Imidazole derivative,

A widely prescribed drug for the treatment of gastric ulcers with the generic name cimetidine is a synthetic imidazole derivative Firefly luciferm is a thiazole derivative that IS the naturally occurring light emitting substance present m fireflies... 

Clotrimazole. The imidazole derivative clotrimazole (6) was iatroducedia 1969. Clotrimazole [23593-75-1] or l-((9-chloro-a,a-diphenylbenzyl)imidazole is a water-iasoluble antimycotic for topical appHcation, with a broad-spectmm activity against mycoses of the skin and the vagiaa. 

Miconazole. Miconazole nitrate [22832-87-7] (Fig. 2), the 1-phenethyl-imidazole derivative first described in 1969, interferes at low doses with the cytochrome P-450 dependent ergosterol biosynthesis in yeasts and fungi. The result is accumulation of C-14 methylated sterols on the one hand and reduction of the ergosterol levels in the membranes on the other hand (12). Analogous to clotrimazole, this leads to a disturbance in the membranes it results in inhibition of ceU repHcation, mycelium development (in C. albicans) and finally, ceU death. High concentrations of miconazole, which may be achieved with topical use, disturb the orientation of phosphoHpids in the membranes, which produces leaks (13). 

Alloxan forms an oxime (1007) which is the same compound, violuric acid, as that formed by nitrosation of barbituric acid likewise, a hydrazone and semicarbazone. Reduction of alloxan gives first alloxantin, usually formulated as (1008), and then dialuric acid (1004 R = OH) the steps are reversible on oxidation. Vigorous oxidation with nitric acid and alkaline hydrolysis both give imidazole derivatives (parabanic acid and alloxanic acid, respectively) and thence aliphatic products. Alloxan and o-phenylenediamine give the benzopteridine, alloxazine (1009) (61MI21300). 

An alternative method involves reaction of an a-acylaminoketone (12) with a primary amine and subsequent ring closure of the resultant Schiff s base (13) with phosphoryl chloride. This enables the introduction of a 1-substituent as in (14) to be carried out efficiently, and if the amine were replaced with a monosubstituted hydrazine, the imidazole derivative (IS) resulted (78LA1916). 

The irradiation of imidazole derivatives such as 81 gave isomeric compounds 82 (Scheme 30) (67TL5315 69T3287). Dewar isomers are invoked to justify the observed photochemical behavior. 

Pyrrole, pyridine, pyrazole, and imidazole derivatives as insecticides and acari-cides 99UK773. 

Pteridine, pyrimidine, pyrrole, and imidazole derivatives as natural compounds of marine origin influencing larval settlements and metamorphosis of marine sessile organisms 99YZ457. 

If the displacement reaction is carried out between imidazole derivative and thiophene analogue the antifungal agent tiaconazole (40) results. A rather slight variant of... 

An imidazole derivative which is also a hypotensive agent by virtue of adrenergic a-2-receptor blockade is imiloxan (75). Its synthe.sis begins by conversion of 2-cyanomethyl-1,4-benzodioxane (72) to its iminosMhylether with anhydrous HC in clhanol (73). Reaction of the latter with aminoacetaldehyde diethylacetal and subsequent acid treatment produces the imidazole ring (74). Alkylation of 74 with ethyl iodide mediated by sodium hydride completes the synthesis [251. 

The action of triethylamine or 4-methylmorpholine on the imidazole derivatives 1 results in the formation of 4,5-dihydro-l/f-l,2-benzodiazepines 2, which eliminate imidazole on heating with ethanolic sodium ethoxide to give H-, 2-benzodiazepines 3.121 Details for compound 3 (R1 = Ph, R2 = Me) only were reported it was stated that other derivatives were obtained similarly but details were not given. 

Tetrahydroimidazo[5,l-c][l,2,4]triazine 474 was prepared (79KGS1540) by treating imidazole derivatives 472 or 473 with hydrazine. Compound 473 was obtained by reaction of the respective imidazole with 1,2-dibromoethane or by the reaction of the alcohol derivative 471 with phosphorus tribromide. On the other hand, chlorination of471 with thionyl chloride gave 472 (Scheme 100). 

Besides high effectiveness in the diastereoselective control of nucleophilic addition reactions, another major goal in the design of chiral auxiliaries is the use of readily available, chiral starting materials. The hexahydro-l//-pyrrolo[l,2-c]imidazole derivatives 9a-e are examples which use the inexpensive amino acid L-proline (7) as starting material. 

Interactions of histidine and other imidazole derivatives with transition metal ions in chemical and biological systems. R. J. Sundberg and R. B. Martin, Chem. Rev., 1974, 74, 471-517 (517). 

In 2004, Alterman et al. used a microwave-assisted Ullmann-type protocol for the synthesis of N-(f-butyl)-3-[4-(lH-imidazol-l-yl)benzyl]-5-isobutylthiophene-2-sulfonamide (Scheme 106) [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloro-formate finally gave the target compound for biological evaluation as selective angiotensin II AT2 receptor agonist. The IH-imidazole derivative, however, showed only a low affinity for the AT2 receptor (Ki value > 10 p,M). 

The mechanism of the reaction has not been eiuddated. Presumably iodine eliminates the imidazole ring from N-substituted imidazole derivatives such as clotrimazole, and this then couples with diazotized sulfanilic acid to yield an azo dye. 

Note The reaction is very specific for N-substituted imidazole derivatives. In serum investigations the detection limit was 50 ng clotrimazole per milliliter serum. The reagent can be employed on silica gel, kieselguhr and Si 50000 layers. 

Solid-phase, parallel-synthesis approaches to the imidazole derivatives 49 <96TL937>, 50 and 51 <96TL835>, 52 <96TL751>, and 53 <96TL4865> were also reported in 1996. 

Imidazole derivatives 380 Imperatorin 65 Impregnation of TLC layers 86 -with caffeine 86 -with silver nitrate 86 -with tungstate 86 Indeno(l,2,3-cd)pyrene 39,85 Indicators, pH- 303 -, reagents 45 Indium cations 144 Indoleacetic acid 45... 

Treatment of the sulfoxide 1222 a with tert-butyldimethylsilyl chloride 85 a and excess imidazole in DMF at 25 °C furnishes the imidazole derivative 1223a in 70% yield, whereas the phenyl derivative 1222b affords, besides 47% of 1223b , the cyclized product 1224 in 24% yield and 94 a and imidazole hydrochloride [34] (Scheme 8.14). Reaction of 1225 with N-(trimethylsilyl)imidazole 1219 at 170°C affords 1226 in 50% yield [35]. 

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