Synthesis and structure-affinity relationships of selective high-affinity 5-HT4 receptor antagonists: Application to the design of new potential single photon emission computed tomography tracers

Journal of Medicinal Chemistry

Volumn 55, Issue 22, 2012, Pages 9693-9707

  Dubost, Emmanuelle ^a   Dumas, Noé ^b   Fossey, Christine ^a   Magnelli, Rosa ^a   Butt Gueulle, Sabrina ^a   Ballandonne, Céline ^a   Caignard, Daniel H ^c   Dulin, Fabienne ^a   Sopkova De Oliveira Santos, Jana ^a   Millet, Philippe ^b   Charnay, Yves ^b   Rault, Sylvain ^a   Cailly, Thomas ^a   Fabis, Frederic ^a  

^a UNIVERSITÉ DE CAEN   (France)

^b GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^c INSTITUT DE RECHERCHES SERVIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLORO 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 2 FLUORO 6 (1 PROPYLPIPERIDIN 4 YL )METHYLOXYPHENANTHRIDINE; 2 METHOXY 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 2 METHYL 6 ( 1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 3 CHLORO 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 3 FLUORO 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 3 METHYL 6 ( 1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 4 C HLORO 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 4 FLUORO 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 4 IODO 6 (1 PROPYLPIPERIDIN 4 YL)METHYLOXYPHENANTHRIDINE; 4 METHOXY 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 4 METHYL 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 5 (1 PROPYLPIPERIDIN 4 YL)METHYLOXYBENZO[C] 2,6 NAPHTHYRIDINE; 5 (1 PROPYLPIPERIDIN 4 YL)METHYLOXYBENZO[H] 1,6 NAPHTHYRIDINE; 6 (1 PROPYLPIPERIDIN 4 YL)METHYLOXYPHENANTHRIDINE; 6 {1 [ 3 (4 IODOPHENYL ) PROPYL] PIPERIDIN 4 YL} METHYLOXYPHENANTHRIDINE; 7 FLUORO 5 (1 PROPYLPIPERIDIN 4 YL)METHYLOXYBENZO[H] 1,6 NAPHTHYRIDINE; 7 FLUORO 5 {1 [3 (4 IODOPHENYL)PROPYL]PIPERIDIN 4 YL} METHYLOXYBENZO[H] 1,6 NAPHTHYRIDINE; 7 FLUORO 6 ( 1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 7 IODO 5 (1 PROPYLPIPERIDIN 4 YL)METHYLOXYBENZO[H] 1,6 NAPHTHYRIDINE; 8 FLUORO 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 8 METHOXY 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 8 NITRO 6 (1 PROPYLPIPERIDIN 4 YL)METHYLOXYPHENANTHRIDINE; 9 FLUORO 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; 9 METHYL 6 (1 PROPYLPIPERIDIN 4 YL) METHYLOXYPHENANTHRIDINE; FLUORINE; PHENANTHRIDINE DERIVATIVE; SEROTONIN ANTAGONIST; TRACER; TRICYCLIC AROMATIC COMPOUND; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; ATOM; DRUG DESIGN; DRUG SYNTHESIS; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ANIMALS; DIOXANES; DRUG DESIGN; HUMANS; IODINE RADIOISOTOPES; LIGANDS; MICE; MOLECULAR PROBES; PIPERIDINES; RADIOLIGAND ASSAY; RADIOPHARMACEUTICALS; RECEPTORS, SEROTONIN, 5-HT4; SEROTONIN 5-HT4 RECEPTOR ANTAGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON;

EID: 84870005809     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300943r     Document Type: Article

References (57)

1. Dumuis, A.; Bouhelal, R.; Sebben, M.; Bockaert, J. A 5-HT receptor in the central nervous system, positively coupled with adenylate cyclase, is antagonized by ICS 205930 Eur. J. Pharmacol. 1988, 146, 187-188
2. Dumuis, A.; Bouhelal, R.; Sebben, M.; Cory, R.; Bockaert, J. A non-classical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system Mol. Pharmacol. 1988, 34, 880-887
3. 4R ligands: State of arts and clinical applications Curr. Top. Med. Chem. 2010, 10, 527-553
4. Lucas, G. Serotonin receptors type 4: A new hope? Curr. Drug Targets 2009, 10, 1085-1095
5. Beattie, D. T.; Smith, J. A. M. Serotonin pharmacology in the gastrointestinal tract: A review Naunyn-Schmiedeberg's Arch. Pharmacol. 2008, 377, 181-203
6. Qvigstad, E.; Brattelid, T.; Sjaastad, I.; Andressen, K. W.; Krobert, K. A.; Birkeland, J. A.; Sejersted, O. M.; Kaumann, A. J.; Skomedal, T.; Osnes, J. B.; Levy, F. O. Appearance of a ventricular 5-HT4 receptor-mediated inotropic response to serotonin in heart failure Cardiovasc. Res. 2005, 65, 869-878
7. 4 receptors TIPS 1995, 16, 391-398
8. Matsumoto, M.; Togashi, H.; Mori, K.; Hueno, K.; Ohashi, S.; Kogima, T.; Yoshioka, M. Evidence for involvement of central 5-HT4 receptors in cholinergic function associated with cognitive processes: Behavioural, electrophysiological, and neurochemical studies J. Pharmacol. Exp. Ther. 2001, 296, 676-682
9. 4 receptor agonists and antagonists in learning Pharmacol., Biochem. Behav. 1997, 56, 347-351
10. 4 receptor and Alzheimer's disease: The amyloid connection Exp. Neurol. 2007, 205, 325-329
11. 4 receptors inhibits secretion of beta-amyloid peptides and increases neuronal survival Exp. Neurol. 2007, 203, 274-278
12. 4 receptors is mediated by increases in CART in the nucleus accumbens Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 16335-16340
13. Lucas, G.; Rymar, W.; Du, J.; Mnie-Filali, O.; Bisgaard, C.; Manta, S.; Lambas-Senas, L.; Wiborg, O.; Haddjeri, N.; Pineyro, G.; Sadikot, A. F.; Debonnel, G. Serotonin(4) (5-HT(4)) receptor agonists putative antidepressant with a rapid onset of action Neuron 2007, 55, 712-725
14. Manabe, N.; Wong, B. S.; Camilleri, M. New generation 5-HT4 receptor agonists: Potential for for treatment of gastrointestinal motility disorders Expert Opin. Invest. Drugs 2010, 19, 765-775
15. Moser, P. C.;, E.; Bergis, O.; Jegham, S.; Lochead, A.; Duconseille, E.; Terranova, J.-P.; Caille, D.; Berque-Bestel, I.; Lezoualc'h, F.; Fischmeister, R.; Dumuis, A.; Bockaert, J.; George, P.; Soubrie, P.; Scatton, B. SL65.0155, a novel 5-hydroxytryptamine4 receptor partial agonist with potent cognition-enhancing properties J. Pharmacol. Exp. Ther. 2002, 302, 731-742
16. Mohler, E. G.; Shacham, S.; Noiman, S.; Lezoualc'h, F.; Robert, S.; Gastineau, M.; Rutkowski, J.; Marantz, Y.; Dumuis, A.; Bockaert, J.; Gold, P. E.; Ragozzino, M. E. VRX-03011, a novel 5-HT4 agonist, enhances memory and hippocampal acetylcholine efflux Neuropharmacology 2007, 53, 563-573
17. Wong, D. F.; Gründer, G.; Brasić, J. R. Brain imaging research: Does the science serve clinical practice? Int. Rev. Psychiatry 2007, 19, 541-558
18. Gibson, R. E.; Burns, H. D.; Hamill, T. G.; Eng, W. S.; Francis, B. E.; Ryan, C. Non-invasive radiotracer imaging as a tool for drug development Curr. Radiopharm. Des. 2000, 6, 973-989
19. Pike, V. W.; Halldin, C.; Nobuhara, K.; Hiltunen, J.; Mulligan, R. S.; Swahn, C.-G.; Karlsson, P.; Olsson, H.; Hume, S. P.; Hirani, E.; Whalley, J.; Pilowsky, L. S.; Larson, S.; Schnell, P.-O.; Ell, P. J.; Farde, L. Radioiodinated SB 207710 as a radioligand in vivo: Imaging of brain 5-HT4 receptors with SPET Eur. J. Nucl. Med. Mol. Imaging 2003, 30, 1520-1528
20. 4 receptor radioligand for PET imaging in man Curr. Radiopharm. 2008, 1, 110-114
21. Kornum, B. R.; Lind, N. M.; Gillings, N.; Marner, L.; Andersen, F.; Knudsen, G. M. J. Cereb. Blood Flow Metab. 2009, 29, 186-196
22. Madsen, K.; Haahr, M. T.; Marner, L.; Keller, S. H.; Baaré, W. F.; Svarer, C.; Hasselbalch, S. G.; Knudsen, G. M. Age and sex effects on 5-HT(4) receptors in the human brain: A [(11)C]SB207145 PET study J. Cereb. Blood Flow Metab. 2011, 31, 1475-1481
23. Marner, L.; Gillings, N.; Madsen, K.; Erritzoe, D.; Baaré, W. F.; Svarer, C.; Hasselbalch, S. G.; Knudsen, G. M. Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET Neuroimage 2010, 50, 855-861
24. 4 receptor ligands as prospective imaging probes for positron emission tomography J. Med. Chem. 2010, 53, 7035-7047
25. 4 receptors: Binding profile and pharmacological characterization J. Med. Chem. 2003, 46, 138-147
26. Lemaitre, S.; Lepailleur, A.; Bureau, R.; Butt-Gueulle, S.; Lelong-Boulouard, V.; Duchatelle, P.; Boulouard, M.; Dumuis, A.; Daveu, C.; Lezoualc'h, F.; Pfeiffer, B.; Dauphin, F.; Rault, S. Novel antagonists of serotonin-4 receptors: Synthesis and biological evaluation of pyrrolothienopyrazines Bioorg. Med. Chem. 2009, 17, 2607-2622
27. Dubost, E.; Magnelli, R.; Cailly, T.; Legay, R.; Fabis, F.; Rault, S. General method for the synthesis of substituted phenanthridin-6(5 H)-ones using a KOH-mediated anionic ring closure as the key step Tetrahedron 2010, 66, 5008-5016
28. Donohue, S. R.; Varnäs, K.; Jia, Z.; Gulyás, B.; Pike, V. W.; Halldin, C. Synthesis and in vitro autoradiographic evaluation of a novel high affinity radioiodinated ligand for imaging brain cannabinoid subtype-1 receptors Bioorg. Med. Chem. Lett. 2009, 19, 6209-6212
29. 4 receptors by GR 113808 Br. J. Pharmacol. 1993, 110, 1172-1174
30. 4 receptors by SB 207710, a selective and high affinity 5-HT4 receptor antagonist Naunyn-Schmiedeberg's Arch. Pharmacol. 1994, 349, 546-548
31. Kenakin, T. Efficacy as a vector: The relative prevalence and paucity of inverse agonism Mol. Pharmacol. 2004, 66, 2-11
32. Cherezov, V.; Rosenbaum, D. M.; Hanson, M. A.; Rasmussen, S. G.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Kuhn, P.; Weis, W. I.; Kobilka, B. K.; Stevens, R. C. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor Science 2007, 318, 1258-1265
33. Rosenbaum, D. M.; Cherezov, V.; Hanson, M. A.; Rasmussen, S. G.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Yao, X. J.; Weis, W. I.; Stevens, R. C.; Kobilka, B. K. GPCR Engineering yields high-resolution structural insights into β2 adrenergic receptor function Science 2007, 318, 1266-1273
34. Moukhametzianov, R.; Warne, T.; Edwards, P. C.; Serrano-Vega, M. J.; Leslie, A. G.; Tate, C. G.; Schertler, G. F. Two distinct conformations of helix 6 observed in antagonist-bound structures of a beta1-adrenergic receptor Proc. Natl, Acad. Sci. U. S. A. 2011, 108, 8228-8232
35. Rivail, L.; Giner, M.; Gastineau, M.; Berthouze, M.; Soulier, J.-L.; Fischmeister, R.; Lezoualc'h, F.; Maigret, B.; Sicsic, S.; Berque-Bestel, I. New insights into the human 5-HT4 receptor binding site: Exploration of a hydrophobic pocket Br. J. Pharmacol. 2004, 143, 361-370
36. 1-adrenergic receptor Nature 2011, 469, 241-244
37. Wu, H.; Wacker, D.; Katritch, V.; Mileni, M.; Han, G. W.; Vardy, E.; Liu, W.; Thompson, A. A.; Huang, X. P.; Carroll, F. I.; Mascarella, S. W.; Westkaemper, R. B.; Mosier, P. D.; Roth, B. L.; Cherezov, V.; Stevens, R. C. Structure of the human κ-opioid receptor in complex with JDTic Nature 2012, 485, 327-332
38. Waterhouse, R. N. Determination of lipophilicity and its use as a predictor of blood brain barrier penetration of molecular imaging agents Mol. Imaging Biol. 2005, 5, 376-389
39. Bedjeguelal, K.; Rabot, R.; Kaloun El, B.; Mayer, P.; Marchand, A.; Rahier, N.; Schambel, P.; Bienayme, H. Pyrazolopyridine derivatives as anticancer agent. PCT Int. Appl. WO 2011045344 (A1), 2011.
40. Kristensen, J. L.; Vedsø, V.; Begtrup, M. Synthesis of pentacyclic 13-azadibenzo[ a, de ]anthracenes via anionic cascade ring closure J. Org. Chem. 2003, 68, 4091-4092
41. Heiss, C.; Marzi, E.; Mongin, F.; Schlosser, M. Remote trimethylsilyl groups interfering with the ortho deprotonation of fluoroarenes and chloroarenes Eur. J. Org. Chem. 2007, 669-675
42. Kawaksaki, M.; Goto, M.; Kawabata, S.; Kometani, T. The effect of vinyl esters on the enantioselectivity of the lipase-catalysed transesterification of alcohols Tetrahedron: Asymmetry 2001, 12, 585-596
43. 4 receptors in guinea pig and rat brain Br. J. Pharmacol. 1993, 109, 618-624
44. 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
45. 2 ligandsfor probing signal transduction pathways essential for antipsychotic efficacy Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 18488-18493
46. Jain, E.; Bairoch, A.; Duvaud, S.; Phan, I.; Redaschi, N.; Suzek, B. E.; Martin, M. J.; McGarvey, P.; Gasteiger, E. Infrastructure for the life sciences: Design and implementation of the UniProt website BMC Bioinf. 2009, 10, 136-155
47. Shi, J.; Blundell, T. L.; Mizuguchi, K. FUGUE: Sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties J. Mol. Biol. 2001, 310, 243-257
48. Zhou, H.; Zhou, Y. Fold recognition by combining sequence profiles derived from evolution and from depth-dependent structural alignment of fragments Proteins 2005, 58, 321-328
49. Altschul, S. F.; Madden, T. L.; Schäffer, A. A.; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D. J. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs Nucleic Acids Res. 1997, 25, 3389-3402
50. Schäffer, A. A.; Aravind, L.; Madden, T. L.; Shavirin, S.; Spouge, J. L.; Wolf, Y. I.; Koonin, E. V.; Altschul, S. F. Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements Nucleic Acids Res. 2001, 29, 2994-3005
51. Soding, J. Protein homology detection by HMM-HMM comparison Bioinformatics 2005, 21, 951-960
52. Pons, J. L.; Labesse, G. @TOME-2: A new pipeline for comparative modeling of protein-ligand complexes. Nucleic Acids Res., 2009, 37, Web Server issue W485-W491.
53. Eswar, N.; Eramian, D.; Webb, B.; Shen, M.; Sali, A. Protein structure modeling with MODELLER Methods Mol. Biol. 2008, 426, 145-159
54. Eisenberg, D.; Lüthy, R.; Bowie, J. U. VERIFY3D: Assessment of protein models with three-dimensional profiles Methods Enzymol. 1997, 277, 396-404
55. Gracy, J.; Chiche, L.; Sallantin, J. Improved alignment of weakly homologous protein sequences using structural information Protein Eng. 1993, 6, 821-829
56. Jones, G.; Willett, P.; Glen, R. C. Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation J. Mol. Biol. 1995, 245, 43-53
57. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 1997, 267, 727-748