Effect of modifications of the alkylpiperazine moiety of trazodone on 5HT(2A) and α1 receptor binding affinity

Journal of Medicinal Chemistry

Volumn 42, Issue 3, 1999, Pages 336-345

  Giannangeli, Marilena ^a   Cazzolla, Nicola ^a   Luparini, Maria Rita ^a   Magnani, Maurizio ^a   Mabilia, Massimo ^b   Picconi, Giuseppe ^a   Tomaselli, Mauro ^a   Baiocchi, Leandro ^a,c  

^a Università Politecnica delle Marche ACRAF Gruppo Angelini   (Italy)

^b S IN Soluzioni Informatiche   (Italy)

^c UNIVERSITY OF CHIETI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 [3 [4 (3 CHLOROPHENYL) 1 PIPERAZINYL] 1 METHYLPROPYL] 1,2,4 TRIAZOLO[4,3 A]PYRIDIN 3 ONE DIHYDROCHLORIDE MONOHYDRATE; 2 [3 [4 (3 CHLOROPHENYL) 2 METHYL 1 PIPERAZINYL] PROPYL] 1,2,4 TRIAZOLO[4,3 A]PYRIDIN 3 ONE HYDROCHLORIDE; 4 (3 CHLOROPHENYL)PIPERAZINE; ALKYLPIPERAZINE; ALPHA 1 ADRENERGIC RECEPTOR; CITALOPRAM; DESIPRAMINE; KETANSERIN; MEPYRAMINE; PENTAZOCINE; PIPERAZINE DERIVATIVE; PRAZOSIN; PRECLAMOL; SEROTONIN 2A RECEPTOR; SULPIRIDE; TRAZODONE; TRIAZOLOPYRIDINE DERIVATIVE; TRIPROLIDINE; TRITIUM; UNCLASSIFIED DRUG;

ANIMAL TISSUE; AORTA; ARTICLE; BINDING AFFINITY; BRAIN MEMBRANE; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG SYNTHESIS; MALE; NONHUMAN; RAT; RECEPTOR BINDING; STEREOCHEMISTRY; SWINE; VAS DEFERENS;

COMPUTER SIMULATION; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; PIPERAZINES; RECEPTOR, SEROTONIN, 5-HT2A; RECEPTORS, ADRENERGIC, ALPHA-1; RECEPTORS, SEROTONIN; SEROTONIN UPTAKE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; TRAZODONE;

EID: 0032974891     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970700n     Document Type: Article

References (32)

1. 1c receptors and antidepressants. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 1994, 18 (3), 563-574.
2. (b) Moller, H. J.; Volz, H. P. Drug treatment of depression in the 1990s. Drugs 1996, 52 (5), 625-638.
3. Goodnick, P. J.; Benitez, A. Expert Opin. Invest. Drugs 1995, 4 (10), 935-943.
4. Hartig, P. R. Molecular Pharmacology of serotonin receptors. Experientia, Suppl. 1994, 71P, 93-102.
5. Broekkamp, C. L. E.; Leysen, D.; Peeters, B. W. W. M. M.; Pinder, R. M. Prospect for improved antidepressant. J. Med. Chem. 1995, 38 (23), 4615-4633.
6. (a) Silvestrini, B. U.S. Patent 3,381,009.
7. (b) Marek, G. J.; McDougle, C. J.; Price, H.; Seiden, L. S. A comparison of trazodone and fluoxetine: implications for a serotonergic mechanism of antidepressant action. Psycopharmacologv 1992, 109, 2-11.
8. (a) Wiczynska, B.; et al. Antidepressant profile of 9-methyl-2-[3-(4-phenyl-1-piperazinylpropyl)]-1,2,3,4-tetrahydro-β- carbolin-1-one (B-193). Pol. J. Pharmacol. Pharm. 1989, 41 (4), 331-344.
9. (b) Caliendo, G.; et al. Synthesis and trazodone-like pharmacological profile of 1-and 2-[3-(4-phenyl-1-piperazinyl-propyl]benzotriazoles. Eur. J. Med. Chem. 1993, 28, 969-974.
10. 2-1,2,4-triazolm-3-one. U.S. Patent 3857845, 1974.
11. Temple, D. L., Jr.; Lobeck, W. G., Jr. Phenoxyethyl-1,2,4-triazol-3-ones antidepressants. U.S. Patent 4338317, 1982.
12. Kauffmann, T.; Haeker, H.; Kosel, C.; Vogt, K. Z., Hydrazination of heterocycles II. Naturforsch. 1959, 14b, 601-602.
13. Baiocchi, L.; Giannangeli, M. Sintesi del trazodone e dei suoi possibili metaboliti. Boll. Chim. Farm. 1974, 113, 152-164.
14. Pinza, M.; Dorigotti, L.; Pifferi, G. Synthesis, adrenolytic and vasodilator properties of new 2,2,6-trimethylpiperazines. Eur. J. Med. Chem. 1976, 5, 395-398.
15. Wright, W. B.; Brabander, H. J.; Hardy, R. A. Central nervous system depressant. I. 1-Amino-alkyl-3-aryl derivatives of 2-imidazolinone, 2-imidazolilidenethione and tetrahydro-2 (1H)-pyrimidinone. J. Med. Chem. 1966, 9 (6), 852-857.
16. Baiocchi, L. Alkyl derivatives of trazodone. EP Patent 0623131, 1996.
17. Gibson, M. S.; Bradshaw, M. S. The Gabriel synthesis of primary amines. Angew. Chem., Int. Ed. Engl. 1968, 7, 919-930.
18. Baiocchi, L.; Cioli, V. Pharmacologically active enantiomers. PCT/EP94/02061, 1994.
19. Gerrard, W.; Kenyon, J.; Phillips, H. The replacement of ethyl (+) lactate by halogens and the molecular dissymmetry of derivatives of ethyl lactate which contain the sulphin group. J. Chem. Soc. 1937, 153-158.
20. Badia, A.; Beemejo, P.; Jane, F. Pre and postsynaptic effects of sulpiride in the rat isolated vas deferens. J. Pharm. Pharmacol 1982, 34, 266-268.
21. 2 receptors mediating contraction in vascular smooth muscle. J. Pharmacol. Exp. Ther, 1981, 218, 421-425.
22. (b) Myers, J. H.; Mecca, T. E.; Webb, R. C. Direct and sensitizing effects of serotonin agonist and antagonist on vascular smooth muscle. J. Cardiovasc. Pharmacol.
23. SPARTAN version 4.1, Wavefunction, Inc., 18401 Von Karman Ave, #370, Irvine, CA 92715.
24. (a) Caccia, S.; Ballabio, M.; Samarin, R.; Zanini, M. G.; Garattini, S. M-chlorophenylpiperazine a central 5-hydroxytriptamine agonist, is a metabolite oftrazodone. J. Pharm. Pharmacol. 1981, 33, 477-478.
25. (b) Li, A. A.; Mareck, G. I.; Hand, T. H.; Seiden, L. S. Antidepressant-like effects of trazodone on a behavioral screen, are mediated by trazodone, not the metabolite m-chlorophenylpiperazine. Eur. J. Pharmacol. 1990, 777, 137-144.
26. Eisai Co., Ltd. Derivatives of theophylline and theobromine. Belg. BE 890,222, 1982.
27. Nissan Chemical Industries, Ltd. Alanine derivatives as plant growth regulators. Jpn. Kokai Tokyo Koho 1985; JP 60,109,504.
28. Novascreen Division of Oceanic Biosciences Corp., 7170 Standard Dr., Hanover, MD 21076-1334.
29. Bonaccorsi, A. Sperimentazione farmacologica su organi isolati; Boringhieri, 1972.
30. Tayo, F. M. Occurrence of excitatory dopaminoceptors in the rat and guinea-pig deferens. Clin. Exp. Pharmacol. Physiol. 1979, 6, 275-279.
31. Tallarida, R. J.; Murray, R. B. Manual of Pharmacologic calculations with computer programs; Springer-Verlag: New York, 1987.
32. Patil, P. N.; Fudge, K.; Jacobowitz, D. Steric aspects of adrenergic drugs. XVIII. α-adrenergic receptors of mammalian aorta. Eur. J. Pharmacol. 1972, 19, 79-87.