Month 2016 Synthesis of Some New Azoloazines with Potent Anti-inflammatory and Analgesic Activity Dina H. Dawood, a Rabab S. Jasass, b Mohamed M. Amin, c Thoraya A. Farghaly, b,d and Eman M. H. Abbas a * a Department of Chemistry of Natural and Microbial Products, National Research Centre, Dokki, 12622 Giza, Egypt b Chemistry Department, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukkarramah 21955, Saudi Arabia c Department of Pharmacology, Medical Division, National Research Centre, 33 EL Bohouthst (former EL Tahrirst), Dokki, 12622 Giza, Egypt d Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt * E-mail: eman_m69@yahoo.com Received April 12, 2016 DOI 10.1002/jhet.2746 Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com). Starting from pyrimidine-2-thiones, a set of new fused triazoles, thiazoles, and thiazines has been ob- tained. The mechanistic pathway and structures of all the novel products were ascertained on the foundation of spectral information and elemental analyses. The analgesic and anti-inflammatory activities of all the pre- pared compounds were predestined. The outcomes disclosed that all of the examined samples revealed po- tent activity. Moreover, the relation between the structure and the activity has been researched. J. Heterocyclic Chem., 00, 00 (2016). INTRODUCTION An increasing interest and an absolute requirement for finding of new, eclectic, and promising inhibitors with an improved protection and efficacy profile has promoted us toward layout unprecedented anti-inflammatory and analge- sic agents. The inflammation is a biotic rejoinder to a con- catenation of biochemical reactions whose major function is defense of the body from infection and settle of tissue damage due to injury. Many heterocyclic compounds were proved to have pharmacological significance as anti- inflammatory and analgesic agents such as pyrimidines, qiunazolines, thiazoles, triazoles, and thiazines [1–12]. Ex- amples of the most reactive agents are proquazone and fluproquazone [13,14] which have quinazoline ring (Fig. 1). The overall anti-inflammatory profile of proquazone is analogous with that of indomethacin. It is notewor- thy that proquazone is the first powerful anti- inflammatory drug of a non-acidic kind. Also, meloxicam is an anti-inflammatory medication with analgesic and temperature-reducer effects (Fig. 1). In continuation of our efforts in synthesis of bioactive heterocyclic compounds [15–22], we became inter- ested here to design new polyheterocyclic ring sys- tems having qiunazoline, thiazole, triazole, and/or thiazine rings to investigate their anti-inflammatory and analgesic activities which are expected to have potent activity. RESULTS AND DISCUSSION The starting compounds 2a,b were prepared via the reaction of benzylidene (1a,b) with thiourea in ethyl alco- hol containing potassium hydroxide (Scheme 1). The latter compounds 2a,b have thiourea residue, which is known to be an intermediate for the synthesis of several azoles and azines. Thus, the interaction of 2a, b with hydrazonoyl chlorides 3 in dioxan in the existence of a base catalyst yielded only one isolated product. The spectroscopic information assured the reaction product 6a–h via s-alkylation to give the intermediate 4 then followed by Smiles rearrangement to give the intermediate 5 with elimination of HCl and H 2 S molecules, respectively (Scheme 2). Also, 1 H NMR of 6 showed the absence of any signals for NH protons. Furthermore, in order to synthesize fused thiazole ring with quinazoline and cyclohepta-pyrimidine, the thione derivatives 2a,b were reacted with diverse types of α- haloketone or α-haloester, as represented in Schemes 3 and 4. The structure of compounds 7, 9, 10, and 11 was deduced by spectral information and elemental analyses (see the Experimental section). In addition, condensation of the thiazole derivatives 7a,b with substituted benzaldehydes afforded product 8 (Scheme 3). The formation of compounds 8a–h was assured by alter- nate synthesis via multi-component reaction of compounds 2a,b, chloroacetic acid, and benzaldehyde derivatives. © 2016 Wiley Periodicals, Inc.