Identification of novel pyrazole acid antagonists for the EP sub(1) receptor
The discovery, synthesis and structure-activity relationship (SAR) of a novel series of EP sub(1) receptor antagonists is described. Pyrazole acid 4, identified from a chemical array, had desirable physicochemical properties, an excellent in vitro microsomal inhibition and cytochrome P450 (CYP450) p...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2006-09, Vol.16 (18), p.4767-4771 |
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| Sprache: | eng |
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| container_end_page | 4771 |
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| container_issue | 18 |
| container_start_page | 4767 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 16 |
| creator | McKeown, Stephen C Hall, Adrian Giblin, Gerard MP Lorthioir, Olivier Blunt, Richard Lewell, Xiao Q Wilson, Richard J Brown, Susan H Chowdhury, Anita Coleman, Tanya Watson, Stephen P Chessell, Iain P Pipe, Adrian Clayton, Nick Goldsmith, Paul |
| description | The discovery, synthesis and structure-activity relationship (SAR) of a novel series of EP sub(1) receptor antagonists is described. Pyrazole acid 4, identified from a chemical array, had desirable physicochemical properties, an excellent in vitro microsomal inhibition and cytochrome P450 (CYP450) profile and good exposure levels in blood. This compound had an ED sub(50) of 1.3 mg/kg in a rat pain model. A range of more potent analogues in the in vitro assay was identified using efficient array chemistry. These EP sub(1) antagonists have potential as agents in the treatment of PGE sub(2) mediated pain. |
| doi_str_mv | 10.1016/j.bmcl.2006.06.086 |
| format | Article |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2006-09, Vol.16 (18), p.4767-4771 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17045781 |
| source | Elsevier ScienceDirect Journals |
| title | Identification of novel pyrazole acid antagonists for the EP sub(1) receptor |
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