%0 Journal Article
%A Hudkins, Robert L.
%A Johnson, Neil W.
%A Angeles, Thelma S.
%A Gessner, George W.
%A Mallamo, John P.
%D 2007
%T Synthesis and Mixed Lineage Kinase Activity of Pyrrolocarbazole and Isoindolone Analogs of
(+)K-252a
%U https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Mixed_Lineage_Kinase_Activity_of_Pyrrolocarbazole_and_Isoindolone_Analogs_of_K_252a/3027310
%R 10.1021/jm051074u.s001
%2 https://acs.figshare.com/ndownloader/files/4729675
%K MLK activity
%K aryl rings B
%K SAR
%K Mixed Lineage Kinase Activity
%X Structural modification of the indolecarbazole natural product (+)K-252a identified structural requirements
for MLK activity and a novel series of potent fused pyrrolocarbazole MLK1/3 inhibitors. The SAR revealed
that the lactam regiochemistry, the shape of the heterocycle, and aryl rings B and F are important to MLK
activity. Heteroatom and alkyl replacement of the N-12 and/or N-13 indole nitrogen atoms identified the
nonplanar dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7-one (8) and corresponding 5,7-dione (7) as potent
cell-permeable MLK1/3 family-selective leads with in vitro activity comparable to that of (+)K-252a and
determined them to be 2- to 3-fold more potent than the aglycone natural product K-252c.
%I ACS Publications