Tetrahydropyridin-4-yl indoles with a combination of...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C548S469000, C546S001000, C544S242000

Reexamination Certificate

active

11294657

ABSTRACT:
The present invention relates to a group of novel tetrahydropyridin-4-yl indoles with a dual mode of action: serotonin reuptake inhibition and affinity for dopamine-D2receptors, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said tetrahydropyridin-4-yl indoles. The invention also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect.The invention relates to novel tetrahydropyridin-4-yl indoles of the formula.and tautomers, stereoisomers, prodrugs, N-oxides, pharmacologically acceptable salts, hydrates and solvates thereof,wherein:R1is hydrogen, halogen, alkyl(C1-3) or alkoxy(C1-3), CN or CF3,R2is hydrogen or alkyl(C1-3),R3is hydrogen or alkyl(C1-3),Z is hydrogen or alkyl(C1-3), alkoxy(C1-3) or alkylthio(C1-3),A is hydrogen or alkyl(C1-3), orA and Z together form a saturated or (partly) unsaturated 5- or 6-membered ring which may be substituted with halogen, alkyl (C1-3) or phenyl, in which ring Z represents carbon, sulfur of nitrogen.

REFERENCES:
patent: 487014 (1929-11-01), None
patent: 0 138 280 (1985-04-01), None
patent: 0 189 612 (1986-08-01), None
patent: 0 376 607 (1990-07-01), None
patent: 0378 255 (1990-07-01), None
patent: 0 900 792 (1999-03-01), None
patent: 1 378 080 (1974-12-01), None
patent: WO 97/36893 (1997-10-01), None
patent: WO 99/05140 (1999-02-01), None
patent: WO 99/51575 (1999-10-01), None
patent: WO 00/23441 (2000-04-01), None
patent: WO 00/43382 (2000-07-01), None
patent: WO 00/69424 (2000-11-01), None
patent: WO 01/14330 (2001-03-01), None
patent: WO 02/066473 (2002-08-01), None
patent: WO 2004/020437 (2004-03-01), None
patent: WO 2004/052886 (2004-06-01), None
patent: WO 2004/054972 (2004-07-01), None
Adcock, et al., “Fluorine-19 Substituent Chemical Shifts,” Aust. J. Chem. vol. 23, pp. 1921-1937, (1970).
Badger, et al., “Thionaphthencarboxylic Acids,” Journal of the Chemical Society, pp. 2624-2630, (1957).
Beattie, et al., “The Synthesis of Nine Chloroidonaphthalenes,” Journal of The Chemical Society, pp. 50-52, (1934).
Berg, et al., “The Search for Chemotherapeutic Amidines. Part X Substituted 4:4′-Diamidino-αω-diphenoxyalkanes and -diphenyl Ethers,” Journal of The Chemical Society, pp. 642-648, (1949).
Bickel, “The Pharmacology and Biochemistry of N-Oxides,” Pharmacological Reviews, 21(4), pp. 325-355, (1969).
Buchan, et. al., “The Chlorination of Iodophenols. The Chlorination of o-Iodophenol,” Journal of The Chemical Society, pp. 137-145, (1931).
Campos et al., “A General Synthesis of Substituted Indoles from Cyclic Enol Ethers and Enol Lactones,” Organic Letters, vol. 6, No. 1, pp. 79-82, (2004).
Costall et al., “Climbing Behavior Induced by Apormorphine in Mice: A Potential Model for the Detection of Neurolaptic Activity,” Eur. J. Pharmacol., vol. 1, pp. 39-50 (1978).
Davison et al., “Nitrone dipolar Cycloaddition routes to piperidines and indolizidines, Part 9. Formal synthesis of (−)-pinidine and total synthesis of (−)-histrionicotoxin, (+)-histrionicotoxin and (−)-histrioncotoxin 235A,” J. Chem. Soc., Perkins Trans. 1, pp. 1494-1514, (2002).
Feenstra et al. “Antiparkinsonian Antidepressant Anxiolytic Dopamine D2Partial Agonist 5-HT 1aAgonist,” Drugs of the Future, vol. 26, No. 2, pp. 128-132, (2001).
Feenstra et al., “New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D2 receptor and serotonin 5HT1A receptor affinities,” Bioorg. & Med. Chem. Lett., 11, pp. 2345-2349 (2001).
Finger et al., “Aromatic Fluorine Compounds. VIII. Plant Growth Regulators and Intermediates,” pp. 94-101 , (1959).
Huang et al., “Expanding Pd-Catalyzed C-N Bond-Forming Processes: The First Amidation of Aryl Sulfonates, Aqueous Amination, and Complementarity with Cu-Catalyzed Reactions,” J. AM. Chem. Soc., vol. 125, No. 22, pp. 6653-6655, 2003.
Jacobs, B.L., “An Animal Behaviour Model for Studying Central Seratongergic. Synapses,” Life Sci., vol. 19, No. 6, pp. 777-785 (1976).
Leclerc, et al., “5-Halobenzothiophene Analogues of Melatonin: Synthesis and Affinity for mt1 and MT2 Receptors in Man,” Pharm. Pharmacol. Commun., pp. 61-65, (2000).
Mancuso, et al., “Activated Dimethyl Sulfoxide: Useful Reagents for Synthesis,” Int'l. Journal of Methods in Synthetic Organic Chemistry, pp. 165-248, (1981).
Ruchardt et al., “Durchfuhrung der Jacobsonschen Indazolsynthese im Eintopfverfahren,” Liebigs Ann. Chem, pp. 908-927, (1980).
Samuel Weiss et al., “Corticotropin-Peptide Regulation of Intracellular Cyclic AMP Production in Cortical Neurons in Primary Culture,” Journal of Neurochemistry, vol. 45, No. 3, pp. 869-874, (1985).
Searles, “The Reaction of Trimethylene Oxide with Grignard Reagents and Organolithium Compounds,” Trimethylene Oxide with Grignard and Organolithium Reagents, p. 124-125, (1951).
Timms et al., “Bioorganic and Medicinal Chemistry Letters,” vol. 14, No. 10, pp. 2469-2472, (2004).
Van Hes et al, Bioorganic and Medicinal Chemistry Letters, vol. 13, No. 3, pp. 405-408, (2003).
Yoram Solomon, et al., “A Highly Sensitive Adenylate Cyclase Assay,” Analytical Biochemistry 58, pp. 541-548, (1974).
Yu, et al., “20-Hydroxyeicosatetraenoic Acid (20-HETE): Structural Determinants for Renal Vasoconstriction,” Bioorg. Med. Chem. 11, pp. 2803-2821, (2003).
Creese, et al., “[3H]-Spiroperidol Labels Dopamine Receptors in Pituitary and Brain,” Eur. J. Pharmacol., vol. 46., pp. 377-381, (1977).
Habert, et al., “Characterisation of [3H]-paroxetine Binding to Rat Cortical Membranes,” Eur. J. Pharmacol., vol. 118, pp. 107-114, (1985).
Stella, “Prodrugs as Therapeutics,” Expert Opin. Ther. Patents, vol. 14, No. 3, pp. 277-280, (2004).
King, “Bioisosteres, Conformational Restriction, and Pro-drugs—Case History: An Example of a Conformational Restriction Approach,” Medicinal Chemistry: Principles and Practice, pp. 206-225, (ISBN 0-85186-494-5), (1994).
Organic Process Research and Development, vol. 1, No. 4, pp. 300-310, (1997).
Ettmayer, et al., “Lessons Learned from Marketed and Investigational Prodrugs,” J. Med. Chem., 47, pp. 2393-2404, (2004).
Van Der Heyden, et al., “A Rapidly Acquired One-Way Conditioned Avoidance Procedure in Rats as a Primary Screening Test for Antipsychotics: Influence of Shock Intensity on Avoidance Performance”, Behavioural Brain Research, vol. 31, pp. 61-67, (1988).
Van Der Poel, et al., “Temporal Patterning of Ultrasonic Distress Calls in the Adult Rat: Effects of Morphine and Benzodiazepines”, Psycho-pharmacology, vol. 97, pp. 147-148, (1989).
Boschman, et al., “Invitro Inhibition of ADP-induced platelet Aggregation by O- (aminoalkyl) oxime ethers,” European J. of Medicinal Chem., vol. 15, No. 4, pp. 351-356 (Jul. 1980).
Tims, et al. “SAR Development of a Selective 5-HT1D Antagonist/Serotonin Reuptake Inhibitor Lead Using Rapid Parallel Synthesis,” Bioorg. Med. Chem. vol. 14, No. 10, pp. 2469-2472, (2004).
Van Hes, et al., “SLV310, A Novel, Potential Antipsychotic, Combining Potent Dopamine D2 Receptor Antagonism with Serotonin Reuptake Inhibition,” Biorg. Med. Chem., vol. 13, No. 3, pp. 405-408, (2003).

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

Tetrahydropyridin-4-yl indoles with a combination 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 Tetrahydropyridin-4-yl indoles with a combination of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Tetrahydropyridin-4-yl indoles with a combination of... will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3947134

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