Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies.
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Lin X, Murray JM, Rico AC, Wang MX, Chu DT, Zhou Y, Del Rosario M, Kaufman S, Ma S, Fang E, Crawford K, Jefferson AB
Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies.
Bioorg Med Chem Lett. 2006 Aug 15;16(16):4163-8. Epub 2006 Jun 9.
- PubMed ID
- 16765046 [ View in PubMed]
- Abstract
A series of 2-pyrimidyl-5-amidothiophenes has been synthesized and evaluated for AKT inhibition. SAR studies resulted in potent inhibitors of AKT with IC(50) values as low as single digit nanomolar as represented by compound 2aa. Compound 2aa showed cellular activity including antiproliferation and downstream target modulation. Selectivity profile is described. A co-crystal of 2aa with PKA is determined and discussed.