Molecular basis of peripheral vs central benzodiazepine receptor selectivity in a new class of peripheral benzodiazepine receptor ligands related to alpidem

Journal of Medicinal Chemistry

Volumn 39, Issue 21, 1996, Pages 4275-4284

  Anzini, Maurizio ^a   Cappelli, Andrea ^a   Vomero, Salvatore ^a   Giorgi, Gianluca ^a   Langer, Thierry ^b   Bruni, Giancarlo ^a   Romeo, Maria R ^a   Basile, Anthony S ^c  

^a UNIVERSITY OF SIENA   (Italy)

^b UNIVERSITY OF INNSBRUCK   (Austria)

^c NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPIDEM; BENZODIAZEPINE RECEPTOR; IMIDAZOPYRIDINE DERIVATIVE; PYRROLE DERIVATIVE; QUINOLINE DERIVATIVE; RECEPTOR SUBTYPE;

ANIMAL TISSUE; ARTICLE; BINDING COMPETITION; DRUG ACTIVITY; DRUG DESIGN; DRUG EFFECT; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; RAT; X RAY DIFFRACTION;

ANIMALS; ANTI-ANXIETY AGENTS; BINDING, COMPETITIVE; CEREBRAL CORTEX; DRUG DESIGN; FLUNITRAZEPAM; IMIDAZOLES; ISOQUINOLINES; MODELS, MOLECULAR; PROTEIN CONFORMATION; PYRIDINES; RATS; RECEPTORS, GABA-A; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0029793981     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960325j     Document Type: Article

References (29)

1. Fryer, R. I. Ligand Interaction at the Benzodiazepine Receptor. In Comprehensive Medicinal Chemistry; Hansch, C., Sammes, P. G., Taylor, J. B., Eds.; C. A. Ramsden Pergamon Press: New York, 1990; Vol. 3, Chapter 12.8, pp 539-566 and references cited therein.
2. 3H]Diazepam Binding. Proc. Natl. Acad. Sci U.S.A. 1977, 74, 3805-3809.
3. 3H]Diazepam Binding Sites on Rat Heart and Kidney. Biochem. Pharmacol. 1982, 31, 589-590.
4. Gavish, M.; Katz, Y.; Bar-Ami, S.; Weizman, R. Biochemical, Physiological, and Pathological Aspects of the Peripheral Benzodiazepine Receptor. J. Neurochem. 1992, 58, 1589-1601.
5. Peripheral Benzodiazepine Receptors; Giesen-Crouse, E., Ed.; Academic Press: London, 1993.
6. Kozikowski, A. P.; Ma, D.; Brewer, J.; Sun, S.; Costa, E.; Romeo, E.; Guidotti, A. Chemistry, Binding Affinities, and Behavioral Properties of a New Class of "Antineophobic" Mitochondrial DBI Receptor Complex (mDRC) Ligands. J. Med. Chem. 1993, 36, 2908-2920.
7. (a) Bourguignon, J. J. Endogenous and Synthetic Ligand of Mitochondrial Benzodiazepine Receptors: Structure-Affinity Relationships. In Peripheral Benzodiazepine Receptors; Giesen-Crouse, E., Ed.; Academic Press: London, 1993; pp 59-85.
8. (b) Costa, E.; Romeo, E.; Auta, J.; Papadopoulos, V.; Kozikowski, A. P.; Guidotti, A. Is There a Pharmacology of Brain Steroidogenesis? In Neurosteroid and Brain Function, Fidia Research Fundation Symposium Series; Costa, E., Paul, S. M., Eds.; Thieme Medical Publisher, Inc.: New York, 1991; pp 171-176.
9. Romeo, E.; Auta, J.; Kozikowski, A. P.; Ma, D.; Papadopoulos, V.; Puia, G.; Costa, E.; Guidotti, A. 2-Aryl-3-Indoleacetamides (FGIN-1): A New Class of Potent and Specific Ligands for the Mitochondrial DB1 Receptor (MDR). J. Pharmacol. Exp. Ther. 1992, 262, 971-978,
10. Kozikowski, A. P.; Ma, D.; Romeo, E.; Auta, J.; Papadopoulos, V.; Puia, G.; Costa, E.; Guidotti, A. Synthesis of (2-Arylindol-3-yl)acetamides as Probes of Mitochondrial Steroidogenesis - A New Mechanism for GABAA Receptor Modulation. Angew. Chem., Int. Ed. Engl. 1992, 31, 1060-1062.
11. Tebib, S.; Bourguignon, J. J.; Wermuth, C. G. The Active Analogue Approach Applied to the Pharmachophore Identification of Benzodiazepine Receptor Ligands. J. Comput.-Aided Mol. Des. 1987, 1, 153-170 and references cited therein.
12. Tomczuk, B. E.; Taylor, C. R.; Moses, L. M.; Sutherland, D. B.; Lo, Y. S.; Johnson, D. N.; Kinnier, W. B.; Kilpatrick, B. F. 2-Phenyl-3H- imidazo[4,5-b]pyridine-3-acetamides as Non-Benzodiazepine Anticonvulsants and Anxiolytics. J. Med. Chem. 1991, 34, 2993-3006.
13. 3 Receptor Antagonists Based on Arylpiperazine Skeleton: Synthesis, Structure, Biological Activity and CoMFA Studies. J. Med. Chem. 1995, 38, 2692-2704.
14. (b) Cappelli, A.; Anzini, M.; Vomero, S.; Menziani, M. C.; De Benedetti, P. G.; Sbacchi, M.; Mennuni, L. Synthesis, Biological Evaluation, and Quantitative Receptor Docking Simulation of 2-Acylaminoethyl-1,4-benzodiazepines as Novel Tifluadom-Like Ligands with High Affinity and Selectivity for κ-Opioid Receptors. J. Med. Chem. 1996, 39, 860-872.
15. Borea, P. A.; Gilli, G.; Bertolasi, V.; Ferretti, V. Stereochemical Features Controlling Binding and Intrinsic Activity Properties of Benzodiazepine-Receptor Ligands. Mol. Pharmacol. 1987, 31, 334-344.
16. Georges, G.; Vercauteren, D. P.; Vanderveken, D. J.; Horion, R.; Evrard, G.; Fripiat, J. G.; Andre, J. M.; Durant, F. Structural and Electronic Analysis of Peripheral Benzodiazepine Ligands: Description of the Pharmacophoric Elements for Their Receptor. Int. J. Quant. Chem. Quant. Biol. Symp. 1990, 17, 1-25.
17. Adams, D. R.; Dominguez, J. N.; Perez, J. A. Synthesis of Quinolines by Reaction of Anilinobutenoates with Vilsmeier Reagent. Tetrahedron Lett. 1983, 24, 517-518.
18. Anzini, M.; Cappelli A.; Vomero, S. Synthesis of 2-Substituted 2,3-dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinolin-3-ones as Potential Peripheral Benzodiazepine Receptor Ligands. Heterocycles 1994, 38, 103-111.
19. Georges, G. J.; Vercauteren, D. P.; Evrard, G. H.; Durant, F. V.; George, P. G.; Wick, A. E. Characterization of the Physico-Chemical Properties of the Imidazopyridine derivative Alpidem. Comparison with Zolpidem. Eur. J. Med. Chem. 1993, 28, 323-335.
20. Lentini, G.; Bourguignon, J. J.; Wermuth, C. G. Ligands of the Peripheral-Type Benzodiazepine Binding Sites (PBS): Structure-Activity Relationships and Computer-Aided Conformational Analysis. In QSAR: Rational Approaches to the Design of Bioactive Compounds; Silipo, C., Vittoria, A., Eds.; Elsevier Science Publishers B.V.: Amsterdam, 1991; pp 257-260.
21. 1H-NMR spectrum shows the presence of two different rotamers in equilibrium. For the sake of simplification the integral intensities are not given.
22. SHELXTL PC, Siemens Analytical X-Ray Instruments, Inc., Madison, WI; Rel. 4.1, 1990.
23. SYBYL 6.1, Tripos Assoc., 1699 S. Hanley Rd., Suite 303, St. Louis, MO 63144.
24. Clark, M.; Cramer, R. D., III; Van Opdenbosch, N. Validation of the General Purpose TRIPOS 5.2 Force Field. J. Comput. Chem. 1989, 10, 982-1012.
25. Gasteiger, J.; Marsili, M. Iterative Partial Equalization of Orbital Electronegativity - A Rapid Access to Atomic Charges. Tetrahedron 1980, 36, 3219-3288.
26. Mohler, H.; Okada, T. Benzodiazepine Receptor: Demonstration in the Central Nervous System. Science 1977, 198, 849-851.
27. Anzini, M.; Cappelli, A.; Vomero, S.; Cagnotto, A.; Skorupska, M. Synthesis and Benzodiazepine Receptor Affinity of 2,3-Dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinolin-1-one and 3-Carbethoxy-4-phenylquinoline Derivatives. Farmaco 1992, 47, 191-202.
28. (a) Basile, A. S.; Klein, D. C.; Skolnick, P. Characterization of Benzodiazepine Receptors in the Bovine Pineal Gland: Evidence for the Presence of an Atypical Binding Site. Mol. Brain. Res. 1986, 1, 127-135.
29. (b) Basile, A. S.; Ostrowsky, N.; Skolnick, P. Aldosterone Reversible Decrease in the Density of Renal Peripheral Benzodiazepine Receptors in the Rat After Adrenalectomy. J. Pharmacol. Exp. Ther. 1987, 240, 1006-1013.