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. Author manuscript; available in PMC: 2009 Jan 15.
Published in final edited form as: Bioorg Med Chem Lett. 2007 Dec 3;18(2):494–497. doi: 10.1016/j.bmcl.2007.11.104

Table 1.

Structure, anti-malarial activity and microsomal metabolism of 2-oxo-tetrahydro-1,8-naphthyridine-based PFTIs

Compd. X R1 R2 Malaria PFT enzyme % inhibition at the indicated inhibitor concentration (nM) ED50 for inhibition of parasite growth in vitro (nM)1 Microsome metabolism half time (min)2
        500 50 5 0.5 3D7 K1 Naph THQ
16 Br graphic file with name nihms39753t1.jpg H 74 28 0 0 >5000 >5000 ND ND
17 CN graphic file with name nihms39753t2.jpg H 94 66 32 15 >5000 >5000 ND ND
18 CN graphic file with name nihms39753t3.jpg graphic file with name nihms39753t4.jpg 99 98 80 27 420 300 52 15.6
19 CN graphic file with name nihms39753t5.jpg graphic file with name nihms39753t6.jpg 91 48 3 0 3100 >5000 15 ND
20 CN graphic file with name nihms39753t7.jpg graphic file with name nihms39753t8.jpg 98 95 71 16 350 175 >120 5.4
21 CN graphic file with name nihms39753t9.jpg graphic file with name nihms39753t10.jpg 97 88 33 0 320 310 ND 3.8
1

ED50 is the concentration of compound that 50% inhibits the growth of parasites (chloroquine sensitive strain 3D7 or chloroquine resistant strain K1) in red blood cell cultures (measured according to ref. 6).

2

Given is the half-time for loss of parent compound when incubated with mouse liver microsomes according to the procedure given in ref. 6. Compounds tested are: 1) Column labeled Naph, the 2-oxo-tetrahydro-1,8-naphthyridines shown in the table; 2) Column labeled THQ, the corresponding tetrahydroquinoline-based PFT (analogs of 1) with the same R1 and R2 groups as the indicated 2-oxo-tetrahydro-1,8-naphthyridine. ND is not determined.