Aryl substituted pyrimidines and the use thereof

Details Aryl substituted pyrimidines and the use thereof Aryl substituted pyrimidines and the use thereof

2007-06-12

2007-06-12

Wilson, James O. (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C544S224000, C544S242000

Reexamination Certificate

active

10386483

ABSTRACT:
This invention relates to a method of treating disorders responsive to the blockade of sodium ion channels using novel aryl-substituted pyrimidine compounds of Formula I:or a pharmaceutically acceptable salt, or solvate thereof, wherein A, R1, R2, R3and R4are defined in the specification. The invention is also directed to the use of compounds of Formula I for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as antitinnitus agents, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.

REFERENCES:
patent: 4492792 (1985-01-01), Fujii et al.
patent: 5118686 (1992-06-01), Coates et al.
patent: 5232945 (1993-08-01), Hulin
patent: 5463071 (1995-10-01), Himmelsbach et al.
patent: 5569655 (1996-10-01), Dority, Jr. et al.
patent: 5589477 (1996-12-01), Chokai et al.
patent: 5602156 (1997-02-01), Kohn et al.
patent: 5728704 (1998-03-01), Mylari et al.
patent: 5744492 (1998-04-01), Kohn et al.
patent: 5795905 (1998-08-01), McCarthy et al.
patent: 5866578 (1999-02-01), Mylari et al.
patent: 5874440 (1999-02-01), Pamukcu et al.
patent: 6096766 (2000-08-01), Baker et al.
patent: 6239136 (2001-05-01), Pamukcu et al.
patent: 6335354 (2002-01-01), Hogenkamp
patent: 6414011 (2002-07-01), Hogenkamp et al.
patent: 2002/0006947 (2002-01-01), Hogenkamp et al.
patent: 2002/0040025 (2002-04-01), Hogenkamp et al.
patent: 2003/0022914 (2003-01-01), Maul et al.
patent: 2003/0055088 (2003-03-01), Shao et al.
patent: 2003/0069292 (2003-04-01), Hogenkamp et al.
patent: 2003/0073724 (2003-04-01), Shao et al.
patent: 2003/0109521 (2003-06-01), Sun et al.
patent: 1 122 533 (1962-01-01), None
patent: 0 019 811 (1980-12-01), None
patent: 0 395 328 (1990-10-01), None
patent: 0395328 (1990-10-01), None
patent: 0 665 224 (1994-04-01), None
patent: 2 052 487 (1981-01-01), None
patent: 2281295 (1995-03-01), None
patent: 05-058997 (1993-03-01), None
patent: WO 94/07867 (1994-04-01), None
patent: WO 94/26721 (1994-11-01), None
patent: WO 95/07695 (1995-03-01), None
patent: WO 95/11235 (1995-04-01), None
patent: WO 95/11235 (1995-04-01), None
patent: WO 96/39400 (1996-12-01), None
patent: WO 99/62518 (1999-12-01), None
patent: WO 00/66565 (2000-11-01), None
patent: WO 01/10842 (2001-02-01), None
patent: WO 01/27119 (2001-04-01), None
patent: WO 01/39777 (2001-06-01), None
Kampe et al., “2-cyano-3-ethoxyacrylamides . . . ”, Angewandte Chemie (1982), 94(7), 543-544.
Bredereck, H., et al., “Synthese des Pyrimido [4,5-d]pyrimidins,”Chem. Ber.106:3743-3752, Verlag Chemie (1973).
Coburn, R.A. and Taylor, M.D., “Mesoionic Purinone Analogs. VIII. Synthesis and Properties of Mesoionic 5-Substituted-6-methylimidazo [1,2-c]pyrimidine-2, 7-diones,”J. Heterocyclic. Chem.19:567-572, HeteroCorporation (1982).
Dong, L., et al., “Studies on the Reaction of amindines with α-chloro-α, β-unsaturated nitriles,”Gaodeng Xuexiao Huaxue Xuebao8:885-890, Gao deng xue wen ke xue bao wen zhai lian he bian ji bu (1987).
Guo, H.-Z. and Jia, J.-S., “Mass Spectra of 2-Aryl-4-Cyanoimidazoles and 2-Aryl-4-Aminopyrimidines,”Acta Pharm. Sinica22:608-611, Chinese Pharmaceutical Association (1987).
Haroyan, H.A., et al., “Pyrimidine Derivatives XLIV. Synthesis and Some Reactions of 2-Phenyl-4-Oxy-5- (p-Alkoxybenzyl)-6-Methylpyrimidines,”Arm. Khim. Zh.28:653-657 (1975).
Kaluzhskikh, A.N., et al., “Azines and Azoles. CIV. Reactions of 4-Chloro-2-phenyl-6H-1,3-thiazin-6-one with Nitrogenous Bases,”Russ. J. Gen. Chem.67:1126-1131, Maik Hayka/Interperiodica Publishing (1997).
Kramer, M.S., et al., “Pyrimidine derivatives. XLVI. Synthesis of diethylenimides of 2-phenyl-5-(p-alkoxybenzyl)-6-methyl-4-pyrimidylamidophosphoric acids,”Armyanskii Khimicheskii Zhurnal30:752-755, Aramdeiia nauk Arminaskoi SSR (1977).
Medwid, J.B., et al., “Preparation of Triazolo [1,5-c]pyrimidines as Potential Antiasthma Agents,”J. Med. Chem.33:1230-1241, American Chemical Society (1990).
Melik-Oganodzhangan, R.G., et al., “Study in a Series of New Pyrimidine Derivatives,” in:Tezisy Dokl.—Sov—Indiiskii Simp. Khim. Prir. Soedin,5th Ed., Akad. Nauk Armyanskoi SSR, pp. 56 (1978).
Nishino, T., et al., “The Reaction of 2-Dimethoxymethyl-3-Methoxypropionitrile with Benzamidine,”Tetrahedron Letters40:4321-4324, Pergamon Press (1968).
Nishino, T., et al., “The Reaction Mechanism of 2-Dimethoxymethyl-3-methoxypropiononitrile with Acetamidine. III. The Reaction with Benzamidine,”Bull. Chem. Soc. Japan46:253-259, The Chemical Society of Japan (1973)
Oostveen, E.A. and van der Plas, H.C., “Ring transformations in reactions of heterocyclic compounds with nucleophiles. Reactions of 4(6)-alkoxy-1-ethyl- and 4,6-dialkoxy-1-ethyl-pyrimidinium tetrafluoroborates with liquid ammonia,”Recl. Trav. Chim. Pays-Bas96:183-187, Societe chimique neerlandaise (1977).
Sakamoto, T., et al., “Studies on Pyrimidine Derivatives, XXXV. Iodination of 2-Aminopyrimidines, 4-Aminopyrimidines, and 4-Pyrimidinones with Iodine Chloridein situ,” Synthesis3:252-254, Georgg Thieme Verlag (1984).
Singh, B. and Lesher, G.Y., “Three Convenient and Novel Syntheses of 4-Amino-2-arylpyrimidines,”J. Heterocycl. Chem.14:1413-1414, HeteroCorporation (1977).
Singh, B., et al., “An Efficient and Facile Synthesis of Novel 2-Arylpyrido[2,3-d]pyrimidin-5 (8H)-ones,”Synlett9:549-550, Georg Thieme Verlag (1990).
Smyrl, N.R. and Smithwick III, R.W., “Hydroxide-Catalyzed Synthesis of Heterocyclic Aromatic Amine Derivatives from Nitriles,”J. Heterocyclic Chem.19:493-496, HeteroCorporation (1982).
Städeli, W. and von Philipsborn, W., “15N-NMR. Studies of Aminopyridines, Aminopyrimidines and of Some Diazine N-Oxides,”Helv. Chim. Acta63:504-522, Verlag Helvetica Chimica Acta (1980).
Van Meeteren, H.W. and Van Der Plas, H.C., “Ring Transformations in Reactions of Heterocyclic Halogeno Compounds with Nucleophiles (XX) Pyrimidines (XXII). Conversion of some 5-substituted 4-chloro-2-phenyl-pyrimidines into open-chain compounds by potassium amide in liquid ammonia,”Recl. Trav. Chim.90:105-116, Societe chimique neerlandaise (1971).
Wamhoff, H. and Materne, C., “The Reaction of 2-Amino-3-ethoxycarbonyl-4,5-dihydrofurans with Amidines and Hydrazines,”Liebigs Ann. Chem.754:113-118, Verlag Chemie GMBH (1971).
Yoneda, F., et al., “Dimethylamination and Nitrosation of Pyrimidines with N-Nitrosodimethylamine,”Chem. Pharm. Bull.21:260-263, Pharmaceutical Society of Japan (1973).
Yoneda, F., et al., “A New Synthesis of Purines,”J.C.S. Chem. Commun.14:551, Royal Society of Chemistry (1974).
Dialog File 351, Accession No. 10105405, Derwent WPI English language abstract of WO 94/26721 (Document AN2).
Patent Abstracts of Japan, English language abstract for JP 05-058997 (Document AP1).
STNEasy, Chemical Abstracts Service, English language abstract for Dong, L., et al., “Reaction of amindines with α-chloro-α, β-unsaturated nitriles,”Gaodeng Xuexiao Huaxue Xuebao8:885-890, Gao deng xue wen ke xue bao wen zhai lian he bian ji bu (1987) (Document AT1).
STNEasy, Chemical Abstracts Service, English language abstract for Kramer, M.S., et al., “Pyrimidine derivatives, XLVI. Synthesis of diethylenimides of 2-phenyl-5-(p-alkoxybenzyl)-6-methyl-4-pyrimidylamidophosphoric acids,”Armyanskii Khimicheskii Zhurnal30:752-755, Aramdeiia nauk Arminaskoi SSR (1977) (Document AR3).
STNEasy, Chemical Abstracts Service, English language abstract for Melik-Oganodzhangan, R.G., et al., in:Tezisy Dokl.—Sov.—Indiiskii Simp. Khim. Prir. Soedin,5th Ed., Akad. Nauk Armyanskoi SSR, pp. 56 (1978) (Docu

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