Synthesis and preliminary screening of novel indole-3-methanamines as 5-HT4 receptor ligands

European Journal of Medicinal Chemistry

Volumn 44, Issue 7, 2009, Pages 2952-2959

  Hanna Elias, Amir ^a   Manallack, David T ^a   Berque Bestel, Isabelle ^b,c   Irving, Helen R ^a   Coupar, Ian M ^a   Iskander, Magdy N ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITÉ PARIS SACLAY   (France)

^c INSERM U869   (France)

Author keywords

5 HT4 ligands; 5 HT4 receptor model; Indole analogues

Indexed keywords

1 (5 METHOXY 1H INDOL 3 YL) N (PIPERIDIN 4 YLMETHYL)METHANAMINE; 1 (5 METHOXY 1H INDOL 3 YL) N (PYRIDIN 2 YLMETHYL)METHANAMINE; 1 (5 METHOXY 1H INDOL 3 YL) N [(5 METHYLFURAN 2 YL)METHYL]METHANAMINE; 1 (5 METHOXY 1H INDOL 3 YL) N [3 (TRIFLUOROMETHYL)BENZYL]METHANAMINE; 1 (5 METHOXY 1H INDOL 3 YL) N [4 (TRIFLUOROMETHOXY)BENZYL]METHANAMINE; 1 (6,6 DIMETHYLBICYCLO[3.1.1]HEPTAN 2 YL) N [(5 METHOXY 1H INDOL 3 YL)METHYL]METHANAMINE; 1 (BENZO[D][1,3]DIOXOL 4 YL) N [(5 METHOXY 1H INDOL 3 YL)METHYL]METHANAMINE; 1 ADAMANTYL N [(5 METHOXY 1H INDOL 3 YL)METHYL]METHANAMINE; 2 METHOXY 4 [[[(5 METHOXY 1H INDOL 3 YL)METHYL]AMINO]METHYL]PHENOL; 3 (1H IMIDAZOL 1 YL) N [(5 METHOXY 1H INDOL 3 YL)METHYL]PROPAN 1 AMINE; 4 [2 [[(5 METHOXY 1H INDOL 3 YL)METHYL]AMINO]ETHYL]BENZENESULFONAMIDE; 4 [2 [[(5 METHOXY 1H INDOL 3 YL)METHYL]AMINO]ETHYL]PHENOL; 5 METHOXYTRYPTAMINE; INDOLE 3 METHANAMINE DERIVATIVE; METHYLAMINE; N BENZYL 1 (5 METHOXY 1H INDOL 3 YL)METHANAMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL] 2 (PIPERAZIN 1 YL)ETHANAMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL] 2 (PYRROLIDIN 1 YL)ETHANAMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL] 2 MORPHOLINOETHANAMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL] 2 PHENOXYETHANAMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL] 3 (PYRROLIDIN 1 YL)PROPAN 1 AMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL] 4 METHYLPIPERAZIN 1 AMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL]BICYCLO[2.2.1]HEPTAN 2 AMINE; N [(5 METHOXY 1H INDOL 3 YL)METHYL]MORPHOLIN 4 AMINE; N1 [(5 METHOXY 1H INDOL 3 YL)METHYL] N2 (5 NITROPYRIDIN 2 YL)ETHANE 1,2 DIAMINE; SEROTONIN 4 RECEPTOR; SEROTONIN AGONIST; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; STRUCTURE ACTIVITY RELATION;

EID: 67349131127     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2009.01.015     Document Type: Article

References (28)

1. 4 receptor ligands: applications and new prospects. Journal of Medicinal Chemistry 45 3 (2003) 1-26
2. 7 receptor splice variants: are they important?. Current Neuropharmacology 5 4 (2007) 224-231
3. Testa R., Guarneri L., Angelico P., Velasco C., Poggesi E., Cimlia A., and Leonardi A. Effect of different 5-hydroxytryptamine receptor subtype antagonists on the micturition reflex in rats. BJU International 87 3 (2001) 256-264
4. Ruth M., Hamelin B., Rohss K., and Lundell L. The effect of mosapride, a novel prokinetic, on acid reflux variables in patients with gastro-esophageal reflux disease. Alimentary Pharmacology and Therapeutics 12 1 (1998) 35-40
5. Camilleri M., and Choi M.G. Review article: irritable bowel syndrome. Alimentary Pharmacology and Therapeutics 11 1 (1997) 3-15
6. 4 agonist, prokinetic treatment of irritable bowel syndrome. Drugs of the Future 24 1 (1999) 38-44
7. Maxton D.G., Morris J., and Whorwell P.J. Selective 5-hydroxytryptamine antagonism: a role in irritable bowel syndrome and functional dyspepsia?. Alimentary Pharmacology and Therapeutics 10 4 (1996) 595-599
8. De Ponti F., Poluzzi E., and Montanaro N. Organising evidence on QT prolongation and occurrence of Torsades de Pointes with non-antiarrhythmic drugs: a call for consensus. European Journal of Clinical Pharmacology 57 3 (2001) 185-209
9. De Ponti F., and Tonini M. Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs 61 3 (2001) 317-332
10. FDA. FDA announces discontinued marketing of GI drug, zelnorm, for safety reasons. Available from: (2007). http://www.fda.gov/bbs/topics/NEWS/2007/NEW01597.html
11. 4 agonist activities using molecular field analysis. Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry 2 2 (1999) 153-158
12. 4 agonists using CoMFA and receptor based alignment. European Journal of Medicinal Chemistry 41 1 (2006) 16-26
13. Froldi G., Silvestrin B., Dorigo P., and Caparrotta L. Gramine: a vasorelaxing alkaloid acting on 5-HT(2A) receptors. Planta Medica 70 4 (2004) 373-375
14. Barker E.L., Moore K.R., Rakhshan F., and Blakely R.D. Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. Journal of Neuroscience 19 12 (1999) 4705-4717
15. 6 receptor ligand templates. Bioorganic & Medicinal Chemistry Letters 13 19 (2003) 3355-3359
16. 4 receptor by site-directed mutagenesis and molecular modeling. British Journal of Pharmacology 130 3 (2000) 527-538
17. Rubenstein L.A., and Osman R. The interaction between 5-hydroxytryptamine and tryptophan: a serotonin receptor model. Journal of Molecular Structure (Theochem) 81 3-4 (1991) 321-342
18. C.H. Lin, J.C. Sih, S.P. Tanis, Preparation of indole-3-methanamines useful as antidiabetic, antiobesity and antiatherosclerotic agents. WO 9207829 (1992) pp. 77.
19. Alemany A., Fernandez Alvarez E., and Martinez Lopez J.M. Enzyme inhibitors. XV. Preparation of 3-(propargylaminomethyl)indoles. Bulletin de la Societe Chimique de France (1975) 1223-1227
20. Jorgensen W.L. Glide (2007), Schrodinger, LLC, New York
21. Friesner R.A., Murphy R.B., Repasky M.P., Frye L.L., Greenwood J.R., Halgren T.A., Sanschagrin P.C., and Mainz D.T. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. Journal of Medicinal Chemistry 49 (2006) 6177-6196
22. Maestro (2008), Schrodinger, LLC, New York, NY
23. Rasmussen S.G.F., Choi H.-J., Rosenbaum D.M., Kobilka T.S., Thian F.S., Edwards P.C., Burghammer M., Ratnala V.R.P., Sanishvili R., Fischetti R.F., Schertler G.F.X., Weis W.I., and Kobilka B.K. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450 7168 (2007) 383-387
24. Rosenbaum D.M., Cherezov V., Hanson M.A., Rasmussen S.G.F., Thian F.S., Kobilka T.S., Choi H.-J., Yao X.-J., Weis W.I., Stevens R.C., and Kobilka B.K. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318 5854 (2007) 1266-1273
25. 1-adrenergic G-protein coupled receptor. Nature (London, United Kingdom) (2008)
26. 4 receptors in the human and guinea-pig brain. NeuroReport 4 11 (1993) 1239-1242
27. 4(i). Naunyn-Schmiedeberg's Archives of Pharmacology 369 6 (2004) 616-628
28. ACD/Labs. ACD/pKa DB (2006), Advanced Chemistry Development, Inc., Toronto, Canada