Azoles biologically active

Imidazo[ 1,2-e]thiazoles biological activity, 6, 1024 reactions, 6, 1041 synthesis, 6, 1048 Imidazo[2, l-6]thiazoles electrophilic substitution, 6, 979 synthesis, 6, 992, 993, 1010, 1018 Imidazo[3,l-6]thiazoles synthesis, 6, 986 Imidazo[5,l-6]thi azoles biological activity, 6, 1024 synthesis, 6, 1017 Imidazo[2,l-6]thiazolium chloride synthesis, 6, 1013... 

Benzimidazolo[l,2-c]thiatri azoles synthesis, 6, 612 Benz[cd]indazole antiaromaticity, 5, 208 Benz[cd]indazole, dihydroaromaticity, 5, 208 Benz[e]indolizine synthesis, 4, 466 Benzipiperylon biological activity, 5, 296 Benz[/]isoindoles synthesis, 4, 266... 

The recent reviews by Jager (11) and Kramer et al (12) describe the synthetic routes and biological activity of selected tritylimidazoles, trityltriazoles and other variously substituted N-azole fungicides. The information that follows will describe certain structural activity relationships of selected EBI fungicides containing pyridine and pyrimidine heterocyclic moieties. 

The biological activity of azoles and their derivatives (indoles, purines, etc.) and their abundance as structural motif in natural products made them a prime target and test ground in the development of catalytic transformations. This chapter is mainly dedicated to the reactions of monocyclic five membered heterocycles and indole. The chemistry of other condensed systems of importance, such as purines, is discussed in Chapter 8. 

Differences in the biological properties of the enantiomers have also been reported for other azole products that possess one or more chiral centers in the molecule. These few results clearly show that, as in many other biologically active classes of compounds, the... 

Biological activities are of interest for 1,2,3-selenadiazoles. 4,5-Dihydronaphtho[l,2-<7][l,2,3]selenadiazoles showed antifungal activity <2003FA63>. The antimicrobial and antiaflatoxigenic activities of 4-substituted-l,2,3-selenadi-azoles were investigated <1996PS155>. 

The azoles occupy an important place in the chemistry of heterocyclic compounds. Their unique properties and specific biological activity attract much attention of scientists worldwide. A much used and convenient method for the preparation of... 

Table 1 Selected azole-based fungicides and corresponding retention factors in solvent mixtures. H NMR data supplied by author. All derivatives were biologically active against Candida albicans...

Based on these results, the proposed mode of action of uniconazole (ES pure) is illustrated as an example in Figure 11. Although each of the methods used in this study is already known, the combined application of these methods enables to reduce the number of conceivable active conformations and hence the steric fit evaluation can be performed with high accuracy. The remaining problem is how the azole compounds interact with the non-active sites of enzymes. This is surely related to the difference of biological activity between the optical isomers. 

The high basicity of imidazole in comparison with other azoles has been attributed to the stability of the symmetrical imidazolium cation. That pyrazole is less basic can be ascribed to extra destabilization of the 7r-system on protonation <8iJHCl 189). Imidazole s pATj value of close to seven has ramifications for the biological activity of the histidine unit, for example, the two imidazole rings of His 12 and Hisl 19 in Ribonuclease A act as both acid and basic catalysts in the hydrolytic cleavage of RNA <91ACR317>. Some pK. values for substituted imidazoles are tabulated in Table... 

Syntheses of biologically active azine and azole derivatives 01MI91. 

Among nitrogen-containing heterocycles, azoles and pyrimidines play a major role because of their biological activity. Many azoles are useful in the preparation of... 

Starting from the hypothesis that azo compounds with an ability to form active carbonium ions in vivo are biologically active, Biichel et al. (1972,1975) synthesised several derivatives of 1-trityl azoles. They established in extensive research work that the derivatives particularly active are those which contain only one substituent in one of the phenol rings, and in which the azole ring remains unsubstituted. This led to the very active antimycotic clotrimazole (see Section 5.7.1), which nowadays plays an important role in the local therapy of human mycoses, and to fluo-trimazole, of specific activity against powdery mildews. 

Lithiation is regioselective for the 2-position in the 1,3-azoles and for the 5-position in the 1,2-azoles. The facility with which 1,3-diazoliuni cations form ylides (carbenes) by 2-deprotonation is at the heart of the biological activity of thiamine pyrophosphate. 

Furet, P. Batzl, C. Bhatnagar, A. Francotte, E. RUis, G. Lang, M. Aromatase inhibitors synthesis, biological activity, and binding mode of azole-type compounds, J.Med.Chem., 1993,36, 1393-1400. 

A series of 5-trifluoromethyl-l,2,4-oxadiazoles are patented as potential pesticides [114] and testedfor biological activity [115]. Morerecently, trifluoromethyl-1,2,4-oxadiazole derivatives such as 235 have been evaluated as cannabinoid antagonists [116] Besides these recent reports, one of the major debated bioactivity concerning fluorinated azoles is the efficiency of PTC124, also known with the name of Ataluren 236, which was claimed to promote the readthrough of nonsense premature stop codons (Fig. 6) [117,118]. 

Various reviews have been published about this topic. Jeschke and Leroux [2] pubhshed about the medical apphcation of a-fluorinated ethers. Leroux and Pazenok [1] wrote about the synthesis and the properties of trifluoromethyl ethers. Leroux, Jeschke and Schlosser [3b] reviewed the properties of a-fluorinated ethers, thioethers and amines. The work of Boiko [4a] is dedicated to aromatic and heterocyclic perfluoralkyl sulfides. Vovk and Gakh [4b] gave a detailed review about trifluoro-methoxy containing azoles and azines. This review summarized the literature data on synthesis and biological activity of trifluoromethoxy, difluoromethoxy and a-fluorinated sulfides derivatives of five and six membered heterocycles. 

The synthesis and chemistry of pyrazoles, imidazoles, and 1,2,3-triazoles were actively pursued in 2006. A review on the cross-coupling reactions on azoles with two and more heteroatoms for pyrazoles and imidazoles has been published <06EJO3283>. Publications relating to 1,2,4-triazole and tetrazole chemistry were not particularly well represented this year. The solid-phase and combinatorial chemistry of these ring systems have not been investigated compared to past years. No attempt has been made to incorporate all the exciting chemistry or biological applications that have been published this year. 

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