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Rapid access towards follow-up NOP receptor agonists using a knowledge based approach |
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| Authors: | Ronald Palin John K Clark Louise Evans Helen Feilden Dan Fletcher Niall M Hamilton Andrea K Houghton Philip S Jones Duncan McArthur Brian Montgomery Paul D Ratcliffe Alasdair RC Smith Aaron Sutherland Mark A Weston Grant Wishart |
| Institution: | aDepartment of Chemistry, Schering-Plough Research Institute, Newhouse, Lanarkshire ML1 5SH, UK;bDepartment of Pharmacology, Schering-Plough Research Institute, Newhouse, Lanarkshire ML1 5SH, UK;cDepartment of Molecular Pharmacology, Schering-Plough Research Institute, Newhouse, Lanarkshire ML1 5SH, UK |
| Abstract: | A knowledge based approach has been adopted to identify novel NOP receptor agonists with simplified hydrophobes. Substitution of the benzimidazol-2-one piperidine motif with a range of hydrophobic groups and pharmacophore guided bio-isosteric replacement of the benzimidazol-2-one moiety was explored. Compound 51 was found to be a high affinity, potent NOP receptor agonist with reduced affinity for the hERG channel. |
| Keywords: | NOP/ORL1 agonist Antinociception hERG Pharmacophore |
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