Transition metal complexes of 1,2- dihydroquinazolinone derivative, an emerging class of analgesic and anti-inflammatory agents Dayananda S. Badiger, a Ramesh B. Nidavani, b Rekha S. Hunoor, a Basavaraj R. Patil, a Ramesh S. Vadavi, a V. M. Chandrashekhar, b Iranna S. Muchchandi b and Kalagouda B. Gudasi a * A new 1,2-dihydroquinazolinone, 2-(2-hydroxy-phenyl)-3-[1-(2-oxo-2H-chromen-3-yl)-ethylideneamino]-2,3-dihydro-1H-quinazolin- 4-one (L) and its Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes have been prepared. These were characterized by elemental, spectral [UV–visible, IR, NMR ( 1 H, 13 C and 2D heteronuclear correlation) and mass], conductance, magnetic susceptibility and thermal studies. The physicochemical data indicate that the ligand behaves as tridentate with ONO donor sequence towards the metal ions, and trigonal bipyramidal geometry was assigned for complexes. The ligand and its metal complexes were eval- uated for their in vivo anti-inflammatory and analgesic activity. The tested compounds have shown excellent activity, which are almost equipotent to the standard used in the study. Copyright © 2011 John Wiley & Sons, Ltd. Keywords: dihydroquinazolinone; trigonal bipyramidal; metal complex; analgesic activity; anti-inflammatory activity Introduction Quinazolinone is an exciting motif as regards its pharmacological importance and is a building block for about 150 naturally occur- ring alkaloids. [1] They have been studied as an effective anticonvul- sant, [2] anti-inflammatory, analgesic and cyclooxygenase-2 (COX-2) inhibitor. [3–6] Proquazone, 1-isopropyl-7-methyl-4-phenylquinazoline- 2(1H)-one, [7] fluoroquazone, 4-(4-fluorophenyl)-7-methyl-1-propan-2- yl-quinazoline-2-one, [8] and tryptanthrin, indolo[2,1-b]quinazoline alkaloid, [9] are well-known anti-inflammatory drugs bearing an quinazolinone nucleus. These came to notice as third-generation non-steroidal anti-inflammatory agents (NSAIDs) that are superior in protection and effectiveness and are comparable with indo- methacin, which is already in use as a drug. Quinazolin-4(3H)-ones with 2,3-disubstitution are reported to possess remarkable analgesic, anti-inflammatory and anticonvul- sant activities. It has also been reported that substitution by different aryl or heteroaryl moieties at the second or third position of the quinazolinone nucleus markedly influences the anti- inflammatory activity. [10] Subsequently, 1,2-dihydroquinazolinones were reported to possess greater potent activity compared to fully aromatic quinazolinones. [11] Quinazoline-4(3H)-ones have also drawn the attention of coordination chemists, as they adopt various binding modes with transition and main group metal ions which have a positive effect on their activity. These bioactive molecules can act as monoden- tate or bidentate ligands, [12,13] and their coordination capacity can be further increased if aldehydes or ketones that contain additional functional group(s) in position(s) suitable for chelating are used for their preparation. Several coumarins isolated from plants or of synthetic origin pos- sess significant anti-inflammatory and analgesic activities. [14–18] Moreover, coumarin and related derivatives have been used as inhibitors of lipoxygenase (LOX) and COX pathways of arachidonic acid metabolism. [17] One of the most well-studied coumarin-based anti-inflammatory drugs is cloricromene (8-monochloro-3-b- diethylaminoethyl-4-methyl-7-ethoxy-carbonylmethoxy coumarin) and several synthetic analogues of this compound have been recently reported and tested for their anti-inflammatory and antiox- idant activities. [19] Earlier we have documented transition metal complexes of 1, 2-dihydroquinazoline-4-(3H)-ones exhibited comparatively good analgesic and anti-inflammatory activities. [20–22] In view of these facts and in continuation of our earlier work on coordination chemistry, we have substituted coumarin as heteroaryl moiety and 2-hydroxybenzaldehyde as aryl moiety at the second and third position of the quinazoline nucleus to obtain 2-(2-hydroxyphenyl)- 3-[1-(2-oxo-2H-chromen-3-yl)-ethylideneamino]-2,3-dihydro- 11H-quinazolin-4-one ( L). Here we report the synthesis and characterization of transition metal complexes of L and their comparative in-vivo anti-inflammatory and analgesic activities. Experimental Protocols Chemistry Methyl anthranilate, hydrazine hydrate, 2-hydroxybenzaldehyde and hydrated metal chloride salts (S.D. Fine Chemicals, India), * Correspondence to: Kalagouda B. Gudasi, Department of Chemistry, Karnatak University, Pavate Nagar, Dharwad-580 003, Karnataka, India. E-mail: kbgudasi- @gmail.com a Department of Chemistry, Karnatak University, Dharwad-580003, Karnataka, India b H. S. K. College of Pharmacy, Bagalkot-587101, Karnataka, India Appl. Organometal. Chem. 2011, 25, 876–882 Copyright © 2011 John Wiley & Sons, Ltd. Full Paper Received: 6 September 2011 Revised: 23 September 2011 Accepted: 6 October 2011 Published online in Wiley Online Library: 29 November 2011 (wileyonlinelibrary.com) DOI 10.1002/aoc.1855 876