8-Acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one derivatives as orphanin FQ receptor agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 16, 1999, Pages 2343-2348

  Wichmann, Jürgen ^a   Adam, Geo ^a   Röver, Stephan ^a   Cesura, Andrea M ^a   Dautzenberg, Frank M ^a   Jenck, François ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

1,3,8 TRIAZASPIRO[4.5]DECAN 4 ONE DERIVATIVE; ANXIOLYTIC AGENT; NOCICEPTIN; OPIATE RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; ENANTIOMER; LOCOMOTION; MAZE TEST; NONHUMAN; RAT; REACTION ANALYSIS; STEREOCHEMISTRY; TRANQUILIZING ACTIVITY;

ANIMALS; ANTI-ANXIETY AGENTS; CELL LINE; CRICETINAE; EXPLORATORY BEHAVIOR; HUMANS; IMIDAZOLES; RATS; RECEPTORS, OPIOID; SPIRO COMPOUNDS;

EID: 0033575662     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00385-6     Document Type: Article

References (19)

1. (a) Reinscheid, R. K.; Nothacker, H. P.; Bourson, A.; Ardati, A.; Henningsen, R. A.; Bunzow, J. R.; Grandy, D. K.; Langen, H.; Monsma, F. R., Jr.; Civelli, O. Science, 1995, 270, 792.
2. (b) Meunier, J. C.; Mollereau, C.; Toll, L.; Suaudeau, C.; Moisand, C.; Alvinerie, P.; Butour, J. L.; Guillemot, J. C.; Ferrara, P.; Monsarrat, B.; Mazarguil, H.; Vassart, G.; Parmentier, M.; Costentin, J. Nature (London), 1995, 377, 532.
3. Mollereau, C.; Parmentier, M.; Mallieux, P.; Butour, J.-L.; Moisand, C.; Chalon, P.; Caput, D.; Vassart, G.; Meunier, J.-C. FEBS Lett. 1994, 341, 33.
4. (a) Chen, Y.; Fan, Y.; Liu, J.; Mestek, A.; Tian, M.; Kozak, C. A.; Yu, L. FEBS Lett. 1994, 347, 279.
5. (b) Bunzow, J. R.; Saez, C.; Mortrud, M.; Bouvier, C.; Williams, J. T.; Low, M.; Grandy, D. K. FEBS Lett. 1994, 341, 33.
6. (a) Meunier, J. C. Eur. J. Pharmacol, 1997, 340, 1.
7. (b) Conner, M.; Vaughan, C. W.; Chieng, B.; Christie, M. J. Br. J. Pharmacol., 1996, 119, 1614.
8. (a) Fukuda, K.; Kato, S.; Mori, K.; Nishi, M.; Takeshima, H.; Iwabe, N.; Miyata, T.; Houtani, T.; Sugimoto, T. FEBS Lett. 1994, 343, 42.
9. (b) Nothacker, H. P.; Reinscheid, R.; Mansour A.; Henningsen, R. A.; Ardati, A.; Monsma, F. J., Jr.; Watson, S. J.; Civelli, O. Proc. Natl. Acad. Sci. USA, 1996, 93, 8677.
10. (c) Darland, T.; Heinricher, M. M.; Grandy, D. K. Trends Neurosci. 1998, 21, 215.
11. Jenck, F.; Moreau, J.-L.; Martin, J. R.; Kilpatrick, G. J.; Reinscheid, R. K.; Monsma, F. J., Jr.; Nothacker, H.-P.; Civelli, O. Proc. Natl. Acad. Sci. USA, 1997, 94, 14854.
12. Roever, S.; Adam, G.; Cesura, A. M.; Dautzenberg, F. M.; Galley, G.; Jenck, F.; Monsma, F. R., Jr.; Wichmann, J. J. Med. Chem. submitted.
13. Hu, Y.; Ziffer, H.; Silverton, J. V. Can. J. Chem., 1989, 67, 60.
14. Thompson, A. S.; Humphrey, G. R.; DeMarco, A. M.; Mathre, D. J.; Grabowski, E. J. J. J. Org. Chem., 1993, 58, 5886.
15. Tschaen, D. M.; Abramson, L.; Cai, D.; Desmond, R.; Dolling, U.-H.; Frey, L.; Karady, S.; Shi, Y.-J.; Verhoeven, T. R. . J. Org. Chem., 1995, 60, 4324.
16. (a) Adapa, I. D.; Toll, L. Neuropeptides, 1996, 31, 403.
17. (b) Albrecht, E.; Samovilova, N. N.; Oswald, S.; Baeger, I.; Berger, H. Mol. Pharmacol., 1998, 286, 896.
18. This test is based on the natural aversion of rodents for open spaces and uses a maze with two open and two closed arms; the time spent, the distance moved and the number of entries into open arms are indices of neophobic anxiety in animals. Anxiolytics increase and anxiogenics decrease these measures.
19. Distance moved in the closed arms of the plus-maze was recorded as measures of spontaneous general activity. Forced motor performance was evaluated in a traction test that consisted of forcing rats to grasp a horizontally strung wire and forelimb grip strength was quantitatively assessed using a digital strain gauge.