Claims for Patent: 8,420,656

Summary for Patent: 8,420,656

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):	Follmann; Markus (Wulfrath, DE), Stasch; Johannes-Peter (Solingen, DE), Redlich; Gorden (Bochum, DE), Ackerstaff; Jens (Dusseldorf, DE), Griebenow; Nils (Dormagen, DE), Kroh; Walter (Wuppertal, DE), Knorr; Andreas (Erkrath, DE), Becker; Eva-Maria (Wuppertal, DE), Wunder; Frank (Wuppertal, DE), Li; Volkhart Min-Jian (Velbert, DE), Hartmann; Elke (Wuppertal, DE), Mittendorf; Joachim (Wuppertal, DE), Schlemmer; Karl-Heinz (Wuppertal, DE), Jautelat; Rolf (Haan, DE), Bierer; Donald (Haan, DE)
Assignee:	Bayer Intellectual Property GmbH (Monheim, DE)
Application Number:	13/111,856
Patent Claims:	1. A compound of formula (I) ##STR00045## in which R.sup.1 represents hydrogen or (C.sub.1-C.sub.4)-alkyl, where (C.sub.1-C.sub.4)-alkyl may be substituted by one or two substituents independently of one another selected from the group consisting of fluorine and trifluoromethyl, and their N-oxides, salts, and salts of the N-oxides. 2. The compound of the formula (I) according to claim 1 in which R.sup.1 represents hydrogen or methyl, where methyl may be substituted by a trifluoromethyl substituent, and salts thereof. 3. The compound of the formula (I) according to claim 1, selected from the group consisting of: methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]pyrimidin-5-yl}carbamate; methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]pyrimidin-5-yl}methylcarbamate; methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]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-y- l]pyrimidin-5-yl}carbamate hydrochloride; methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]pyrimidin-5-yl}carbamate sulphate; methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]pyrimidin-5-yl}carbamate phosphate; methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]pyrimidin-5-yl}carbamate mesylate; methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]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-y- l]pyrimidin-5-yl}carbamate maleate; and methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-y- l]pyrimidin-5-yl}carbamate nitrate. 4. A process for preparing a compound of claim 1, wherein a compound of the formula (II) ##STR00046## [A] is reacted in an inert solvent in the presence of hexabutyltin and a suitable palladium catalyst with intermediate formation of a tin species with the compound of the formula (III) ##STR00047## to give the compound of the formula (IV) ##STR00048## this is then reduced in an inert solvent with a suitable reducing agent to give the compound of the formula (V) ##STR00049## and this is then reacted in the presence of a suitable base in the presence or absence of a solvent with methyl chloroformate to give the compound of the formula (I-A) ##STR00050## or [B] the compound of the formula (II) is reacted in an inert solvent with copper cyanide to give the compound of the formula (VI) ##STR00051## this is then, under acidic conditions, converted into the compound of the formula (VII) ##STR00052## this is subsequently reacted in an inert solvent in the presence of a suitable base with the compound of the formula (VIII) ##STR00053## to give the compound of the formula (IX) ##STR00054## and this is then reduced in an inert solvent in the presence of a suitable reducing agent to give the compound (V), and this is subsequently reacted further according to process [A] to give compound (I-A), or [C] the compound of the formula (I-A) is reacted in an inert solvent in the presence of a suitable base with a compound of the formula (X) R.sup.1A--X.sup.1 (X), in which R.sup.1A represents (C.sub.1-C.sub.4)-alkyl, where (C.sub.1-C.sub.4)-alkyl may be substituted by one or two substituents independently of one another selected from the group consisting of fluorine and trifluoromethyl, and X.sup.1 represents a leaving group such as, for example, halogen, in particular bromine or iodine, trichloromethanesulphonate, mesylate or tosylate to give a compound of the formula (I-B) ##STR00055## in which R.sup.1A has the meaning given above, and the resulting compounds of the formulae (I-A) and (I-B) are, where appropriate, converted with the appropriate (i) solvents and/or (ii) acids or bases into their solvates, salts and/or solvates of the salts. 5. A pharmaceutical formulation comprising a compound of claim 1 and an inert, non-toxic, pharmaceutically suitable excipient. 6. A pharmaceutical composition comprising a compound of claim 1 and a further active compound selected from the group consisting of an organic nitrate, an NO donor, a cGMP-PDE inhibitor, an agent having antithrombotic activity, an agent for lowering blood pressure, and an agent for altering lipid metabolism. 7. A compound of the formula: ##STR00056## or a salt thereof.