Bisquinolines

Piperaquine, a bisquinoline, is a rapid acting blood schizontocide. The mode of action is unknown. 

Self-assembly methods have been used to form zinc bisquinoline assemblies with high refractive index and film uniformity.287... 

Jen and coworkers [680,681] reported PLEDs based on variations of the above-mentioned 6,6 -bisquinoline copolymers (579-582), containing conjugated and nonconjugated linkers (Chart... 

Several other 6,6 -bisquinoline-based copolymers (583, 584) have been reported [682] (Chart... 

Piperaquine1 Bisquinoline Treatment of P falciparum infection in fixed combination with dihydroartemisinin... 

In the search for quinoline compounds that evade the resistance problem, bisquinolines were found very promising being active against CQ-resistant strains [123]. The ferrocenyl bisquinoline (Fig. 19) remained more efficient on the Dd2 CQ-... 

As unique C2-symmetric transition metal complexes, the atropisomeric (Rp,Rp)-2,2 -bi([2]paracyclo[2]-5,8-quinolinophane) (52) and (Rp,Rp)-1,1 -bi([2]paracyclo [2]-5,8-isoquinolinophane) (53) were prepared from (/ p)-4-amino- and (Rp)-4-carboxy-[2.2]paracyclophanes, respectively. The CD spectra of 52 and 53 were significantly different from each other (Fig. 14) [60]. The bisquinoline moieties are in almost planar orientation in 2,2 -isomer 52 and the origin of chirality is ascrib-able primarily to the paracyclophane structure. In contrast, the main source of chirality in l,l -isomer 53 is the distorted bisquinoline chromophores (i.e., the axial chirality). 

The bisquinoline known as piperaquine (137) was synthesized in 1966 at the Shanghai Pharmaceutical Industry Research Institute. Piperaquine was found to be active against chloroquine-resistant falciparum malaria. In order to delay resistance, it is used in combination therapy, including with dihydroartemisinin, a derivative of the Chinese plant product artemisinin, first isolated in 1972. 

Homochiral 3,3 -dimethyl-2,2 -bisquinoline N,N -dioxide serves as a Lewis base catalyst for asymmetric hydrocyanation of aromatic N-(diphenylmethyl)imines, although the enantioselectivity is still modest (37-77% ee) [659]. 

The SAR studies in 7-chloro-4-substituted aminoquinolines have been carried out by Bass et al. [17]. These authors used regression analysis of a large variety of 4-aminoquinolines and observed that their findings are in close resemblance with the model proposed by Hahn and Co-workers [18]. In a further probe to study the role of the 4-substituted amino function in evoking the antimalarial activity in quinolines, a number of 7-chloro-4-substituted quinolines (12) were prepared, but none exhibited noteworthy antimalarial activity [19-23]. Some bisquinolines of type 13-15 have also been synthesized, of which 14 and 15 have been shown to exhibit potent antimalarial activity [23-25]. 

Several bisquinolines, such as piperaquine have notable activity and longer duration of action against chloroquine-resistant malaria (Fig. 16.19). In a recent study, bis(aminoacridine) derivatives with different linker were evaluated for their antiparasitic activityThe activity profile of these compounds was strongly dependent upon the nature and the length of the connecting linker between the heterocyclic rings. 

Vennerstrom, J.L., Ellis, W.Y., Ager, A.L. Jr, Anderson, S.L., Gerena, L. and Milhous, W.K. (1992) Bisquinolines. 1. NJ4-bis(7-chloroqui-nolin-4-yl) alkanediamines with potential against chloroquine-resistant malaria. J. Med. Chem. 35 2129-2134. 

Following this pioneering work, the bisquinoline rhenium tricarbonyl core 5 was used to prepare various bioconjugates (Scheme 11.4). For example, Zubieta and CO workers coupled 5 to vitamin B12, thymidine, and folate derivatives [50-52]. 

Hajos and co-workers observed an unexpected Dimroth rearrangement in their synthesis of linearly fused [l,2,4]triazolo[l,5-6]bisquinoline ring systems. Diaminium salts substituted at the 4 position... 

In 2011, Murakami and coworkers [82] reported that chiral NHC ligands having a 2,2 -bisquinoline-based Cj symmetric skeleton were efficient ligands in the palladium-catalyzed intramolecular a-arylation of amides to afford 3,3-disubstituted oxindoles with good yield and enantioselectivity (Scheme 8.44). The two fused rings attached to the NHC core played an important role in the reaction mechanism. 

In a Schlenk flask is added TMEDA PdMcj (0.01 mmol), 2,2 -bisquinoline-based symmetric NHC ligand (Scheme 8.44) (0.01 mmol), NaOfBu (0.3 mmol), Af-(2-bromophenyl)-J T-methyl-2-phenylpropanamide... 

Multilayer Growth, Optical Properties, and Film Uniformity of Zinc-Bisquinoline Assemblies... 

Scheme I illustrates the self-assembly growth of zinc-bisquinoline from 8,8 -dihydroxy-5,5 -biquinoline (bisquinoline). The reaction of bisquinoline with Zn(Et)2 is almost instantaneous. Figure 1 illustrates the ellipsometrically determined film thicknesses as a function of dip cycle. The two markedly different regimes (Stage I and Stage II) with growth rates of 8.3 and 26.5 A/dip cycle (d.c.) respectively, indicate a complex film growth. Films thicker than 250 A maintain the 26.5 A/d.c. growth rate as far as we have measured (c.a. 1,275 A).

Scheme 1. Schematic representation of the self-assembly growth of poly(zinc-bisquinoline).

Figure 1. Ellipsometrically determined thickness versus successive dip cycles for the poly(zinc-bisquinoline) self-assembly process.

Figure 4. Index of refraction of poly(zinc-bisquinoline) from the Cauchy fit model.

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