Synthesis and SAR of highly potent and selective dopamine D 3-receptor antagonists: Quinolin(di)one and benzazepin(di)one derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 3, 2006, Pages 658-662

  Geneste, Hervé ^a   Backfisch, Gisela ^a   Braje, Wilfried ^a   Delzer, Jürgen ^a   Haupt, Andreas ^a   Hutchins, Charles W ^b   King, Linda L ^a   Lubisch, Wilfried ^a   Steiner, Gerd ^c   Teschendorf, Hans Jürgen ^a   Unger, Liliane ^a   Wernet, Wolfgang ^a  

^a ABBOTT GMBH AND CO KG   (Germany)

^b ABBOTT LABORATORIES   (United States)

^c BASF SE   (Germany)

Author keywords

Atypical antipsychotics; Dopamine D3 receptor antagonists

Indexed keywords

1,3,4,5 TETRAHYDRO BENZO[B]AZEPIN 2 ONE; 1H QUINOLINE 2,4 DIONE; 3,4 DIHYDRO 1H BENZO[B]AZEPINE 2,5 DIONE; 3,4 DIHYDRO 1H QUINOLIN 2 ONE; 3,4,4A,10B TETRAHYDRO 4 PROPYL 2H,5H [1]BENZOPYRANO[4,3 B][1,4]OXAZIN 9 OL; A 706149; BENZAZEPINE DERIVATIVE; DOPAMINE 3 RECEPTOR BLOCKING AGENT; KETONE DERIVATIVE; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; DRUG SYNTHESIS; HUMAN; HUMAN TISSUE; NONHUMAN; RAT; REGULATORY MECHANISM; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZAZEPINES; DOPAMINE ANTAGONISTS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; QUINOLONES; RATS; RECEPTORS, DOPAMINE D3; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA;

EID: 29544433208     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.10.035     Document Type: Article

References (31)

1. A. Hackling, R. Ghosh, S. Perachon, A. Mann, H.-D. Höltje, C.G. Wermuth, J.-C. Schwartz, W. Sippl, P. Sokoloff, and H. Stark J. Med. Chem. 46 2003 3883 and ref. cited therein
2. Unger, L.; Ladona, F. J. G.; Wernet, W.; Sokoloff, P.; Wicke, K.M.; Gross, G. Poster, 32nd Annual Meeting of the Society for Neuroscience, Orlando, FL, Nov 2-7, 2002; Society for Neuroscience: Washington, DC, 2002; Abs 894.5.
3. Drescher, K.U.; Ladona, F.J.G., Teschendorf, H.J.; Traut, M.; Unger, L.; Wicke, K.M.; Weddige, F.K.; Freeman, A.S.; Gross, G. Poster, 32nd Annual Meeting of the Society for Neuroscience, Orlando, FL, Nov 2-7, 2002; Society for Neuroscience: Washington, DC, 2002; Abs 894.6.
4. C.R. Ashby, Y. Minabe, and G. Stemp J. Pharmacol. Exp. Ther. 294 2000 1166
5. C. Reavill, S.G. Taylor, and M.D. Wood J. Pharmacol. Exp. Ther. 294 2000 1154
6. 3,4-Dihydro-1H-quinolin-2-one derivatives based on a similar pattern are known in the literature for the potential treatment of central nervous system disorders; the length of the alkyl-spacer as well as the substitution pattern on the (het)aromatic moiety of the basic residue determine the affinity and the selectivity for a given target: see, for example Y. Oshiro, Y. Sakurai, S. Sato, N. Kurahashi, T. Tatsuyoshi, T. Kikuchi, K. Tottori, Y. Uwahodo, T. Miwa, and T. Nishi J. Med. Chem. 43 2000 177 (sigma receptor agonists as antidepressants)
7. Steiner, G.; Schellhaas, K.; Szabo, L.; Behl, B.; Garcia-Ladona, F.J.; Unger, L. WO 02/02529, 2002.
8. 1A agonists for treating cerebral ischemia).
9. J. Finkelstein, and A. Brossi J. Heterocycl. Chem. 4 1967 315
10. E. Ziegler, R. Wolf, and Th. Kappe Monatsh. Chem. 96 1965 418
11. W.Y. Chen, and N.W. Gilman J. Heterocycl. Chem. 20 1983 663
12. Mais, F. J.; Fiege, H. DE 3800386, 1990.
13. Chem. Abstr. 112 1990 139056
14. K. Kunick Arch. Pharm. 324 1991 579
15. J.A. Valderrama, H. Pessoa-Mahana, and R. Tapia Synth. Commun. 22 1992 629
16. C. Schultz, A. Link, M. Leost, D.W. Zaharevitz, R. Gussio, E.A. Sausville, L. Meijer, and C. Kunick J. Med. Chem. 42 1999 2909
17. Y. Kanaoka, Y. Hatanaka, and H. Okajima J. Photochem. 28 1985 569
18. The preparation of the building blocks mentioned, typical procedures, and assay setup are described in WO 2005056546, 2005 Chem. Abstr. 143 2005 78097
19. The preparation of the building block QH (Chart1) and derivatives thereof is described in DE 19735410, 1999 Chem. Abstr. 130 1999 182482
20. J.P. Yevich, J.S. New, D.W. Smith, W.G. Lobeck, J.D. Catt, J.L. Minielli, M.S. Eison, D.P. Taylor, L.A. Riblet, and D.L. Temple J. Med. Chem. 29 1986 359
21. K. Wicke, and J. Garcia-Ladona Eur. J. Pharmacol. 424 2001 85
22. C. Hutchins Endocr. J. 2 1994 7
23. Hutchins, C. In Structure and Function of 7TM Receptors; Schwartz, T. W. et al., Eds.; Copenhagen, 1996; pp 213-216.
24. J.L.G. Ruano, C. Pedregal, and J.H. Rodriguez Heterocycles 32 1991 2151
25. www.cerep.com.
26. Measured in % recovery of parent after 1 h incubation at 37°C with liver microsomes (rat, dog, and human: r-d-h) in the presence of NADPH.
27. P. Artursson Crit. Rev. Ther. Drug Carrier Syst. 8 1991 105
28. A.R. Hilgers, R.A. Conradi, and P.S. Burton Pharm. Res. 7 1990 902
29. Given as 'indication' as the error on the measure is increased by the low solubility of the compound.
30. Adapted from T. Kagaya, M. Yonaga, Y. Furuya, T. Hashimoto, J. Kuroki, and Y. Nishizawa Brain Res. 721 1996 229
31. Jongen-Rêlo, A. L.; Drescher, K. U.; Teschendorf, H. J.; Rueter, L. E.; Unger, L.; Gross, G; Schoemaker, H. Poster, 34th Annual Meeting of the Society for Neuroscience, San Diego, CA, Oct 23-27, 2004; Society for Neuroscience: Washington, DC, 2004; Abs 350.2.