Conformationally restricted homotryptamines. 2. Indole cyclopropylmethylamines as selective serotonin reuptake inhibitors

Journal of Medicinal Chemistry

Volumn 48, Issue 19, 2005, Pages 6023-6034

  Mattson, Ronald J ^a   Catt, John D ^a   Denhart, Derek J ^a   Deskus, Jeffrey A ^a   Ditta, Jonathan L ^a   Higgins, Mendi A ^a   Marcin, Lawrence R ^a   Sloan, Charles P ^a   Beno, Brett R ^a   Gao, Qi ^a   Cunningham, Melissa A ^a   Mattson, Gail K ^a   Molski, Thaddeus F ^a   Taber, Matthew T ^a   Lodge, Nicholas J ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (5 CYANO 1H INDOL 3 YL) 1 (N,N DIMETHYLAMINOMETHYL)CYCLOPROPANE; 2 (5 FLUORO 1H INDOL 3 YL) 1 (N,N DIMETHYLAMINOMETHYL)CYCLOPROPANE; 2 [5 FLUORO 1 (4 TOLUENESULFONYL) 1H INDOL 3 YL] 1 (N,N DIMETHYLAMINOMETHYL)CYCLOPROPANE; 5 CYANO 3 [2 (DIMETHYLAMINOMETHYL)CYCLOPROPYL]INDOLE; CITALOPRAM; CYCLOPROPANE DERIVATIVE; DOPAMINE TRANSPORTER; FLUOXETINE; HOMOTRYPTAMINE; INDOLE CYCLOPROPYLMETHYLAMINE; INDOLE DERIVATIVE; METHYLAMINE; N [2 [5 CYANO 1 (4 TOLUENESULFONYL)INDOL 3 YL]CYCLOPROP 1 YL]CARBONYLBORNANE 10,2 SULTAM; NITRILE; NORADRENALIN TRANSPORTER; SEROTONIN; SEROTONIN 1A RECEPTOR; SEROTONIN 6 RECEPTOR; SEROTONIN TRANSPORTER; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRYPTAMINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG CONFORMATION; DRUG POTENCY; DRUG SYNTHESIS; ENANTIOMER; FRONTAL CORTEX; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROGEN BOND; MASS SPECTROMETRY; MICRODIALYSIS; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; RECEPTOR AFFINITY; STEREOCHEMISTRY; X RAY CRYSTALLOGRAPHY;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; CYCLOPROPANES; FRONTAL LOBE; HUMANS; INDOLES; MICRODIALYSIS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; RADIOLIGAND ASSAY; RATS; RECEPTORS, SEROTONIN; SEROTONIN UPTAKE INHIBITORS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRYPTAMINES;

EID: 24944508544     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0503291     Document Type: Article

References (50)

1. Ananth, J. Treatment-resistant depression. Psychother. Psychosom. 1998, 67, 61-70.
2. Lee, K. C.; Feldman, M. D.; Finley, P. R. Beyond depression: evaluation of newer indications and off-label uses for SSRIs. Formulary 2002, 37, 312-319.
3. 1A receptor antagonism/ SSRI activities. Part 1. Bioorg. Med. Chem. Lett. 2003, 13, 1903-1905.
4. 1A receptor antagonism/SSRI activities. Part 2. Bioorg. Med. Chem. Lett. 2003, 13, 2393-2397.
5. 1A receptor antagonism/ SSRI activities. Part 3. Bioorg. Med. Chem. Lett. 2003, 13, 3939-3942.
6. 1A receptor antagonism/SSRI activities. Part 4. Bioorg. Med. Chem. Lett. 2004, 14, 2653-2656.
7. 1A receptor antagonism. Farmaco 2000, 55, 345-353.
8. 1A receptor. Bioorg. Med. Chem. Lett. 2005, 15, 911-914.
9. Wellsow, J.; Machulla, H.-J.; Kovar, K.-A. 3D QSAR of serotonin transporter ligands: CoMFA and CoMSIA studies. Quant. Struct.-Act. Relat. 2002, 21, 577-589.
10. (a) Ravna, A. W.; Edvardsen, O. J. A putative three-dimensional arrangement of the human serotonin transporter transmembrane helices: a tool to aid experimental studies. J. Mol. Graphics Modell. 2001, 20, 133-144.
11. (b) Ravna, A. W.; Sylte, I.; Dahl, S. Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters. J. Pharmacol. Exp. Ther. 2003, 307, 34-41.
12. Chen, F.; Larsen, M. B.; Sanchez, C.; Wiborg, O. The S-enantiomer of R,S-citalopram increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors. Eur. Neuropsychopharmacol. 2005, 15, 193-198.
13. Sanchez, C.; Bogeso, K. P.; Ebert, B.; Reines, E. H.; Braestrup, C. Escitalopram versus citalopram: the surprising role of the R-enantiomer. Psychopharmacology 2004, 174, 163-176.
14. (a) Euvrard, C. R.; Boissier, J. R. Biochemical assessment of the central 5-HT agonist activity of RU 24969 (a piperidinyl indole). Eur. J. Pharmacol. 1980, 63, 65-72.
15. (b) Guillaume, J.; Dumont, C.; Laurent, J.; Nedelec, L. Synthesis of 3-(1,2,3,6-tetrahydropyridin-4-yl)1H-indoles and study of their serotoninergic and antidopaminergic properties. Eur. J. Med. Chem. 1987, 22, 33-43.
16. LeBoulleuc, K. L.; Mattson, R. J.; Mahle, C. D.; McGovern, R. T.; Nowak, H. P.; Gentile, A. J. Bivalent indoles exhibiting serotonergic binding affinity. Bioorg. Med. Chem. Lett. 1995, 5, 123-126.
17. Cipollina, J. A.; Mattson, R. J.; Sloan, C. P. Antidepressant 3-(aminocycloalkenyl)indole-5-nitrile derivatives. U.S. Patent 5,468,767, 1995; CAN 124:175827.
18. Meagher, K. L.; Mewshaw, R. E.; Evrard, D. A.; Zhou, P.; Smith, D. L.; Scerni, R.; Spangler, T.; Abulhaw, S.; Shi, X.; Scheckter, L. E.; Andree, T. H. Studies towards the next generation of antidepressants. Part 1: indolylcyclohexylamines as potent serotonin reuptake inhibitors. Bioorg. Med. Chem. Lett. 2001, 11, 1885-1888.
19. (a) Kaiser, C.; Zirkle, C. L. Cyclopropylamine derivatives and processes for their preparation. U.S. Patent 3,010,971, 1960; CAN 56:79376.
20. (b) Vangveravong, S.; Nichols, D. L. Stereoselective synthesis of trans-2-(indol-3-yl)cyclopropylamines: rigid tryptamine analogs. J. Org. Chem. 1995, 60, 3409-3416.
21. (c) Vangveravong, S.; Kanthasamy, A.; Lucaites, V. L.; Nelson, D. L.; Nichols, D. E. Synthesis and serotonin receptor affinities of a series of trans-2-(indol-3-yl)cyclopropylamine derivatives. J. Med. Chem. 1998, 41, 4995-5001.
22. Denhart, D. J.; Mattson, R. J.; Ditta, J. L.; Macor, J. E. One-pot synthesis of homotryptamines from indoles. Tetrahedron Lett. 2004, 45, 3803-3805.
23. Schmitz, W. D.; Denhart, D. J.; Brenner, A. B.; Ditta, J. L.; Mattson, R. J.; Mattson, G. K.; Molski, T. F.; Macor, J. E. Homotryptamines as potent and selective serotonin reuptake inhibitors (SSRIs). Bioorg. Med. Chem. Lett. 2005, 15, 1619-1621.
24. (a) Vangveravong, S.; Kanthasamy, A.; Lucaites, V. L.; Nelson, D. L.; Nichols, D. E. Synthesis and serotonin receptor affinities of a series of trans-2-(indol-3-yl)cyclopropylamine derivatives. J. Med. Chem. 1998, 41, 4995-5001.
25. 1A receptors. Bioorg. Med. Chem. Lett. 1996, 6, 415-420.
26. Indoles from 2-methylnitrobenzenes by condensation with formamide acetals followed by reduction: (a) Batcho, A. D.; Leimgruber, W. 4-benzyloxyindole (1H-indole, 4-(phenylmethoxy)-). Org. Synth. 1985, 63, 214-225.
27. (b) For 4-, 6-, and 7-cyanoindole: Clark, R. D.; Repke, D. B. Some observations on the formation of 1-hydroxyindoles in the Leimgruber-Batcho indole synthesis. J. Heterocycl. Chem. 1985, 22, 121-125.
28. (c) For 5- and 6-(trifluoromethyl)indole: Bromidge, S. M. Preparation of pyridinioarylcarbamoylindoline derivatives as serotonin receptor antagonists. WO 9737989, 1997.
29. H-, 4-F-, 5-MeO-, and 5-BnO-indole-3-carboxaldehyde were commercially available.
30. Netz, D. F.; Seidel, J. L. Diethyl (N-methoxy-N-methylcarbamoylmethy) phosphonate, a useful Emmons-Horner-Wittig reagent. Tetrahedron Lett. 1992, 33, 1957-1958.
31. (a) Still, W. C.; Gennari, C. Direct synthesis of Z-unsaturated esters. A useful modification of the Horner-Emmons olefination. Tetrahedron Lett. 1983, 24, 4405-4408.
32. (b) Beckmann, M.; Hildebrandt, H.; Winterfeldt, E. Pure enantiomers from retro-Diels-Alder processes. Tetrahedron: Asymmetry 1990, 1, 335-345.
33. (c) Carter, N. B.; Nadany, A. E.; Sweeneny, J. B. Recent developments in the synthesis of furan-2(5H)-ones. J. Chem. Soc., Perkin Trans. 1 2002, 2324-2342.
34. An alternative enantioselective synthesis has been described separately: Marcin, L. R.; Denhart, D. J.; Mattson, R. J. Catalytic asymmetric diazoacetate cyclopropanation of 1-tosyl-3-vinylindoles. A Route to conformationally restricted homotryptamines. Org. Lett. 2005, 7, 2651-2654.
35. Cecil, A. R. L.; Hu, Y.; Vicent, M. J.; Duncan, R.; Brown, R. C. D. Total Synthesis and preliminary biological evaluation of cis-solamin isomers. J. Org. Chem. 2004, 69, 3368-3374.
36. Blier, P. Pharmacology of rapid-onset antidepressant treatment strategies. J. Clin. Psychiatry 2001, 62 (Suppl. 15), 12-17.
37. Taber, M. T.; Wright, R. N.; Molski, T. F.; Clarke, W. J.; Brassil, P. J.; Denhart, D. J.; Mattson, R. J.; Lodge, N. J. Neurochemical, pharmacokinetic, and behavioral effects of the novel selective serotonin reuptake inhibitor BMS-505130. Pharmacol., Biochem. Behav. 2005, 80, 521-528.
38. Gundertofte, K.; Bøgesø, K. P.; Liljefors, T. A Stereoselective Pharmacophoric Model of the Serotonin Re-uptake Site. In Computer-Assisted Lead Finding and Optimization: Current Tools for Medicinal Chemistry; van de Waterbeemd, H., Testa, B., Folkers, G., Eds.; Verlag Helvetica Chimica Acta: Basel, Switzerland, 1997; pp 443-459.
39. 6) receptor antagonists in rodent models of learning. J. Pharmacol. Exp. Ther. 2003, 307 (2), 682-691.
40. 1A antagonist. Bioorg. Med. Chem. Lett. 2003, 13, 285-288.
41. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel-an integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J. Comput. Chem. 1990, 11, 440-467.
42. Polak, E.; Ribiere, G. Note sur la Convergence de Méthodes de Directions Conjuguées (Note on the convergence of methods of conjugates). Rev. Fr. Inf. Rech. Oper. 1969, 16, 35-43.
43. Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 1996, 118, 11225-11236.
44. Still, W. C.; Tempczyk, A.; Hawlely, R. C.; Hendrickson, T. A. Semianalytical treatment of solvation for molecular mechanics and dynamics. J. Am. Chem. Soc. 1990, 112, 6127-6129.
45. For a description of the B3LYP hybrid functional used, see the following. Jaguar 5.5 Operating Manual; Schrödinger, LLC: Portland, OR, 2004, and references therein.
46. Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; John Wiley & Sons: New York, 1986; Chapter 4.
47. Tidwell, R. R.; Geratz, J. D.; Dubovi, E. J. Aromatic amidines. Comparison of their ability to block respiratory syncytial virus induced cell fusion and to inhibit plasmin, urokinase, thrombin, and trypsin. J. Med. Chem. 1983, 26, 294-298.
48. Yamada, F.; Somei, M. The chemistry of indoles. Part XXXVIII. A convenient synthetic approach to 4-substituted indoles. Heterocycles 1987, 26, 1173-1176.
49. Pedras, M.; Soledade, C.; Ahiahonu, A.; Pearson, W. K. Probing the phytopathogenic stem rot fungus with phytoalexins and analogues: unprecedented glucosylation of camalexin and 6-methoxycamalexin. Bioorg. Med. Chem. 2002, 10, 3307-3312.
50. Kalir, A.; Balderman, D. Improved synthesis of some fluoroindoles. Isr. J. Chem. 1968, 6, 927-932.