Kinetic studies on the reactions of various 9-chloroacridines with some arylsulphonyl hydrazides and antiinflammatory and kinase inhibition activitiy of the products

Abstract

9-Chloro-2,4(un)substituted acridines (1a-e) have been condensed with benzenesulphonyl hydrazide (2a), p-toluene sulphonyl hydrazide (2b), and 4-methoxybenzenesulphonyl-hydrazides (2c) to obtain the corresponding condensed products 3a-o. The structures of all the compounds synthesized have been confirmed by spectroscopic methods. Antiinflammatory and kinase inhibition activities of all the compounds (3a-o) have been investigated. Compounds 3e, h, i, n exhibit good and 3a-d, f, g,J-m,o exhibit moderate anti-inflammatory activity. Kinetic studies on the concerned aromatic nucleophilic substitution (SNAr) have been carried out in methanol (MeOH). Another three reactions of 1a with suphonyl hydrazide 2a-c have been studied in DMSO under the same conditions for compari son. The base catalysed mechanism (modified heteroconjugate BH+SB, BH+B) has been proposed for the reaction in MeOH. The effect of substituents on the benzene ring of the sulphonyl hydrazide is in the order: MeO>Me>H, reflecting the importance of electron-donating behaviour of the substituent in enhancing the nucleophilcity of hydrazide group and also in stabilizing the zwitterionic complex