Discovery and Characterization of ACT-335827, an Orally Available, Brain Penetrant Orexin Receptor Type1 Selective Antagonist

被引：74

作者：

Steiner, Michel A. ^{[1
]}

Gatfield, John ^{[1
]}

Brisbare-Roch, Catherine ^{[1
]}

Dietrich, Hendrik ^{[1
]}

Treiber, Alexander ^{[1
]}

Jenck, Francois ^{[1
]}

Boss, Christoph ^{[1
]}

机构：

[1] Actel Pharmaceut Ltd, CH-4123 Allschwil, Switzerland

来源：

CHEMMEDCHEM | 2013年 / 8卷 / 06期

关键词：

anxiety; neurotransmitters; orexin receptor antagonists; peptides; sleep; SLEEP; PROMOTION; SYSTEM;

D O I：

10.1002/cmdc.201300003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Stress relief: Orexin neuropeptides regulate arousal and stress processing through orexin receptor type1 (OXR-1) and 2 (OXR-2) signaling. A selective OXR-1 antagonist, represented by a phenylglycine-amide substituted tetrahydropapaverine derivative (ACT-335827), is described that is orally available, penetrates the brain, and decreases fear, compulsive behaviors and autonomic stress reactions in rats. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：898 / 903

页数：6

共 18 条

[1]

Aissaoui H., 2001, Int. Patent, Patent No. [2001068609, WO2001068609]

[2] The Orexin Antagonist SB-649868 Promotes and Maintains Sleep in Men with Primary Insomnia [J].

Bettica, Paolo ;

Squassante, Lisa ;

Zamuner, Stefano ;

Nucci, Gianluca ;

Danker-Hopfe, Heidi ;

Ratti, Emiliangelo .

SLEEP, 2012, 35 (08) :1097-1104

[3]

Boss C., 2012, Int. PCT Pub., Patent No. [WO2012/025877 A1, 2012025877]

[4] Orexin Receptor Antagonism: A New Principle in Neuroscience [J].

Boss, Christoph ;

Brisbare-Roch, Catherine ;

Jenck, Francois ;

Aissaoui, Hamed ;

Koberstein, Ralf ;

Sifferlen, Thierry ;

Weller, Thomas .

CHIMIA, 2008, 62 (12) :974-979

[5] Promotion of sleep by targeting the orexin system in rats, dogs and humans [J].

Brisbare-Roch, Catherine ;

Dingemanse, Jasper ;

Koberstein, Ralf ;

Hoever, Petra ;

Aissaoui, Hamed ;

Flores, Susan ;

Mueller, Celia ;

Nayler, Oliver ;

van Gerven, Joop ;

de Haas, Sanne L. ;

Hess, Patrick ;

Qiu, Changbin ;

Buchmann, Stephan ;

Scherz, Michael ;

Weller, Thomas ;

Fischli, Walter ;

Clozel, Martine ;

Jenck, Francois .

NATURE MEDICINE, 2007, 13 (02) :150-155

[6] Discovery of the Dual Orexin Receptor Antagonist [(7R)-4-(5-Chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the Treatment of Insomnia [J].

Cox, Christopher D. ;

Breslin, Michael J. ;

Whitman, David B. ;

Schreier, John D. ;

McGaughey, Georgia B. ;

Bogusky, Michael J. ;

Roecker, Anthony J. ;

Mercer, Swati P. ;

Bednar, Rodney A. ;

Lemaire, Wei ;

Bruno, Joseph G. ;

Reiss, Duane R. ;

Harrell, C. Meacham ;

Murphy, Kathy L. ;

Garson, Susan L. ;

Doran, Scott M. ;

Prueksaritanont, Thomayant ;

Anderson, Wayne B. ;

Tang, Cuyue ;

Roller, Shane ;

Cabalu, Tamara D. ;

Cui, Donahui ;

Hartman, George D. ;

Young, Steven D. ;

Koblan, Ken S. ;

Winrow, Christopher J. ;

Renger, John J. ;

Coleman, Paul J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (14) :5320-5332

[7] Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant [J].

Dietrich, Hendrik ;

Jenck, Francois .

PSYCHOPHARMACOLOGY, 2010, 212 (02) :145-154

[8] Hypocretin /orexin contributes to the expression of some but not all forms of stress and arousal [J].

Furlong, Teri M. ;

Vianna, Daniel M. L. ;

Liu, Lu ;

Carrive, Pascal .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2009, 30 (08) :1603-1614

[9] International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology [J].

Gotter, Anthony L. ;

Webber, Andrea L. ;

Coleman, Paul J. ;

Renger, John J. ;

Winrow, Christopher J. .

PHARMACOLOGICAL REVIEWS, 2012, 64 (03) :389-420

[10] Tetrahydroisoquinolines as orexin receptor antagonists: Strategies for lead optimization by solution-phase chemistry [J].

Koberstein, R ;

Aissaoui, H ;

Bur, D ;

Clozel, M ;

Fischli, W ;

Jenck, F ;

Mueller, C ;

Nayler, O ;

Sifferlen, T ;

Treiber, A ;

Weller, T .

CHIMIA, 2003, 57 (05) :270-275

← 1 2 →