Synthesis and pharmacological characterization of bicyclic triple reuptake inhibitor 3-aryl octahydrocyclopenta[c]pyrrole analogues

Journal of Medicinal Chemistry

Volumn 54, Issue 15, 2011, Pages 5283-5295

  Shao, Liming ^a   Hewitt, Michael C ^a,b   Malcolm, Scott C ^a   Wang, Fengjiang ^a   Ma, Jianguo ^a   Campbell, Una C ^a   Spicer, Nancy A ^a   Engel, Sharon R ^a   Hardy, Larry W ^a   Jiang, Zhi Dong ^a   Schreiber, Rudy ^a,c   Spear, Kerry L ^a   Varney, Mark A ^a,d  

^a DAINIPPON SUMITOMO PHARMA CO LTD   (Japan)

^b Department of Structural Biology   (United States)

^c Evotec   (Germany)

^d Cortex Pharmaceuticals ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 ARYL OCTAHYDROCYCLOPENTA[C]PYRROLE; CYTOCHROME P450; DOPAMINE TRANSPORTER; NORADRENALIN TRANSPORTER; OCTAHYDRO 1H ISOINDOLE; POTASSIUM CHANNEL HERG; SEROTONIN TRANSPORTER; TRIPLE REUPTAKE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG PENETRATION; DRUG SYNTHESIS; IC 50; IN VIVO STUDY; INHIBITION KINETICS; MALE; MOUSE; NONHUMAN;

ANIMALS; ANTIDEPRESSIVE AGENTS; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; INHIBITORY CONCENTRATION 50; ISOINDOLES; MICE; MOTOR ACTIVITY; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; PYRROLES; RATS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN UPTAKE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79961214944     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm101312a     Document Type: Article

References (23)

1. Evidence Based Guidelines for Treating Depressive Disorders with Antidepressants: A Revision of the 2000 British Association for Psychopharmacology Guidelines [online]; British Association for Psychopharmacology: Cambridge, UK, 2008; http://www.bap.org.uk/pdfs/ antidepressants.pdf. Accessed on 07/07/2011.
2. Paul, I. A. Excitatory amino acid signaling, major depression and the actions of antidepressants Pharm. News 2001, 8, 33-44 (Pubitemid 34000552)
3. D'Aquila, P. S.; Collu, M.; Gessa, G. L.; Serra, G. The role of dopamine in the mechanism of action of antidepressant drugs Eur. J. Pharmacol. 2000, 405, 365-373
4. Sporn, J.; Ghaemi, S. N.; Sambur, M. R.; Rankin, M. A.; Recht, J.; Sachs, G. S.; Rosenbaum, J. F.; Fava, M. Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review Ann. Clin. Psychiatry 2000, 12, 137-140
5. Millan, M. K. Dual- and Triple-Acting Agents for Treating Core and Comobid Symptoms of Major Depression: Novel Concepts, New Drugs J. Am. Soc. Exp. Neurother. 2009, 6, 53-77
6. Skolnick, P.; Popik, P.; Janowsky, A.; Beer, B.; Lippa, A. S. Antidepressant-like actions of DOV 21,947: a "triple" reuptake inhibitor Eur. J. Pharmacol. 2003, 461, 99-104 (Pubitemid 36174028)
7. Beer, B.; Stark, J.; Krieter, P.; Czobor, P.; Beer, G.; Lippa, A.; Skolnick, P. DOV 216,303, a "Triple" Reuptake Inhibitor: Safety, Tolerability, and Pharmacokinetic Profile J. Clin. Pharmacol. 2004, 44, 1360-1367 (Pubitemid 39518641)
8. Skolnick, P.; Popik, P.; Janowsky, A.; Beer, B.; Lippa, A. S. "Broad spectrum" antidepressants: is more better for the treatment of depression? Life Sci. 2003, 73, 3175-3179 (Pubitemid 37237572)
9. Breuer, M. E.; Chan, J. S.; Oosting, R. S.; Groenink, L.; Korte, S. M.; Campbell, U.; Schreiber, R.; Hanania, T.; Snoeren, M. S.; Waldinger, M.; Olivier, B. The triple monoaminergic reuptake inhibitor DOV216,303 has antidepressant effects in the rat olfactory bulbectomy model and lacks sexual side effects Eur. Neuropharmacol. 2008, 18, 908-916
10. Shao, L.; Wang, F. W.; Malcolm, S. C.; Ma, J.; Hewitt, M. C.; Campbell, U.; Varney, M. A. Discovery of (2 R,4 R)-4-(3,4-dichlorophenyl)- N -methyl-1,2,3,4-tetrahydronaphthalen-2-amine, a triple reuptake inhibitor for the treatment of major depression Bioorg. Med. Chem. 2011, 19, 663-676
11. Shao, L.; Wang, F. W.; Malcolm, S. C.; Hewitt, M. C.; Campbell, U.; Varney, M. A. Discovery of 1-(3,4-dichlorophenyl)- N, N -dimethyl-1,2,3,4- tetrahydroquinolin-4-amine, a dual serotonin and dopamine reuptake inhibitor for the treatment of major depression Bioorg. Med. Chem. Lett. 2011, 21, 520-523
12. Malcolm, S. C.; Ribe, S.; Wang, F.; Hewitt, M. C.; Bhongle, N.; Bakale, R. P.; Shao, L. Efficient and scalable arylation of bicyclic lactones to form quaternary centers using conventional and microwave radiation Tetrahedron Lett. 2005, 46, 6871-6873 (Pubitemid 41583407)
13. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: a useful metric for lead selection Drug Discovery Today 2004, 9, 430-431 (Pubitemid 38510559)
14. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nature Rev. Drug Discovery 2007, 6, 881-890 (Pubitemid 350042396)
15. Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability J. Pharmacol. Toxicol. Methods 2000, 44, 235-249 (Pubitemid 32239479)
16. Navia, M. A.; Chaturvedi, P. R. Design principles for orally bioavailable drugs Drug Discovery Today 1996, 1, 179-189 (Pubitemid 126397604)
17. Perola, E. An Analysis of the Binding Efficiencies of Drugs and Their Leads in Successful Drug Discovery Programs J. Med. Chem. 2010, 53, 2986-2997
18. Stéru, L.; Chermat, R.; Thierry, B.; Simon, P. The tail suspension test: a new method for screening antidepressants in mice Psychopharmacology 1985, 85, 367-370 (Pubitemid 15123115)
19. Gu, H.; Wall, S.; Rudnick, G. Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence J. Biol. Chem. 1994, 269, 7124-7130 (Pubitemid 24217896)
20. Galli, A.; DeFelice, L. J.; Duke, B. J.; Moore, K. R.; Blakely, R. D. Sodium dependent norepinephrine-induced currents in norepinephrine-transporter- transfected HEK-293 cells blocked by cocaine and antidepressants J. Exp. Biol. 1995, 198, 2197-2212
21. Pristupa, Z. B.; Wilson, J. M.; Hoffman, B. J.; Kish, S. J.; Niznik, H. B. Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]GBR12,935 binding Mol. Pharmacol. 1994, 45, 125-135 (Pubitemid 24042291)
22. Eastwood, B. J.; Farmen, M. W.; Iversen, P. W.; Craft, T. J.; Smallwood, J. K.; Garbison, K. E.; Delapp, N. W.; Smith, G. F. The minimum significant ratio: a statistical parameter to characterize the reproducibility of potency estimates from concentration-response assays and estimation by replicate-experiment studies J. Biomol. Screening 2006, 11, 253-261
23. Stéru, L.; Chermat, R.; Thierry, B.; Mico, J.-A.; Lenegre, A.; Steru, M.; Simon, P.; Porsolt, R. D. The automated tail suspension test: a computerized device which differentiates psychotropic drugs Prog. Neuro-Psychopharmacol. Biol. Psychiatry 1987, 11, 659-671 (Pubitemid 18004312)