Synthesis and structure-activity relationships of a new model of arylpiperazines 4. 1-[ω-(4-Arylpiperazin-1-yl)alkyl]-3-(diphenylmethylene)- 2,5-pyrrolidinediones and -3-(9h-fluoren-9-ylidene)-2,5-pyrrolidinediones: Study of the steric requirements of the terminal amide fragment on 5-HT(1A) affinity/selectivity

Journal of Medicinal Chemistry

Volumn 42, Issue 1, 1999, Pages 36-49

  López Rodríguez, María L ^a   Morcillo, M José ^b   Rovat, Tandú K ^a   Fernández, Esther ^a   Vicente, Bruno ^a   Sanz, Antonio M ^a   Hernández, Medardo ^a   Orensanz, Luis ^c  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b UNIVERSIDAD NACIONAL DE EDUCACIÓN A DISTANCIA   (Spain)

^c HOSPITAL RAMÓN Y CAJAL   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 (4 PHENYLPIPERAZIN 1 YL)PROPYL] 3 (DIPHENYLMETHYLENE) 2,5 PYRROLIDINEDIONE; 1 [3 [4 (4 FLUOROPHENYL)PIPERAZIN 1 YL]PROPYL] 3 (DIPHENYLMETHYLENE) 2,5 PYRROLIDINEDIONE; 1 [4 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL] 2 BUTENYL] 3 (DIPHENYLMETHYLENE) 2,5 PYRROLIDINEDIONE; 1 [4 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL] 2 BUTYNYL] 3 (DIPHENYLMETHYLENE) 2,5 PYRROLIDINEDIONE; 1 [4 [4 (4 FLUOROPHENYL)PIPERAZIN 1 YL]BUTYL] 3 (DIPHENYLMETHYLENE) 2,5 PYRROLIDINEDIONE; ADENYLATE CYCLASE; ALPHA 1 ADRENERGIC RECEPTOR; AMINE; DOPAMINE 2 RECEPTOR; HYDANTOIN DERIVATIVE; PIPERAZINE DERIVATIVE; SEROTONIN 1A RECEPTOR; SUCCINIMIDE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; BINDING SITE; DRUG SYNTHESIS; MALE; NONHUMAN; NUCLEAR OVERHAUSER EFFECT; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ADENYLATE CYCLASE; ANIMALS; AORTA, THORACIC; CEREBRAL CORTEX; CORPUS STRIATUM; HIPPOCAMPUS; ISOMETRIC CONTRACTION; MALE; MODELS, MOLECULAR; MUSCLE, SMOOTH, VASCULAR; PIPERAZINES; PYRROLIDINES; RADIOLIGAND ASSAY; RATS; RATS, SPRAGUE-DAWLEY; RATS, WISTAR; RECEPTORS, ADRENERGIC, ALPHA-1; RECEPTORS, DOPAMINE D2; RECEPTORS, SEROTONIN; RECEPTORS, SEROTONIN, 5-HT1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0038316776     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980285e     Document Type: Article

References (48)

1. 1A Affinity/ Selectivity. J. Med. Chem. 1997, 40, 2653-2656.
2. Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M. Modeling of G-Protein-Coupled Receptors: Application to Dopamine, Adrenaline, Serotonin, Acetylcholine, and Mammalian Opsin Receptors. J. Med. Chem. 1992, 35, 3448-3462.
3. Taylor, D. P.; Moon, S. L. Buspirone and Related Compounds as Alternative Anxiolytics. Neuropeptides 1991, 19, 15-19.
4. Levy, A. D.; van de Kar, L. D. Endocrine and Receptor Pharmacology of Serotonergic Anxiolytics, Antipsychotics and Antidepressants. Life Sci. 1992, 51, 83-94.
5. Browne, L. J.; Shaw, K. J. New Anxiolytics. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: New York, 1991; Vol. 26, pp 1-10.
6. 1-Adrenergic Affinity. J. Med. Chem. 1991, 34, 2633-2638.
7. 1A-Selective Agent. Med. Chem. Res. 1992, 2, 88-95.
8. 1A Receptor Antagonists NAN-190 and BMY 7378 are Partial Agonists in the Rat Dorsal Raphe Nucleus In Vitro. Eur. J. Pharmacol. 1992, 211, 211-219.
9. 1A Agonist. J. Pharmacol. Exp. Ther. 1994, 271, 875-883.
10. Björk, L.; Cornfield, L. J.; Nelson, D. L.; Hillver, S.-E.; Andén, N.-E.; Lewander, T.; Hacksell, U. Pharmacology of the Novel 5-Hydroxytryptamine 1A Receptor Antagonist (S)-5-Fluoro-8-hydroxy-2-(dipropylamino)tetralin: Inhibition of (R)-8-Hydroxy-2-(dipropylamino)tetralin-Induced Effects. J. Pharmacol. Exp. Ther. 1991, 258, 58-65.
11. 1A Receptor Antagonist, WAY-100635. Eur. J. Pharmacol. 1995, 281, 81-88.
12. 1A Antagonist Research. Drugs Future 1993, 18, 631-642.
13. 1-Adrenergic Activity. Synthesis and Structure-Affinity Relationships. J. Med. Chem. 1995, 38, 1273-1277.
14. 1A Receptor Ligands. J. Med. Chem. 1997, 40, 574-585.
15. 1A Receptor: A Site-Directed Mutation Study. FEBS Lett. 1992, 312, 259-262.
16. 1A Receptor and Ligands. Protein Eng. 1993, 6, 691-700.
17. 1A Receptor Ligands. J. Med. Chem. 1995, 38, 1942-1954.
18. 1-Arylpiperazines. J. Med. Chem. 1997, 40, 300-312.
19. 1A Receptors in a Series of N4-Substituted Arylpiperazines. J. Med. Chem. 1995, 38, 4044-4055.
20. Ishizumi, K.; Kojima, A.; Antoku, F. Synthesis and Anxiolytic Activity of N-Substituted Cyclic Imides (1R*,2S*,3R*,4S*)-N-[4-[4-(2-Pyrimidinyl)-1-piperazinyl] butyl]-2,3-bicyclo[2.2.1]-heptanedicarboximide (Tandospirone) and Related Compounds. Chem. Pharm. Bull. 1991, 39, 2288-2300.
21. Cipollina, J. A.; Ruediger, E. H.; New, J. S.; Wire, M. E.; Shepherd, T. A.; Smith, D. W.; Yevich, J. P. Synthesis and Biological Activity of the Putative Metabolites of the Atypical Antipsychotic Agent Tiospirone. J. Med. Chem. 1991, 34, 3316-3328.
22. 2 Receptor Affinity for N-[3-(4-Aryl-1-piperazinyl)propyl] Derivatives of 3,4-Dihydroquinolin-2(1H)-one and its Isomeric Isoquinolinones. Med. Chem. Res. 1992, 2, 82-87.
23. 2A Receptor Ligands. Arch. Pharm. Pharm. Med. Chem. 1996, 329, 283-290.
24. 1A Receptor Agonists and Definition of a Steric Model of this Site. Eur. J. Med. Chem. 1989, 24, 31-37.
25. 1A Receptor Ligands: Synthesis and Structure-Affinity Relationships. J. Med. Chem. 1995, 38, 4303-4308.
26. 1A Receptor of 1-Aryl-4-[(1-tetralin)alkyl]piperazines. 2. J. Med. Chem. 1995, 38, 942-949.
27. 1A Receptor Affinity, and Selectivity. 3. J. Med. Chem. 1996, 39, 3195-3202.
28. 1A Receptor Affinity of 1-Phenyl-4-[ω-(α- or β-tetralinyl)alkyl]piperazines. 4. J. Med. Chem. 1996, 39, 4928-4934.
29. 1A Receptor Ligand. Bioorg. Med. Chem. Lett. 1996, 6, 689-694.
30. 1A Receptor Agonist. J. Med. Chem. 1996, 39, 4439-4450.
31. 1 Receptors. A Comparison of CoMFA Models. J. Med. Chem. 1997, 40, 1648-1656.
32. Ohki, S.; Ozawa, N.; Yabe, Y.; Matsuda, H. Anticholinergic Agents. Synthesis of 1,1,4-Trimethyl- and 1,1,5-Trimethyl-3-diphenylmethylenepyrrolidmium Halides. Chem. Pharm. Bull. 1976, 24, 1362-1370.
33. Stobbe, H. Condensation des Benzophenons mit Bernsteinsäureester. Ann. 1899, 308, 89-114.
34. Campbell, N.; Fairfull, A. E. S. The Condensation of Fluorenone and Ethyl Succinate. J. Chem. Soc. 1949, 1102-1106.
35. Wu, Y.-H.; Smith, K. R.; Rayburn, J. W.; Kissel, J. W. Psychosedative Agents. N-(4-Phenyl-1-piperazinylalkyl)-Substituted Cyclic Imides. J. Med. Chem. 1969, 12, 876-881.
36. Hayao, S.; Schut, R. N. New Sedative and Hypotensive Phenylpiperazine Amides. J. Org. Chem. 1961, 26, 3414-3419.
37. 50) of an Enzymatic Reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
38. 1A Receptor. J. Biol. Chem. 1989, 264, 14848-14852.
39. INSIGHT II, version 97.0; Biosym Technologies.
40. Norman, M. H.; Minick, D. J.; Rigdon, G. C. Effect of Linking Bridge Modifications on the Antipsychotic Profile of Some Phthalimide and Isoindolinone Derivatives. J. Med. Chem. 1996, 39, 149-157.
41. Igarashi, J.; Nishimura, T.; Sunagawa, M. Conformational Analysis of an Anxiolytic Agent: Tandospirone in Aqueous Solution. Bioorg. Med. Chem. Lett. 1997, 7, 1659-1664.
42. 1A Receptor. J. Med. Chem. 1990, 33, 633-641.
43. 3H]Prazosin Binding to Central Nervous System Regions of Male and Female Rats. Neurosci. Lett. 1984, 49, 193-197.
44. 2 Receptors. Pharmacol. Toxicol. 1988, 63, 118-121.
45. Lowry, O. H.; Rosebrough, N. J.; Farr, A. L.; Randall, R. J. Protein Measurement with the Folin Phenol Reagent. J. Biol. Chem. 1951, 193, 265-275.
46. Morin, D.; Zini, R.; Querol-Ferrer, V.; Sapena, R.; Tillement, J. P. A Method to Measure Simultaneously Cyclic AMP and Inositol Phosphate Accumulation in Rat Brain Slices. J. Neurochem. 1991, 56, 1114-1120.
47. Salomon, Y. Adenylate Cyclase Assays. In Advances in Cyclic Nucleotide Research; Brooker, G., Greengaard, P., Robinson, G. A., Eds.; Raven Press: New York, 1979; Vol. 110, pp 35-55.
48. Arunlakshana, O.; Schild, H. O. Some Quantitative Uses of Drug Antagonists. Br. J. Pharmacol. 1959, 14, 48-58.