Structural requirements to obtain highly potent and selective 18 kDa translocator protein (TSPO) ligands

Current Topics in Medicinal Chemistry

Volumn 11, Issue 7, 2011, Pages 860-886

  Taliani, Sabrina ^a   Pugliesi, Isabella ^a   da Settimo, Federico ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

18 kDa translocator protein (TSPO); Binding affinity; Selective ligands; Steroi dogenic activity; Structure activity relationships

Indexed keywords

ADENINE NUCLEOTIDE TRANSLOCASE; ALPIDEM; BENZODIAZEPINE DERIVATIVE; BENZODIAZEPINE RECEPTOR; BENZOTHIAZEPINE DERIVATIVE; BENZOXAZEPINE DERIVATIVE; CLONAZEPAM; DIAZEPAM; ISOQUINOLINE DERIVATIVE; ISOQUINOLINECARBOXAMIDE DERIVATIVE; LIGAND; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE; PYRROLOBENZOXAZEPINE DERIVATIVE; QUINOLINECARBOXAMIDE DERIVATIVE; RO 54864; TRANSLOCATOR PROTEIN; UNCLASSIFIED DRUG; VOLTAGE DEPENDENT ANION CHANNEL;

ALZHEIMER DISEASE; APOPTOSIS; ARTICLE; BINDING AFFINITY; CALCIUM HOMEOSTASIS; CELL DIFFERENTIATION; CELL GROWTH; CHOLESTEROL TRANSPORT; COMPARATIVE MOLECULAR FIELD ANALYSIS; DRUG BINDING SITE; DRUG SELECTIVITY; DRUG STRUCTURE; HUNTINGTON CHOREA; IC 50; IMMUNOREGULATION; LIGAND BINDING; LIPID METABOLISM; MITOCHONDRIAL RESPIRATION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STEROIDOGENESIS; STRUCTURE ACTIVITY RELATION;

ANILIDES; ANIMALS; ANTI-ANXIETY AGENTS; ANTINEOPLASTIC AGENTS; BENZODIAZEPINES; HUMANS; IMMUNE SYSTEM DISEASES; IMMUNOLOGIC FACTORS; INDOLEACETIC ACIDS; ISOQUINOLINES; LIGANDS; MICE; MITOCHONDRIA; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIAL MEMBRANES; NEOPLASMS; NEURODEGENERATIVE DISEASES; PYRIDINES; RATS; RECEPTORS, GABA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79953660905     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802611795165142     Document Type: Article

References (116)

1. Braestrup, C.; Squires, R. F. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H) diazepam binding. Proc. Natl. Acad. Sci. USA, 1977, 74, 3805-3809.
2. Gavish, M.; Bachman, I.; Shoukrun, R.; Katz, Y.; Veenman, L.; Weisinger, G.; Weizman, A. Enigma of the peripheral benzodi-azepine receptor. Pharmacol. Rev., 1999, 51, 619-640.
3. Papadopoulos, V. Peripheral-type benzodiazepine/diazepam binding inhibitor receptor: biological role in steroidogenic cell function. Endocr. Rev., 1993, 14, 222-240.
4. Sprengel, R.; Werner, P.; Seeburg, P. H.; Mukhin, A. G; Santi, M. R.; Grayson, D. R.; Guidotti, A.; Krueger, K. E. Molecular cloning and expression of cDNA encoding a peripheral-type benzodi-azepine receptor. J. Biol. Chem., 1989, 264, 20415-20421.
5. Parola, A. L.; Stump, D. G.; Pepperl, D. J.; Krueger, K. E.; Regan, J. W.; Laird, H. E. 2nd. Cloning and expression of a pharmacologically unique bovine peripheral-type benzodiazepine receptor iso-quinoline binding protein. J. Biol. Chem., 1991, 266, 14082-14087.
6. Joseph-Liauzun, E.; Farges, R.; Delmas, P.; Ferrara, P.; Loison, G. J. The Mr 18,000 subunit of the peripheral-type benzodiazepine receptor exhibits both benzodiazepine and isoquinoline carboxamide binding sites in the absence of the voltage-dependent anion channel or of the adenine nucleotide carrier. J. Biol. Chem., 1997, 272, 28102-28106.
7. Papadopoulos, V.; Baraldi, M.; Guilarte, T. R.; Knudsen, T. B.; Lacapere, J. J.; Lindemann, P.; Norenberg, M. D.; Nutt, D.; Weiz-man, A.; Zhang, M.; Gavish, M. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol. Sci., 2006, 27, 402-409.
8. Bernassau, J. M.; Reversat, J. L.; Ferrara, P.; Caput, D.; Le Fur, G. A 3D model of the peripheral benzodiazepine receptor and its implication in intra mitochondrial cholesterol transport. J. Mol. Graph., 1993, 11, 236-244.
9. Farges, R.; Joseph-Liazun, E.; Shire, D.; Caput, D.; Le Fur, G.; Ferrara, P. Site-directed mutagenesis of the peripheral benzodi-azepine receptor: identification of amino acids implicated in the binding site of Ro 5-4864. Mol. Pharmacol., 1994, 46, 1160-1167.
10. Boujrad, N.; Vidic, B.; Papadopoulos, V. Acute action of chori-ogonadotropin on Leydig tumor cells: changes in the topography of the mitochondrial peripheral-type benzodiazepine receptor. Endo-crinol., 1996, 137, 5727-5230.
11. Anholt, R. R.; Pedersen, P. L.; De Souza, E. B.; Snyder, S. H. The peripheral-type benzodiazepine receptor. Localization to the mito-chondrial outer membrane. J. Biol. Chem., 1986, 261, 576-583.
12. Antkiewicz-Michaluk, L.; Guidotti, A.; Krueger, K. E. Molecular characterization and mitochondrial density of a recognition site for peripheral-type benzodiazepine ligands. Mol. Pharmacol., 1988, 34, 272-278.
13. Lacapère, J. J.; Papadopoulos, V. Peripheral-type benzodiazepine receptor: structure and function of a cholesterol-binding protein in steroid and bile acid biosynthesis. Steroids, 2003, 68, 569-585.
14. Olson, J. M.; Ciliax, B. J.; Mancini, W. R.; Young, A. B. Presence of peripheral-type benzodiazepine binding sites on human erythrocyte membranes. Eur. J. Pharmacol., 1988, 152, 47-53.
15. McEnery, M. W.; Snowman, A. M.; Trifiletti, R. R.; Snyder, S. H. Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. Proc. Natl. Acad. Sci. USA, 1992, 89, 3170-3174.
16. Galiegue, S.; Tinel, N.; Casellas, P. The peripheral benzodiazepine receptor: a promising therapeutic drug target. Curr. Med. Chem., 2003, 10, 1563-1572.
17. Li, H.; Degenhardt, B.; Teper, G.; Papadopoulos, V. Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide. Proc. Natl. Acad. Sci. USA, 2001, 98, 1267-1272.
18. Li, H.; Degenhardt, B.; Todin, D.; Yao, Z. X.; Tasken, K.; Papado-poulos, V. Identification, localization, and function in steroidogenesis of PAP7: a peripheral-type benzodiazepine receptor- and PKA (RIalpha)-associated protein. Mol. Endocrinol., 2001, 15, 2211-2228.
19. Casellas, P.; Galiegue, S.; Basile, A. S. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem. Int., 2002, 40, 475-486.
20. Syapin, P. J.; Skolnick, P. Characterization of benzodiazepine binding sites in cultured cells of neural origin. J. Neurochem., 1979, 32, 1047-1051.
21. Papadopoulos, V.; Lecanu, L.; Brown, R. C.; Han, Z.; Yao, Z.-X. Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders. Neuroscience, 2006, 138, 749-756.
22. Benavides, J.; Fage, D.; Carter, C.; Scatton, B. Peripheral type benzodiazepine binding sites are a sensitive indirect index of neu-ronal damage. Brain Res., 1987, 421, 167-172.
23. Wilms, H.; Claasen, J.; Röhl, C.; Sievers, J.; Deuschl, G.; Lucius, R. Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: evidence from activated microglial cells in vitro. Neurobiol. Dis., 2003, 14, 417-424.
24. James, M. L.; Selleri, S.; Kassiou, M. Development of Ligands for the peripheral benzodiazepine receptor. Curr. Med. Chem. 2006, 13, 1991-2001.
25. Snyder, M. J.; Van Antwerpen, R. Evidence for a diazepam-binding inhibitor (DBI) benzodiazepine receptor-like mechanism in ecdysteroidogenesis by the insect prothoracic gland. Cell Tissue Res. 1998, 294, 161-168.
26. Ferrero, P.; Costa, E.; Conti-Tronconi, B.; Guidotti, A. A diazepam binding inhibitor (DBI)-like neuropeptide is detected in human brain. Brain Res., 1986, 399, 136-142.
27. Slobodyansky, E.; Guidotti, A.; Wambebe, C.; Berkovich, A.; Costa, E. Isolation and characterization of a rat brain triakon-tatetraneuropeptide, a posttranslational product of diazepam binding inhibitor: specific action at the Ro 5-4864 recognition site. J. Neurochem., 1989, 53, 1276-1284.
28. Scarf, A. M.; Ittner, L. M.; Kassiou, M. The Translocator protein (18 kda): central nervous system disease and drug design. J. Med. Chem., 2009, 52, 581-592.
29. Taliani, S.; Da Settimo, F.; Da Pozzo, E.; Chelli, B.; Martini, C. Translocator protein ligands as promising therapeutic tools for anxiety disorders. Curr. Med. Chem., 2009, 16, 3359-3380.
30. Bitran, D.; Foley, M.; Audette, D.; Leslie, N.; Frye, C. A. Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat. Psychopharmacology, 2000, 151, 64-71.
31. Bribes, E.; Bourrie, B.; Casellas, P. Ligands of the peripheral ben-zodiazepine receptor have therapeutic effects in pneumopathies in vivo. Immunol. Lett., 2003, 88, 241-247.
32. Farges, R. C.; Torres, S. R.; Ferrara, P.; Ribeiro-do-Valle R. M. Involvement of steroids in anti-inflammatory effects of peripheral benzodiazepine receptor ligands. Life Sci., 2004, 74, 1387-1395.
33. Veenman, L.; Gavish, M. The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development. Pharmacol. Ther., 2006, 110, 503-524.
34. Kassiou, M.; Meikle, S. R.; Banati, R. B. Ligands for peripheral benzodiazepine binding sites in glial cells. Brain Res Brain Res Rev., 2005, 48, 207-210.
35. Heydari, B.; Le Melledo, J. M. Low pregnenolone sulphate plasma concentrations in patients with generalized social phobia. Psychol. Med., 2002, 32, 929-933.
36. Strohle, A.; Romeo, E.; Di Michele, F.; Pasini, A.; Yassouridis, A.; Holsboer, F.; Rupprecht, R. GABA(A) receptor-modulating neuro-active steroid composition in patients with panic disorder before and during paroxetine treatment. Am. J. Psychiatry, 2002, 59, 145-147.
37. Brambilla, F.; Biggio, G.; Pisu, M. G.; Bellodi, L.; Perna, G.; Bog-danovich-Djukic, V.; Purdy, R. H.; Serra, M. Neurosteroid secretion in panic disorder. Psychiatry Res., 2003, 118, 107-116.
38. Weizman, R.; Tanne, Z.; Granek, M.; Karp, L.; Golomb, M.; Tyano, S.; Gavish, M. Peripheral benzodiazepine binding sites on platelet membranes are increased during diazepam treatment of anxious patients. Eur. J. Pharmacol., 1987, 138, 289-292.
39. Ferrarese, C.; Appollonio, I.; Frigo, M.; Perego, M.; Piolti, R.; Trabucchi, M.; Frattola, L. Decreased density of benzodiazepine receptors in lymphocytes of anxious patients: reversal after chronic diazepam treatment. Acta Psychiatr. Scand, 1990, 82, 169-173.
40. Rocca, P.; Ferrero, P.; Gualerzi, A.; Zanalda, E.; Maina, G.; Ber-gamasco, B.; Ravizza, L. Peripheral-type benzodiazepine receptors in anxiety disorders. Acta Psychiatr. Scand, 1991, 84, 537-544.
41. Rocca, P.; Beoni, A.M.; Eva, C.; Ferrero, P.; Zanalda, E.; Ravizza, L. Peripheral benzodiazepine receptor messenger RNA is decreased in lymphocytes of generalized anxiety disorder patients. Biol. Psychiatry, 1998, 43, 767-773.
42. Johnson, M. R.; Marazziti, D.; Brawman-Mintzer, O.; Emmanuel, N. P.; Ware, M. R.; Morton, W. A.; Rossi, A.; Cassano, G. B.; Lydiard, R. B. Abnormal peripheral benzodiazepine receptor density associated with generalized social phobia. Biol. Psychiatry, 1998, 43, 306-309.
43. Gavish, M.; Laor, N.; Bidder, M.; Fisher, D.; Fonia, O.; Muller, U.; Reiss, A.; Wolmer, L.; Karp, L.; Weizman, R. Altered platelet peripheral-type benzodiazepine receptor in posttraumatic stress disorder. Neuropsychopharmacology, 1996, 14, 181-186.
44. Marazziti, D.; Rotondo, A.; Martini, C.; Giannaccini, G.; Lucac-chini, A.; Pancioli-Guadagnucci, M. L.; Diamond, B. I.; Borison, R.; Cassano, G. B. Changes in peripheral benzodiazepine receptors in patients with panic disorder and obsessive-compulsive disorder. Neuropsychobiology, 1994, 29, 8-11.
45. Rocca, P.; Beoni, A. M.; Eva, C.; Ferrero, P.; Maina, G.; Bogetto, F.; Ravizza, L. Lymphocyte peripheral benzodiazepine receptor mRNA decreases in obsessive-compulsive disorder. Eur. Neuro-psychopharmacology, 2000, 10, 337-340.
46. Soreni, N.; Apter, A.; Weizman, A.; Don-Tufeled, O.; Leschiner, S.; Karp, L.; Gavish, M. Decreased platelet peripheral-type benzo-diazepine receptors in adolescent inpatients with repeated suicide attempts. Biol. Psychiatry, 1999, 46, 484-488
47. Marazziti, D.; Dell'Osso, B.; Baroni, S.; Masala, I.; Di Nasso, E.; Giannaccini, G.; Conti, L. Decreased density of peripheral benzo-diazepine receptors in psychiatric patients after a suicide attempt. Life Sci., 2005, 77, 3268-3275.
48. Dell'Osso, L.; Da Pozzo, E.; Carmassi, C.; Trincavelli, M. L.; Ciapparelli, A.; Martini, C. Lifetime manic-hypomanic symptoms in post-traumatic stress disorder: relationship with the 18 kDa mi-tochondrial translocator protein density. Psychiatry Res., 2010, 15,139-143.
49. Pini, S.; Martini, C.; Abelli, M.; Muti, M.; Gesi, C.; Montali, M.; Chelli, B.; Lucacchini, A.; Cassano, G. B. Peripheral-type benzodi-azepine receptor binding sites in platelets of patients with panic disorder associated to separation anxiety symptoms. Psychopharmacology, 2005, 181, 407-411.
50. Chelli, B.; Pini, S.; Abelli, M.; Cardini, A.; Lari, L.; Muti M.; Gesi, C.; Cassano, G. B.; Lucacchini, A.; Martini, C. Platelet 18kDa translocator protein density is reduced in depressed patients with adult separation anxiety. Eur. Neuropsychopharmacol., 2008, 18, 249-254.
51. Nakamura, K.; Fukunishi, I.; Nakamoto, Y.; Iwahashi, K.; Yoshii, M. Peripheral-type benzodiazepine receptors on platelets are correlated with the degrees of anxiety in normal human subjects. Psychopharmacology. 2002, 162, 301-303.
52. Doorduin, J.; de Vries, E. F.; Dierckx, R. A.; Klein, H. C. PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders. Curr. Pharm. Des., 2008, 14, 3297-3315.
53. Venneti, S.; Lopresti, B. J.; Wiley, C. A. The peripheral benzodiazepine receptor (translocator protein 18 kDa) in microglia: from pathology to imaging. Prog. Neurobiol., 2006, 80, 308-322.
54. Kozikowski, A. P.; Kotoula, M.; Ma, D.; Boujrad, N.; Tückmantel, W.; Papadopoulos, V. Synthesis and biology of a 7-nitro-2,1,3-benzoxadiazol-4-yl derivative of 2-phenylindole-3-acetamide: a fluorescent probe for the peripheral-type benzodiazepine receptor. J. Med. Chem., 1997, 40, 2435-2439.
55. Laquintana, V.; Denora, N.; Lopedota, A.; Suzuki, H.; Sawada, M.; Serra, M.; Biggio, G.; Latrofa, A.; Trapani, G.; Liso, G. N-Benzyl-2-(6,8-dichloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N-(6-(7-nitrobenzo[c][1,2,5]oxadiazol-4-ylamino)hexyl)acetamide as a New fluorescent probe for peripheral benzodiazepine receptor and microglial cell visualization. Bioconjug. Chem., 2007, 18, 1397-1407.
56. Taliani, S.; Simorini, F.; Sergianni, V.; La Motta, C.; Da Settimo, F.; Cosimelli, B.; Abignente, E.; Greco, G.; Novellino, E.; Rossi, L.; Gremigni, V.; Spinetti, F.; Chelli, B.; Martini, C. New fluorescent 2-phenylindolglyoxylamide derivatives as probes targeting the peripheral-type benzodiazepine receptor: design, synthesis, and biological evaluation. J. Med. Chem., 2007, 50, 404-407.
57. Taliani S.; Da Pozzo, E.; Bellandi, M.; Bendinelli, S.; Pugliesi, I.; Simorini, F.; La Motta, C.; Salerno, S.; Marini, A. M.; Da Settimo, F.; Cosimelli, B.; Greco, G.; Novellino, E.; Martini, C. Novel irreversible fluorescent probes targeting the 18 kDa translocator protein: synthesis and biological characterization. J. Med. Chem., 2010, 53, 4085-4093.
58. 11C]methylated quinoline-2-carboxamides as potential radioligands for visualization of peripheral benzodiazepine receptors. J. Med. Chem., 2001, 44, 579-585.
59. 11C]methyl-labeled phenoxyphenyl acetamide derivatives as positron emission tomography ligands for the peripheral benzodiazepine receptor: radiosynthesis, uptake, and in vivo binding in brain. J. Med. Chem., 2006, 49, 2735-2742.
60. 131)I]iodo-5-methoxybenzyl)acetamide: A potent iodinated radioligand for the peripheral-type benzodiazepine receptor in brain. J. Med. Chem., 2007, 50, 848-855.
61. 18F]pyrazolo[1,5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography. J. Med. Chem., 2008, 51, 3700-3712.
62. 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors In vivo. J. Med. Chem., 2008, 51, 17-30.
63. Dollé, F.; Luus, C.; Reynolds, A.; Kassiou, M. Radiolabelled molecules for imaging the translocator protein (18kDa) using positron emission tomography. Curr. Med. Chem., 2009, 16, 2899-2923.
64. 18F-labeled ligand for imaging brain peripheral benzodiazepine receptors with pet. J. Med. Chem., 2009, 52, 688-699.
65. 3H]PK 11195, by thermodynamic studies. Life Sci., 1983, 33, 449-457.
66. Mizoule, J.; Gauthier, A.; Uzan, A.; Renault, C.; Dubroeucq, M.C.; Guérémy, C.; Le Fur, G. Opposite effects of two ligands for peripheral type benzodiazepine binding sites, PK 11195 and Ro 5-4864, in a conflict situation in the rat. Life Sci., 1985, 36, 1059-1068.
67. Cappelli, A.; Anzini, M.; Vomero, S.; De Benedetti, P. G.; Menziani, M. C.; Giorgi, G.; Manzoni, C. Mapping the peripheral benzodiazepine receptor binding site by conformationally restrained derivatives of 1-(2-Chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195). J. Med. Chem., 1997, 40, 2910-2921.
68. Cappelli, A.; Mohr, P. G.; Gallelli, A.; Giuliani, G.; Anzini, M.; Vomero, S.; Fresta, M.; Porcu, P.; Maciocco, E.; Concas, A.; Big-gio, G.; Donati, A. Structure-activity relationship in carboxamide derivatives based on the targeted delivery of radionuclides and boron atoms by means of peripheral benzodiazepine receptor ligands. J. Med. Chem., 2003, 46, 3568-3571.
69. Anzini, M.; Cappelli, A.; Vomero, S.; Seeber, M.; Menziani, M. C.; Langer, T.; Hagen, B.; Manzoni, C.; Bourguignon, J. J. Mapping and fitting the peripheral benzodiazepine receptor binding site by carboxamide derivatives. comparison of different approaches to quantitative ligand-receptor interaction modeling. J. Med. Chem., 2001, 44, 1134-1150
70. Fiorini, I.; Nacci, V.; Ciani, S. M.; Garofalo, A.; Campiani, G.; Savini, L.; Novellino, E.; Greco, G.; Bernasconi, P.; Mennini, T. Novel ligands specific for mitochondrial benzodiazepine receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives. Synthesis, structure-activity relationships, and molecular modelling studies. J. Med. Chem., 1994, 37, 1427-1438.
71. Greco, G.; Novellino, E.; Fiorini, I.; Nacci, V.; Campiani, G.; Ciani, S. M.; Garofalo, A.; Bernasconi, P.; Mennini, T.A. Comparative molecular field analysis model for 6-arylpyrrolo[2,1-d][1,5]benzothiazepines binding selectively to the mitochondrial benzodiazepine receptor. J. Med. Chem., 1994, 37, 4100-4108.
72. Campiani, G.; Nacci, V.; Fiorini, I.; De Filippis, M. P.; Garofalo, A.; Ciani, S. M.; Greco, G.; Novellino, E.; Manzoni, C.; Mennini, T. New pyrrolobenzothiazepine derivatives as molecular probes of the peripheral-type benzodiazepine receptor (PBR) binding site. Eur. J. Med. Chem., 1997, 32, 241-252.
73. Campiani, G.; Nacci, V.; Fiorini, I.; De Filippis, M. P.; Garofalo, A.; Ciani, S. M.; Greco, G.; Novellino, E.; Williams, D. C., Zis-terer, D. M.; Woods, M. J.; Mihai, C.; Manzoni, C.; Mennini, T. Synthesis, biological activity, and sars of pyrrolobenzoxazepine derivatives, a new class of specific peripheral-type benzodiazepine receptor ligands. J. Med. Chem., 1996, 39, 3435-3450.
74. Campiani, G.; Ramunno, A.; Fiorini, I.; Nacci, V.; Morelli, E.; Novellino, E.; Goegan, M.; Mennini, T.; Sullivan, S.; Zisterer, D. M.; Williams, C. D. Synthesis of new molecular probes for investigation of steroid biosynthesis induced by selective interaction with peripheral type benzodiazepine receptors (PBR). J. Med. Chem., 2002, 45, 4276-4281.
75. Okubo, T.; Yoshikawa, R.; Chaki S.; Okuyama S.; Nakazato A. Design, synthesis and structure-activity relationships of ary-loxyanilide derivatives as novel peripheral benzodiazepine receptor ligands. Bioorg. Med. Chem., 2004, 12, 423-438.
76. Okuyama, S.; Chaki, S.; Yoshikawa, R.; Ogawa, S.-I.; Suzuki, Y.; Okubo, T.; Nakazato, A.; Nagamine, M.; Tomisawa, K. Neuro-pharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106. Life Sci., 1999, 64, 1455-1464.
77. Trapani, G.; Franco, M.; Ricciardi, L.; Latrofa, A.; Genchi, G.; Sanna, E.; Tuveri, F.; Cagetti, E.; Biggio, G.; Liso, G. Synthesis and binding affinity of 2-Phenylimidazo[1,2-a]pyridine derivatives for both central and peripheral benzodiazepine receptors. a new series of high-affinity and selective ligands for the peripheral type. J. Med. Chem., 1997, 40, 3109-3118.
78. Trapani, G.; Franco, M; Latrofa, A.; Ricciardi, L.; Carotti, A.; Serra, M.; Sanna, E.; Biggio, G.; Liso, G. Novel 2-phenylimidazo[1,2-a]pyridine derivatives as potent and selective ligands for peripheral benzodiazepine receptors. Synthesis, binding affinity, and in vivo studies. J. Med. Chem., 1999, 42, 3934-3941.
79. Trapani, G.; Laquintana, V.; Denora, N.; Trapani, A.; Lopedota, A.; Latrofa, A.; Franco, M; Serra, M.; Pisu, M.G.; Floris, I.; Sanna, E.; Biggio, G.; Liso, G. Structure-activity relationship and effects on neuroactive steroid synthesis in a series of 2-phenylimidazo[1,2-a]pyridineacetamide peripheral benzodiazepine receptors ligands. J. Med. Chem., 2005, 48, 292-305.
80. Denora, N.; Laquintana, V.; Pisu, M. G.; Dore, R.; Murru, L.; Tra-pani, G.; Latrofa, A.; Trapani, A.; Sanna, E. 2-phenylimidazo[1,2-a]pyridine compounds containing hydrophilic groups as potent and selective ligands for peripheral benzodiazepine receptors: synthesis, binding affinity and electtrophysiological studies. J. Med. Chem., 2008, 51, 6876-6888.
81. 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.
82. 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 DBI receptor (MDR). J. Pharmacol. Exp. Ther., 1992, 262, 971-978.
83. Primofiore, G.; Da Settimo, F.; Taliani, S.; Simorini, F.; Patrizi, M. P.; Novellino, E.; Greco, G.; Abignente, E.; Costa, B.; Chelli, B.; Martini, C. N,N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodi-azepine receptor. J. Med. Chem., 2004, 47, 1852-1855.
84. Da Settimo, F.; Simorini, F.; Taliani, S.; La Motta, C.; Marini, A. M.; Salerno, S.; Bellandi, M.; Novellino, E.; Greco, G.; Cosimelli, B.; Da Pozzo, E.; Simola, N.; Morelli, M.; Martini, C. Anxiolytic-like effects of N,N-Dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis. J. Med. Chem., 2008, 51, 5798-5806.
85. Selleri, S.; Bruni, F.; Costagli, C.; Costanzo, A.; Guerrini, G.; Ciciani, G.; Costa, B.; Martini, C. 2-Arylpyrazolo[1,5-a]pyrimidin-3-ylacetamides. New potent and selective peripheral benzodi-azepine receptor ligands. Bioorg. Med. Chem., 2001, 9, 2661-2671.
86. Selleri, S.; Gratteri, P.; Costagli, C.; Bonaccini, C.; Costanzo, A.; Melani, F.; Guerrini, G.; Ciciani, G.; Costa, B.; Spinetti, F.; Martini, C.; Bruni, F. Insight into 2-phenylpyrazolo[1,5-a]pyrimidin-3-ylacetamides as peripheral benzodiazepine receptor ligands: synthesis, biological evaluation and 3D-QSAR investigation. Bioorg. Med. Chem., 2005, 13, 4821-4834.
87. Da Settimo, F.; Taliani, S.; Trincavelli, M. L.; Montali, M.; Martini, C. GABAA/Bz receptor subtypes as targets for selective drugs. Curr. Med. Chem., 2007, 14, 2680-2701.
88. 3H]Ro 5-4864. Mol. Pharmacol., 1982, 22, 26-32.
89. Gavioli, E. C.; Duarte, F. S.; Bressan, E.; Ferrara, P.; Farges, R. C.; Monteiro De Lima, T. C. Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor ligand, in forced swimming test. Eur. J. Pharmacol., 2003, 471, 21-26.
90. Porsolt, R. D.; Bertin, A.; Jalfre, M. Behavioral despair in mice: a primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther., 1977, 229, 327-336.
91. Porsolt, R. D.; Le Pichon, M.; Jalfre, M. Depression: a new animal model sensitive to antidepressant treatments. Nature, 1977, 266, 730-732.
92. Porsolt, R. D.; Anton, G.; Blavet, N.; Maurice, J. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 1978, 47, 379-391.
93. Mizoule, J.; Gauthier, A.; Uzan, A.; Renault, C.; Dubroeucq, M. C.; Guérémy, C.; Le Fur, G. Opposite effects of two ligands for peripheral type benzodiazepine binding sites, PK 11195 and Ro 5-4864, in a conflict situation in the rat. Life Sci., 1985, 36, 1059-1068.
94. Nacci, V.; Fiorini, I.; Garofalo, A.; Cagnotto, A. Research on compound with psychotropic activity. IX. Synthesis of 6-p-methoxyphenylpyrrolo[2,1-d][1,5]benzothiazepines and evaluation of their affinity at BDZ and GABA receptor subtypes. Farmaco, 1990, 45, 545-557.
95. Dalpiaz, A.; Bartolasi, V.; Borea, P. A.; Nacci, V.; Fiorini, I.; Campiani, G.; Mennini, T.; Manzoni, C.; Novellino, E.; Greco, G. A concerted study using binding measurements, X-ray structural data, and molecular modeling on the stereochemical features responsible for the affinity of 6-arylpyrrolo[2,1-d][1,5] benzothi-azepine toward mitochondrial benzodiazepine receptors. J. Med. Chem., 1995, 38, 4730-4738.
96. Diaz-Arauzo, H.; Evoniuk, G. E.; Skolnick, P.; Cook, J. M. The agonist pharmacophore of the benzodiazepine receptor. Synthesis of a selective anticonvulsant/anxiolytic. J. Med. Chem., 1991, 34, 1754-1756.
97. Campiani, G.; Fiorini, I.; De Filippis, M. P.; Ciani, S. M.; Garofalo, A.; Nacci, V.; Giorgi, G.; Sega, A.; Botta, M.; Chiarini, A.; Bu-driesi, R.; Bruni, G.; Romeo, M. R.; Manzoni, C.; Mennini, T. Cardiovascular Characterization of Pyrrolo[2,1-d][1,5] benzothi-azepine derivatives binding selectively to the peripheral-type ben-zodiazepine receptor (PBR): From dual PBR affinity and calcium antagonist activity to novel and selective calcium entry blockers. J. Med. Chem., 1996, 39, 2922-2938.
98. 3H]DAA 1106, a novel and selective ligand for peripheral benzodiazepine receptors. Eur. J. Pharmacol., 1999, 371, 197-204.
99. Culty, M.; Silver, P.; Nakazato, A.; Gazouli, M.; Li, H.; Mu-ramatsu, M.; Okuyama, S.; Papadopoulos, V. Peripheral benzodi-azepine receptor binding properties and effects on steroid synthesis of two new phenoxyphenyl-acetamides derivatives, DAA1097 and DAA1106. Drug Develop. Res., 2001, 52, 475-484.
100. 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
101. Belloli, S.; Moresco, R. M.; Matarrese, M.; Biella, G.; Sanvito, F.; Simonelli, P.; Turolla, E.; Olivieri, S.; Cappelli, A.; Vomero, S.; Galli-Kienle, M.; Fazio, F. Evaluation of three quinoline carboxamide derivatives as potential radioligands for the in vivo pet imaging of neurodegeneration. Neurochem. Int., 2004, 44, 433-440.
102. Hawthorne, M. F.; Maderna, A. Applications of radiolabelled boron clusters to the diagnosis and treatment of cancer. Chem. Rev., 1999, 99, 3421-3434.
103. Valliant, J. F.; Morel, P.; Schaffer, P.; Kaldis, J. H. Carboranes as Ligands for the Preparation of Organometallic Tc and Re Radiopharmaceuticals. Synthesis of [M(CO)3(n5-2,3-C2B9H11)]- and rac-[M(CO)3(n5-2-R-2,3-C2B9H10)]-(M)Re,99Tc;R)CH2-CH2CO2H) from [M(CO)3Br3]2-. Inorg. Chem.,2002, 41, 628-630.
104. Langer, S. Z.; Arbilla, S.; Benavides, J.; Scatton, B. Zolpidem and alpidem: two imidazopyridines with selectivity for omega 1- and omega 3-receptor subtypes. Adv. Biochem. Psychopharmacol, 1990, 46, 61-72.
105. Bourguignon, J. J. Endogenous and synthetic ligands of mitochondrial benzodiazepine receptors: structure-affinity relationships. In Peripheral benzodiazepine receptors; Giesen-Crouse, E.; Ed.; Academic Press: London, 1993; pp. 59-85.
106. Lentini, G.; Bourguignon, J. J.; Wermuth, C. G. Ligands of the peripheral-type benzodiazepine bindimg site (PBS): structure-activity relationships and computer-aided conformational analysis. In QASAR: Rational Approaches to the Design of Bioactive Compounds; Silipo, C; Vittoria, A.; Elsevier Science Publishers B.V.: Amsterdam, 1991; pp 257-260.
107. 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
108. Serra, M.; Madau, P.; Chessa, M. F.; Caddeo, M.; Sanna, E.; Tra-pani, G.; Franco, M.; Liso, G.; Purdy, R. H.; Barbaccia, M. L.; Biggio, G. 2-phenylimidazo[1,2-a]pyridine derivatives as ligands for peripheral benzodiazepine receptors: stimulation of neuroster-oid synthesis and anticonflict action in rats. Br. J. Pharmacol, 1999, 127, 177-187.
109. Cinone, N.; Hötje, H. D.; Carotti, A. Development of a unique 3D interaction model of endogenous and synthetic peripheral benzodiazepine receptor ligands. J. Comput. Aided Mol. Des., 2000, 14, 753-768.
110. Anzini, M.; Cappelli, A.; Vomero, S.; Giorgi, G.; Langer, T.; Bruni, G.; Romeo, M. R.; Basile, A. S. Molecular Basis of peripheral vs central benzodiazepine receptor selectivity in a new class of peripheral benzodiazepine receptor ligands related to alpidem. J. Med. Chem., 1996, 39, 4275-4284.
111. Cappelli, A.; Giuliani, G.; Valenti, S.; Anzini, M.; Vomero, S.; Giorgi, G.; Sogliano, C.; Maciocco, E.; Biggio, G.; Concas, A. Synthesis and structure-activity relationship studies in peripheral benzodiazepine receptor ligands related to alpidem. Bioorg. Med. Chem., 2008, 16, 3428-3437.
112. Auta J.; Romeo, E.; Kozikowski, A.; Ma, D.; Costa, E.; Guidotti, A. Participation of mitochondrial diazepam binding inhibitor receptors in the anticonflict, antineophobic and anticonvulsant action of 2-aryl-3-indoleacetamide and imidazopyridine derivatives. J. Pharmacol. Exp. Ther., 1993, 265, 649-656.
113. Romeo, E.; Cavallaro, S.; Korneyev, A.; Kozikowski, A. P.; Ma, D.; Polo, A.; Costa, E.; Guidotti, A. Stimulation of brain steroi-dogenesis by 2-aryl-indole-3-acetamide derivatives acting at the mitochondrial diazepam-binding inhibitor receptor complex. J. Pharmacol. Exp. Ther. 1993, 267, 462-471.
114. Liao, Y.; Kozikowski, A. P.; Guidotti, A.; Costa, E. Synthesis and pharmacological evaluation of benzofuran-acetamides as "antineo-phobic" mitochondrial DBI receptor complex ligands. Bioorg. Med. Chem., 1998, 8, 2099-2102.
115. Okubo, T.; Yoshikawa, R.; Chaki, S.; Okuyama, S.; Nakazato, A. Design, synthesis, and structure-activity relationships of novel tet-racyclic compounds as peripheral benzodiazepine receptor ligands. Bioorg. Med. Chem., 2004, 12, 3569-3580.
116. Da Settimo, A.; Primofiore, G.; Da Settimo, F.; Marini, A. M.; Novellino, E.; Greco, G.; Martini, C.; Giannaccini, G.; Lucacchini, A. Synthesis, structure-activity relationships, and molecular modeling studies of N-(indol-3-ylglyoxylyl)benzylamine derivatives acting at the benzodiazepine receptor. J. Med. Chem., 1996, 39, 5083-5091.