1.
Bioorg Med Chem Lett
; 16(3): 628-32, 2006 Feb.
Article
in English
| MEDLINE
| ID: mdl-16275076
ABSTRACT
The synthesis and SAR of a series of pyrrolopyridazine MEK inhibitors are reported. Optimal activity was achieved by incorporation of a 4-phenoxyaniline substituent at C4 and an acylated amine at C6.
Subject(s)
Enzyme Inhibitors/pharmacology , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Pyridazines/chemical synthesis , Pyrroles/chemical synthesis , Acylation , Amines/chemistry , Aniline Compounds/chemistry , Animals , Drug Design , Humans , Pyridazines/pharmacology , Pyrroles/pharmacology , Rats , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 15(7): 1895-9, 2005 Apr 01.
Article
in English
| MEDLINE
| ID: mdl-15780629
ABSTRACT
Tetrahydroquinoline-based small molecule inhibitors of farnesyltransferase (FT) have been identified. Lead compounds were shown to have nanomolar to sub-nanomolar activity in biochemical assays with excellent potency in a Ras-mutated cellular reversion assay. BMS-316810 (9e), a 0.7 nM FT inhibitor, was orally-active in a nude mouse tumor allograft efficacy study.
