Library oxadiazoles

Cosford et al. [60] have used a commercial Syiris Africa system [14] to S3mthe-size a library of 1,2,4-oxadiazoles (Scheme 27). By a multistep procedure using connected microreactors in a single sequence, the procedure was performed in an efficient way the intermediate product purification was avoided and the reaction time was considerably reduced from several days to 30 min. 

Scheme 30 Preparation of oxadiazole libraries using polymer-supported reagents...

Scheme 33 Rapid generation of libraries of 1,2,4-oxadiazoles using solid-phase reagents...

Two complementary methodologies were designed for rapid generation of libraries of 3,5-disubstituted 1,2,4-oxadiazoles from widely available carboxylic acids and amidoximes [93]. Both methods employed solid-phase reagents to simplify the purification process. Carboxylic acids were directly condensed with amidoximes in the presence of HBTU and an excess of PS-BEMP in acetonitrile (150 °C, 15 min). Alternatively, carboxylic acids were in situ converted to acid chlorides (with PS - PPI13/CCI3CN in THF) and subsequently reacted with amidoximes to furnish disubstituted oxadiazoles in good to excellent yields (Scheme 33). 

Among some recent papers, the same researchers (78) reported the synthesis of two libraries of piperazines and piperidines containing 1086 and 835 discretes, respectively, via one-step alkylation or acylation of several scaffolds. Bhat et al. (79) used the same instmment to prepare a 26-member library of paclitaxel C7 esters via a three-step procedure. An array of twenty 1,2,4-oxadiazoles (80) was prepared through... 

A library of 2,5-disubstituted-l,3,4-oxadiazoles have been synthesized under microwave irradiation and screened for their tyrosinase inhibition activities [32]. 

Khan et al. (2005) performed and reported tyrosinase inhibition studies of a combinatorial library of 2,5-disubstituted-l,3.4-oxadiazoles (25-43) [47]. The library of oxadiazoles was synthesized under microwave irradiation [47]. The synthetic steps involved for these compounds are shown in Scheme 2. Among the compounds from the library, 29 (30-[5-(40-bromophenyl)-1,3,4-oxadiazol-2-yl]pyridine, for structure see Fig. 6) exhibited the most potent (ICso = 2.18 xM) inhibition against tyrosinase, which has found to be more potent than the standard potent inhibitor L-mimosine (IC50 = 3.68 [xM, for structure see Fig. 1) [47]. 

Table 2 shows the structure-activity relationships of the compound library of the 2,5-disubstituted 1,3,4-oxadiazoles 25-43 against the enzyme... 

An 18-member library of 5-isoxazol-4-yl-[l,2,4]oxadiazoles 14 was prepared on solid-phase through nitrile oxide 1,3-DC to resin-bound alkynoate ester 10 <04JOC1470>. 

Monocyclic and Bicyclic aromatic heterocycles such as imidazoles, thiazoles, thiadiazoles, oxazoles, oxadiazoles quinazolines, indoles, benzimidazoles, purines pyrido[43-d]pyri-midines, thiazolo[5,4-d]pyrimidines, thiazolo[4,5-d]pyrimidines, oxazolo[5,4-d]pyrimi-dines and thieno[2,3-d]pyrimidines are renowned pharmacophores in drug discovery. These special structures are well explained and exemplified in chemical compound libraries. In this chapter, several types of thiazole based heterocyclic scaffolds such as mono-cyclic or bicyclic systems synthesis and their biological activities studies are presented, which are not frequently present in books and reviews. We mention the first importance of synthetic route of various thiazole based compounds and their applications in medicinal chemistry in this chapter. 

The application of fluorinated furazan is rather limited for synthesis and reactivity. Most studied derivative is 3-amino-4-trifluoromethyl-l,2,5-oxadiazole, which is commercially available. Nevertheless, in recent years, some perspective applications have been envisaged. In the agrochemical field a large library (more than 300 derivatives) of A-(4-triflnoromethyl-l,2,5-oxadiazol-3-yl)benzamides 257 has been prepared and considered for herbicidal activity [ 140], while l-(4-fluoro-1,2,5-oxadiazol-3-yl)pyrazole derivatives 258 were claimed as herbicides and plant growth regulators (Fig. 14) [141]. 

As mentioned so far, methylnitroisoxazolone 10 serves as a precursor of carbamoylnitrile oxide 6 upon treatment with only water under mild conditions, in which any special reagents, conditions, and manipulations are not necessary. The nitrile oxide 6 reacts with alkynes 15, alkenes 17, nitriles 29, and 1,3-dicarbonyl compounds 34 to afford corresponding carbamoyl-substituted isoxazoles 16, isoxazolines 18, 1,2,4-oxadiazoles 28, and isoxazoles 33, respectively (Scheme 9.17). The electron-withdrawing carbamoyl group realizes the cycloaddition with electron-rich dipolarophiles, which is inverse electron-demand 1,3-dipolar cycloaddition. Furthermore, the carbamoyl group also plays a role of an activator of the dipolarophile. This mefliodology will be useful for the construction of a new library of functionalized compounds. 

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