Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists
Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of clinical candidate AMG 517. Clinical candidate AMG 517 ( 1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2008-09, Vol.18 (18), p.5118-5122 |
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| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
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| Online-Zugang: | Volltext |
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| Zusammenfassung: | Analogs with various substituents at the R region of
3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of clinical candidate AMG 517.
Clinical candidate AMG 517 (
1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of
3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of
1. Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to
1. |
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| ISSN: | 0960-894X 0968-0896 1464-3405 1464-3391 |
| DOI: | 10.1016/j.bmcl.2008.07.112 |