2-aminoquinoline inhibitors

Ki values 50-200 jlM) were optimised. One of the 2-aminoquinoline inhibitor (63, Ki 0.37 jlM) demonstrated oral bioavailability (38%). The 2-naphthamidine derivative (64) did not show oral bioavailability. 

Leishmaniasis - Over 100 compounds with known antiparasitic activity were tested against Leishmania mexieana mexicana M379, Leishmania tropica major Pj and Leishmania donovani HV3 in cell culture.114 Several antimalarial compounds including 5-, 6- and 8-aminoquinolines, quinazolines, amidinoureas and dihydrofolate reductase inhibitors showed sufficient activity to warrant further study. 

A. Maraval, S. Franco, C. Vialas, G. Pratviel, M.A. Blasco and B. Meunier, Porphyrin-aminoquinoline conjugates as telomerase inhibitors, Org. Biomol. Chem., 2003, 1, 921-927. 

C25H22N4OS, Mr 506.47, an aminoquinoline quinone antibiotic isolated for the first time in 1960 from Streptomyces flocculus and other streptomycetes it is structurally related to lavendamycin, forms coffee-brown to black platelets (mp. 275 °C) or brown needles (mp. 262-263 °C). The antibiotic activity of S. is based on an impairment of the matrix function of DNA by covalent bonding in the ratio antibiotic DNA base pairs of 1 2000 and single strand cleavages. S. also exhibits antitumor activity and immunosuppressive properties, it is used as an inhibitor of reverse transcriptase of retroviruses LD50 (dog p.o.) 0.5 mg/kg, (mouse p.o.) 2.3 mg/kg. 

Figure 2 Murcko structures for bioactive molecules, (a) Quinoline as Murcko framework of bioactive aminoquinolines after removing side chains and (b) different levels of structural simplification of Hsp90 inhibitor NVP-AUY922 provide different structural levels of scaffolds.

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