pyrazoline derivatives and evaluated for antioxidant activity at 1000, 500, 250, 100, 50, 25 and 10 mg.ml-1 concentrations against standard drug ascorbic acid. Six compounds showed excellent Antioxidant activity as compared with ascorbic acid.

Reported anti-inflammatory activities of pyrazole derivatives

A series of 5-ethyl-2-amino-3-pyrazolyl-4-methylthiophenecarboxylate (21) were prepared by Hafez et al. The compounds were evaluated for anti-inflammatory, analgesic and ulcerogenic activities. Among the compounds studied, compounds containing the substituted hydrazide at C-3 position showed more potent anti-inflammatory activity than the standard drug (Indomethacin and Aspirin), without ulcerogenit

Jadhav et al synthesized a new series of fluoro substituted pyrazoline derivatives and The newly synthesized compounds were characterized and screened for their in vivo anti-inflammatory activity.Compound was found to be more potent than standard drug Diclofen

Flora F. Barsoum et al (2009) synthesized bis (3-aryl-4, 5-dihydro-1H Pyrazole-1-thio carboxamide derivatives. The derivative with substitution, A = 4-O (CH2)2O-4’, R =Ph, showed potent anti-inflammatory activity.

Adnan A. bechit et al (2008) synthesized thiazolyl and thaidiazolyl derivatives of 1H-Pyrazole. Potent derivative showed significant anti-inflammatory activity by the cotton pellet granuloma method of rat paw edema bioassay.

Asuncio´n Burguete et al (2007) Synthesized substituted pyrazole derivatives and evaluated them for their anti-inflammatory activities. These derivatives showed good anti-inflammatory activity against carrageenan induced rat paw edema te

Nesrin Go¨khan-Kelekc et al (2007) synthesized novel pyrazole derivatives, compound exhibited anti-inflammatory activity using carrageenan induced paw edema method and aceticacid induced increased capillary permeability comparable to that of indomethacin with no ulcerogenic effec

Reported anti-microbial activities of pyrazole derivatives

Samir Bondock et al, 2010 synthesized a series of substituted pyrazole derivatives. The given compound was found to exhibit the most potent in-vitro antifungal activity with MICs (6.25 μ/ml) against A. fumigatus and F. Oxysporum Comparable with Chloroamphenicol.

Smaail Radi et al, (2010) synthesized novel pyrazole derivatives and these derivatives were evaluated for their antimicrobial activity determined by agar plate Diffusion technique. Antibacterial activity: Against antibacterial strains Escherichia coli and determined by agar plate diffusion method.Antifungal activity: Against two fungal strains Saccharomyces cerevisae. and Fusarium oxysporum , f.ablica

Compounds R

2c -4-NO2-C6H4

2e -2-OH-C6H4

2f -4-Cl- C6H4

S. K. Sahu et al (2008) synthesized novel pyrazoline derivatives. The derivatives 2c, 2e and 2f showed potent Antimicrobial activity; Antibacterial activity; by hinton agar (Hi-media) plates by agar diffusion cup-plate method for Staphylococcus aureus, salmonella typhi and E. coli. Antifungal activity; was tested on sabouraud dextrose agar plates by cup-plate method gainst Candida albicans and Aspergillus niger) .

Radhakrishnan sridhar et al (2004) synthesized 1-H Pyrazole carboxylate derivatives and screened for antimicrobial activities; Antibacterial activity; Against four human pathogenic bacterias, Escherichia coli, Pseudomonas aeuroginosa, Enterobacter facecalis and Staphylococcus aureus. Antifungal activity: Against five pathogenic fungi such as, against five pathogenic fungi such as, Rhizochonia solani, Fusaricom oxysperum, Curuvularia lunata, Bipolaris oryzae and Alernarnia alternate.

Boyer et al developed a novel series of conformationally-restricted oxazolidinones which possessed a fused pyrazole ring substituted with various alkyl, aryl and heteroaryl substituents. A number of analogs exhibited potent activity against both Gram positive and fastidious Gram-negative organisms.

The regioselective synthesis of 1-heteroaryl-5-amino-4-phenylpyrazoles and 1-heteroaryl-5-amino-3-methyl-4-phenyl pyrazoles was achieved by the treatment of heteroaryl hydrazines with phenylformylacetonitrile and phenylacetylacetonitrile, respectively by Aggarwal et al. All the fourteen compounds were tested for their in vitro antibacterial activity against three Gram-positive and two Gram-negative bacteria.

Kumar et al treated 1,1,1-trifluoromethyl-3-cyano-3-phenylpropanone with several heteroaryl hydrazines in refluxing ethanol that afforded 1-heteroaryl-5-amino-4-phenyl-3-trifluoromethylpyrazoles.The compounds were tested for their antibacterial property against six Gram-positive and three Gram-negative bacteria.

Dawane et al prepared several 1-(4-(4’-chlorophenyl)-2-thiazolyl)-3-aryl-5-(2-butyl-4-chloro-1H-imidazol-5yl)-2-pyrazoline. All the synthesized compounds were tested for their antimicrobial activities against Escherichia coli (MTCC 2939), Salmonella typhi (MTCC98), Staphylococcus aureus (MTCC 96), Bacillus subtilis (MTCC 441), Aspergillus Niger (MTCC 281), Trichoderma viridae (MTCC 167), Penicillium chrysogenum (MTCC 160), Fusarium moniliforme (MTCC156) and Candida albicans (MTCC 183). Most of the compounds showed potent antibacterial and antifungal activity.

In search for a new antimicrobial agent, a series of benzufuran based 1,3,5-substituted analogues were synthesized by Rangaswamy et al. The tested compounds exhibited good antimicrobial activity at concentration 1.0 and 0.5mg/ml compared with standard, streptomycin and fluconazole respectively.

Vijesh et al, synthesized the new pyrazole derivatives containing triazoles and benzoxazoles as potent antimicrobials. The compound having 2,5-dichlorothiophene substituent on pyrazole moiety and a triazole ring showed significant antimicrobial activity.

Reported antitumor activities of pyrazole derivative:

Pyrazole derivatives exhibit a wide range of biological properties including promising antitumor activity.

R1 R2

3, 4- 2CH3 4-OCH3

Peng-cheng LV et al, (2010) synthesized a series of pyrazole derivatives. The compound having high antiproliferative activity against MCF-7 with IC50 0.08 μM.

Compounds R5 R6 R7 R8 8b

-H -OH -H -H

Michael S. Christodoulo (2010) et al synthesized a new series of trisubtituted pyrazole derivatives and screened the compounds for anti-antiangiogenic activity. Compounds containing the fused pyrazole[4,3-c]quinololine motifs emerged as potent anti-angiogenic compounds, which also had the ability to inhibit the growth of human breast (MCF-7) and cervical (Hela) carcinoma cells in vitro.

Ronghui Lin et al (2007) synthesized 3, 4-disubstituted pyrazole derivatives. The analogues showed potent and selective cyclindependent kinase inhibitory activities and inhibited invitro cellular proliferation in various human cells.

Bai et al synthesized a new series of novel 1-acyl-3-amino-1, 4, 5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives were designed and synthesized. These derivatives were initially evaluated for their in vitro anticancer activity against human colon carcinoma HCT-116 cell line, and compound was chosen for further evaluation there in vitro activity against other five human cancer cell lines. The results indicate that most of the target compounds have considerable in vitro anticancer activity.

Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered by Lv et al. Compounds exhibited significant EGFR inhibitory activity. Compound,3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide displayed the most potent EGFR inhibitory activity.

Reported anticonvulsant properties of pyrazole moety

R = H, CH3, OCH3, NH2

Abdel-Aziz et al synthesized some newer pyrazole derivatives and tested them for the anticonvulsant activity against PTZ induced seizures in mice. Three compounds exhibited remarkable protective effect against clonic seizures induced by ip injection of PTZ at a dose level of 20 mg kg−1. The results of anticonvulsant activity are nearly close to phenobarbital sodium at a dose level of 30 mg kg−1and more potent than phenytoin sodium at a dose level of 30 mg kg−1.

Mitchinson et al synthesized 2,5-dihydropyrazolo[4,3-c]pyridin-3-ones that were GABAA receptor benzodiazepine binding site ligands with functional selectivity for the _3 subtype over the _1 subtype. SAR studies to optimize this functional selectivity were Described.

Some unsymmetrical Ri-exocyclic and Nendocyclic derivatives from benzoylation of 3- and 5-aminopyrazole were prepared by Michon et al with the aim of comparing their anticonvulsant activity towards the MES and scMET tests. Unambiguous proof of their structure was obtained from heteronuclear long-range correlation spectroscopy and NOE difference spectra. Only the N-exe-pyrazole benzamides showed good protection with respect to these Tests.

R = CH3, C2H5, C3H7, cyclohexyl, benzyl, phenyl R1 = H, CH3

Several thiourea and urea derivatives were prepared by the reaction of 4-aminopyrazoles with substituted isothiocyanates or isocyanates. The novel compounds were tested anticonvulsant activity using by pentylenetetrazole-induced seizure (PTZ) and maximal electroshock seizure (MES) tests.Among the tested compounds, thiourea derivatives were afforded 90 and 100% protection in PTZ and MES tests at 50 mg/kg, respectively. Urea derivatives were afforded 82 and 100% protection both at 25 and 50 mg/kg.

A series of 6-substituted-2- [(1-acetyl-5-substituted)-2-pyrazolin-3-yl] aminobenzothiazole (7) were synthesized using appropriate synthetic route and evaluated experimentally against maximal electroshock test. Selected compounds were evaluated for neurotoxicity, hepatotoxicity and behavioral study.The most active compound, 6-methyl-2-[(1-acetyl-5-(4-chlorophenyl))-2- pyrazolin-3-yl]aminobenzothiazole exhibited an ED50 of 25.49 mmol/kg, TD50 of 123.87 mmol/kg and high protective index (PI) of 4.86 compared to standard drug phenytoin.

Twelve 1-phenyl-, 1-thiocarbamoyl- and 1-Nsubstituted thiocarbamoyl-3-(2-furyl)-5- phenyl/(2-furyl)-2-pyrazoline derivatives were synthesized. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (Metrazol) (scMet.) tests, neurotoxicities were determined by rotarod toxicity test on albino mice. 1,5-Diphenyl-3-(2-furyl)-2-pyrazoline, 1-Nallylthiocarbamoyl-3-(2-furyl)-5-phenyl-2 pyrazoline, 1-N-allylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline and 1Nphenylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline were active at 100-300 mg/kg dose levels. 1-Thiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline, 1-N-methylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline and 1-Nethylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline were found protective against MES and scMet. at 30-300 mg/kg dose levels

The synthesis of a new series of 4-arylhydrazono-2-pyrazoline-5-ones (11) was described by Kucukguzela et al. Compounds were evaluated for anticonvulsant activity. One compound showed 40% protection against pentylenetetrazole-induced seizures in albino Swiss mice.

R = Br, I, Me, OEt, OMe, SMe R1 = 2-furyl, 3-furyl

The synthesis and the binding study of new 3-arylesters and 3-heteroarylpyrazolo[5,1 c][1,2,4]benzotriazine 5-oxide 8-substituted were reported by Guerrini et al. The nature of these substituents (in terms of lipophilic and electronic features) seemed to influence the binding affinity. High-affinity ligands were studied in mice in vivo for their pharmacological effects, considering six potential benzodiazepine actions: anxiolyticlike effects, muscle relaxant effects, motor coordination, anticonvulsant action, spontaneous motor activity, and ethanol potentiating action. Two compounds showed an inverse-agonist profile. These compounds were evaluated also for their binding at benzodiazepine site on GABAA receptor complex (GABAA/BzR complex) subtype to evaluate their subtype selectivity.

R/Ar = H, CH3, Ph, o-OCH3Ph, p-OCH3Ph

3-pyridyl, 2-furyl, 2-thienyl, 2-pyrrolyl

Guerrini et al further reported the synthesis and binding studies of a series of 3-acylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides 8-substituted . High-affinity ligands at benzodiazepine site on GABAA receptor complex (GABAA/BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a ‘hydrogen-bond acceptor ring’ at position 3 is synergic with an electron donor substituent at position 8, while a ‘hydrogen-bond donor ring’ is synergic with a withdrawing substituent.Three compounds were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and memory modulation, and ethanol potentiating action. To rationalize and qualitatively interpret the GABAA/Bz binding affinities of compounds a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein–ligand complex.

Reported antidepressant activities of pyrazole derivatives:

Palaska et al [16] synthesized ten new 3, 5-Diphenyl-2-pyrazoline derivatives and evaluated their antidepressant activities by the ‘Porsolt Behavioral Despair Test’ on Swiss-Webster mice.

1. 3-(4-Methoxyphenyl)-5-(3, 4-dimethoxyphenyl)-2-pyrazoline ,

2. 3-(4-methoxyphenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-2-pyrazoline and

3. 3-(4-chlorophenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-2-pyrazoline reduce 41.94 - 48.62% immobility times at 100 mg.kg-1 dose level.

In addition, it was found that 4-methoxy and 4-chloro substituents on the phenyl ring at position 3 of the pyrazoline ring increased the antidepressant activity; the replacement of these groups by bromo and methyl substituents decreased activity.

Prasad et al [17] synthesized five new 1, 3, 5-Triphenyl-2-pyrazolines and another five new 3-(2” Hydroxynaphthalen-1”-yl)-1, 5-diphenyl-2-pyrazolines and evaluated their antidepressant activity by the Porsolt behavioral despair test on Swiss-Webster mice .

1. 1-Phenyl-3-(2”-hydroxyphenyl)-5-(4’-dimethylaminophenyl)-2-pyrazoline ,

2. 5-(4’-Dimethylaminophenyl)-1,3-diphenyl-2-pyrazoline,

3. 1-Phenyl-3-(2”-hydroxynaphthalen-1”-yl)-5-(3’,4’,5’-trimethoxyphenyl)-2-pyrazoline,

4. 1-Phenyl-3-(4”-methylphenyl)-5-(4’-dimethylaminophenyl)-2-pyrazoline and

5. 1-Phenyl-3-(4”-bromophenyl)-5-(4’-dimethyl amino phenyl)-2-pyrazoline Reduced immobility times 25.63-59.25% at 100 mg.kg-1 dose level.

In addition, it was found that the compounds possessing electron-releasing groups such as dimethyl amino, methoxy and hydroxyl substituents, on both the aromatic rings at positions 3 and 5 of pyrazolines, considerably enhanced the antidepressant activity when compared to the pyrazolines having no substituents on the phenyl rings. Kelekci et al synthesized a new series of pyrazoline derivatives and evaluated for antidepressant, anxiogenic and MAO-A and -B inhibitory activities by in vivo and in vitro tests respectively. Most of the synthesized compounds showed high activity against both the MAO-A and MAO-B isoforms. However, none of the novel compounds showed antidepressant activity except for .The reason for such biological properties was investigated by computational methods using recently published crystallographic models of MAO-A and MAO-B. These were due to the differences in the intermolecular hydrophobic and H-bonding of ligands to the active site of each MAO isoforms.

Jayaprakash et al synthesized several 3, 5-Diaryl carbothioamide pyrazolines designed as mycobactin analogs (mycobacterial siderophore) and evaluated their antidepressant and MAO inhibitory activity; because, they were in the search of designing antitubercular molecules with reduced MAO-inhibitory activity (since pyrazoline has antidepressant and MAO inhibitory activity). They found that antitubercular compound was also selective inhibitor of MAO-B.

Reported antimycobacterial activities of pyrazole derivatives

Mamolo et al synthesized 5-Aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4, 5-dihydro-1H-pyrazole derivatives and tested for their in vitro antimycobacterial activity. The compounds showed an interesting activity against a strain of M. tuberculosis and a human strain of M. tuberculosis.

Ozdemir et al [39] synthesized new 1-[(N, N-disubstituted thiocarbamoylthio) acetyl]-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives and evaluated for in vitro antimycobacterial Activity against M. tuberculosis H37Rv.

Shaharyar et al synthesized several phenoxy acetic acid derivatives and evaluated for their antimycobacterial activities against M. tuberculosis H37Rv.

Reported antiamoebic activities of pyrazole derivatives

Budakoti et al [54] synthesized a variety of 3-(3-Bromophenyl)-5-phenyl-1-(thiazolo [4,5-b] quinoxaline-2-yl)-2-pyrazoline derivatives and screened for their antamoebic activity against HMI:IMSS strain of E. histolytica by microdilution method and compared the IC50 values with the standard drug metronidazole. Some of the quinoxaline derivatives showed less IC50 values than metronidazole. All the compounds were non-toxic.

Budakoti et al [55] synthesized new Pd (II) complexes with 1- N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives and evaluated their antiamoebic activity by microdilution method against HM1: IMSS strain of E. histolytica and compared the results with the standard drug metronidazole. Generally palladium complexes showed better activity than their corresponding ligands. Compound showed better IC50 = 0.05 μM as compared to metronidazole IC50 = 1.82 μM.

Abid et al [56] synthesized new 1-N-substituted thiocarbamoyl-3-phenyl-2-pyrazoline derivatives and evaluated their in vitro antiamoebic activities against E.histolytica in comparison with metronidazole used as reference substance. Out of the 30 compounds screened for antiamoebic activity, 10 were found to be better inhibitors of E. histolytica since they showed lesser IC50 values than metronidazole. The preliminary results indicated that the presence of 3-chloro or 3-bromo substituent on the phenyl ring at position 3 of the pyrazoline ring enhanced the antiamoebic activity as compared to unsubstituted phenyl ring.

Reported insecticidal activity of pyrazole derivatives

Silver et al synthesized pyrazoline-type insecticides and examined the mechanism of action of these compounds based on available electrophysiological, pharmacological and toxicological information and found to act at neuronal target sites.

Reported mao inhibitory activities of pyrazole derivatives

Chimenti et al synthesized a series of N1-propanoyl-3, 5-diphenyl-4, 5-dihydro-(1H)-pyrazole derivatives and assayed as inhibitors of MAO-A and MAO-B isoforms. These showed inhibitory activity with micromolar values and MAO-A selectivity and found to be useful as co-adjuvants in the treatment of Parkinson’s disease (PD) and Alzheimer’s disease.

Reported hypotensive activities of pyrazole derivatives

Turan-Zitouni et al [60] synthesized some 1-(4-Arylthiazol-2-yl)-3, 5-diaryl-2-pyrazoline derivatives and investigated their hypotensive activity by the tail-cuff method using clonidine as reference standard. All examined compounds showed appreciable hypotensive activities.

Reported cholesterol inhibitory activities of pyrazole derivatives

Jeong et al synthesized a series of 3-(3, 5-Di-tert-butyl-4-hydroxyphenyl)-5-(multi-substituted 4-hydroxyphenyl)-2-pyrazolines and evaluated their inhibitory action on acyl-CoA: cholesterol acyltransferase.

Reported photoluminiscence activities of pyrazole derivatives:

Wang et al synthesized 5-(9-Anthryl)-3-(4-nitrophenyl)-1-phenyl-2-pyrazoline (ANPP) and screened its photoluminescence property. The absorption of anthryl moiety at about 325-400 nm superimposed on the broader absorption of 3-(4-Nitrophenyl)-1-phenyl-2-pyrazoline moiety peaked at 420 nm. Photo-induced intramolecular energy transfer from the anthryl to pyrazoline moiety exists simultaneously with the charge transfer from N1 to C3 in the pyrazoline moiety in the excited state and both compete with each other.

Jin et al synthesized Triphenyl pyrazoline derivatives (TPPs) bearing electron withdrawing and pushing substitutents and investigated their photoluminiscent property in the solution and doped in poly (N-vinylcarbazole) (PVK) thin films. When TPPs were doped into PVK films the photoluminescence intensity was enhanced with increasing TPPs concentration. It indicated that the energy transfer from PVK to TPPs has happened. The pyrazoline derivative with both electron withdrawing and pushing substituents was the optimistic candidate for electroluminescent emitter due to higher transfer efficiency from electric energy to light energy as well as larger luminance.

Lu et al [10] synthesized a novel pyrazoline derivative 3-(4-Methoxyphenyl)-5-[4-(1, 1 dimethylethylphenyl)]-4, 5-dihydro-1-phenyl 1-H-Pyrazole (P3) and investigated for its light emitter property in blue organic electroluminescent devices. It had hole-transporting ability, good film-formation, and excellent PL property. The device with a structure of ITO/PVK/P3/Al could emit blue light (451 nm.)

CONCLUSION:

Pyrazole is a unique template that is associated with several biological activities. This article highlightened research work of many researchers reported in literature for different pharmacological activities on pyrazole compounds synthesized. The review has presented comprehensive details of pyrazole analogues, potent compounds reported for particular pharmacological activity and the method or technique involved in evaluation process. More investigations must be carried out to evaluate more activities of pyrazole for many diseases whose treatment are difficult in the medical sciences

FUTURE PROSPECTIVE:

1)Several economical and social merits have been prospected for compounds with effects like antiinflammation, antimicrobial and others.

2)Pyrazoles are an important class of compounds for new drug development that attracted much attention.

3) Several pyrazole derivatives have been synthesized as target structures and evaluated for their biological activities.

4)The cytotoxicity of the reported compounds in the review indicate good safety associated with many of the pyrazole derivatives, however, the need for standardized method for cytotoxicity evaluation is required for better understanding of the compounds safety and the safety-structure relationships.

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Received on 10.10.2015 Accepted on 05.12.2015

Asian J. Pharm. Tech. 2015; Vol. 5: Issue 4, Oct. - Dec., Pg 201-213

DOI: 10.5958/2231-5713.2015.00030.6