Quinolines based series

Several steroid-based compounds have been shown to differentially reduce transactivation with only minimal effects of transrepression (see Figure 15.3-9) [102, 103]. In the nonsteroidal class of GR ligands, a quinoline-based series of compounds, particularly ones with an aryl substituent at the C5 position, yielded a trend toward a preferred transactivation/transrepression profile in cellular assays. Some of these ligands also showed a more promising therapeutic window for selective in vivo effects [104, 105]. In another study, a nonsteroidal GR ligand, ZK 216348, has been reported... 

One final series of quinoline-based ligand complexes (in which there is no steric effect) has been found to be rather unusual248,251,252. The ligand i-bq is expected to behave as a substituted bpy. [Ru(i-bq)3]2+ has a potential (III/II) of 1.12 v indicating less stabilization of ruthenium(II) than in [Ru(bpy)3]2+ 252). The epsilon value is nearly twice that of [Ru(bpy)3]2+, suggesting that the compound should be an efficient emitter. It turns out that in this complex an entirely different luminescence mechanism is operative. [Ru(i-bq)3]2+ shows ligand-centered luminescence, which is unusual in a ruthenium com-... 

There are two reasons for the great interest being shown in artemisinin and its derivatives. First, there is little cross resistance with Plasmodium falciparum between the members of this series and the quinoline-based antimalarials like chloroquine (203). On the contrary, significant potentiation of effect is observed in combination with chloroquine analogs such as mefloquine (204). Second, the high lipid solubility of, for example, arte-mether ensures rapid penetration into the CNS, so these sesquiterpene lactones are first-... 

The isoeluotropic series obtained for quinoline on various adsorbents is developed with solvents from different selectivity groups (Table 4). It is clearly seen that the highest ARm values were obtained for quinoline bases on Horisil with dichloromethane, 2-propanol, and other modifiers, which proves highest selectivity of separation in this system. 

The identification of FLAP as the molecular target for MK-886 led to the establishment of radioligand binding assays to identify inhibitors that were more potent than MK-886 and were derived from novel chemical series [68]. These studies resulted in the identification at Merck Frosst of quinoline-based FLAP antagonists such as L-674,573 and quinoline-indole hybrids (termed quindoles) such as MK-591 [45,46,69,70]. A number of companies have now identified LT synthesis inhibitors that are known to interact with FLAP, such as Bay X 1005, WAY 50,295 and REV-5901 [14,43,47,48,71,72]. 

A. Lilienkampf, J. Mao, B. Wan, Y. Wang, S.G. Franzblau, A.P. Kozikowski, Structure-activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating Mycobacterium tuberculosis, J. Med. Chem. 52 (2009) 2109-2118. 

Preparation o the key intermediate for the chloroquinoline series starts with Shiff base formation of metachloroaniline with ethyl oxaloacetate (66). Heating of the intermediate leads to cyclization into the aromatic ring and consequent formation of the quinoline ring (67). Saponification of the ester to the acid... 

The natural extension of this series to the quinoline analog of AC 252,925 was then undertaken. The synthesis route used is based on the work of E. C. Taylor which employed anthranil as a precursor to a quinoline-2,3-dicarboxylic acid derivative (11). The sequence is shown in Scheme V. 

The electrochemical properties of another series of Cu(I) complexes, based on substituted bipyridine and quinoline derivatives, have been also investigated68 (Fig. 17.31). To stabilize the Cu(I) oxidation state of Cu(I) polypyridine complexes, electron-withdrawing substitutents like esters have been considered. The same effect was also obtained with pyridyl-quinoline and biquinoline complexes, thanks to the increased 7i-accepting properties of the quinoline condensed aromatic ring. 

By GC/MS analysis, quinoline (I) and isoquinoline (II) comprise the first homolog in the -11(N) Z series. Table IX presents mole data, calculated per lOOg of feedstock, for the bases comprising the 129-139 molecular-weight series. It is interesting to note that the moles of I and II in the feed are ca. 

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