Activity of 2,5-disubstituted

Xu et al. [44] reported the microwave assisted synthesis and antifungal activity of 2,5-disubstituted-l,3,4-oxadiazoles containing azulene moiety. The 5-aryl-2-(3-methylazulen-l-yl)-l,3,4-oxadiazoles (Lv) were obtained by the microwave... 

Bi L, Zhang Y, Zhao M, et al. (2005). Novel synthesis and anti-inflammatory activities of 2,5-disubstituted-dioxacycloalkanes. Bioorg. Med. Chem. 13 5640-5646. 

A one-pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from acids and acyl hydrazides has recently been reported. The method involves an activation of an acid with carbonyl diimidazole followed by the addition of benzoyl hydrazide and then the addition of CBr4 and Ph3P. Under the conditions, the dehydration proceeds smoothly to provide the desired oxadiazoles in high yields <2006TL4827>. 

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

Chen et al. [72] have prepared some 2,5-disubstituted derivatives of primaquine. The most notable activity was displayed by 2-methyl-5-( -hexyloxy- and ri-hexylthio)primaquines (57a,b). Both these compounds exhibited blood schizontocidal activity at a dose of 20 and 160 mg/kg, respectively [45]. Another series of 2,5-disubstituted primaquines, represented by the general formula 58, have been... 

Table 2 The structure-activity relationships of the compound library of 2,5-disubstituted...

Koketsu M et al. (2002) Inhibitory effects of l,3-selenazol-4-one derivatives on mushroom tyrosinase. Chem Pharm Bull (Tokyo) 50(12) 1594-1596 Khan MT et al. (2005) Structure-activity relationships of tyrosinase inhibitory combinatorial hbrary of 2,5-disubstituted-l,3,4-oxadiazole analogues. Bioorg Med Chem 13(10) 3385-3395... 

Jiang S, Tala SR, Lu H et al (2011) Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41. Bioorg Med Chem Lett 21 6895-6898... 

Synthesis of 2,5-disubstituted 1,3/4-oxadiazoles and their activity as insect growth regulators 06CJO1647. 

The Paal-Knorr synthesis is more commonly used for the synthesis of 2,5-disubstituted furans, especially 2,5-diaryl furans, which have shown significant antiviral activity against RNA viruses. For example, Wilson and co-workers demonstrated that diaryl-substituted diones treated with hydrochloric acid could be used to generate the corresponding 2,5-disubstituted furans in good yields. ... 

The combination of PdCOCOCFjjj, (/ )-C4-TunePhos (217), and ethyl sulfonic acid (Brpnsted acid, activator) catalysed the partial hydrogenation of 2,5-disubstituted... 

Determination of the effect of the thiazole substitution pattern on miticidal activity was the first step in structure-activity optimization (Figure 5). Comparisons were made between substitution about nitrogen (2,4) and substitution about sulfur (2,5). Although all compounds in these series were quite active, the 2,5-disubstituted compounds were 10 to 100 times more active than the 2,4-disubstituted compounds. The 2,4 system is cross-conjugated there is discontinuity in the conjugation across the... 

Several other research teams used the Paal-Knorr condensation to prepare 2,5-disubstituted furans that were investigated as potential enzyme inhibitors. Nagai produced furan 17 via treatment of dione 16 with sulfuric acid and subsequently examined the activity of 17 toward a retenoic acid receptor. Perrier discovered that furan 19, derived from dione 18, is a potent PDE4 inhibitor and may have anti-inflammatory activity. ... 

The ring is in the chain backbone as a 2,5-disubstituted moiety. In these situations the polymer is more resistant to side reactions but some substituents are more susceptible than others to activation by the presence of the ring and promote branching and degradation under the influence of air, particularly at high temperature. This particular behaviour is encountered in some polycondensates as discussed in Section Il-A. 

The imidazole nucleus is often found in biologically active molecules,3 and a large variety of methods have been employed for their synthesis.4 We recently needed to develop a more viable process for the preparation of kilogram quantities of 2,4-disubstituted imidazoles. The condensation of amidines, which are readily accessible from nitriles,5 with a-halo ketones has become a widely used method for the synthesis of 2,4-disubstituted imidazoles. A literature survey indicated that chloroform was the most commonly used solvent for this reaction.6 In addition to the use of a toxic solvent, yields of the reaction varied from poor to moderate, and column chromatography was often required for product isolation. Use of other solvents such as alcohols,7 DMF,8 and acetonitrile9 have also been utilized in this reaction, but yields are also frequently been reported as poor. 

As a strategy for the construction of cyclic ethers, the radical cyclization of jS-alkoxyacrylates was used for the preparation of czs-2,5-disubstituted tetrahy-drofurans and cis-2,6-disubstituted tetrahydropyrans. An example is given with S-alkoxymethacrylate 38 as precursor of the optically active benzyl ether of (+)-methyl nonactate, exclusively formed as the threo product (Reaction 44). ° ... 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

Table 5 Pharmacological activities of 3,6-disubstituted [l,2,4]triazolo[3,4-b][l,3,4]thiadiazoles 139 ...

Siddall and his co-workers (46) have examined the barriers to rotation of a series of 2,6-disubstituted anilides. Af-Ethyl-A/-(2,6-xylyl)formamide (9) was recrystallized as a uranyl nitrate complex, and one isomer, which at equilibrium was favored by a factor of 3 1, was enriched up to a 30 1 ratio. The kinetics of rotation were examined at 0 to 29°C. The Arrhenius activation energy was 26 3 kcal/mol and log A was 18.5 2.4 hr-1. Siddall and Gamer (47) were able to obtain an almost pure isomer (which also predominated at equilibrium 1.3 1 for the ethyl compound and 1.1 1 for the methyl compound) of Ar-alkyl- V-(2-methyl-4,6-dibromophenyl)-l-naphthamide (10). The half-lives of... 

Reactions of 4,5-disubstituted triazoles with appropriate substrates provide very useful methods for building triazolo fused bicyclic or tricyclic systems. 5-Azido-1,2,3-triazoles bearing an appropriate substituent (e.g., CHO, CN, CO2R) at the 4-position can be transformed with active methylene nitriles into tricyclic heterocycles (e.g., (368)) <86BSB679,87BSB587). A new tricyclic system, 5//-1,2,3-triazolo[5,l-c][l,4]benzodiazepine (e.g., (370) and (371)), is prepared by the intramolecular ring closure of triazoles (369) <89JHC1605). 

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