R. J. Watson et al. / Bioorg. Med. Chem. Lett. 18 (2008) 147–151
151
Table 4. Comparison of compounds 1a, 1b and 15 showing improvements in potency and properties
Compound
hCXCR3 (lM) mCXCR3 (lM) Sol (lg/ml) LogD
CLINT (lL/min/mg) CYP 2D6 (lM) PPB (%) % F
1a
1b
15
0.110
0.07
0.007
0.40
0.40
0.006
0.1
0.7
4.95
5.1
72
105
7
0.6
5
>99.9
99.7
93
1
ND
70
40
400
3.1
1.85 log units
15
25
Fold change 1a–15 16
67
10
70
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vides an excellent tool for the elucidation of the role of
CXCR3 in models of human disease.
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