Table 4.

In-vitro biological evaluation of compounds derived by Scheme 4.

		IC50 (nM)*					Microsome stability (min)
Compd.	R1	MMP-13	MMP-2	MMP-8	clogD7.4a	clogPb	rat	mouse	human	Collagen cleavage (20 μM)
2		2.7±0.6	>5000	>5000	4.2	3.0	9	20	12	>90%
52		7.1±0.8	>5000	1100±236	3.6	3.3	9	26	12	>90%
53		>5000	nd	nd	3.3	2.7	14	110	59	nd
54		18±4.9	nd	nd	3.2	2.5	10	31	21	40%
55		38±7.5	>5000	>5000	3.3	1.5	4	12	96	65%
56		148±8.5	nd	nd	3.8	3.3	5	20	82	nd

^*The IC₅₀ values for MMP-1, MMP-9, and MT1-MMP are >5 μM for all compounds. nd = not determined.

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

^bCalculated with ChemDraw.