Halo-8-hydroxyquinolines

A Mannich reaction with 5-halo-8-hydroxyquinolines has led to a series of 7-aminomethyl-5-halo-8-hydroxyquinolines with potent in vitro and in vivo activity against E. histolytica [116]. The most effective compound was found to be 7-(N,N-diethylaminomethyl)-5-chloro-8-hydroxyquinoline (79) [117], which exhibited activity against intestinal amoebiasis in man [112]. 

Halo-8-hydroxyquinolines, especially 5,7-dihalo-8-hydroxyquinolines transgress the parent compound (Oxine, Section 11.4) in antimicrobial activity... 

The extraction of metal ions depends on the chelating ability of 8-hydroxyquinoline. Modification of the stmcture can improve its properties, eg, higher solubility in organic solvents (91). The extraction of nickel, cobalt, copper, and zinc from acid sulfates has been accompHshed using 8-hydroxyquinohne in an immiscible solvent (92). In the presence of oximes, halo-substituted 8-hydroxyquinolines have been used to recover copper and zinc from aqueous solutions (93). Dilute solutions of heavy metals such as mercury, ca dmium, copper, lead, and zinc can be purified using quinoline-8-carboxyhc acid adsorbed on various substrates (94). 

In 1944, Albert, Gibson and Rubbo [541] found that Cu(II)(8-hydroxy-quinoline)2 was much more effective as a bactericidal and fungicidal agent than 8-hydroxyquinoline (8-HQ). Copper complexes of halo-substituted 8-HQ have been found by Gershon [542] to be even more effective than Cu(II)(8-HQ)2. In addition, both 8-HQ [543] and its copper complex [544] have been found to have antiviral activity. It was suggested that the parent compound inhibited the RNA-dependent DNA polymerase of chick myeloblastosis virus and its copper complex produced the same effect with the RNA-dependent DNA polymerase of the tumourogenic Rous sarcoma virus. 

Modification of the Heterocyclic Portion of the Quinoline, This investigation involved the preparation of 2- and 3-substituted-4-phenoxyquinolines using the chemistry previously described as well as derivatization of the lead compound and investigation of other ring systems. Figure 5 summarizes the preparation of quinazoline (13.141 and cinnoline (15) analogs and also details the preparation of 3-halo analogs from 4-hydroxyquinoline. 

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