Identification of a new series of non-peptidic NK3 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 5, 2011, Pages 1498-1501

  Juhl, Karsten ^a   Hansen, Tore ^a,b   Kehler, Jan ^a   Khanzhin, Nikolay A ^a   Nørgaard, Morten B ^a   Ruhland, Thomas ^a   Larsen, Dorrit B ^a   Jensen, Klaus G ^a   Steiniger Brach, Björn ^a   Nielsen, Søren M ^a   Simonsen, Klaus B ^a  

^a H LUNDBECK A S   (Denmark)

^b UNIVERSITY OF OSLO   (Norway)

Author keywords

Cyclopropane; NK3 antagonist; Schizophrenia; Senktide induced hypoactivity

Indexed keywords

2 AMINOMETHYL 1 ARYL CYCLOPROPANE CARBOXAMIDE DERIVATIVE; AMIDE; NEUROKININ 3 RECEPTOR ANTAGONIST; SENKTIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BRAIN; CONTROLLED STUDY; DRUG EXPOSURE; DRUG IDENTIFICATION; DRUG RECEPTOR BINDING; GERBIL; HUMAN; HUMAN CELL; IN VIVO STUDY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

AMIDES; ANIMALS; CARBOXYLIC ACIDS; CYCLOPROPANES; DISEASE MODELS, ANIMAL; GERBILLINAE; MOLECULAR STRUCTURE; PEPTIDES; RECEPTORS, NEUROKININ-3; STRUCTURE-ACTIVITY RELATIONSHIP;

GERBILLINAE;

EID: 79951721802     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.12.135     Document Type: Article

References (16)

1. X. Langlois, C. Wintmolders, P. te Riele, J.E. Leysen, and M. Jurzak Neuropharmacology 40 2001 242
2. M. Nagano, F. Saitow, E. Haneda, S. Konishi, M. Hayashi, and H. Suzuki Br. J. Pharmacol. 147 2006 316
3. M. Rigby, R. O'Donnel, and N.M.J. Rupniak J. Comp. Neurol. 490 2005 335
4. J.S. Albert, and W. Potts Expert Opin. Ther. Patents 16 2006 925
5. P.W. Smith, and L.A. Dawson Recent Pat. CNS Drug Discov. 3 2008 1
6. L.A. Dawson, and P.W. Smith Curr. Pharm. Des. 16 2010 344
7. K.B. Simonsen, K. Juhl, B. Steiniger-Brach, and S.M. Nielsen Curr. Opin. Drug Discovery Dev. 13 2010 379
8. H.Y. Meltzer, L. Arvanitis, D. Bauer, and W. Rein Am. J. Psychiatry 161 2004 975
9. V. Mesnage, J.L. Houeto, A.M. Bonnet, I. Clavier, I. Arnulf, F. Cattelin, F.G. Le, P. Damier, M.L. Welter, and Y. Agid Clin. Neuropharmacol. 27 2004 108
10. G. Kronenberg, P. Berger, R.F. Tauber, B. Bandelow, V. Henkel, and I. Heuser Pharmacopsychiatry 38 2005 24
11. 125I-labelled NKA from the cloned hNK3 receptor.
12. S. Shuto, S. Ono, Y. Hase, N. Kamiyama, H. Takada, K. Yamashita, and A. Matsuda J. Org. Chem. 61 1996 915
13. The lactone-precursors to 31-42, 44-48 (analogues of 4) were synthesized from (R)-(-)-epichlorohydrin and the appropriate benzyl cyanide as described in Ref. 7.
14. 2, 0.1 M potassium phosphate buffer (pH 7.4), in a total volume of 100 μl, and stopping the incubations at time points 0, 5, 15, 30 and 60 min with 1:1 v/v acetonitrile. t is subsequently scaled to the metabolic competence of a whole liver using 45 mg microsome/g liver, 20 g liver/kg and standard body weight 70 kg.
15. M. Larsen, R. Holm, K.G. Jensen, C. Sveigaard, B. Brodin, and C.U. Nielsen Eur. J. Pharm. Sci. 39 2010 68
16. M. Jung, J.C. Michaud, R. Steinberg, M.C. Barnouin, A. Hayar, G. Mons, J. Souilhac, X. Emonds-Alt, P. Soubrié, and G. Le Fur Neuroscience 74 1996 403