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 (<b>1a-e</b>) have been condensed with benzenesulphonyl hydrazide (<b>2a</b>), <i>p-</i>toluene sulphonyl hydrazide (<b>2b</b>), and 4-methoxybenzenesulphonyl-hydrazides (<b>2c</b>) to obtain the corresponding condensed products <b>3a-o</b>. The structures of all the compounds synthesized have been confirmed by spectroscopic methods. Antiinflammatory and kinase inhibition activities of all the compounds (<b>3a-o</b>) have been investigated. Compounds <b>3e, h, i, n</b> exhibit good and <b>3a-d, f, g,J-m,o</b> exhibit moderate anti-inflammatory activity. Kinetic studies on the concerned aromatic nucleophilic substitution (S_NAr) have been carried out in methanol (MeOH). Another three reactions of <b>1a</b> with suphonyl hydrazide <b>2a-c</b> 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 T^±.