attention as potential drugs. The complex fermentation product Staurosprin
is a PKC inhibitor that has shown antineoplastic activity in a range of bio-
logical assays, but proved to be too toxic for use as a drug. The somewhat
simpler analogue, ruboxystaurin shows greater potency and selectivity for
specific PKCs. It has been pursued in the clinic to treat complications
from diabetes. The synthetic acyclic productenzastaurin( 54 )iseven
more specific, inhibiting a subclass of PKCs involved in cell proliferation.
Reaction of the pyridyl methylamine ( 45 ) with methyl acrylate results
in Michael addition of 2 equiv of the reagent to afford the diester ( 46 ).
NO ONH 245CO 2 C 2 H 5CO 2 C 2 H 5NNNH 5 C 2 O 2 C461. tBuOK- LiOH
NNO47C 6 H 5 NH (^2) N
N
NH
48
NC Cl
BCl 3
N
N
NH
49
Cl
O
NaBH 4
heat
50
(COCl) 2
N
N
N
51
N
N
N
O
O
Cl
NH
52
N
N
Et 3 N
HN
NH
HN
OCH(CH 3 ) 2
H+
HN
N NH
O O
N
N
OH
53 54
- COMPOUNDS WITH ONE HETEROATOM 89