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Doi:10.1016/j.jfluchem.2011.06.014Journal of Fluorine Chemistry 132 (2011) 870–877 Contents lists available at ScienceDirect j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / f l u o r Synthesis and biological evaluation of new 3,5-di(triﬂuoromethyl)-1,2,4-triazolesulfonylurea and thiourea derivatives Hassan M. Faidallah a,*, Khalid A. Khan a, Abdullah M. Asiri a,b a Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia b Center of Excellence for Advanced Materials Research, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia Fluorinated 1,2,4-triazoles 3 and benzenesulfonyl urea and thiourea derivatives as well as their cyclic sulfonylthioureas 4–10 were prepared as antimicrobial agents. The chemistry involves the condensation of sulfanilamide derivatives 1 with triﬂuoroacetic anhydride to give N-di(triﬂuoroacetyl)sulfonamides 2 which upon reaction with hydrazine hydrate afforded the corresponding triazole derivatives 3. Reaction of triazole derivative 3a with isocyanates and isothiocyanates gave the corresponding ureas 4 and thioureas 5. Cyclization of thiourea derivatives with ethyl bromoacetate, 1,2-diiodoethane, diethyl oxalate and a-bromoacetophenone derivatives yielded the corresponding 4-oxothiazolidines 7, thiazolidines 8, 4,5-dioxothiazolidines 9 and thiazolines 10. Preliminary biological screening of the prepared compounds revealed signiﬁcant antimicrobial and mild antidiabetic activities.
ß 2011 Elsevier B.V. All rights reserved.
useful way of making a molecule more easily delivered to the active site in the body. Some of the best known drugs have The introduction of ﬂuorine or appropriate ﬂuorinated func- triﬂuoromethyl substitution. These include the SSRI anti-depres- tions into a molecule has become an invaluable tool for medicinal sant ﬂuoxetine and ﬂuvoxamine [7,8], the COX-2 inhibitor chemists [1,2]. Replacing hydrogen and other functional groups celecoxib , the antimalarial drug meﬂoquine , HIV protease with ﬂuorine can have a dramatic effect on the modulation of inhibitor tipranavir , anticancer drug bicalutamide , and electronic, lipophilic and steric parameters, all of which can critically inﬂuence both the pharmacodynamic and pharmacoki- Substituted 1,2,4-triazoles constitute an important class of netic properties of drugs [3,4]. Substitution of ﬂuorine into a organic compounds with wide-ranging pharmacological activi- potential drug molecule not only alters the electronic environ- ties such as antibacterial , antifungal , antimycobacterial ment, but it also inﬂuences the properties of neighboring , anti-inﬂammatory , and anticancer [18,19] activities.
functional groups. It exerts a substantial effect on the molecule’s Some of the ﬂuoro substituted and triﬂuoromethyl substituted dipole moment, the acidity or basicity of other groups nearby, not 1,2,4-triazoles, Fluconazole  and Fluotrimazole  respec- to mention the overall reactivity and stability of the molecule [5,6].
tively, are well known drugs in use. However, none of them have a Triﬂuoromethyl group is recognized in medicinal chemistry as a triﬂuoromethyl group in the triazole ring. Furthermore, ﬂuoro- substituent of distinctive qualities and it is one of the most and triﬂuoromethyl pyrazoles, benzenesulfonyl urea and thiourea lipophilic functional groups known. It provides an extremely derivatives as well as their cyclic sulfonylthioureas were reported by our group to possess hypoglycemic and antimicrobial activities [22–24]. Therefore, it was considered worthwhile to introduce triﬂuoromethyl groups in triazole ring. The current study involves * Corresponding author at: Department of Chemistry, Faculty of Science, King the preparation of ﬂuorinated 1,2,4-triazoles and benzenesulfonyl Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
urea and thiourea derivatives as well as their cyclic sulfonylthiour- E-mail address: [email protected] (H.M. Faidallah).
eas as possible antimicrobial and antidiabetic agents.
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
Steininger neue Tab 25.2.ENDE 26.02.2008 15:43 Uhr Seite 1 Therapie der Influenzavirus -Infektion Ch. SteiningerAbteilung für Infektiologie und Tropenmedizin, Universitätsklinik für Innere Medizin I, Medizinische Universität Wien Schlüsselwörter: Zusammenfassung Key-words: Einleitung Steininger neue Tab 25.2.ENDE 26.02.2008 15:43 Uhr Seite 2 Epidemische Influenza M2-Kana