Monatsh Chem 139, 707–716 (2008) DOI 10.1007/s00706-007-0797-9 Printed in The Netherlands Analgesic and antimicrobial studies of some 2,4-dichloro-5-fluorophenyl containing arylidenetriazolothiadiazines Mari S. Karthikeyan 1 , Bantwal S. Holla 1 , Shalini Shenoy 2 1 Department of Chemistry, Mangalore University, Mangalagangothri, Karnataka, India 2 Department of Microbiology, K.M.C., Mangalore, Karnataka, India Received 3 August 2007; Accepted 3 September 2007; published online 12 May 2008 # Springer-Verlag 2008 Abstract 2,4-Dichloro-5-fluorophenyl containing 7- arylidenetriazolothiadiazines were obtained by the reaction of 4-amino-3-(2,4-dichloro-5-fluorophenyl)- 5-mercapto-1,2,4-triazole with 2,3-dibromo-1,3- diarylpropan-1-ones, and also by the reaction of 4-amino-3-(2,4-dichloro-5-fluorophenyl)-5-mercapto- 1,2,4-triazole with -bromopropenones in the presence of a base. The structure of the 7-arylidenetriazolothia- diazines was confirmed by an alternative synthesis. A plausible mechanism for the formation of 7-arylidene- triazolothiadiazines is proposed. All newly synthe- sized compounds were screened for their analgesic and antimicrobial activities. Compounds bearing 4- chlorophenyl or 3,4-methylenedioxyphenyl moieties at position 7 of the arylidenetriazolothiadiazines showed excellent analgesic activity. Arylidenetria- zolothiadiazines carrying a phenyl, 4-chlorophenyl, 4-methylphenyl, 3,4-dimethoxyphenyl, and 2,4-di- chlorophenyl moieties at position 7 showed excellent antibacterial and antifungal activities. Keywords 2,4-Dichloro-5-fluorophenyltriazole; Dibromo- propan-1-ones; -Bromopropenones; Analgesic; Antimicro- bial activities. Introduction In recent days, active research has been initiated on halogen containing heterocycles, particularly on fluorine containing heterocycles. 2,4-Dichloro-5- fluoroacetophenone is used in the synthesis of drugs like Ciprofloxacin and their analogues [1]. Moreover, incorporation of a fluorine atom can alter the course of reaction as well as biological activities [2–4]. Furthermore, the introduction of a fluorine atom or a CF 3 group into an organic molecule large- ly enhances the pharmacological properties as com- pared with the non-fluorinated analogues. Incorporation of fluorine may also lead to in- creased lipid solubility thereby enhancing the rates of absorption and transport of drugs in vivo. The replacement of hydrogen or a hydroxyl group by fluorine is a strategy widely used in drug develop- ment to alter biological function. Despite the fact that fluorine is bigger than hydrogen, several studies have demonstrated that fluorine is a reasonable hy- drogen mimic and exerts only a minor steric demand at receptor sites [5]. 1,2,4-Triazole derivatives are known to exhibit an- tibacterial, antifungal [6], antitubercular [7], antican- cer [8], anticonvulsant [9], anti-inflammatory, and analgesic properties [10]. Among the pharmacologi- cal profiles of 1,2,4-triazoles, their antimicrobial, an- ticonvulsant, and antidepressant properties seem to be best documented. The arrangement of three basic Correspondence: Mari Sithambaram Karthikeyan, Depart- ment of Chemistry, Mangalore University, Mangalagangothri 574199, Karnataka, India. E-mail: karthims02@rediffmail. com