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. Author manuscript; available in PMC: 2014 Oct 24.
Published in final edited form as: J Med Chem. 2013 Oct 10;56(20):10.1021/jm401266k. doi: 10.1021/jm401266k

Table 5.

Pyridone replacement in vitro and in vivo stability.a

Cmpd HLMb HHc RLMd RHe i.v. Clf
14 24 (M) 21 (L) 202 (L) 29 (M) 53 (L)
16 30 (M) 4 (M) 36 (M) 20 (M) 56 (L)
17 -- 20 (L) -- 65 (L) 75 (L)
18 20 (M) 7 (M) 78 (M) 42 (L) 31 (M)
19 17 (M) 10 (M) 48 (M) 16 (M) 17 (H)
20 5 (H) 9 (M) 10 (H) 9 (M) 23 (M)
21 29 (M) 10 (M) 92 (L) 18 (M) 44 (L)
22 15 (M) 6 (M) 25 (H) 5 (H) 10 (H)
a

Stability category H/M/L = high/medium/low

b

human liver microsome intrinsic clearance, μL/min/mg protein (high stability < 6.5, low stability > 35)

c

human hepatocyte intrinsic clearance, μL/min/106 cells (high stability < 2.8, low stability > 15)

d

rat liver microsome intrinsic clearance, μL/min/mg protein (high stability < 15, low stability > 90)

e

rat hepatocyte intrinsic clearance, μL/min/106 cells (high stability < 5.4, low stability > 29)

f

clearance in rat after 0.5 mg/kg i.v. injection, mL/min/kg (high stability < 20, low stability > 40).