Heteroaryl-substituted diazatricycloalkanes and methods of...

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C514S290000

Reexamination Certificate

active

07732607

ABSTRACT:
The present invention relates to amide and urea derivatives of heteroaryl-substituted diazatricycloalkanes, pharmaceutical compositions including the compounds, methods of preparing the compounds, and methods of treatment using the compounds. More specifically, the methods of treatment involve modulating the activity of the α7 nAChR subtype by administering one or more of the compounds to treat or prevent disorders mediated by the α7 nAChR subtype. The diazatricycloalkanes typically consist of a 1-azabicyclooctane fused to pyrrolidine ring. The substitutent heteroaryl groups are 5- or 6-membered ring heteroaromatics, such as 3-pyridinyl and 5-pyrimidinyl moieties, which are attached directly to the diazatricycloalkane. The secondary nitrogen of the pyrrolidine moiety is substituted with an arylcarbonyl (amide type derivative) or an arylaminocarbonyl (N-arylcarbamoyl) (urea type derivative) group. The compounds are beneficial in therapeutic applications requiring a selective interaction at certain nAChR subtypes. That is, the compounds modulate the activity of certain nAChR subtypes, particularly the α7 nAChR subtype, and do not have appreciable activity toward muscarinic receptors. Radiolabeled versions of the compounds can be used in diagnostic methods.

REFERENCES:
patent: 4922901 (1990-05-01), Brooks et al.
patent: 5187166 (1993-02-01), Kikuchi et al.
patent: 5583140 (1996-12-01), Bencherif et al.
patent: 5597919 (1997-01-01), Dull et al.
patent: 5604231 (1997-02-01), Smith et al.
patent: 5616716 (1997-04-01), Dull et al.
patent: 5663356 (1997-09-01), Ruecroft et al.
patent: 5672601 (1997-09-01), Cignarella
patent: 5712270 (1998-01-01), Sabb
patent: 5852041 (1998-12-01), Cosford et al.
patent: 5853696 (1998-12-01), Elmaleh
patent: 5952339 (1999-09-01), Bencherif et al.
patent: 5969144 (1999-10-01), London et al.
patent: 6310043 (2001-10-01), Bundle et al.
patent: 7101890 (2006-09-01), Czollner et al.
patent: 7115629 (2006-10-01), Gallemi et al.
patent: 2001/0056084 (2001-12-01), Allgeier et al.
patent: 2002/0016371 (2002-02-01), Shytle et al.
patent: 0 297858 (1989-01-01), None
patent: 2 295 387 (1996-05-01), None
patent: WO 94/08992 (1994-04-01), None
patent: WO 96/31475 (1996-10-01), None
patent: WO 96/40682 (1996-12-01), None
patent: WO 97/30998 (1997-08-01), None
patent: WO 98/25619 (1998-06-01), None
patent: WO 99/03859 (1999-01-01), None
patent: WO 99/21834 (1999-05-01), None
patent: WO 99/62505 (1999-12-01), None
patent: WO 00/73431 (2000-12-01), None
patent: WO 01/36417 (2001-05-01), None
patent: WO 02/15662 (2002-02-01), None
patent: WO 02/16355 (2002-02-01), None
patent: WO 02/16356 (2002-02-01), None
patent: WO 02/16357 (2002-02-01), None
patent: WO 02/16358 (2002-02-01), None
patent: WO 02/17358 (2002-02-01), None
patent: WO 02/051841 (2002-07-01), None
patent: WO 2004/076449 (2004-09-01), None
Dorwald F. A. Side Reactions in Organic Synthesis, 2005, Wiley: VCH, Weinheim p. IX of Preface.
Arneric, S., et al., “Preclinical Pharmacology of ABT-418: A Prototypical Cholinergic Channel Activator for the Potential Treatment of Alzheimer's Disease,”CNS Drug Rev., 1(1): 1-26 (1995).
Arneric, S., et al., “Cholinergic channel modulators as a novel therapeutic strategy for Alzheimer's disease,”Exp. Opin. Invest. Drugs, 5(1): 79-100 (1996).
Arneric, S.P., and V.L., Villemagne, et al., (Eds.)Neuronal Nicotinic Receptors: Pharmacology and Therapeutic Opportunities, 235-250 (1998).
Bannon, A.W., et al., “Broad-Spectrum, Non-Opioid Analgesic Activity by Selective Modulation of Neuronal Nicotinic Acetylcholine Receptors,”Science, 279: 77-81 (1998).
Bencherif, M., and J. D. Schmitt, “Targeting Neuronal Nicotinic Receptors: a Path to New Therapies,”Current Drug Targets, 1(4): 349-357 (2002).
Bencherif, M., and R.J. Lukas, “Ligand Binding and Functional Characterization of Muscarinic Acetylcholine Receptors on the TE671/RD Human Cell Line,”J. Pharmacol. Exp. Ther., 257(3): 946-953 (1991).
Bencherif, M., et al., “RJR-2403: A Nicotinic Agonist with CNS Selectivity I: In Vitro Characterization,”J. Pharmacol. Exper. Therapeutics, 279(3): 1413-1421 (1996).
Bencherif M. and R.J. Lukas, “Differential Regulation of Nicotinic Acetylcholine Receptor Expression by Human TE671/RD Cells Following Second Messenger Modulation and Sodium Butyrate Treatments,”Mol Cell Neurosci., 2(1): 52-65 (1991).
Besidsky, Y., et al., “3′-Keto-1-nitro-2-phenylspiro[cyclopropane-3,2′-quinuclidine]: Synthesis and Reactions with Nucleophiles,”J. Heterocyclic Chem., 31: 1321-1326 (1994).
Besidsky, Y., et al., “Synthesis of Perhydro-1,4-ethano-1,5-naphthyridine and Perhydro-4,7-ethanopyrrolo[3,2-b]pyridine Derivatives: Potential NK1-receptor Antagonists. X-Ray Molecular Structures of (4aR*,8S*,8aR*)-6-Oxo-8-phenylperhydro-1,4-ethano-1,5-naphthyridine and (4aR*,7R*,8R*,8aR*)-7,8-Diphenylperhydro-1,4-ethano-1,5-naphthyridine,”J.Chem. Soc., Perkin Trans., 465-480 (1995).
Brioni, J.D., et al., “The Pharmacology of (-)-Nicotine and Novel Cholinergic Channel Modulators,”Adv. Pharmacol., 37: 153-214 (1997).
Broadley, K.J., and D.R. Kelly, “Review Muscarinic Receptor Agonists and Antagonists,”Molecules, 6: 142-193 (2001).
Caulfield, M.P., “Muscarinic Receptors-Characterization, Coupling, and Function,”Pharmac. Ther,. 58: 319-379 (1993).
Cheng, Y-C., and W.H. Prusoff, “Relationship Between the Inhibition Constant (K1) and the Concentration of Inhibitor which Causes 50 Per Cent inhibition (I50) of an Enzymatic Reaction,”Biochem. Pharmacol., 22(23): 3099-3108 (1973).
Chiari, A., et al., “Sex Differences in Cholinergic Analgesia I: A Supplemental Nicotinic Mechanism in Normal Females,”Anesthesiology, 91(5): 1447-1454 (1999).
Damaj, M.I., et al.,“Antinociceptive and Pharmacological Effects of Metanicotine, a Selective Nicotinic Agonist,”J. Pharmacol. Exp. Ther., 291(1): 390-398 (1999).
Decina, P., et al., “Cigarette Smoking and Neuroleptic-Induced Parkinsonism,”Biol. Psychiatry, 28(6): 502-508 (1990).
Dolle, F., et al., “Synthesis and preliminary evaluation of a carbon-11-labelled agonist of the α-7 nicotinic acetylcholine receptor,”J. Labelled Comp. Radiopharm., 44: 785-795 (2001).
Fisher, A., et al., “The Fused Quinuclidine-Valerolactone System,”Tetrahedron, 31(4): 317-325 (1975).
Freedman, R., et al., “Evidence in Postmortem Brain Tissue for Decreased Numbers of Hippocampal Nicotinic Receptors in Schizophrenia,”Biol. Psychiatry, 38(1): 22-33 (1995).
Georgian, V., et al., “Bridged Quinuclidines: Synthesis of 5-Azatricyclo [3.2.1.02,7]octane. Incorporation of a Bridged Quinuclidine Into the Cinchona Aklaloid Skeleton,”Heterocycles, 7(2): 1017-1025 (1977).
Gorbyleva, et al., Khim Geterotsikl. Soedin.,Chem. Abstracts, 98: 34478a, 1232-1237 (1982).
Hall, G.H., and D.M. Turner, “Effects of Nicotine on the Release of3H-Noradrenaline from the Hypothalamus,”Biochemical Pharmacology, 21: 1829-1838 (1972).
Hamon, M., “Neuropharmacology of anxiety: perspectives and prospects,”TiPS, 15: 36-39 (1994).
Harsing, Jr., et al., “Dopamine Efflux from Striatum After Chronic Nicotine: Evidence for Autoreceptor Desensitization,”J. Neurochem., 59(1): 48-54 (1992).
Heeschen, C., et al., “A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors,”J. Clin. Invest., 110(4): 527-536 (2002).
Hery, F., et al., “Control of the Release of Newly Synthetized3H-5-Hydroxytryptamine by Nicotinic and Muscarinic Receptors in Rat Hypothalamic Slices,”Naunyn-Schmiedeberg's Arch. Pharmacol., 296: 91-97 (1977).
Holladay, M.W., et al., “Neuronal Nicotinic Acetylcholine Receptors as Targets for Drug Discovery,”J. Med. Chem., 40(26): 4169-4194 (1997).
Hoyer, D. and H.W.G.M. Boddeke, “Partial agonists, full agonists, antagonists: dilemmas of defi

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Heteroaryl-substituted diazatricycloalkanes and methods of... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Heteroaryl-substituted diazatricycloalkanes and methods of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Heteroaryl-substituted diazatricycloalkanes and methods of... will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-4248995

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.