Synthesis and Biological Activity of Some 3,5-Diaryl- 1-benzothiazolopyrazoline Derivatives: Reaction of Chalcones with 2-Hyrazinobenzothiazoles

A series of 3,5-diaryl-1-benzothiazolopyrazoline derivatives were synthesized by the reaction of appropriately substituted chalcones and 2hydrazinobenzothiazole in ethanol. The synthesized heterocycles have been characterized on the basis of their chemical properties and spectroscopic data. These compounds were tested for biological activity against a variety of test organisms.


Introduction
Heterocycles bearing nitrogen, sulphur and thiazole moieties constitute the core structure of a number of biologically interesting compounds.Pyrazolines are an interesting group of compounds, many of which possess wide-spread pharmacological properties such as analgesic, antipyretic, antidepressant and antirheumatic activities 1,2 and are also known for their pronounced anti-inflammatory activity 3 and are used as potent antidiabetic agents 4,5 .Recently, pyrazolines were reported as a DP-IV inhibitors and antitumor agents [6][7][8] .Some nitrogen heterocyclic compounds were reported to be antiparkinsonian 9 , anticancer 10,11 , antimicrobial [12][13][14][15] and anti-inflammatory agents 16,17 .Due to the interesting activity of various substituted pyrazolines as biological agents considerable attention has been focused on this class.In addition, pyrazolines have played a crucial part in the development of theory in heterocyclic chemistry and also used extensively in organic synthesis [18][19][20][21][22] .Benzothiazole and its derivatives [23][24][25][26][27] have been recognized as a class of medicinal importance.Benzothiazoles have also been screened for their antituberculostic activity 28 .Benzothiazole derivatives represent an extensive group of heterocyclic compounds, several of which have already found application in the medical sphere as medicines 29 as well as in agriculture 30,31 .Many of 2-R substituted benzothiazoles are known as substances with antibacterial and antifungal activities [32][33][34] and are reported also to be active as antineoplastics 35 agent.Keeping in view the biological and clinical importance of benzothiazoles and pyrazolines, in this paper we report the synthesis and biological activity of new 3,5-diaryl-1-benzothiazolopyrazoline derivatives.

General procedures
Melting points were determined by the open tube capillary method and are uncorrected.The purity of the compounds was controlled by thin layer chromatography (TLC).IR spectra were recorded as KBr pellets on Perkin-Elmer spectrum RX1 spectrophotometer.Carbon, hydrogen, nitrogen and sulphur were estimated by Thermo Finnigan FLASH EA 1112 elemental analyzer. 1H-NMR spectra were recorded on Bruker DRX-300 spectrometer at room temperature.Mass spectra were measured on JEOL SX 102/DA-6000 mass spectrometer.Substituted chalcones (1-20) were prepared according to the reported methods.

Synthesis of 2-hydrazinobenzothiazole
To a suspension of 2-aminobenzothiazole (7.5 g) in ethylene glycol (40 mL), hydrazine hydrate (100%, 10 mL) and concentrated hydrochloric acid (10 mL) was added at 5-6 °C.The reaction mixture was refluxed for 2-3 h and cooled to room temperature.The reaction mixture was filtered and resulting precipitate was washed with distilled water.The resulting crude was crystallized from ethanol to obtained brownish black crystalline product.

General procedure for the preparation of compounds(21-40)
A mixture of substituted chalcone (1-20, 10.00 m mol) and 2-hydrazinobenzothiazole (10.00 m mol) in ethanol (50 mL) was refluxed for 5 h and then cooled to room temperature.The precipitate was separated by filtration, washed with water and crystallized from a mixture of alcohol and chloroform (1:1) to obtained 3, 5-diaryl-1-benzothiazolopyrazoline derivatives (Scheme 1).
In conclusion, we have synthesized a systematically substituted series of new 3,5-diaryl-1-benzothiazolopyrazoline derivatives for structure-activity relationship studies.These substituted benzothiazolopyrazolines are very stable compounds, which renders them beneficial substances for biological or pharmacological trials.

, 28, 32, 36, 37, 38, 39 showed
broad range of activity as inhibition zones were found against all plant and human bacteria and fungi.Compound