Imidazo quinoxalines, from

A curious finding among certain imidazo-quinoxalines is a discrepancy in the efficacy results from the TBPS shift assay and direct measurement of chloride currents, the latter method consistently giving higher intrinsic efficacy (426). Further investigation revealed that some compounds have a biphasic dose-response curve in the chloride current assay. For example, (89)potentiates chloride current... 

Monoacylation of 2,3-diaminoquinoxalines has been achieved by reaction with an acid anhydride in THF. Under more vigorous conditions reaction of 2,3-diaminoquinoxalines with acid anhydrides results in ring closure to an imidazo[ ]quinoxaline. Similar ring closures have been carried out with aldehydes, acyl halides, formic acid, orthoesters, and urea. Polycyclic compounds have also been prepared from 2,3-diaminoquinoxaline by reaction with 1,-2-dicarbonyl compounds and 1,2-diamines, as illustrated in Scheme 7. 

Scheme 4.1 Synthesis of imidazo[l,5-a]quinoxalines from acylated derivatives of methyl 2-amino-2-[qiiinoxalin-2(lfl)-onylidene]acetate...

Scheme 4.7 S5oithesis of imidazo[l,5-a]quinoxalines from the reaction of 3-(a-chlorobenzyl) quinoxalinone with potassium thiocyanate...

Scheme 4.8 Synthesis of imidazo[l,5-t2]quinoxalines from ( -3-(l-(2,2-diphenylhydrazono)-l-phenylpropan-2-yl and l,3-diphenylpropan-2-yl)quinoxalin-2(lH)-ones...

Scheme 4.22 Synthesis of imidazo[l,5-a]quinoxaline from quinoxaline and dilithium derivative of /r-toluenesulfonylmethyl isocyanide...

Scheme 4.41 The Pictet-Spengler reaction for the synthesis of imidazo[l,5-a]quinoxalines from 2-(lH-imidazol-l-yl)aminobenzene derivatives...

Scheme 4.76 Synthesis of benz[4,5]imidazo[l,2-a]quinoxalines from A -tosyl-2-haloanilines and 2-(chloromethyl)-l//-benzimidazoles...

Mamedov VA, Kalinin AA, Balandina AA, Rizvanov IKh, Latypov SK (2009) An efficient method for the synthesis of imidazo[l,5-a]quinoxalines from 3-acylquinoxalinones and benzylamines via a novel imidazoannulation. Tetrahedron 65(45) 9412-9420. doi 10.1016/j. tet.2009.08.081... 

A series of imidazo[l,5-a]quinoxaline amides, carbamates, and ureas which have high affinity for the y-aminobutyric acid A/benzodiazepine receptor complex was developed. Compounds within this class have varying activities ranging from antagonists to full agonists. However, most analogs were found to be partial agonists as indicated by [ S]TBPS and Cl current ratios. Many of these... 

The imidazo[l,2-a]quinoxaline scaffold 233 was developed by Krasavin et al. via two isocyanide-based multicomponent reactions sequentially introducing four diversity elements to the final products [70]. The first step involves the synthesis of quinoxaUnes 237 from o-phenylenediamines 234 and followed by the Groebke-Blackbum-Bienayme multicomponent reaction (Scheme 43). The described methodology provides a tool to constmct the medicinally relevant heterocycles. 

From fried beef, another new compound, 2-amino-3,8-dimethy1-imidazo[4,5-/]quinoxaline (MelQx), was isolated, and its structure was confirmed by chemical synthesis (15). The structures of all the compounds isolated from pyrolysates of amino acids and a protein, and from cooked fish and meat, are shown in Table II. 

Imidazo[2, r 2,3]thiazolo[4,5-f>]quinoxalines were obtained in one step from imidazole precursors <02IJH257>. Intramolecular quatemization reactions of either 158 or 159 ultimately afforded quinoxalines 161 from substituted acetanilides 160 <02JCS(P1)790>, and a two-step... 

Some very clever syntheses of pyrazines were reported. Tandem Mn02-mediated oxidation followed by in situ trapping with aromatic or aliphatic 1,2-diamines was shown to give rise to quinoxalines, dihydropyrazines, pyrazines, and piperazines without the need to isolate highly reactive 1,2-dicarbonyl intermediates <03CC2286>. A new intramolecular cyclization route to highly substituted chiral 6,7-dihydro-5//-imidazo[l,5-a]pyrazin-8-ones like 157 from Meldrum s acid was developed <030L3907>, and 5-chloropyrido[3,4-6]pyrazines were prepared from 1,2-dicarbonyl compounds and 2-chloro-3,4-diaminopyridine <03H(60)925>. A synthesis of... 

LCAO calculations have been performed on this heterocycle, and the resulting electron density map suggests that the 4-position is the most susceptible to nucleophilic substitution. The ultraviolet spectrum in methanol of imidazo[l,2-a]quinoxaline has a maximum at 315 nm and a minimum at 266 nm. The compound is a moderately weak base with a pKa (50% ethanol) of 4.6. No evidence for the site of protonation has been published, although the 3-position seems favored both from the theoretical calculations and by comparison with imidazo[l,2-a]pyrazines (see Chapter XXI). 

The aromatic ring system has been prepared both from quinoxaline intermediates and from 1-phenylimidazoles. Reaction of the 2-chloroquinoxalines 1 with aminoacetaldehyde dimethylacetal followed by acid treatment of the resultant aminoacetals gave imidazo[l,2-ajquinoxaline (2) and its 4-phenyl derivative (3). Compound 3 was the... 

Imidazo[4,5-h]quinoxalines have invariably been prepared from quinoxaline intermediates. Almost twenty years elapsed between the first reported synthesis of the ring system and the next publication containing an extensive study of the utility of reagents for converting 2,3-diaminoquinoxalines into 2-substituted imidazo[4,5-h]quinoxalines. ... 

PyrroIo[l,2,3- e]quinoxalines wore unexpected products from 1,3-dipolar cycloaddition of dihydroimidazolium ylides with unsaturated a-bromoketones <01TL3951>. A rapid synthesis of substituted imidazo[2,l- ]thiazoies under microwave conditions has been published <01SC1257>. Inverse electron demand cycloadditions of 2-substituted imidazoles with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylatc produced imidazo[4,5-dlpyridazines in good yields <01T5497>. 

FIGURE 7.3 Suggested pathway for the formation of imidazo-quinolines and hnidazo-quinoxalines. (Adapted from Jagerstad, M. et al. 1998. Z. Lebensm. Unters. Forsch. A 207 419-427. With permission.)... 

The pyridinyl substituent in position 1 of 1,10-bis- 3-phenyl-1-(pyridin-3-yl)imidazo[l,5-cj]quinoxalin-4-on-5-yl decane 149, which then would be subjected to alkylation with alkyl dihalides with the formation of pyridinium salts, opens the possibility of building imid-azoquinoxaline macrocycles with two pyridinium salt fragments. The interaction of l,10-bis(imidazoquinoxaline)decane 149 with the m-xylylenediamine in acetonitrile solution at high dilution brings about the P,7 -diphenyl,-l, 7 -dioxa-l,7(l, 5)-diimidazo[l,5-a]qunoxalina,-2(3,1),6(1,3)-dipyridina,-4(l,3)-benzenacycloheptadecaphane-2, 6, -ylium dibromide 150 in a 60% yield. Unfortunately, the analytically pure sample of 150 when separated from the reaction mixture was only 25% (2013EJMC345). 

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