Synthesis, evaluation and computational studies on a series of acetophenone based 1-(aryloxypropyl)-4-(chloroaryl) piperazines as potential atypical antipsychotics

European Journal of Medicinal Chemistry

Volumn 45, Issue 6, 2010, Pages 2656-2662

  Bali, Alka ^a   Sharma, Komal ^a   Bhalla, Abhishek ^a   Bala, Suman ^a   Reddy, Dinesh ^a   Singh, Anant ^a   Kumar, Anil ^a  

^a PANJAB UNIVERSITY   (India)

Author keywords

1,4 Diaryl substituted piperazine derivatives; Atypical antipsychotics; CNS agents; Log BB; Physicochemical similarity

Indexed keywords

1 (2 CHLOROBENZOYL) PIPERAZINE; 1 (2 CHLOROBENZYL) PIPERAZINE; 1 (4 CHLOROBENZOYL) PIPERAZINE; 1 (4 CHLOROBENZYL) PIPERAZINE; 1 [2 (3 CHLOROPROPOXY)PHENYL]ETHANONE; 1 [4 (3 CHLOROPROPOXY)PHENYL]ETHANONE; 1,4 BIS(2 CHLOROBENZYL)PIPERAZINE; 1,4 BIS(2 CHLOROBENZYL)PIPERAZINE ETHANONE; 1,4 BIS(4 CHLOROBENZYL)PIPERAZINE; 2 [3 {4 (2 CHLOROBENZOYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; 2 [3 {4 (2 CHLOROBENZYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; 2 [3 {4 (4 CHLOROBENZOYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; 2 [3 {4 (4 CHLOROBENZYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; 4 [3 {4 (2 CHLOROBENZOYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; 4 [3 {4 (2 CHLOROBENZYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; 4 [3 {4 (4 CHLOROBENZOYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; 4 [3 {4 (4 CHLOROBENZYL) PIPERAZIN 1 YL}PROPOXY]PHENYL ETHANONE; ACETOPHENONE DERIVATIVE; CLOZAPINE; KETANSERIN; NEUROLEPTIC AGENT; PIPERAZINE DERIVATIVE; RISPERIDONE; UNCLASSIFIED DRUG; ZIPRASIDONE;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIPSYCHOTIC ACTIVITY; ARTICLE; BLOOD BRAIN BARRIER; CHROMATOGRAPHY; CLIMBING; COMPUTER PROGRAM; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFECT; DRUG PENETRATION; DRUG SYNTHESIS; FEMALE; MALE; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; STEREOTYPY;

ACETOPHENONES; ANIMALS; ANTIPSYCHOTIC AGENTS; BLOOD-BRAIN BARRIER; COMPUTATIONAL BIOLOGY; FEMALE; MALE; MICE; PHYSICOCHEMICAL PROCESSES; PIPERAZINES; SOFTWARE;

EID: 77950861250     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2010.02.008     Document Type: Article

References (28)

1. Jibson M.D., Glick I.D., and Tandon R. Schizophrenia and other psychotic disorders. Focus 2 (2004) 17-30
2. Seeman P., and Van Tol H.H.M. Dopamine receptor pharmacology. Trends Pharmacol. Sci. 15 (1994) 264-270
3. Seeman P. Dopamine receptors: clinical correlates. In: Bloom F.E., and Kupfer D.V. (Eds). Psychopharmacology: The Fourth Generation of Progress (1995), Raven Press, New York 295-302
4. Davis K.L., Kahn R.S., Ko G., and Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am. J. Psychiatry 148 (1991) 1474-1486
5. Simpson G.M., Pi E.H., and Sramek J.J. Adverse effects of antipsychotic agents. Drugs 21 (1981) 138-151
6. Costall B., and Naylor R.J. The importance of the ascending dopaminergic systems to the extrapyramidal and mesolimbic brain areas for the cataleptic action of the neuroleptic and cholinergic agents. Neuropharmacology 13 (1974) 353-364
7. Meltzer H.Y. Commentary on clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99 (1989) S18-S27
8. Griffith R.W., and Saameli K. Clozapine and agranulocytosis. Lancet 2 (1975) pp. 657-657
9. Melkersson K., and Dahl M.L. Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs 64 (2004) 701-723
10. Schwartz J.T., and Brotman A.W. A clinical guide to antipsychotic drugs. Drugs 44 (1992) 981-992
11. 4 selective ligands. Bioorg. Med. Chem. Lett. 13 (2003) 2921-2924
12. 3-receptor antagonists: quinolin(di)one and benzazepin(di)one derivatives. Bioorg. Med. Chem. Lett. 16 (2006) 658-662
13. 2C receptors. Eur. J. Med. Chem. 35 (2000) 83-95
14. 1 adrenergic affinity and a low potential for extrapyramidal effects. J. Med. Chem. 37 (1994) 1060-1062
15. 6 receptor antagonists. Bioorg. Med. Chem. Lett. 15 (2005) 379-383
16. Xu R., Lever J.R., and Lever S.Z. Synthesis and in vitro evaluation of tetrahydroisoquinolinyl benzamides as ligands for σ receptors. Bioorg. Med. Chem. Lett. 17 (2007) 2594-2597
17. Weigl M., and Wunsch B. Synthesis of bridged piperazines with σ receptor affinity. Eur. J. Med. Chem. 42 10 (2007) 1247-1262
18. Kinkead B., Shahid S., Owens M.J., and Nemeroff C.B. Effects of acute and subchronic administration of typical and atypical antipsychotic drugs on the neurotensin system of the rat brain. J. Pharmacol. Exp. Ther. 67 (2000) 67-73
19. In: Vogel H.G. (Ed). Drug Discovery and Evaluation: Pharmacological Assays. third ed. (2007), Springer 761-762
20. Bali A., Malhotra S., Dhir H., Kumar A., and Sharma A. Synthesis and evaluation of 1-(quinoliloxypropyl)-4-aryl piperazines for atypical antipsychotic effect. Bioorg. Med. Chem. Lett. 19 (2009) 3041-3044
21. Muruganantham N., Sivakumar R., Anbalagan N., Gunasekhran V., and Leonard J.T. Synthesis, anticonvulsant and antihypertensive activities of 8-substituted quinoline derivatives. Biol. Pharm. Bull. 27 (2004) 1683-1687
22. van de Waterbeemd H., Camenisch G., Folkers G., Chretien J.R., and Raevsky O.A. Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J. Drug Target. 6 (1998) 151-165
23. Kelder J., Grootenhuis P.D.J., Bayada D.M., Delbressine L.P.C., and Ploemen J.P. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm. Res. 16 (1999) 1514-1519
24. Nikolova N., and Jaworska J. Approaches to measure chemical similarity - a review. QSAR Comb. Sci. 22 (2003) 1006-1024
25. Bijev A., Yaneve D., Bocheva A., and Stoev G. Ligand based design, synthesis and preliminary in vivo screening of pyrrole derivatives as potential tricyclic anti-inflammatory agents. Arzneim.-Forsch./Drug Res. 56 (2006) 753-759
26. Zhao Y.H., Abraham M.H., Ibrahim A., Fish P.V., Cole S., Lewis M.L., deGroot M.J., and Reynolds D.P. Predicting penetration across the blood brain barrier from simple descriptors and fragmentation schemes. J. Chem. Inf. Model. 47 (2007) 170-175
27. Iyer M., Mishra R., Han Y., and Hopfinger A. Predicting blood-brain partitioning of organic drugs using membrane-interaction QSAR analysis. Pharm. Res. 19 (2002) 1611-1621