44A, February 2005, pp. 232-240. Kinetic studies on the reactions of various 9-chloroacridines with some arylsulphonyl hydrazides and antiinflammatory and ...
Indi an Journal of Chemi stry Vol. 44A, February 2005, pp . 232-240
Kinetic studies on the reactions of various 9-chloroacridines with some arylsulphonyl hydrazides and antiinflammatory and kinase inhibition activitiy of the products Sham M Sandhi 1, Gurudas Bhattachaijee 1*, Rafid K Jameel', Ashok Kumar2 & Kiran Baja/ 'Departm ent o f Chemi stry, Indian In stitute of T ec hnology Roork ee. Roork ee 247 667 , Indi a 2
Department of Pharmacology, L.L.R.M. M edica l College, Meerut. M eerut 250 004 , Indi a Email: word gfcy@ isc .iit r.erner.in Received 18 Ju11 e 2004: reviser/ 15 Oece111ber 2004
9-Chloro-2,4(u n)substituted acri dines ( la-e) have been co ndensed with benzenes ulphony l hydrazide (2a). ptoluenes ulphony l hydrazide (2b), and 4-me thoxybenzenesulphony l-hydrazides (2c) to obtain th e co rrespondin g co ndensed products 3a-o. The structures of all th e co mpounds sy nthes ized have been co nfirmed by spectroscopic meth ods. An tiinflammatory and kinase inhibition acti vities of all the co mpounds (3a-o) have been in ves ti gated. Compou nds 3e,h,i,n ex hibit good and 3a-d,f,gJ-m,o ex hibit moderate anti-inllammatory acti vity. Kineti c studi es on th e co ncerned aro matic nucleophili c substituti on (SNAr) have been carried ou t in meth anol (MeOH). Another three reaction s of la wit h suphony l hydrazide 2a-c have been studi ed in DMSO under the same co nditi ons for compari son. The base cata lysed mechani sm (modifi ed heteroco njugate BH+SB, BH+B) has been proposed for th e reaction in M eOH . Th e effec t of substituents on the benzene ring of th e sulphony l hydrazide is in the order: M eO>M e> H, retlectin g the importance of electron-donating beha viour of th e substituent in enhancing the nucleophil city of hydrazide group and al so in stabili zing the zwiueri oni c co mplex T±. IPC Code: lnt.CI
7
BOIJ
Acridine derivatives possess in g fungicida l' , 2 antiparasitic , antiinflammatory and analgesic 3 activiti es have been reported in the lite rature. A few acridine derivatives (v iz., azacrine, proflavine, mepacrine and aminacrine) al so possess antibacterial and antimalari al activities 4 . Another acridine derivative, amsacrine, has been useful as an antitumor 5 dru g . In view of the wide range of useful biological activities of th ese derivatives, we continued our search for potential a ntiinflamm atorl·7 and 8 anticancer ·
