A Therapeutic Journey of 5-Pyrazolones as a Versatile Scaffold: A Review

Abstract

A sizeable proportion of currently marketed drugs come from heterocycles. The heterocyclic moiety 5-pyrazolone is well known five membered ring containing nitrogen. Derivatives of this wonder nucleus have exhibited activities as diverse as antimicrobial, anti-inflammatory, analgesic, antidepressant, anticonvulsant, antidiabetic, antihyperlipidemic, antiviral, antitubercular, antioxidant, anticancer and antiviral including action against severe acute respiratory syndrome (SARS) or 3C protease inhibitor. A number of drugs based on this motif have already made it to the market. Standard texts and literature on medicinal chemistry cite different approaches for the synthesis of 5-pyrazolones. The present review provides an insight view to 5-pyrazolone synthesis, their biological profile and structure activity relationship studies.

One pot-like regiospecific access to 1-aryl-1H-pyrazol-3(2H)-one derivatives and evaluation of the anticancer activity

“…Specifically, in the reaction involving the aniline 5a, we isolated, beside the expected product, a new compound firstly detected by GC-MS spectroscopy, where the fragmentation pattern agreed with the typical isotope rate in agreement with a tri-Cl derivative of type 8 [presence of peaks M+ m/z 276 (100%), 278 (96.8%), 280 (31.5%)]. Further confirmations were furnished by 1 H and 13 C NMR spectroscopic data. Thus, in the course of the above sequential reaction carried out in a one pot procedure, a competitive nucleophilic substitution of the nitro group occurred, leading to the 1-(2,4,6-trichlorophenyl)-pyrazolone derivative 8.…”

“…Thus, to reach the 1-(o-aminoaryl)-pyrazol-3-one derivatives 9a-i, we performed the reduction of the nitro group with Fe/AcOH for the chlorine derivatives, and for the others by using classical catalytic conditions with Pd/C 10% in EtOH under H2 (4 atm) in a Paar-like reactor (Scheme 4). All compounds were fully characterized by 1 H, 13 C NMR, GC-MS, IR spectroscopy and microanalysis. All experimental data agreed with the proposed structures.…”

“…General. 1 H and 13 C NMR spectra were recorded in CDCl3 or DMSO-d6 solution as specified below, using a Bruker AC-E series 200/300/400 MHz spectrometer. As internal reference, the residual peak of the solvent was calibrated, at d 7.26 and 2.50 ppm, respectively for CDCl3 and DMSO-d6 or using TMS as internal reference.…”

“…"a" means "apparent" for close coupling constant and the number of equivalent group are indicated after the sign "x". Carbon attribution, namely C, CH, CH2 and CH3 were determined by 13 C and DEPT 135. IR spectra were recorded with bromoform on a NaCl window with a Bruker Alpha FT/IR spectrophotometer.…”

“…1 From a medicinal chemistry point of view, much modern research pays particular attention to the discovery of new anticancer agents with optimal biological activities, and many efforts have been directed towards the synthesis of small molecules characterized by a heterocyclic scaffold. In this context, a large number of derivatives containing nitrogen atoms in the central core, (for example, pyridine and pyrimidine, [2][3][4] indole, 5 imidazole, 6 quinoline, 7,8 pyrazole and pyrrolizine 9,10 and pyrazolone derivatives, [11][12][13] and others [14][15][16] ) have been described in literature and some of them have already been approved as therapeutics, thus showing great potential in the treatment of cancer.…”