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Thiophene substituted acylguanidines as BACE1 inhibitors |
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| Authors: | Fobare William F Solvibile William R Robichaud Albert J Malamas Michael S Manas Eric Turner Jim Hu Yun Wagner Erik Chopra Rajiv Cowling Rebecca Jin Guixan Bard Jonathan |
| Institution: | Chemical and Screening Sciences, Wyeth Research, CN8000, Princeton, NJ 08543-8000, USA. fobarew@wyeth.com |
| Abstract: | A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay. |
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