IP Library Granted Patent US 9,266,885
Granted Patent B2
US 9,266,885 · App. 14/552,122 · Granted Feb 23, 2016

Substituted 5-fluoro-1H-pyrazolopyridines and their use

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Quick Facts
Patent No.
US 9,266,885
App. No.
14/552,122
Granted
Feb 23, 2016
Kind
B2
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.

Claims (65)

1. A method of treating hypertension or pulmonary hypertension in humans and animals comprising administering an effective amount of a compound of formula (I)

in which

R 1 represents hydrogen or (C 1 -C 4 )-alkyl,

where (C 1 -C 4 )-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

to a human or animal in need thereof.

2. The method of claim 1 , wherein in the compound of formula (I)

R 1 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 and

methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate nitrate.

4. The method of claim 1 , wherein the compound of formula (I) is :

5. A method of treating pulmonary hypertension in humans and animals comprising administering an effective amount of a compound of formula (I)

in which

R 1 represents hydrogen or (C 1 -C 4 )-alkyl,

where (C 1 -C 4 )-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.

6. The method of claim 5 , wherein in the compound of formula (I)

R 1 represents hydrogen or methyl,

where methyl may be substituted by a trifluoromethyl substituent,

or a salt thereof.

7. The method of claim 5 , 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-fluorobenzyI)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate maleate and

methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}lcarbamate nitrate.

8. The method of claim 5 , wherein the compound of formula (I) is:

9. A method of treating hypertension in humans and animals comprising administering an effective amount of a compound of formula (I)

in which

R 1 represents hydrogen or (C 1 -C 4 )-alkyl,

where (C 1 -C 4 )-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

to a human or animal in need thereof.

10. The method of claim 9 , wherein in the compound of formula (I)

R 1 represents hydrogen or methyl,

where methyl may be substituted by a trifluoromethyl substituent,

or a salt thereof.

11. The method of claim 9 , 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 and

methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-Yl]pyrimidin-5-yl}carbamate nitrate.

12. The method of claim 9 , wherein the compound of formula (I) is:

Assignments (6)
CHANGE OF PATENTEE ADDRESS Recorded Feb 8, 2021
From: ADVERIO PHARMA GMBH
To: ADVERIO PHARMA GMBH
Reel/Frame 056907/0570 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 4, 2021
From: FOLLMANN, MARKUS; STASCH, JOHANNES-PETER; REDLICH, GORDEN; ACKERSTAFF, JENS; GRIEBENOW, NILS; KROH, WALTER; KNORR, ANDREAS; BECKER, EVA-MARIA; WUNDER, FRANK; LI, VOLKHART MIN-JIAN; HARTMANN, ELKE; MITTENDORF, JOACHIM; SCHLEMMER, KARL-HEINZ; JAUTELAT, ROLF; BIERER, DONALD
To: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT
Reel/Frame 055151/0491 →
NUNC PRO TUNC ASSIGNMENT Recorded Feb 4, 2021
From: BAYER PHARMA AKTIENGESELLSCHAFT
To: BAYER INTELLECTUAL PROPERTY GMBH
Reel/Frame 055152/0031 →
CHANGE OF NAME Recorded Feb 4, 2021
From: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT
To: BAYER PHARMA AKTIENGESELLSCHAFT
Reel/Frame 055222/0814 →
CORRECTIVE ASSIGNMENT TO CORRECT THE APPLICATION NUMBER 14217644 PREVIOUSLY RECORDED AT REEL: 034577 FRAME: 0443. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Jan 21, 2015
From: BAYER INTELLECTUAL PROPERTY GMBH
To: ADVERIO PHARMA GMBH
Reel/Frame 034839/0604 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2014
From: BAYER INTELLECTUAL PROPERTY GMBH
To: ADVERIO PHARMA GMBH
Reel/Frame 034577/0443 →