Discovery of highly potent and selective α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists containing an isoxazolylpyridine ether scaffold that demonstrate antidepressant-like activity. Part II

Journal of Medicinal Chemistry

Volumn 55, Issue 22, 2012, Pages 9998-10009

  Yu, Li Fang ^a   Eaton, J Brek ^b   Fedolak, Allison ^c   Zhang, Han Kun ^a   Hanania, Taleen ^c   Brunner, Dani ^c,d   Lukas, Ronald J ^b   Kozikowski, Alan P ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b BARROW NEUROLOGICAL INSTITUTE   (United States)

^c PSYCHOGENICS INC   (United States)

^d Howard Hughes Medical Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [5 [5 (2 PYRROLIDINYLMETHOXY) 3 PYRIDINYL 3 ISOXAZOLYL]ETHANOL; 2 [5 [5 (AZETIDIN 2 YLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL]ETHANOL; 2 [5 [5 [(1 METHYL 2 PYRROLIDINYL)METHOXY] 3 PYRIDINYL] 3 ISOXAZOLYL]ETHANOL; 2 [5 [5 [(3 AZABICYCLO(3 1 0) 2 HEXYL)METHOXY] 3 PYRIDINYL] 3 ISOXAZOLYL]ETHANE; 2 [5 [5 [(3 AZABICYCLO(3 1 0) 2 HEXYL)METHOXY] 3 PYRIDINYL] 3 ISOXAZOLYL]ETHANOL; 2 [[5 [3 [2 [TERT BUTYL(DIMETHYL)SILANYLOXY]ETHYL] 5 ISOXAZOLYL] PYRIDIN 3 YLOXY]METHYL]PYRROLIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 3 (2 AZETIDINYLMETHOXY) 5 (3 ETHYL 5 ISOXAZOLYL)PYRIDINE; 3 (2 AZETIDINYLMETHOXY) 5 [3 (2 METHOXYETHYL) 5 ISOXAZOLYL]PYRIDINE; 3 (2 AZETIDINYLMETHOXY) 5 [3 (3 FLUOROPROPYL) 5 ISOXAZOLYL]PYRIDINE; 3 (2 AZETIDINYLMETHOXY) 5 [3 (3,3 DIFLUOROPROPYL) 5 ISOXAZOLYL]PYRIDINE; 3 (2 AZETIDINYLMETHOXY) 5 [3 (3,3,3 TRIFLUOROPROPYL) 5 ISOXAZOLYL]PYRIDINE; 3 [5 [5 (2 PYRROLIDINYLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL] 1 PROPANOL; 4 [2 [5 [5 (2 AZETIDINYLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL]ETHYL]MORPHOLINE; 4 [2 [5 [5 (2 PYRROLIDINYLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL]ETHYL]MORPHOLINE; ANTIDEPRESSANT AGENT; AZETIDINE; EPIBATIDINE; ETHYLCARBAMIC ACID 2 [5 [5 (2 AZETIDINYLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL]ETHYL ESTER; ETHYLCARBAMIC ACID 2 [5 [5 (2 PYRROLIDINYLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL]ETHYL ESTER; NICOTINE; NICOTINIC AGENT; NICOTINIC RECEPTOR ALPHA4BETA2; PHENYLCARBAMIC ACID 2 [5 [5 (2 AZETIDINYLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL]ETHYL ESTER; PHENYLCARBAMIC ACID 2 [5 [5 (2 PYRROLIDINYLMETHOXY) 3 PYRIDINYL] 3 ISOXAZOLYL]ETHYL ESTER; PYRIDINE DERIVATIVE; SERTRALINE; UNCLASSIFIED DRUG; VARENICLINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIDEPRESSANT ACTIVITY; ARTICLE; BINDING AFFINITY; CHEMICAL MODIFICATION; CONTROLLED STUDY; DEPRESSION; DOSE RESPONSE; DRUG DESIGN; DRUG DOSE COMPARISON; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; ION TRANSPORT; MALE; MOUSE; NONHUMAN;

ANIMALS; ANTIDEPRESSIVE AGENTS; HUMANS; ISOXAZOLES; MALE; MICE; MICE, INBRED BALB C; MOTOR ACTIVITY; NEUROBLASTOMA; NICOTINIC AGONISTS; PROTEIN BINDING; RADIOLIGAND ASSAY; RECEPTORS, NICOTINIC; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SWIMMING;

EID: 84870031815     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301177j     Document Type: Article

References (24)

1. Changeux, J. P. Nicotine addiction and nicotinic receptors: lessons from genetically modified mice Nature Rev. Neurosci. 2010, 11, 389-401
2. Gotti, C.; Clementi, F.; Fornari, A.; Gaimarri, A.; Guiducci, S.; Manfredi, I.; Moretti, M.; Pedrazzi, P.; Pucci, L.; Zoli, M. Structural and functional diversity of native brain neuronal nicotinic receptors Biochem. Pharmacol. 2009, 78, 703-711
3. McGehee, D. S.; Heath, M. J.; Gelber, S.; Devay, P.; Role, L. W. Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors Science 1995, 269, 1692-1696
4. Shytle, R. D.; Silver, A. A.; Lukas, R. J.; Newman, M. B.; Sheehan, D. V.; Sanberg, P. R. Nicotinic acetylcholine receptors as targets for antidepressants Mol. Psychiatry 2002, 7, 525-535
5. Mineur, Y. S.; Picciotto, M. R. Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis Trends Pharmacol. Sci. 2010, 31, 580-586
6. Philip, N. S.; Carpenter, L. L.; Tyrka, A. R.; Price, L. H. Nicotinic acetylcholine receptors and depression: a review of the preclinical and clinical literature Psychopharmacology (Berlin) 2010, 212, 1-12
7. Caldarone, B. J.; Harrist, A.; Cleary, M. A.; Beech, R. D.; King, S. L.; Picciotto, M. R. High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation Biol. Psychiatry 2004, 56, 657-664
8. Rabenstein, R. L.; Caldarone, B. J.; Picciotto, M. R. The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not beta2- or alpha7-nicotinic acetylcholine receptor subunit knockout mice Psychopharmacology (Berlin) 2006, 189, 395-401
9. Caldarone, B. J.; Wang, D.; Paterson, N. E.; Manzano, M.; Fedolak, A.; Cavino, K.; Kwan, M.; Hanania, T.; Chellappan, S. K.; Kozikowski, A. P.; Olivier, B.; Picciotto, M. R.; Ghavami, A. Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380 Psychopharmacology (Berlin) 2011, 217, 199-210
10. Andreasen, J. T.; Nielsen, E. O.; Christensen, J. K.; Olsen, G. M.; Peters, D.; Mirza, N. R.; Redrobe, J. P. Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test J. Psychopharmacol. 2011, 25, 1347-1356
11. Lippiello, P. M.; Beaver, J. S.; Gatto, G. J.; James, J. W.; Jordan, K. G.; Traina, V. M.; Xie, J.; Bencherif, M. TC-5214 (S -(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity CNS Neurosci. Ther. 2008, 14, 266-277
12. A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD). http://clinicaltrials. gov/ct2/show/NCT01157078?term=TC5214&rank=17; U.S. National Institutes of Health: Bethesda, MD, 2011; (accessed December 29, 2011).
13. Sullivan, J. P.; Donnelly-Roberts, D.; Briggs, C. A.; Anderson, D. J.; Gopalakrishnan, M.; Piattoni-Kaplan, M.; Campbell, J. E.; McKenna, D. G.; Molinari, E.; Hettinger, A. M.; Garvey, D. S.; Wasicak, J. T.; Holladay, M. W.; Williams, M.; Arneric, S. P. A-85380 [3-(2(S)-azetidinylmethoxy) pyridine]: in vitro pharmacological properties of a novel, high affinity alpha4beta2 nicotinic acetylcholine receptor ligand Neuropharmacology 1996, 35, 725-734
14. Gotti, C.; Riganti, L.; Vailati, S.; Clementi, F. Brain neuronal nicotinic receptors as new targets for drug discovery Curr. Pharm. Des. 2006, 12, 407-428
15. Turner, J. R.; Castellano, L. M.; Blendy, J. A. Nicotinic partial agonists varenicline and sazetidine-A have differential effects on affective behavior J. Pharmacol. Exp. Ther. 2010, 334, 665-672
16. Zhang, H.; Tuckmantel, W.; Eaton, J. B.; Yuen, P. W.; Yu, L. F.; Bajjuri, K. M.; Fedolak, A.; Wang, D.; Ghavami, A.; Caldarone, B.; Paterson, N. E.; Lowe, D. A.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P. Chemistry and behavioral studies identify chiral cyclopropanes as selective alpha4beta2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile J. Med. Chem. 2012, 55, 717-724
17. Liu, J.; Yu, L. F.; Eaton, J. B.; Caldarone, B.; Cavino, K.; Ruiz, C.; Terry, M.; Fedolak, A.; Wang, D.; Ghavami, A.; Lowe, D. A.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P. Discovery of isoxazole analogues of sazetidine-A as selective alpha4beta2-nicotinic acetylcholine receptor partial agonists for the treatment of depression J. Med. Chem. 2011, 54, 7280-7288
18. Rollema, H.; Shrikhande, A.; Ward, K. M.; Tingley, F. D., III; Coe, J. W.; O'Neill, B. T.; Tseng, E.; Wang, E. Q.; Mather, R. J.; Hurst, R. S.; Williams, K. E.; de Vries, M.; Cremers, T.; Bertrand, S.; Bertrand, D. Preclinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence Br. J. Pharmacol. 2010, 160, 334-345
19. Carroll, F. I.; Ware, R.; Brieaddy, L. E.; Navarro, H. A.; Damaj, M. I.; Martin, B. R. Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2′-fluoro-3′-(substituted phenyl)deschloroepibatidine analogues. Novel nicotinic antagonist J. Med. Chem. 2004, 47, 4588-4594
20. Rueter, L. E.; Donnelly-Roberts, D. L.; Curzon, P.; Briggs, C. A.; Anderson, D. J.; Bitner, R. S. A-85380: a pharmacological probe for the preclinical and clinical investigation of the alphabeta neuronal nicotinic acetylcholine receptor CNS Drug Rev. 2006, 12, 100-112
21. Liu, J.; Eaton, J. B.; Caldarone, B.; Lukas, R. J.; Kozikowski, A. P. Chemistry and pharmacological characterization of novel nitrogen analogues of AMOP-H-OH (Sazetidine-A, 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol) as alpha4beta2-nicotinic acetylcholine receptor-selective partial agonists J. Med. Chem. 2010, 53, 6973-6985
22. Lukas, R. J.; Fryer, J. D.; Eaton, J. B.; Gentry, C. L. Some methods for studies of nicotinic acetylcholine receptor pharmacology. In Nicotinic Receptors and the Nervous System; Levin, E. D., Ed.; CRC Press: Boca Raton, FL, 2002; pp 3-27.
23. Lukas, R. J.; Norman, S. A.; Lucero, L. Characterization of Nicotinic Acetylcholine Receptors Expressed by Cells of the SH-SY5Y Human Neuroblastoma Clonal Line Mol. Cell Neurosci. 1993, 4, 1-12
24. Eaton, J. B.; Peng, J. H.; Schroeder, K. M.; George, A. A.; Fryer, J. D.; Krishnan, C.; Buhlman, L.; Kuo, Y. P.; Steinlein, O.; Lukas, R. J. Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably and heterologously expressed in native nicotinic receptor-null SH-EP1 human epithelial cells Mol. Pharmacol. 2003, 64, 1283-1294