Benzyl-1h-pyrazolo[3,4-b]pyridines and use thereof

Patent metadata

Field	Value
Publication number	US-2016145271-A1
Application number	US-201414903347-A
Country	US
Kind code	A1
Filing date	Jul 8, 2014
Priority date	Jul 10, 2013
Publication date	May 26, 2016
Grant date	—

Abstract

The present application relates to novel benzyl-1H-pyrazolo[3,4-b]pyridines, 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.

First claim

1 . A compound the formula (I):

in which
R 1 represents hydrogen or fluorine,
R 2 represents hydrogen or fluorine,
R 3 represents hydrogen, chlorine or fluorine,
R 4 represents hydrogen, chlorine, fluorine or methyl,
with the proviso that at least two of the radicals R 1 , R 2 , R 3 or R 4 are different from hydrogen,
R 5 represents hydrogen or fluorine,
R 6 represents methyl,
R 7 represents methyl,
or
R 6 and R 7 together with the carbon atom to which they are attached form a cyclopropyl ring,
and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides or salts thereof.

2 . A compound having the systematic name 3-[1-(2,3-difluorobenzyl)-5-fluoro-6-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one and the structural formula (I-A):

and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides or salts thereof.

3 . A compound having the systematic name 3-[1-(2,3-difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one and the structural formula (I-B):

and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides or salts thereof.

4 . A compound having the systematic name 3-[5-fluoro-1-(2-fluoro-4-methylbenzyl)-6-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one and the structural formula (I-C):

and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides or salts thereof.

5 . A compound having the systematic name 3-[5-fluoro-6-methyl-1-(2,3,6-trifluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one and the structural formula (I-I):

and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides or salts thereof.

6 . A compound having the systematic name 3-[1-(2,3-difluoro-4-methylbenzyl)-5-fluoro-6-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-e][1,2,4]triazin-6-one and the structural formula (I-Q):

and the N-oxides, salts, solvates, salts of the N-oxides and solvates of the N-oxides or salts thereof.

7 . (canceled)

8 . (canceled)

9 . A medicament comprising the compound of claim 1 in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

10 . A medicament comprising the compound of claim 1 in combination with a 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.

11 . (canceled)

12 . A method for treatment and/or prophylaxis of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischaemias, vascular disorders, renal insufficiency, thromboembolic disorders, fibrotic disorders, arteriosclerosis, dementia disorders and erectile dysfunction in humans and animals, comprising administering an effective amount of compound of claim 1 to a human or animal in need thereof.

13 . A medicament comprising the compound of claim 2 in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

14 . A medicament comprising the compound of claim 3 in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

15 . A medicament comprising the compound of claim 4 in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

16 . A medicament comprising the compound of claim 5 in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

17 . A medicament comprising the compound of claim 6 in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

18 . A medicament comprising the compound of claim 2 in combination with a 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.

19 . A medicament comprising the compound of claim 3 in combination with a 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.

20 . A medicament comprising the compound of claim 4 in combination with a 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.

21 . A medicament comprising the compound of claim 5 in combination with a 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.

22 . A medicament comprising the compound of claim 6 in combination with a 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.

23 . A method for treatment and/or prophylaxis of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischaemias, vascular disorders, renal insufficiency, thromboembolic disorders, fibrotic disorders, arteriosclerosis, dementia disorders and erectile dysfunction in humans and animals, comprising administering an effective amount of the compound of claim 2 to a human or animal in need thereof.

24 . A method for treatment and/or prophylaxis of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischaemias, vascular disorders, renal insufficiency, thromboembolic disorders, fibrotic disorders, arteriosclerosis, dementia disorders and erectile dysfunction in humans and animals, comprising administering an effective amount of the compound of claim 3 to a human or animal in need thereof.

25 . A method for treatment and/or prophylaxis of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischaemias, vascular disorders, renal insufficiency, thromboembolic disorders, fibrotic disorders, arteriosclerosis, dementia disorders and erectile dysfunction in humans and animals, comprising administering an effective amount of the compound of claim 4 to a human or animal in need thereof.

26 . A method for treatment and/or prophylaxis of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischaemias, vascular disord

Assignees

• Bayer Pharma AG

Inventors

• Vakalopoulos Alexandros
• Gromov Alexey
• Follmann Markus
• Brockschnieder Damian
• Stasch Johannes-Peter
• Marquardt Tobias
• Tersteegen Adrian
• Wunder Frank
• Redlich Gorden
• Lang Dieter
• Li Volkhart Min-Jian

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title