IP Library › Granted Patent US 9,012,450

Granted Patent B2

US 9,012,450 · App. 13/730,730 · Granted Apr 21, 2015

Substituted heteroaryl aldehyde compounds and methods for their use in increasing tissue oxygenation

Inventors: Brian Metcalf (Moraga, CA); Chihyuan Chuang (Millbrae, CA); Jeffrey Warrington (San Mateo, CA); Kumar Paulvannan (San Jose, CA); Matthew P. Jacobson (San Francisco, CA); Lan Hua (Mountain View, CA); Bradley Morgan (Moraga, CA)

Assignees: Global Blood Therapeutics, Inc.; Cytokinetics, Inc.; The Regents of the University of California

C07D487/04 C07D213/80 C07D471/04 C07D401/14 C07D401/12 C07D213/69

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Quick Facts

Patent No.: US 9,012,450
App. No.: 13/730,730
Granted: Apr 21, 2015
Kind: B2

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USPTO Patent Center↗ Full Patent PDF↗

Abstract

Provided are substituted heteroaryl aldehydes and derivatives thereof that act as allosteric modulators of hemoglobin, methods and intermediates for their preparation, pharmaceutical compositions comprising the modulators, and methods for their use in treating disorders mediate by hemoglobin and disorders that would benefit from increased tissue oxygenation.

Claims (52)

1. A compound selected from the group consisting of:

5-(imidazo[1,2-a]pyridin-8-ylmethoxy)-2-methoxyisonicotinaldehyde,

3-hydroxy-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

3-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methoxyisonicotinaldehyde,

5-((2-(1-cyclobutyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde,

3-chloro-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

3-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methylisonicotinaldehyde,

3-chloro-5-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

3-methyl-5-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-(2-methoxyethoxy)-5-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-methoxy-5-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-(2-methoxyethoxy)-5-((2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-methoxy-5-((2-(o-tolyl)pyridin-3-yl)methoxy)isonicotinaldehyde,

5-((2-(1-cyclopentyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde,

5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-(2-methoxyethoxyl)isonicotinaldehyde,

5-((2-(1-(2,2-difluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde,

2-methoxy-5-((2′-methoxy-[2,3′-bipyridin]-3-yl)methoxy)isonicotinaldehyde,

5-((3-(1-isopropyl-1H-pyrazol-5-yl)pyrazin-2-yl)methoxy)-2-methoxyisonicotinaldehyde,

3-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-6-methylpicolinaldehyde,

2-(2-methoxyethoxy)-5-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-methoxy-5-((2-(1-propyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-methoxy-5-((2-(1-(2-methoxyethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-methoxy-5-((2-phenylpyridin-3-yl)methoxy)isonicotinaldehyde,

5-((2-(1-isopropyl-4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde,

3-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)picolinaldehyde,

5-((3-(1-isopropyl-1H-pyrazol-5-yl)pyridin-4-yl)methoxy)-2-methoxyisonicotinaldehyde,

2-methyl-5-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

2-methyl-5-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

3-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde, and

3-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

or pharmaceutically acceptable salt thereof.

2. The compound of claim 1 the group consisting of: having the formula:

3-hydroxy-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde,

or pharmaceutically acceptable salt thereof.

3. The compound of claim 1 having the formula:

3-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methoxyisonicotinaldehyde; or pharmaceutically acceptable salt thereof.

4. The compound of claim 1 having the formula:

3-chloro-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde; or pharmaceutically acceptable salt thereof.

5. The compound of claim 1 having the formula:

3-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methylisonicotinaldehde;

or pharmaceutically acceptable salt thereof.

6. The compound of claim 1 having the formula:

3-chloro-5-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde; or pharmaceutically acceptable salt thereof.

7. The compound of claim 1 having the formula:

3-methyl-5-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde; or pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a compound of claim 1 .

9. A pharmaceutical composition comprising a compound of claim 2 .

10. A pharmaceutical composition comprising a compound of claim 3 .

11. A pharmaceutical composition comprising a compound of claim 4 .

12. A pharmaceutical composition comprising a compound of claim 5 .

13. A pharmaceutical composition comprising a compound of claim 6 .

14. A pharmaceutical composition comprising a compound of claim 7 .

Assignments (10)

RELEASE OF SECURITY INTEREST Recorded Oct 6, 2022

From: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT

To: GLOBAL BLOOD THERAPEUTICS, INC.

Reel/Frame 061620/0186 →

SECOND AMENDED AND RESTATED PATENT SECURITY AGREEMENT Recorded Dec 22, 2021

From: GLOBAL BLOOD THERAPEUTICS, INC.

To: BIOPHARMA CREDIT PLC

Reel/Frame 058575/0921 →

AMENDED AND RESTATED PATENT SECURITY AGREEMENT Recorded Dec 9, 2020

From: GLOBAL BLOOD THERAPEUTICS, INC.

To: BIOPHARMA CREDIT PLC

Reel/Frame 054664/0871 →

SECURITY INTEREST Recorded Dec 20, 2019

From: GLOBAL BLOOD THERAPEUTICS, INC.

To: BIOPHARMA CREDIT PLC

Reel/Frame 051396/0312 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 27, 2015

From: CYTOKINETICS, INC.

To: GLOBAL BLOOD THERAPEUTICS, INC.

Reel/Frame 035272/0422 →