New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: Chemistry and pharmacological evaluation

Journal of Medicinal Chemistry

Volumn 42, Issue 12, 1999, Pages 2235-2244

  Liao, Yi ^a   Venhuis, Bastiaan J ^a   Rodenhuis, Nienke ^a   Timmerman, Wia ^a   Wikström, Håkan ^a   Meier, Eddie ^b   Bartoszyk, Gerd D ^c   Böttcher, Henning ^c   Seyfried, Christoph A ^c   Sundell, Staffan ^d  

^a UNIVERSITY OF GRONINGEN   (Netherlands)

^b H LUNDBECK A S   (Denmark)

^c MERCK KGAA   (Germany)

^d UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

2 (TRIFLUOROMETHYLSULFONYLOXY) 11 (4 METHYL 1 PIPERAZINYL)DIBENZO[B,F][1,4]OXAZEPINE; 2 (TRIFLUOROMETHYLSULFONYLOXY) 11 (4 METHYL 1 PIPERAZINYL)DIBENZO[B,F][1,4]THIAZEPINE; 2 (TRIFLUOROMETHYLSULFONYLOXY) 8 CHLORO 11 (4 METHYL 1 PIPERAZINYL) 5H DIBENZO[B,E][1,4]DIAZEPINE; BENZAZEPINE DERIVATIVE; CLOTIAPINE; CLOZAPINE; CLOZAPINE DERIVATIVE; GMC 1 169; GMC 2 83; GMC 3 06; GMC 61 39; HALOPERIDOL; LOXAPINE; NEUROLEPTIC AGENT; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CATALEPSY; CONTROLLED STUDY; DOSE RESPONSE; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; MALE; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; RECEPTOR AFFINITY; SCORING SYSTEM; SUBCUTANEOUS DRUG ADMINISTRATION;

ANIMALS; ANTIPSYCHOTIC AGENTS; BENZAZEPINES; BRAIN; CATALEPSY; CHO CELLS; CRICETINAE; DOPAMINE ANTAGONISTS; HUMANS; MALE; MICE; MOLECULAR STRUCTURE; PIPERAZINES; RATS; RATS, WISTAR; RECEPTOR, MUSCARINIC M1; RECEPTORS, ADRENERGIC, ALPHA; RECEPTORS, DOPAMINE; RECEPTORS, HISTAMINE H1; RECEPTORS, MUSCARINIC; RECEPTORS, SEROTONIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033578044     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm991005d     Document Type: Article

References (54)

1. Schmutz, J. Neuroleptic piperazinyl-dibenzo-azepines. Chemistry and structure-activity relationships. Arzneim.-Forsch 1975, 25, 712-720.
2. Ögren, S. O. The behavioural pharmacology of typical and atypical antipsychotic drugs. In Handbook of Experimental Pharmacology; Csernansky, J. G., Ed.; Springer: New York, 1996; Vol. 120, pp 225-226.
3. Liégelois, J.-F. F.; Bruhwyler, J.; Rogister, F. A.; Delarge, J. E. Diarylazepine derivatives as potential atypical neuroleptic drugs: Recent Advances. Curr. Med. Chem. 1995, 1, 471-501.
4. Kane, J.; Honigfeld, G.; Singer, J.; Meltzer, H. Clozapine for the treatment-resistant schizophrenic. Arch. Gen. Psychiatry 1988, 45, 789-796.
5. Schaus, J. M.; Bymaster, F. P. Dopaminergic approaches to antipsychotic agents. Annu. Rep. Med. Chem. 1998, 33, 1-10.
6. Meltzer, H.; Matsubara, S.; Lee, J. C. Classification of typical and antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin-2 pKi values. J. Pharmacol. Exp. Ther. 1989, 251, 238-246.
7. Baldessarini, R.; Frankenburg, F. Clozapine: a novel antipsychotic agent. N. Engl. J. Med. 1991, 324, 746-754.
8. Jackson, D. M.; Ryan, C.; Evenden, J.; Mohell, N. Preclinical findings with new antipsychotic agents: what makes them atypical? Acta Psychiatry Scand. 1994, 89, 41-48.
9. Idänpäan-Heikkilä, J.; Alhava, E.; Olkinuora, M.; Palva, P. Agranulocytosis during treatment of clozapine. Eur. J. Clin. Pharmacol. 1977, 11, 193-198.
10. Lieberman, J. A.; Johns, C. A.; Kane, J. M.; Rai, K.; Pisciotta, A. V.; Saltz, B. L.; Howard, A. Clozapine-induced agranulocytosis: non-cross-reactivity with other psychotropic drugs. J. Clin. Psychiatry 1988, 49, 271-277.
11. Buchanan, R. W. Clozapine: efficacy and safety. Schizophren. Bull. 1995, 21, 579-591.
12. Casey, D. E. Side effect profiles of new antipsychotic agents. J. Clin. Psychiatry 1996, 57, 40-52.
13. Wilson, W. H.; Claussen, A. M. Seizures associated with clozapine treatment in a state hospital. J. Clin. Psychiatry 1994, 55, 184-188.
14. Hacksell, U.; Jackson, D. M.; Mohell, N. Does the dopamine receptor subtype selectivity of antipsychotic agents provide useful leads for the development of novel therapeutic agents? Pharmacol. Toxicol. 1995, 76, 320-324.
15. Leysen, J. E.; Gommeren, W.; Eens, A.; de Chaffoy de Courcelles, D.; Stoof, J. C.; Janssen, P. A. Biochemical profile of risperidone, a new antipsychotic. J. Pharmacol. Exp. Ther. 1988, 247, 661-670.
16. Sánchez, C.; Arnt, J.; Dragsted, N.; Hyttel, J.; Lembøl, H. L.; Meier, E.; Perregaard, J.; Skarsfeldt, T. Neurochemical and in vivo pharmacological profile of Sertindole, a limbic-selective neuroleptic compound. Drug Dev. Res. 1991, 22, 239-250.
17. Liégelois, J.-F. F.; Rogister, F. A.; Bruhwyler, J.; Damas, J.; Nguyen, T. P.; Inarejos, M.-O.; Chleide, E. M. G.; Mercier, M. G. A.; Delarge, J. E. Pyridobenzoxazepine and pyridobenzothiazepine derivatives as potential central nervous system agents: Synthesis and neurochemical study. J. Med. Chem. 1994, 37, 519-525.
18. Phillips, S. T.; de Paulis, T.; Baron, B. M.; Siegel, B. W.; Seeman, P.; Van Tol, H. H. M.; Guan, H.-C.; Smith, H. E. Binding of 5H-dibenzo[b,e][1,4]diazepine and chiral 5H-dibenzo[a,d]cycloheptene analogues of clozapine to dopamine and serotonin receptors. J. Med. Chem. 1994, 37, 2686-2696.
19. Moore, N. A.; Calligaro, D. O.; Wong, D. T.; Bymaster, F.; Tye, N. C. The pharmacology of olanzapine and other new antipsychotic agents. Curr. Opin. Invest. Drugs 1993, 2, 281-293.
20. Goldstein, J. M.; Arvanitis, L. A. ICI 204,636 (Seroquel): A dibenzothiazepine atypical antipsychotic. Review of preclinical pharmacology and highlights of phase II clinical trials. CNS Drug Rev. 1995, 1, 50-73.
21. Eichenberger, E. Pharmacology of fluperlapine compared with clozapine. Arzneim.-Forsch. 1984, 34, 110-113.
22. Chakrabarti, J. K.; Horsman, L.; Hotten, T. M.; Pullar, I. A.; Tupper, D. E.; Wright, F. C. 4-Piperazinyl-10H-thieno[2,3-b][1,5]-benzodiazepines as potential neuroleptics. J. Med. Chem. 1980, 23, 878-884.
23. Froimowitz, M.; Ramsby, S. Conformational properties of semirigid antipsychotic drugs: the pharmacophore for dopamine D-2 antagonist activity. J. Med. Chem. 1991, 34, 1707-1714.
24. Liao, Y.; DeBoer, P.; Meier, E.; Wikström, H. Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine. Identification of a novel atypical neuropleptic. J. Med. Chem. 1997, 40, 4146-4153.
25. 1D receptors. Bioorg. Med. Chem. 1998, 6, 1469-1479.
26. 1D receptor agonist properties of novel 2-[5-(trifluoromethyl-sulfonyloxy)-indolyl]ethylamines and their use as synthetic intermediates. J. Med. Chem. 1996, 39, 4717-4726.
27. Sonesson, C.; Waters, N.; Svensson, K.; Carlsson, A.; Smith, M. W.; Piercey, M. F.; Meier, E.; Wikström, H. Substituted 3-phenylpiperidines: new centrally acting dopamine autoreceptor antagonists. J. Med. Chem. 1993, 36, 3188-3196.
28. Sonesson, C.; Boije, M.; Svensson, K.; Ekman, A.; Carlsson, A.; Romero, A. G.; Martin, I. J.; Duncan, J. N.; King, L. J.; Wikström, H. Orally active central dopamine and serotonin receptor ligands: 5-, 6-, 7-, and 8-([(trifluoromethyl)sulfonyl]oxy]-2-(di-n-propylamino)tetralins and the formation of active metabolites in vivo. J. Med. Chem. 1993, 36, 3409-3416.
29. Sonesson, C.; Barf, T.; Nilsson, J.; Dykstra, D.; Carlsson, A.; Svensson, K.; Smith, M. W.; Martin, I. J.; Duncan, J. N.; King, L. J.; Wikström, H. Synthesis and evaluation of pharmacological and pharmacokinetic properties of monopropyl analogues of 5-, 7-and 8-trifluoromethylsulfonyloxy-2-aminotetralins. J. Med. Chem. 1995, 38, 1319-1329.
30. 3 receptor preference and improved pharmacokinetic properties. Bioorg. Med. Chem. Lett. 1994, 4, 689-694.
31. Gerson, S, L.; Arce, C.; Meltzer, H. Y. N-Demethylclozapine: a clozapine metabolite that suppresses hemopoiesis. Br. J. Haematol. 1994, 86, 555-561.
32. 2 receptors? Psychopharmacology 1998, 138, 213-214.
33. 2 receptors. To be published.
34. Hunziker, F.; Lauener, H.; Schmutz, J. 11-Dialkylamino-5-dibenzo[b,e][1,4]diazepines. Patent No. Fr. 1,334,944 (CI. A 61k, C 07d); Assignee: Wander, A. A.-G. 1963; Chem. Abstr. 61, 3127d.
35. Hunziker, F.; Lauener, H.; Schmutz, J. 11-Dialkylamino-5-dibenzo[b,e][1,4]diazepines. Patent No. Fr. 1,334,944 (CI. A 61k, C 07d); Assignee: Wander, A. A.-G. 1963; Chem. Abstr. 61, 3127d.
36. Hunziker, F.; Lauener, H.; Schmutz, J. Zur chemie und pharmakologie von in 10-stellung basisch substituierten 5-dibenzo-[b,e][1,4]-diazepin-derivaten. Arzneim.-Forsch. 1963, 13, 324-328.
37. Brewster, K.; Clarke, R. J.; Harrison, J. M.; Inch, T. D.; Utley, D. Preparation of the eight monohydroxydibenz[b,f][1, 4]oxazepine-11(10H)-ones. J. Chem. Soc., Perkin Trans. 1976, 12, 1286-1290.
38. Pelz, K.; Jirkovsky, I.; Adlerova, E.; Metysova, J.; Protiva, M. Collect. Czech. Chem. Commun. 1968, 33, 1895-1910.
39. Petcher, T. J.; Weber, H.-P. Conformations of some semirigid neuroleptic drugs. Part 1. Crystal structures of loxapine, clozapine, and HUF-2046 monohydrate {2-chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine, 8-chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,e][1,4]diazepine, and 2-chloro-11-(4-methylpiperazin-2-yl)dibenzo[b,e][1,4]diazepine monohydrate}. J. Chem. Soc., Perkin Trans. II 1976, 1415-1420.
40. Alves-Rodrigues, A.; Leurs, R.; Willems, E.; Timmerman, H. Binding of clozapine metabolites and analogues to the histamine H3 receptor in rat brain cortex. Arch. Pharmacol. Pharm. Med. Chem. 1996, 329, 413-416.
41. Sindelar, K.; Dlabac, A.; Protiva, M. Noncataleptic neuroleptics; 8-Chloro-2-hydroxy-11(4-methylpiperazino[b,e]-1,4-diazepine as a potential metabolite of clozapine. Collect. Czech. Chem. Commun. 1978, 43, 309-314.
42. 2 measures and effect of selective lesions. J. Neurol. Transm. 1987, 68, 171-189.
43. 2 receptor density in corpus striatum in mice. Acta Pharmacol. Toxicol. 1986, 59, 387-391.
44. 2 receptors in corpus striatum of rats. Pharmacol. Toxicol. 1987, 61, 126-129.
45. Klockow, M.; Greiner, H. E.; Haase, A.; Schmitges, C. J.; Seyfried, C. Studies on the receptor profile of Bisoprolol. Arzneim.-Forsch./Drug Res. 1986, 36, 197-200.
46. 1 affinity in a series of piperazine ring substituted 1-piperazino-3-arylindans with potential atypical antipsychotic activity. J. Med. Chem. 1995, 38, 4380-4392.
47. Arnt, J.; Lembøl, H. L.; Meier, E.; Pedersen, H. Discriminative stimulus properties of the muscarinic receptor agonists Lu 26-046 and O-Me-THPO in rats. Evidence for involvement of different muscarinic receptor subtypes. Eur. J. Pharmacol. 1992, 218, 139-169.
48. 3-antagonistic properties. Drug Dev. Res. 1997, 40, 1-16.
49. 1 receptor in the brain. Life Sci. 1984, 34, 597-605.
50. Bartoszyk, G. D.; Harting, J.; Minck, K.-O. Roxindole: Psychopharmacological profile of a dopamine D2 autoreceptor agonist. J. Pharmacol. Exp. Ther. 1996, 276, 41-48.
51. Stanley, M. E.; Glick, S. D. Interaction of drug effects with testing procedures in the measurement of catalepsy. Neuropharmacology 1976, 15, 393-394.
52. Protais, P.; Costentin, J.; Schwartz, J. C. Climbing behavior induced by apomorphine in mice: a simple test for the study of dopamine receptors in striatum. Psychopharmacology 1976, 50, 1-6.
53. Carlsson, A; Kehr, W.; Lindqvist, M. Agonist-antagonist interaction on dopamine receptors in brain, as reflected in the rates of tyrosine and tryptophan hydroxylation. J. Neural Transm. 1977, 40, 99-113.
54. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 1997, 23, 3-25.