| Title : Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors - Goodman_2009_Bioorg.Med.Chem.Lett_19_27 |
| Author(s) : Goodman KB , Bury MJ , Cheung M , Cichy-Knight MA , Dowdell SE , Dunn AK , Lee D , Lieby JA , Moore ML , Scherzer DA , Sha D , Suarez DP , Murphy DJ , Harpel MR , Manas ES , McNulty DE , Annan RS , Matico RE , Schwartz BK , Trill JJ , Sweitzer TD , Wang DY , Keller PM , Krawiec JA , Jaye MC |
| Ref : Bioorganic & Medicinal Chemistry Lett , 19 :27 , 2009 |
|
Abstract :
Endothelial lipase (EL) activity has been implicated in HDL catabolism, vascular inflammation, and atherogenesis, and inhibitors are therefore expected to be useful for the treatment of cardiovascular disease. Sulfonylfuran urea 1 was identified in a high-throughput screening campaign as a potent and non-selective EL inhibitor. A lead optimization effort was undertaken to improve potency and selectivity, and modifications leading to improved LPL selectivity were identified. Radiolabeling studies were undertaken to establish the mechanism of action for these inhibitors, which were ultimately demonstrated to be irreversible inhibitors. |
| PubMedSearch : Goodman_2009_Bioorg.Med.Chem.Lett_19_27 |
| PubMedID: 19058966 |
| Gene_locus related to this paper: human-LIPG |
| Inhibitor | GSK-264220A |
| Gene_locus | human-LIPG |
Goodman KB, Bury MJ, Cheung M, Cichy-Knight MA, Dowdell SE, Dunn AK, Lee D, Lieby JA, Moore ML, Scherzer DA, Sha D, Suarez DP, Murphy DJ, Harpel MR, Manas ES, McNulty DE, Annan RS, Matico RE, Schwartz BK, Trill JJ, Sweitzer TD, Wang DY, Keller PM, Krawiec JA, Jaye MC (2009)
Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors
Bioorganic & Medicinal Chemistry Lett
19 :27
Goodman KB, Bury MJ, Cheung M, Cichy-Knight MA, Dowdell SE, Dunn AK, Lee D, Lieby JA, Moore ML, Scherzer DA, Sha D, Suarez DP, Murphy DJ, Harpel MR, Manas ES, McNulty DE, Annan RS, Matico RE, Schwartz BK, Trill JJ, Sweitzer TD, Wang DY, Keller PM, Krawiec JA, Jaye MC (2009)
Bioorganic & Medicinal Chemistry Lett
19 :27