Bioorganic & medicinal chemistry letters, 2015-06, Vol.25 (12), p.2488-2492
2015
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Details
- Autor(en) / Beteiligte
- Titel
- Identification of MK-8133: An orexin-2 selective receptor antagonist with favorable development properties
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2015-06, Vol.25 (12), p.2488-2492
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2015
- Quelle
- ScienceDirect
- Beschreibungen/Notizen
- Molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that were selective for the OX2R subtype leading to MK-8133. [Display omitted] Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm for the treatment of insomnia and related disorders. Herein, molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that were selective for the OX2R subtype. Judicious selection of the substituents on the pyridine ring and benzamide groups led to 6b; which was highly potent, OX2R selective, and exhibited excellent development properties.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2015.04.066Titel-ID: cdi_proquest_miscellaneous_1683357406
- Format
- –
- Schlagworte
- Animals, Antagonist, Dogs, GPCR, Half-Life, Insomnia, Mice, Orexin, Orexin Receptor Antagonists - chemistry, Orexin Receptor Antagonists - pharmacokinetics, Orexin Receptor Antagonists - therapeutic use, Orexin Receptors - chemistry, Orexin Receptors - metabolism, Piperidines - chemistry, Piperidines - pharmacokinetics, Piperidines - therapeutic use, Protein Binding, Pyrimidines - chemistry, Rats, Sleep, Sleep Initiation and Maintenance Disorders - drug therapy, Sleep Initiation and Maintenance Disorders - veterinary, Structure-Activity Relationship, Triazoles - chemistry, Triazoles - pharmacokinetics, Triazoles - therapeutic use