Claims for Patent: 8,921,377

Summary for Patent: 8,921,377

Title:	Substituted 5-fluoro-1H-pyrazolopyridines and their use
Abstract:	The present application relates to novel substituted 5-fluoro-1H-pyrazolopyridines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.
Inventor(s):	Markus Follmann, Johannes-Peter Stasch, Gorden Redlich, Jens Ackerstaff, Nils Griebenow, Walter Kroh, Andreas Knorr, Eva-Maria Becker, Frank Wunder, Volkhart Min-Jian Li, Elke Hartmann, Joachim Mittendorf, Karl-Heinz Schlemmer, Rolf Jautelat, Donald Bierer
Assignee:	Adverio Pharma GmbH
Application Number:	US13/851,373
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,921,377
Patent Claims:	1. A method of treatment of heart failure in humans and animals by administration of an effective amount of at least one compound of formula (I) in which R1 represents hydrogen or (C1-C4)-alkyl, where (C1-C4)-alkyl may be substituted by one or two substituents independently of one another selected from the group consisting of fluorine and trifluoromethyl, or a salt thereof. 2. The method of claim 1, wherein in the compound of formula (I) R1 represents hydrogen or methyl, where methyl may be substituted by a trifluoromethyl substituent, or a salt thereof. 3. The method of claim 1, wherein the compound of formula (I) is selected from the group consisting of: methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}(2,2,2-trifluoroethyl)carbamate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate hydrochloride methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate sulphate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate phosphate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate mesylate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate ethane-1,2-disulphonate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate maleate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate nitrate. 4. A method of treatment of heart failure comprising administering to a human or animal an effective amount of a pharmaceutical composition, comprising a compound of formula (I) and an inert, non-toxic, pharmaceutically suitable excipient, wherein the compound of formula I is: in which R1 represents hydrogen or (C1-C4)-alkyl, where (C1-C4)-alkyl may be substituted by one or two substituents independently of one another selected from the group consisting of fluorine and trifluoromethyl, or a salt thereof. 5. The method of claim 4, wherein the pharmaceutical composition further comprises further active compound selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism. 6. The method of claim 4, wherein in the compound of formula (I): R1 represents hydrogen or methyl, where methyl may be substituted by a trifluoromethyl substituent, or a salt thereof. 7. The method of claim 4, wherein the compound of formula (I) is selected from the group consisting of: methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}(2,2,2-trifluoroethyl)carbamate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate hydrochloride methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate sulphate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate phosphate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate mesylate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate ethane-1,2-disulphonate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate maleate methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate nitrate. 8. The method of claim 4, wherein the compound of formula (I) is: 9. The method of claim 1, wherein the compound of formula (I) is: 10. The method of claim 1, wherein the heart failure is chronic heart failure. 11. The method of claim 4, wherein the heart failure is chronic heart failure. 12. A method of treatment of chronic heart failure comprising administering to a human or animal an effective amount of a compound of formula: or a salt thereof.