Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-02-28
2003-07-15
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S233200, C514S314000, C544S363000, C546S167000
Reexamination Certificate
active
06593324
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to therapeutically active derivatives of quinoline, including the pharmaceutically acceptable salts and esters thereof, and their use as alpha-2 antagonists.
BACKGROUND
Some compounds exhibiting alpha adrenergic activity are well known in the art. Those compounds may be used for the treatment of a wide variety of diseases and conditions of the peripheric system and the central nervous system (CNS).
The alpha adrenergic receptors are divided into alpha-1 and alpha-2 adrenoceptors, each of which are further divided into subtypes. Accordingly, alpha-2 adrenoceptors in humans have been subdivided into three pharmacological subtypes known as alpha-2A, alpha-2B and alpha-2C adrenoceptors. A fourth subtype, alpha-2D, is known in rat, bovine and porcine and it corresponds to alpha-2A in man. These subtypes have a distinct distribution in human and animal tissues. For instance, alpha-2C adrenoceptors are concentrated in the CNS, and they appear to play a role in the modulation of various CNS-mediated behavioural and physiological responses.
Compounds that are non-specific to any of the above-mentioned alpha-2 subtypes, and compounds that are specific to certain alpha-2 subtypes, are already known. For example, atipamezole is a non-specific alpha-2 antagonists. Atipamezole has been described in, for example, EP-A-183 492 (cf. p.13, compound XV) and A. Haapalinna et al., Naunyn-Schimiedeberg's Arch. Pharmacol. Vol. 356, 1997, p.570-582. U.S. Pat. No. 5,902,807 describes compounds that are selective antagonists for the alpha-2C subtype and may be used in the treatment of mental illnesses, e.g. mental disturbances induced by stress. Such compounds include, for example, MK-912 and BAM-1303. Furthermore, WO-A-99 28300 discloses substituted imidazole derivatives having agonist-like activity for alpha-2B or 2B/2C adrenoceptors. The disclosures of all documents cited above in this paragraph are incorporated by reference herein.
As to the derivatives of quinoline, Medicinskaja parazitologija I parazitarnye bolezni, vol.5, 1991, 55-7 (Mikhailitsyn F. S. et al.) and J. Med. Chem., vol.20(8), 1977, 987-996 (Cain F. C. et al.) describe, for example, acridine derivatives as anticancer and/or antiparasitic agents. In addition, a publication by Adams et al in 1985 (Mol. Pharm. 27, 480-491) reports on the binding of diquinolines, diacridines and a number of monoacridines on rat brain alpha-1-, alpha-2- and beta-adrenoceptors.
SUMMARY OF THE INVENTION
An object of the present invention is to provide further antagonists of alpha-2 adrenoceptors that can be used for the treatment of diseases or conditions of the pheripheric or central nervous system where alpha-2 antagonists are indicated to be useful. Accordingly, an object of the present invention is to provide further compounds to be used as alpha-2 antagonist agents in the treatment of mammals, including humans and animals.
Another object of the present invention is to provide further compounds useful as selective alpha-2C antagonist agents for the treatment of various disorders or conditions of the central nervous system where alpha-2C antagonists are indicated to be useful.
REFERENCES:
patent: 6288082 (2001-09-01), Wissner et al.
patent: 0 183 492 (1986-06-01), None
patent: WO 96/09294 (1996-03-01), None
patent: WO 99/28300 (1999-06-01), None
Sathi et al., “New Quinolines as Potential CNS Agents,” Arch. Pharm. 316, 767-772 (1983).
Radzikowski et al., “New Antitumor Compounds. Biological studies. IV. Antitumor properties of 21 new acridine derivatives,” Acc. No. 1967: 401919 XP 002901810.
Kozyreva et al., “Synthesis and Study of the Anthelmintic Acttivity of Some N-Heterocycles Containing 4-(4′-Diethylcarbamoyl-1′-Piperazinyl) Phenylamine Substituents,” Acc. No. 1972: 400153 XP 002901811.
Klopman et al., “Computer-Automated Structure Evaluation of Antileukemic 9-Anilinoacridines,” Acc. No. 1987:628423 XP 002901812.
Mikailitsyn F.S. et al., Medicinskaja Parazitologija 1 parazitarnye bolezni, vol. 5, pp. 55-57 (1991).
Anti Haapalinna et al., “Evaluation of the effects of a specific &agr;2-adrenoceptor antagonist, atipamozole, on &agr;1- and &agr;2-adrenoceptor subtype binding, brain neurochenistry and behaviour in comparison with yohimbine”, Naunyn-Schmiedeberg's Arch Pharmacol, vol. 356, pp. 570-582 (1997).
Bruce Cain et al., “Potential Antitumor Agents. 23. 4′-(9-Acridinylamino)alkanesulfonanilide Congeners Bearing (Hydrophilic Functionality”, Journal of Medicinal Chemistry, vol. 20, No. 8, pp. 987-996 (1977).
Adrienne Adams et al., “Interaction of DNA-Intercalating Antitumor Agents with Andrenoceptors”, Molecular Pharmacology, vol. 27, pp. 480-491 (1985).
William Denny et al., “Pontetial Antitumor Agents. 36. Quantitative Relationships between Experimental Antitumor Activity, Toxicity, and Structure for the General Class of 9-Anilinoacridine Antitumor Agents”, J. Med. Chem., vol. 25, pp. 276-315 (1982).
Anne Marjamäki et al., “Stable expression of recombinant human &agr;2-adrenoceptor subtypes in two mammalian cell lines: characterization with [3H]rauwolscine binding, inhibition of adenylate cyclase and RNase protection assay”, Biochimica et Biophysica Acta, vol. 1134 pp. 169-177 (1992).
Jeffrey Jasper et al., “Ligand Efficacy and Potency at Recombinant &agr;2Adrenergic Receptors”, Biochemical Pharmacology, vol. 55, pp. 1035-1043 (1998).
Katariina Pohjanoksa et al., “&agr;2-Adrenoceptor regulation of adenylyl cyclase in CHO cells: dependence on receptor density, receptor subtype and current activity of adenylyl cyclase”, Eur. Journal of Pharmacology, vol. 335, pp. 53-63 (1997).
Harry Scheinin et al., “Behavioural and neurochemical effects of antipamezole, a novel &agr;2-adrenoceptor antagonist”, Eur. Journal of Pharmacology, vol. 151, pp. 35-42 (1988).
Jukka Sallinen et al., “Genetic Alteration of &agr;2c-Adrenoceptor Expression in Mice: Influence on Locomotor, Hypothermic, and Neurochemical Effects of Dexmedetomine, a Subtype-Nonselective &agr;2-Adrenoceptor Agonist”, Molecular Pharmacology, vol. 51 pp. 36-46 (1997).
Sallinen et al., “Genetic alteration of the &agr;2-adrenoceptor subtype c in mice effects the development of behavioral despair and stress-induced increases in plasma corticosterone levels”, Molecular Psychiatry, vol. 4, pp. 443-452 (1999).
Timo Kauppila et al., “Effects of atipamezole, a novel &agr;2-adrenoceptor antagonist, in open-field, plus-maze, two compartment exploratory, and forced swimming tests in the rat”, Eur. Journal of Pharmacology, vol. 205 pp. 117-182 (1991).
Steven Southwick et al., “Noradrenergic and Serotonergic Function in Posttraumatic Stress Disorder”, Arch Gen. Psychiatry, vol. 54, pp. 749-758 (1997).
Crawley et al., “Baseline Exploratory Activity Predicts Anxiolytic Responsiveness to Diazepam in Five Mouse Strains”, Brain Research Bulletin, vol. 8, pp. 609-612 (1982).
Sallinen et al., “D-Amphetamine and L-5-Hydroxytryptophan-Induced Behaviours in mice with Genetically-Altered expression of the &agr;2c-Adrenergic Receptor Subtype”, Neuroscience, vol. 86, No. 3, pp. 959-965 (1998).
Jukka Sallinen et al., “Adrenergic &agr;2c-Receptors Modulate the Acoustic Startle Reflex, Prepulse Inhibition, and Aggression in Mice”, The Journal of Neuroscience, vol. 18 (8), pp. 3035-3042 (1998).
Markus Björklund et al., “&agr;2c-Adrenoceptor-Overexpressing Mice Are Impaired in Excuting Nonspatial Escape Strategies”, Molecular Pharmacology, vol. 54, pp. 569-576 (1998).
Engström Mia
Haapalinna Antti
Hoffrén Anna-Marja Katariina
Höglund Iisa
Sallinen Jukka
Finnegan Henderson Farabow Garrett & Dunner LLP
Liu Hong
Orion Corporation
Raymond Richard L.
LandOfFree
Dervatives of quinoline as alpha-2 antagonists does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Dervatives of quinoline as alpha-2 antagonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Dervatives of quinoline as alpha-2 antagonists will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3020144