Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2009-08-27
2011-10-25
Henley, III, Raymond (Department: 1629)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S236200, C514S259100, C514S259500, C514S281000
Reexamination Certificate
active
08044050
ABSTRACT:
The present invention relates to derivatives of imidazo[1,2-a]azines of formula I,in which R, R1 to R3, X, Y and n have the meanings indicated in the claims, which modulate the transcription of endothelial nitric oxide (NO) synthase and are valuable pharmacologically active compounds. Specifically, the compounds of formula I upregulate the expression of the enzyme endothelial NO synthase and can be applied in conditions in which an increased expression of said enzyme or an increased NO level or the normalization of a decreased NO level is desired. The invention further relates to processes for the preparation of compounds of formula I, to pharmaceutical compositions comprising them, and to the use of compounds of formula I for the stimulation of the expression of endothelial NO synthase or for the treatment of various diseases including cardiovascular disorders such as atherosclerosis, thrombosis, coronary artery disease, hypertension and cardiac insufficiency, for example.
REFERENCES:
patent: 4716169 (1987-12-01), Heider et al.
patent: 0185346 (1986-06-01), None
patent: WO 99/47153 (1999-09-01), None
patent: WO 00/03746 (2000-01-01), None
patent: WO 02/064146 (2002-08-01), None
patent: WO 02/064545 (2002-08-01), None
patent: WO 02/064546 (2002-08-01), None
patent: WO 02/064565 (2002-08-01), None
patent: WO 2004/014369 (2004-02-01), None
patent: WO 2004/014372 (2004-02-01), None
patent: WO 2004/014842 (2004-02-01), None
patent: WO 2004/094425 (2004-11-01), None
patent: WO 2007/034282 (2007-03-01), None
Wang, et al., 6-Chloro-2-4-Fluorophenyl)Imidazo[1,2-b]-Pyridazine, Acta Crystallographica, Section E, vol. e61, No. 12, pp. 4030-4031, (2005).
Barlin, G. B., et. al., Imidazo [1,2-b] Pyridazines. XX*t Syntheses of Some 3-Acylaminomethyl-6-(Chloro, Fluoro, Methoxy, Methylthio, Phenoxy and Phenylthio)-2-(Phenyl, 4-t-Butyiphenyl, 4-Cyclohexylphenyl, B-Naphthyl and Styryl) Imidazo [1,2-b] Pyridazines and Their Interaction with Central and Peripheral-Type Benzodiazepine Receptors, Aust. J. Chem., vol. 49, pp. 451-461, (1996).
Barlin, G. B., et. al., Imidazo[1,2-b] Pyridazines. XII* Syntheses and Central Nervous System Activities of Some Substituted Imidazo [1,2-b]Pyridazines and Related Imidazo [1,2-a]Pyridines, Imidazo [1,2-a]Pyrimidines and Imidazo [1,2-a]Pyrazines, Aust, J. Chem., (1992), vol. 45, pp. 877-888.
Barraclough, P., et. al., Inotropic 2-Arylimidazol[1,2-a]Pyrimidines, Eur. J. Med. Chem., (1992) vol. 27, pp. 207-217.
Bjorklund, M. D., et. al.,, 3,3-Dinitrobutyl-1,2,4-Oxadiazoles (1) , J. Heterocyclic Chem., vol. 17, (1980), pp. 819-821.
Bose, D.S., et. al., A Practical Method for the Preparation of Nitriles from Primary Amides Under Non-Acidic Conditions, Synthesis 1999 (1) pp. 64-65.
Endres, M., et al. , Stroke Protection By 3-Hydroxy-3-Methylglutaryl (HMG)—CoA Reductase Inhibitors Mediated By Endothelial Nitric Oxide Synthase, Proc. Natl. Acad. Sci. USA, 95 (1998) 8880-8885.
Katsifis, A., et. al., Synthesis of [123I]Iodine Labelled Imidazo [1,2-b] Pyridazines as Potential Probes for the Study of Peripheral Benzodiazepine Receptors Using SPECT, Radiochim. Acta. vol. 92, pp. 305-309, (2004).
Li, H., et. al., Activation of Protein Kinase Ca and/or e Enhances Transcription of the Human Endothelial Nitric Oxide Synthase Gene, Molecular Pharmacology, vol. 53, pp. 630-637, (1998).
Moroi, et. al., Interaction Of Genetic Deficiency Of Endothelial Nitric Oxide, Gender, and Pregnancy in Vascular Response To Injury In Mice, J. Clin. Invest., 1998 (101) 6 pp. 1225-1232.
Nakayama, et. al., T-786-> C Mutation in the 5′ -Flanking Region Of The Endothelial Nitric Oxide Synthase Gene Is Associated With Coronary Spasm, Circulation 1999 (99) pp. 2864-2870.
Sessa, et. al., Chronic Exercise In Dogs Increases Coronary Vascular Nitric Oxide Production And Endothelial Cell Nitric Oxide Synthase Gene Expression, Circ. Res., 1994 (74) 2, pp. 349-353.
Varenne, O., et al., Percutaneous Gene Therapy Using Recombinant Adenoviruses Encoding Human Herpes Simplex Virus Thymidine Kinase, Human PAI-1, and Human NOS3 in Balloon-Injured Porcine Coronary Arteries, Human Gene Therapy (2000), 11:1329-1339.
Veenmann, L., et. al., The Peripheral-Type Benzodiazepine Receptor and the Cardiovascular System. Implications for Drug Development, Pharmacology & Therapeutics, vol. 110, (2006), pp. 503-534.
Wagner, G., et. al., Synthese Von 3-[Amidinophenyl]-Alaninen Und 3-[Amidinophenyl]-Milchsauren1, Pharmazie, vol. 29, No. 1, (1974), pp. 12-15.
Li, et. al., Discovery of Potent 3,5-Diphenyl-1,2,4-oxadiazole Sphingosine-1-phosphate-1 (S1P1) Receptor Agonists with Exceptional Selectivity against S1P2 and S1P3, J. Med. Chem., 2005 (48) 20, pp. 6169-6173.
Strobel Hartmut
Will David William
Wohlfart Paulus
Zoller Gerhard
Henley III Raymond
Sanofi-Aventis
Scully , Scott, Murphy & Presser, P.C.
LandOfFree
Imidazo[1,2-a]azines and their use as pharmaceuticals does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Imidazo[1,2-a]azines and their use as pharmaceuticals, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Imidazo[1,2-a]azines and their use as pharmaceuticals will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-4272773