Title of article
Structure–activity relationships of 1,5-biaryl pyrroles as EP1 receptor antagonists
Author/Authors
Adrian Hall، نويسنده , , Stephen Atkinson، نويسنده , , Susan H. Brown، نويسنده , , Iain P. Chessell، نويسنده , , Anita Chowdhury، نويسنده , , Nicholas M. Clayton، نويسنده , , Tanya Coleman، نويسنده , , Gerard M.P. Giblin، نويسنده , , Robert J. Gleave، نويسنده , , Beverley Hammond، نويسنده , , Mark P. Healy، نويسنده , , Matthew R. Johnson، نويسنده , , Anton D. Michel، نويسنده , , Alan Naylor، نويسنده , , Riccardo Novelli، نويسنده , , David J. Spalding، نويسنده , , Sac P. Tang، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2006
Pages
6
From page
3657
To page
3662
Abstract
The preliminary SAR of a series of novel 1,5-biaryl pyrrole EP1 receptor antagonists derived from compound 1 is described. Replacement of the benzyl group of 1 with isosteric groups was investigated. The most effective replacement was found to be the isobutyl group. The cyclopentylmethyl and cyclohexylmethyl groups were also effective benzyl replacements. The cyclohexylmethyl derivative 19 demonstrated the lowest metabolic clearance within this series. In addition, several high affinity substituted benzyl analogues were also identified. Compound 39 was found to have good bioavailability in rats and demonstrated efficacy in the established FCA preclinical model of inflammatory pain with a calculated ED50 of 9.2 mg/kg.
Keywords
EP1 antagonist , pyrrole , isostere , pain , Established FCA
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2006
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
797051
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