Anilino function

Practolol (Figure 8.13) was the prototype cardioselective p-adrenoceptor blocking agent. Selectivity was achieved by substitution in the para position with an acetyl anilino function. The similarity of this drug with those outlined above is obvious. Practolol caused severe skin and eye lesions in some patients which led to its withdrawal from the market [6]. These lesions manifested as a rash, hyperkeratosis, scarring, even perforation of the cornea and development of a fibrovascular mass in the conjunctiva, and sclerosing peritonitis. Some evidence is available that the drug is oxidatively metabolized to a reactive product that binds irreversibly to tissue pro-... 

Carbutamide was the first oral anti-diabetic, and the prototype for the sul-phonamide type of agent. Carbutamide caused marked bone marrow toxicity in man, but derivatives of this, not containing the anilino function, such as tolbutamide... 

Figure 8.15), were devoid of such toxicity. As for many of the agents featured in this section the structural similarity between carbutamide and tolbutamide clearly implicates the anilino function as the toxicophore. 

A bifunctional autocatalytic effect of azinones in general is possible in certain nucleophilic reactions such as amination. Zollinger has found that 2-pyridone is the best catalyst for anilino-dechlorination of various chloroazines. It seems likely that examples of autocatalysis will be found when the substrate contains an azinone moiety. The azinone hy-products of displacement reactions may also function in this way as catalysts for the main reaction. 

As with other electrophilic substitution reactions, there is practically no work available on the halogenation of isoxazoles with functional substituents. The only instance that indicates that the general pattern holds true here is the extremely rapid bromination of 3-anilino-5-phenylisoxazole (65), in which the isoxazole ring is the first to react with 1 mole of bromine, yielding... 

The reaction is best carried out in the appropriate anhydrous aldehyde or ketone, which thus functions as reactant and solvent, or in ethanol, in the presence of an optimum of 1.5 equivalents of strong acid per equivalent of arylbiguanide (base). Acetic acid as a catalyst produces, anomalously, the "base-catalysed anilino-triazines (126, 443). The reaction time varies from one hour to two weeks. The rates diminish in the following order ... 

The amine function in Pcs was also found to be versatile as it allows for the facile incorporation of other photoactive or electroactive species. In particular such amino-functionalized Pcs can be easily reacted with perylene dianhydride to undergo formation of the corresponding diimides such as 18 (Fig. 13) [90-92], The Pc building blocks, carrying either a spacered amino or an anilino group, respectively, were thus implemented into the perylene structure by melting of the two components in imidazole to result in the construction of the corresponding multicomponent assemblies. The pathway toward such structures can also be performed by first introduction of the phthalonitrile to the perylene followed by the formation of the macrocycle [93],... 

FIGURE 25 (PLATE 2). Summary of electronic distribution in the anilino radical (2 A") (a) Bond distances (A), NBO charges [bracket, in au] and Wiberg indices (parentheses, in au). (b) Topology of the electron density determined from atom-in-molecule calculations p(r) = electron density, L = Laplacian of the density defined as L(r) = — V2p(r) and s = ellipticity of the bond critical point, (c) Laplacian map of the density, (d) Isosurfaces of the electron localization function, ELF = 0.87 the values are the populations of the valence basins, (e) Spin density in the molecular plane... 

A wide variety of modifications have been made to MPPP, including modification of the ester functionality, variation in the nitrogen substituent, substitution on the piperidine ring, etc. (see Ref 405). The propionyl chain is the optimum length, and hydrolysis of the ester to the corresponding alcohol usually results in compounds with little if any activity. Several JV-phenylalkyl substitutions such as phenethyl increase potency in some cases [i.e., the anilino-... 

However, S again increases if a second thiophene is placed at the opposite side, resulting in 51. TPA of this chromophore is comparable to that of 49. Thus, the thiophene unit at the left side is an appropriate donor in this series. It functions similarly as the anilino group in 49. 

Fig. 5. Relative average oxygen yield per flash [q>(fci)] in chloroplasts as a function of between flashes, in the absence and presence of ANT 2a [2-(4-chloro)anilino-3,5-dinitrothiophene]. Figure source Renger (1972) The action of 2-aniiinothiophene as acceierators of the deactivation reactions in the water-spiitting enzyme system of photosynthesis. Biochim Biophys Acta 256 433.

This type of approach constitutes a convenient synthesis of 5-functionalized thiazoles. 2,4-Diamino-S-acylthiazoles (292) can be prepared by reacting a-haloketones with alkyl- or aryl-3-amidinothioureas (290) in the presence of triethylamine <86S353> with iV-(anilino)benzylidenc-JV,iV -disubstituted thioiurcas (291), the reaction affords 2-amino-4-aryl-5-acyltWazoles (293). In contrast, the corresponding iV-benzoylthioureas (294) afford mainly 5-benzoyl derivatives (295)... 

---