Computer Aided Drug Design, Synthesis and Pharmacological Evaluation of Some Novel Pyrazolone Derivatives

Abstract

In the present research work, the main motto was to develop new chemical entities as potential anticancer, anti-inflammatory, anthelmintic and antimicrobial agent. The design of anticancer agents was performed by molecular docking studies. 2-D QSAR studies of the newly synthesized compounds as (5a-5e) and (6a-6e) were performed. The starting material 3-methyl-1-substituted-1H-pyrazol-5(4H)-ones (1a-1b) were synthesized in high yields according to reported method using domestic microwave oven by the treatment of ethyl aetoacetate with appropriate 1-phenylhydrazine or 1-(2,4-dinitrophenyl)hydrazine. 4-acetyl- 3-methyl-1-substituted-1H-pyrazol-5(4H)-ones (2a-2b) were prepared by the acetylating of (1a-1b) with corresponding acid chloride following Jensen’s procedure. 4-(3- (substituted)acryloyl)-3-methyl-1-(substituted)-1H-pyrazol-5(4H)-ones as chalcone derivatives (3a-3e) and (4a-4e) were prepared by reacting (2a-2b) with substituted aromatic aldehydes by using 70% sodium hydroxide in ethanol. 4-(2-amino-6-(substituted)pyrimidin- 4-yl)-3-methyl-1-(substituted)-1H-pyrazol-5(4H)-one (5a-5e) and (6a-6e) were prepared by reacting (3a-3e) and (4a-4e) with guanidine hydrochloride. Finally (5a-5e) and (6a-6e) reacted with different substituted aromatic aldehydes to give corresponding Schiff bases (7a- 7e) and (8a-8e) in very good yields. The structures of new compounds are characterized by TLC, FTIR, 1H NMR and Mass spectral data. The compounds (5a-5e) and (6a-6e) have been screened for their in vivo and in vitro anticancer, anti-inflammatory activities. The compounds (7a-7e) and (8a-8e) have been screened for their anthelmintic and antimicrobial activities.