Arylamine moiety

Imidazo[l,5-a]quinoxalines 178-180, containing an arylamine moiety in the 4-position, are inhibitors of the Src-family kinases p56Lck the 50 % inhibition concentrations (IC50) of these compounds are 170.2, 2.0 and 1.7 nmol L, respectively (Chen et al. 2002a, b, c). The presence of an amide group in the 8-position, along with the 4-arylamine substituent, confers to compound 181 the ability to irreversibly inhibit Bmton s tyrosine kinase (BTK) (IC50 = 1.93 nmol L ) (Kim et al. 2011). This compound is used in the treatment of rheumatoid arthritis. 

By introducing the hole transport arylamine as an end cap for an anthracene backbone, Lin et al. designed a series of novel materials (207-212) (Scheme 3.65) [247]. The aim of these dual function materials is to combine the emitting property of the blue anthracene lumino-phore with the hole transport property of the triarylamine to simplify the device fabrication steps. Though the introduction of the arylamino moieties produces moderate QE (f 20%) for these materials, the OLEDs using them as emitters as well as HTMs demonstrate only moderate EL performance with a maximum luminance of 12,922 cd/m2 and 1.8 lm/W with CIE (0.15, 0.15). 

The arylamine 780b required for the total synthesis of carbazomycin B (261) was obtained by catalytic hydrogenation, using 10% palladium on activated carbon, of the nitroaryl derivative 784 which was obtained in six steps and 33% overall yield starting from 2,3-dimethylphenol 781 (see Scheme 5.85). Electrophilic substitution of the arylamine 780b with the iron-complex salt 602 provided the iron complex 787 in quantitative yield. The direct, one-pot transformation of the iron complex 787 to carbazomycin B 261 by an iron-mediated arylamine cyclization was unsuccessful, probably because the unprotected hydroxyarylamine moiety is too sensitive towards the oxidizing reaction conditions. However, the corresponding 0-acetyl derivative... 

As noted for heteroatom attachment in 8-oxo-dG and C8-arylamine adducts, attachment of the Ph moiety to the C-8 site of dG enhances the one-electron donor characteristics of the purine nucleoside. The redox properties of 8-/>-X-Ph-dG (X = OH, OCH3, CH3, H, CN, CHO) adducts have been studied by cyclic voltammetry in anhydrous DMF. The C8-aryl adducts exhibited irreversible one-electron oxidation peaks with half-peak potentials ( p/2) ranging from 0.85 V versus saturated calomel electrode (SCE) for 8-/>-PhOH-dG (X = OH) up to 1.11 V/SCE for 8- -CHO-Ph-dG. All adducts were oxidized more readily than dG, which gave p/2= 1.14 V/SCE in DMF (Table 2). 

Carbazomycin G and H have been isolated from Streptoverticillium ehimense [38]. In nature carbazomycin G occurs as a racemic mixture and the same is assumed for carbazomycin H. Garbazomycin G was reported to show antifungal activity. The two compounds share a unique structure, namely the carbazole-l,4-quinol moiety. Starting from the appropriate iron complex salt, iron-mediated arylamine cydization provides a simple route to both alkaloids (Scheme 15.10) [39]. 

Carbon-bonded adducts are also obtained by the reaction of DNBF in DMSO with A.iV-dimethylaniline, 4-methylaniline, 3,5-dimethylaniline and 2,6-dimethylaniline. Several of the carbon-bonded arylamine complexes are isolated as the zwitterions or the potassium salts. Addition of DNBF to 21 in DMSO in the presence of 2 equivalents of Et3N gave the complex in which aniline is attached to two DNBF moieties via the carbon and nitrogen atoms. The nitrogen-bonded adduct (24) is formed in a rapid equilibrium (kinetically favored), whereas formation of the carbon-bonded adducts 21 and 22 is slower but irreversible (thermodynamically favored). 

The N-acetyl transferase (NAT) polymorphism is one of the earliest pharmacogenetic targets recognized and characterized. NATs are Phase II enzymes that catalyze the transfer. of an acetyl moiety from acetyl-CoA to homocychc and heterocyclic arylamines and hydrazines. Substrates include drugs, carcinogens, toxicants, and possibly endogenous compounds. Slow metabolizer phenotypes, which may affect up to 90% of some populations, are manifested by changes in protein expression, protein stability, and enzyme kinetics. 

Acetylation Reactions. The major enzyme system catalyzing acetylation reactions is arylamine N-acetyltransferase (arylamine acetylase EC 2.3.1.5 NAT). Two enzymes have been characterized, NATl and NAT2 the latter has two closely related isoforms NAT2A and NAT2B whose levels are considerably reduced in the liver of slow acetylators (68,69). The cofactor of AT-acetyltransferase is acetylcoenzyme A (CoA-S-Ac, 29 with R = acetyl) (Fig. 13.24) where the acetyl moiety is bound by a thioester linkage. 

A in Fig. 13.25). This is the reaction formally catalyzed by EC 2.3.1.118 with acetyl-CoA acting as the acetyl donor the JV-hydroxy metabolites of a number of arylamines are known substrates. The same conjugates can be formed by intramolecular AT,0-acetyl transfer, when an arylhydroxamic acid (an AT-aiyl-JV-hydro y-acetamide) is substrate of, e.g., EC 2.3.1.56 (reaction 3-B). In addition, such an arylhydroxamic acid can transfer its acetyl moiety to an acetyltransferase, which can then acetylate an... 

Arylamines undergo. V-contains titanium tetraisopn the amino group is unhinder Homoallyl alcohols. homoallylic alcohols in the three-component condensat moiety from allene and ary 1 indium. A relayed process tl intricacy of such a reaction... 

One of the most versatile approaches to highly functionalized carbazoles is the sequential palladium-catalyzed C-N/C-C coupling for assembly of the central pyrrole moiety. Many total syntheses of naturally occurring carbazole alkaloids are following this route. The initial C-N bond formation by a palladium(0)-cata-lyzed Buchwald-Hartwig amination of aryl halides or triflates 94 with arylamines 31 affords the diarylamines 95 (Scheme 24) [139,140]. Oxidative cyclization of the diarylamines 95 to the carbazoles 32 proceeds via a double C-H bond activation and is achieved in the presence of palladium(ll) compounds. 

An alternative route for the preparation of polymers containing arylamine side-chains is the construction of polymers from monomers that have triarylamine moieties pendant to... 

Thus, a sequence for the assembly of the components of protoasukamycin 252 was proposed involving first the chain extension of 3,4-AHBA to the activated lower polyketide chain, chain extension of cyclohexanecarboxylic to the activated upper chain in parallel, followed by transfer of the upper chain to the arylamine nitrogen, and finally amide bond formation between the activated carboxyl group of the resulting assembly and the nitrogen of the aminocyclopentenolone moiety to give 252 [259],... 

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