2VIJ

Bace-1 Inhibitors Part 3: Identification of Hydroxy Ethylamines (Heas) with Nanomolar Potency in Cells.

Beswick, P., Charrier, N., Clarke, B., Demont, E., Dingwall, C., Dunsdon, R., Faller, A., Gleave, R., Hawkins, J., Hussain, I., Johnson, C.N., Macpherson, D., Maile, G., Matico, R., Milner, P., Mosley, J., Naylor, A., O'Brien, A., Redshaw, S., Riddell, D., Rowland, P., Skidmore, J., Soleil, V., Smith, K.J., Stanway, S., Stemp, G., Stuart, A., Sweitzer, S., Theobald, P., Vesey, D., Walter, D.S., Ward, J., Wayne, G.

(2008) Bioorg Med Chem Lett 18: 1022

• PubMed: 18171615 Search on PubMed
• DOI: https://doi.org/10.1016/j.bmcl.2007.12.020
• Primary Citation of Related Structures:  
  2VIJ


• PubMed Abstract: 
  

  This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.

   View More

---

Organizational Affiliation: 

Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK.