Pyrazole : A potent drug candidate with various Pharmacological activities

http://dx.doi.org/10.21276/IJRDPL.22780238.2018.7(2).2941-2948 ABSTRACT: Aromatic organic heterocycle containing pyrimidine scaffolds. Pyrazole possess, a five-membered hetero aromatic ring with two nitrogen atoms. Presence of this nucleus in these Pyrazole skeletons comprise various ranges of pharmacological activities viz. analgesic, antipyretic, anticancer, antiviral, anti-Inflammatory, antioxidants, antimicrobial, anti-diabetic, anticonvulsant & antiarrhythmic. Pyrazole is a multipurpose lead compound which is developed by chemical architecture for effective molecules which are mostly biologically active. Several synthetic routes are accorded for the development of pyrazole containing reactions to afford a novel molecule.


INTRODUCTION
Pyrazoline is characterized by a 5-membered heterocyclic ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions [1].Pyrazolines represent an important class of heterocycles due to their highly pronounced biological and pharmacological activities such as Antimicrobial, Anti-Inflammatory, Antihypertensive [2].Pyrazolines derivative is also important core structures of many pharmaceutical and agrochemical substances [3].A recent approach in treatment of many serious diseases such as cancer, AIDS, cardiovascular diseases and Alzheimer's disease is the development of drugs with multiple actions [2].

GENERAL METHOD OF PREPARATION
Pyrazolines is prepared by treating substituted chalcones with hydrazine monohydrate 95% in absolute ethanol [4].
Pyrazoline is prepared by treating mixture of chalcone with thiosemicarbazide in ethanol or hydrazine hydrate in acetic acid [7].
Substituted acetoacetate react with solution of 40% methylhydrazine and then heated to 65 °C to form substituted pyrazoline [8].

Reflux
Alkyl dihalides react with primary amines or alkyl hydrazines under microwave irradiation via a simple and efficient cyclo condensation in an alkaline aqueous medium to give pyrazoline [10].

Properties of Pyrazoline
Physical: Pyrazole is a π-excessive heterocycle and contains two nitrogen atoms, pyrrole type and pyridine type, at positions 1 and 2. Pyrazole exists in three partially reduced forms.Pyridine type nitrogen is susceptible to electrophilic attack, and the hydrogen atom attached to the nitrogen at position 1 is more acidic then pyrrolic N-H so easily removed by nucleophiles.

Electrophilic attack at nitrogen
Basicity-Pyrazole is weaker base (pKa= 2.52), lower basicity is due to extra destabilization of π-bonding after protonation.

N-Alkylation:
Pyrazoles with -NH group are readily alkylated by CH3I or (CH3)2SO4.In unsymmetrical pyrazoles the position taken by entering alkyl group depend upon alkylating agent and experimental condition. N-Acylation: Michael Addition: N-Unsubstituted pyrazoles undergo Michael addition with activated alkenes and alkynes.

Reaction with Nucleophiles
Nucleophilic attack at carbon:

Anti-Inflammatory Activity
Bekhit et al, reported a series of thiazolyl and thiadiazolyl derivatives of 1H-pyrazole and showing anti-inflammatory activity [11].(pyrazolic chalcones) some compound showed Potent activity against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI50 values ranging from 0.04 to 11.4 lM, from the in vitro assays [24].
Bonesi et al, prepared a series of chalcones and their pyrazoles derivatives and investigated them for Angiotensin I-Converting Enzyme (ACE) inhibitory activity.They have reported the chalcone 2 exerted the highest activity with an IC50 value of 0.219 mM, while the most potent pyrazole was (IC50 value of 0.213 mM) [25].

RESULTS
Pyrazolines are synthetically active substrates and important nitrogen containing 5-membered heterocyclic compounds and which can be used for the synthesis of new heterocyclic compounds and is also used as a raw material for the synthesis of biologically active drug.Many pyrazole derivatives have been made which possess considerable biological activities.This manuscript contains a brief review about different methods which were used for the synthesis of biologically active pyrazole derivatives.
Pyrazole is a colourless solid with m.pt.68-70 o C, boiling point of Pyrazole (186-188 o C) is due to intermolecular hydrogen bonding.two identical and non-separable tautomers due to rapid interconversion of tautomers.Pyrazole contain two type of nitrogen atom pyrrole and pyridine at position 1 and 2 respectively.