SAR of psilocybin analogs: Discovery of a selective 5-HT2C agonist

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 20, 2005, Pages 4555-4559

  Sard, Howard ^a   Kumaran, Govindaraj ^a   Morency, Cynthia ^a   Roth, Bryan L ^b   Toth, Beth Ann ^b   He, Ping ^c   Shuster, Louis ^c  

^a ORGANIX INC   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 METHYLPSILOCIN; 4 FLUORO N,N DIMETHYLTRYPTAMINE; N BUTYLPSILOCIN; PHOSPHATE; PSILOCIN; PSILOCYBINE; SEROTONIN 2C AGONIST; SEROTONIN 2C RECEPTOR; TRYPTAMINE DERIVATIVE; UNCLASSIFIED DRUG;

ALKYLATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BENZYLATION; BLOOD BRAIN BARRIER; DRUG EFFICACY; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SPECIFICITY; LIPOPHILICITY; MOUSE; NONHUMAN; OBSESSIVE COMPULSIVE DISORDER; STRUCTURE ACTIVITY RELATION;

ANIMALS; HUMANS; MICE; PSILOCYBINE; RECEPTOR, SEROTONIN, 5-HT2C; SEROTONIN AGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA;

EID: 24344487206     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.06.104     Document Type: Article

References (31)

1. P.L. Delgado, and F.A. Moreno J. Psychoactive Drugs 30 1998 359
2. Private communication from Dr. Francisco Moreno, University of Arizona, Tucson.
3. B.L. Roth, and D. Shapiro Expert Opin. Ther. Targets 5 2001 685
4. S. Vickers, P. Clifton, C. Dourish, and L. Tecott Psychopharmacology (Berlin) 143 1999 309
5. A. Hofmann, R. Heim, A. Brack, H. Kobel, A. Frey, H. Ott, Th. Petrzilka, and F. Troxler Helv. Chim. Acta 42 1959 1557
6. A. Cerletti, M. Taeschler, and H. Weidmann Adv. Pharmacol. B 6 1968 233
7. L. Fitzgerald, and M. Ennis A. Doherty Annual Reports in Medicinal Chemistry Vol. 37 2002 Academic Press New York 21 30
8. 1H NMR and mass spectral data, and gave satisfactory combustion analyses.
9. F. Troxler, F. Seeman, and A. Hofmann Helv. Chim. Acta 42 1959 2073
10. D.E. Nichols, and S. Frescas Synthesis 935 1999
11. M. Bentov, Z. Pelchowicz, and A. Levy Isr. J. Chem. 2 1964 25
12. D. Repke, W. Ferguson, and D. Bates J. Heterocycl. Chem. 18 1981 175
13. D. Repke, W. Ferguson, and D. Bates J. Heterocycl. Chem. 14 1977 71
14. K. McCormick, K. Kobayashi, S. Goldin, N. Reddy, and J. Meinwald Tetrahedron 49 1993 11155
15. 17-19
16. 18,19
17. R. Rothman, M. Baumann, J. Savage, L. Rauser, A. McBride, S. Hufeisen, and B.L. Roth Circulation 102 2000 2836
18. B.L. Roth, M. Shoham, M. Choudhary, and N. Khan Mol. Pharmacol. 52 1997 259
19. B.L. Roth, M. Choudhary, N. Khan, and A. Uluer J. Pharmacol. Exp. Ther. 280 1997 576
20. L. Fitzgerald, T. Burn, B. Brown, J. Patterson, M. Corjay, P. Valentine, J.-H. Sun, J. Link, I. Abbaszade, J. Hollis, B. Largent, P. Hartig, G. Hollis, P. Meunier, A. Robichaud, and D. Robertson Mol. Pharmacol. 57 2000 75
21. 2C receptor.
22. Jacob, P., III; Shulgin, A. T. In Lin, G. C., Glennon, R. A., Eds.; NIDA Research Monograph 146 (Hallucinogens, an Update); 2000, p 74.
23. Y. Kuraishi, T. Nagasawa, K. Hayashi, and M. Satoh Eur. J. Pharmacol. 275 1995 229
24. T. Yamaguchi, T. Nagasawa, M. Satoh, and Y. Kuraishi Neurosci. Res. 35 1999 77
25. The subjects were male Swiss-Webster mice, 4-6 weeks old, weighing 25-45 g. Mice were housed five per cage, given free access to standard mouse food and water except during experiments, and maintained in a temperature-controlled room (70°F). Serotonin and all test drugs were made up with ascorbic acid (1 mg/mL) to protect against oxidation. Two mice, one a control and the other experimental, were tested each time. Each mouse was separately placed into a plexiglas box. The control mouse was injected with 10 mg/kg ascorbic acid in saline solution (0.9% NaCl) intraperitoneally (ip). For the experimental mouse, test compounds in saline plus ascorbic acid were injected ip. After 5 min, 0.1 mL of 0.4 mg/mL of serotonin in ascorbic acid in saline solution was injected subcutaneously (sc) to the rostral back of each mouse. After the injection of serotonin, the cumulative number of scratches was recorded every 5 min for 30 min.
26. In other experiments, psilocin produced significant inhibition of scratching at a dose of 0.85 mg/kg. Compound 9 at 2 mg/kg was not active.
27. R. Wurtman, A. Arjona, A. Anibal, R. Lee, and A. Pooler Brain Res. 951 2002 135
28. M. Isaac Curr. Top. Med. Chem. 5 2005 59
29. 4 receptors (data not shown).
30. M. Choudhary, S. Craigo, and B. Roth Mol. Pharmacol. 42 1992 627
31. V. Setola, M. Dukat, R. Glennon, and B. Roth Mol. Pharmacol. 68 2005 20