# US 8,569,339 B2 · Soluble guanylate cyclase activators

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- Number: US 8,569,339 B2
- Document ID: US8569339B2
- Status: Granted
- Kind: B2
- Application number: 13/414,991
- Filed: 2012-03-08
- Published: 2013-03-14
- Granted: 2013-10-29
- Earliest claimed: 2011-03-10
- Assignees: Boehringer Ingelheim International GmbH
- Applicants: Jehrod Burnett Brenneman; John D. Huber; Brian Christopher Raudenbush; Christopher Ronald Sarko
- Inventors: Jehrod Burnett Brenneman; John D. Huber; Brian Christopher Raudenbush; Christopher Ronald Sarko
- Web page: https://patentgrep.com/patent/US8569339B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/08: Vasodilators for multiple indications
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 13/08: of the prostate
- A61P 13/10: of the bladder
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/10: for impotence
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: 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
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 29/02: without antiinflammatory effect
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 405/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, A and B are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

## Claims

### Claim 1

A compound of the formula I
wherein:
A is a 5- or 6-membered aryl, heteroaryl or heterocyclyl group;
B is a 5-7 membered heterocyclyl group containing one nitrogen, wherein one carbon of the heterocyclyl group is optionally substituted with an oxo group, or B is a 5-membered heteroaryl group containing at least 2 nitrogens;
R1 and R2 are independently selected from H, C1-4alkyl, C3-6cycloalkyl, tetrahydropyranyl, —CF3, —CH2CF3 and —CH2CH2CO2H;
R3 is selected from H and —CH3;
R4 is selected from H, C1-6alkyl, C3-7cycloalkyl, —C(O)C1-6alkyl, —CH2CF3, —SO2C1-6alkyl, —SO2(CH2)1-3CO2H, —CO2C1-4alkyl, heterocyclyl, aryl, heteroaryl, —(C0-2alkyl)heterocyclyl, —(C1-2alkyl)aryl and —(C1-2alkyl)heteroaryl,
wherein said heterocyclyl is selected from tetrahydrofuranyl, azetidinyl, pyrrolidinyl, pyranyl, tetrahydropyranyl, dioxanyl, thiomorpholinyl, 1,1-dioxo-1λ6-thiomorpholinyl, morpholinyl, piperidinyl, piperazinyl, and azepinyl, and
said heterocyclyl, cycloalkyl, aryl and heteroaryl are optionally substituted with one to two groups independently selected from C1-3alkyl, —CF3, and halogen,
or R4 is optionally not present when B is a heteroaryl group;
R5 is selected from H, —C1-3alkyl, —OCH3, —CF3, —CN and Cl; and
R6 is selected from H and CH3;
provided that R5 and R6 are not both H;
or a salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1 wherein
is a 5- or 6-membered aryl, heteroaryl or heterocyclyl group selected from:
is selected from:
R1 and R2 are independently selected from H, C1-4alkyl, cyclopropyl and —CF3;
R4 is selected from H, C1-6alkyl, C3-7cycloalkyl, —C(O)C1-6alkyl, —CH2CF3, —SO2C1-6alkyl, —SO2(CH2)1-3CO2H, —CO2C1-4alkyl, heterocyclyl, phenyl, heteroaryl, —(C0-2alkyl)heterocyclyl, —(C1-2alkyl)phenyl and —(C1-2alkyl)heteroaryl,
wherein said heterocyclyl is selected from tetrahydrofuranyl and tetrahydropyranyl, and
said heteroaryl is selected from imidazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridinyl, pyrimidinyl, thiazolyl and 4,5,6,7-tetrahydrobenzothiazolyl,
and wherein said heterocyclyl, cycloalkyl, phenyl and heteroaryl are optionally substituted with one to two groups independently selected from methyl, ethyl, —CF3 and fluorine;
R5 is selected from H, —CH3, —CH2CH3, —OCH3, and —CF3; and
R6 is selected from H and —CH3;
provided that R5 and R6 are not both H;
or a salt thereof.

### Claim 3 (depends on 2)

The compound according to claim 2 wherein the group
is selected from
or a salt thereof.

### Claim 4 (depends on 2)

The compound according to claim 2 wherein the group
is selected from:
or a salt thereof.

### Claim 5 (depends on 2)

The compound according to claim 2 wherein the group
is:
or a salt thereof.

### Claim 6 (depends on 4)

The compound according to claim 4 wherein the group
is:
or a salt thereof.

### Claim 7 (depends on 5)

The compound according to claim 5 wherein the group
is:
or a salt thereof.

### Claim 8 (depends on 5)

The compound according to claim 5 wherein the group
is:
or a salt thereof.

### Claim 9

A compound selected from the group consisting of
and the pharmaceutically acceptable salts thereof.

### Claim 10 (depends on 9)

The compound according to claim 9 selected from the group consisting of compound numbers 1-6, 8, 12, 14, 16-35, 37, 38, 48, 50, 51, 53-56, 60-65 and 67-91;
and the pharmaceutically acceptable salts thereof.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient or carrier.

### Claim 12 (depends on 1)

A method of treating a disease or disorder that can be alleviated by sGC activation or potentiation comprising administering a therapeutically effective amount of a compound of claim 1 to patient in need thereof.

### Claim 13 (depends on 12)

The method according to claim 12 wherein the disease or disorder is selected from a cardiovascular disease, inflammatory disease, hepatic fibrotic disorder, renal fibrotic disorder, pulmonary fibrotic disorder and cardiac fibrotic disorder.

### Claim 14 (depends on 12)

The method according to claim 12 where the disease is selected from renal disease, overactive bladder, benign prostatic hyperplasia, erectile dysfunction, Alzheimer's disease, Parkinson's disease and neuropathic pain.