ยป 10

(1) IC50 values (^M) as means of two or more determinations. For experimental details, see Section 2.3.

(2) IC50 values (^M) of Ras proteins in THAC cells (Ha-Ras). >10 means 10-50% inhibition at 10 ^M; >>10 means <10% inhibition at 10 ^M. For experimental details, see Section 2.5.

alkenyl residues at the benzylic position of the side chain are also usually tolerated (data not shown).

We introduced more than 100 different side chains at position 2. The more active BPHI always corresponds to phenylacetyl derivatives, favorably substituted by an methoxy group at the ortho position, with the only surprising exception being a cysteinyl function such as in II-11. The cysteinyl exception may suggest that the side chain at position 2 is likely to be involved, even indirectly, in metal (magnesium or zinc) binding.

Table 2B

Structure of Enzymatic and Cellular FTase Inhibitions of BPHI Modified at Position 3a II/12-23


Chemical structure R3a

Enzymatic FTase inhibition Ha-RajTCA ( I ) Kl-RaySPA ( 1 )

Ras process, inhibition (2)

en nn

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