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Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders


, : Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders. Bioorganic & Medicinal Chemistry Letters 21(18): 5562-5567

The hypothalamic peptides orexin-A and orexin-B are potent agonists of two G-protein coupled receptors, namely the OX(1) and the OX(2) receptor. These receptors are widely distributed, though differentially, in the rat brain. In particular, the OX(1) receptor is highly expressed throughout the hypothalamus, whilst the OX(2) receptor is mainly located in the ventral posterior nucleus. A large body of compelling evidence, both pre-clinical and clinical, suggests that the orexin system is profoundly implicated in sleep disorders. In particular, modulation of the orexin receptors activation by appropriate antagonists was proven to be an efficacious strategy for the treatment of insomnia in man. A novel, drug-like bis-amido piperidine derivative was identified as potent dual OX(1) and OX(2) receptor antagonists, highly effective in a pre-clinical model of sleep.

US$19.90

PMID: 21831639

DOI: 10.1016/j.bmcl.2011.06.086


Other references

Alex Strauch., 1866: Dr. ALEX. STRAUCH has published a most elaborate memoir on recent Crocodiles generally, and on the s. Dr. ALEX. STRAUCH has published a most elaborate memoir on recent Crocodiles generally, and on the species in the St. Petersburg Museum especially (Mem. Acad. Sc.St. Pet. x. no.13, 1866, pp. 120). It is divided into three parts. In the first the a...

I.M.; S.S.Y.; Lam W.K.; Shum D., 1992: An in vitro and in vivo study of nedocromil sodium in the management of chronic bronchial infection. American Review of Respiratory Disease 145(4 PART 2): A807

Cooper, S.D.; Felkins, K.; Baker, T.E.; Hale, T.W., 2015: Transfer of methylprednisolone into breast milk in a mother with multiple sclerosis. High-dose intravenous methylprednisolone, a glucocorticoid with powerful anti-inflammatory activities, has become increasingly important in treating acute relapses of multiple sclerosis (MS). This is a case report of a 36-year-old lactating female...

Nascimento, L.O.; Mendes, C.M.; Savaia, M.A.; Rocha, A.dos.S., 1988: Evaluation of bacterial resistance at an intensive care unit: analysis of 29 antibiotics. Revista do Hospital das Clinicas 43(6): 272-278

Palmer, L.H.len, I., 1986: The Aquarium tester--a fast, inexpensive device for evaluating seed quality. Tree planters' notes US Department of Agriculture Forest Serviceer 37(3): 13-16

Ge, J-Na.; Yu, J-Chun.; Kang, W-Ming.; Ma, Z-Qiang.; Gu, Y-Chao., 2013: Comprehensive analysis of relevant factors on colorectal cancer-related anemia. To analyze the risk factors of colorectal cancer-related anemia. The clinical data of 319 patients with colorectal cancer were retrospectively analyzed for the possible risk factors of tumor-related anemia including tumor location, clinical stage,...

Apone, F.; Ruggiero, A.; Tortora, A.; Tito, A.; Grimaldi, M.Rosaria.; Arciello, S.; Andrenacci, D.; D.L.lio, I.; Colucci, G., 2015: Targeting the diuretic hormone receptor to control the cotton leafworm, Spodoptera littoralis. The cotton leafworm, Spodoptera littoralis Boisduval (Lepidoptera: Noctuidae), is one of the most devastating pests of crops worldwide. Several types of treatments have been used against this pest, but many of them failed because of the rapid deve...

Geisler, C.H.; Simonsen, A.C.; Mortensen, B.T.; Christensen, L.D.; Ersbøll, J.K.; Andersen, N.S.; Dickmeiss, E.; Hansen, M.M., 1996: Autologous stem cell transplantation. From bone marrow to selected blood stem cells: 100 consecutive procedures at a single center. One hundred consecutive autologous stem cell transplants are reported: Non-Hodgkin's lymphoma 51 cases, Hodgkin's disease 27 cases, acute leukaemia 14 cases, multiple myeloma seven cases and chronic myeloid leukaemia one case. Most patie...

Preston, H.B., 1912: Descriptions of a new Helicoid land shell from Cape Colony and a new Succinea from the Zambezi River. Annals and Magazine of Natural History, 9 445

Luce, R.A.; Sigurdsson, S.T.; Hopkins, P.B., 1999: Quantification of formaldehyde-mediated covalent adducts of adriamycin with DNA. Duplex DNA incubated with adriamycin, dithiothreitol (DTT), and Fe3+ under aerobic, aqueous conditions yields double-stranded (DS) DNA bands by denaturing polyacrylamide gel electrophoresis (DPAGE) analysis, characteristic of DNAs which are inters...