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. Author manuscript; available in PMC: 2019 Oct 1.
Published in final edited form as: Bioorg Med Chem. 2018 Aug 20;26(18):4984–4995. doi: 10.1016/j.bmc.2018.08.020

Table 6.

In-vitro biological evaluation of compounds derived from Scheme 8.

IC50(nM)† Microsome stability (min)
Compd. R1 MMP-13 MMP-2 MMP-8 logD7.4a logPb rat mouse human
2 graphic file with name nihms-1507852-t0064.jpg 2.7±0.6 >5000 >5000 4.2 3.0 9 20 12
99 graphic file with name nihms-1507852-t0065.jpg 9.4±1.7* >5000 400±38.0 4.6 3.6 nd nd nd
100 graphic file with name nihms-1507852-t0066.jpg 2.5±0.5* >5000 270±38.0 4.8 3.8 4 28 8
101 graphic file with name nihms-1507852-t0067.jpg 8.4±1.4 nd nd 4.4 3.4 6 29 14
102 graphic file with name nihms-1507852-t0068.jpg 13±2.7 nd nd 4.9 3.9 4 28 13
103 graphic file with name nihms-1507852-t0069.jpg >5000 nd nd 3.7 2.9 nd nd nd
104 graphic file with name nihms-1507852-t0070.jpg 2000±850 nd nd 3.7 2.9 nd nd nd
105 graphic file with name nihms-1507852-t0071.jpg 274±29.0 nd nd 3.1 2.4 nd nd nd
106 graphic file with name nihms-1507852-t0072.jpg 153±13.0 nd nd 3.1 2.0 33 57 160
107 graphic file with name nihms-1507852-t0073.jpg 2600±480 nd nd 1.7 1.9 nd nd nd
108 graphic file with name nihms-1507852-t0074.jpg 1300±110 nd nd 3.5 2.5 nd nd nd
109 graphic file with name nihms-1507852-t0075.jpg 88±5.6 nd nd 3.7 2.5 nd nd nd
110 graphic file with name nihms-1507852-t0076.jpg 1200±200 nd nd 4.3 3.0 41 43 >120
*

IC50 values for MMP-1, MMP-9, and MT1-MMP > 5 μM.

†

Some selectivity profiles among MMP-1, MMP-2, MMP-8, MMP-9 and MT1-MMP were not determined due to either low activity or poor microsomal stability of the compound. nd = not determined.

a

Calculated with Pipeline Pilot workflow application (Accelrys) at pH 7.4.

b

Calculated with ChemDraw.