For research use only. Not for therapeutic Use.
MK-3697 (Cat.No:I000863) is a selective orexin receptor antagonist that acts on orexin receptors OX1R and OX2R. By blocking the binding of orexin neuropeptides, MK-3697 modulates the sleep-wake cycle and promotes sleep. It is being studied for the treatment of insomnia and other sleep disorders, with the aim of improving sleep duration and quality.
| Catalog Number | I000863 |
| CAS Number | 1224846-01-8 |
| Molecular Formula | C23H21N5O3S |
| Purity | ≥95% |
| Target | Orexin 2 receptor antagonist |
| Solubility | DMSO: ≤ 22.5 mg/mL |
| Storage | Store at -20°C |
| IC50 | 0.95 nM(Ki) |
| Reference | 1:Bioorg Med Chem Lett. 2014 Oct 15;24(20):4884-90. doi: 10.1016/j.bmcl.2014.08.041. Epub 2014 Aug 26. Discovery of MK-3697: a selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia.Roecker AJ,Reger TS,Mattern MC,Mercer SP,Bergman JM,Schreier JD,Cube RV,Cox CD,Li D,Lemaire W,Bruno JG,Harrell CM,Garson SL,Gotter AL,Fox SV,Stevens J,Tannenbaum PL,Prueksaritanont T,Cabalu TD,Cui D,Stellabott J,Hartman GD,Young SD,Winrow CJ,Renger JJ,Coleman PJ, PMID: 25248679 DOI: 10.1016/j.bmcl.2014.08.041 </br><span>Abstract:</span> Orexin receptor antagonists have demonstrated clinical utility for the treatment of insomnia. The majority of clinical efforts to date have focused on the development of dual orexin receptor antagonists (DORAs), small molecules that antagonize both the orexin 1 and orexin 2 receptors. Our group has recently disclosed medicinal chemistry efforts to identify highly potent, orally bioavailable selective orexin 2 receptor antagonists (2-SORAs) that possess acceptable profiles for clinical development. Herein we report additional SAR studies within the /’triaryl/’ amide 2-SORA series focused on improvements in compound stability in acidic media and time-dependent inhibition of CYP3A4. These studies resulted in the discovery of 2,5-disubstituted isonicotinamide 2-SORAs such as compound 24 that demonstrated improved stability and TDI profiles as well as excellent sleep efficacy across species. Copyright © 2014 Elsevier Ltd. All rights reserved. |
