# US 2010/0168196 A1 · N-Substituted (Benzoimidazol-2-yl)phenylamines, Processes for Their Preparation, Their Use as a Medicament or Diagnostic Aid, and a Medicament Comprising Them

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- Number: US 2010/0168196 A1
- Document ID: US20100168196A1
- Status: Published application
- Kind: A1
- Application number: 12/722,634
- Filed: 2010-03-12
- Published: 2010-07-01
- Earliest claimed: 2003-02-04
- Assignees: Sanofi-Aventis Deutschland GmbH
- Inventors: Uwe HEINELT; Hans-Jochen LANG; Armin HOFMEISTER; Klaus WIRTH; Martin HUG
- Web page: https://patentgrep.com/patent/US20100168196A1

## CPC

- C07D 235/30: Nitrogen atoms not forming part of a nitro radical
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 13/12: of the kidneys
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 33/00: Antiparasitic agents
- A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P 33/06: Antimalarials
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention is directed to the compound of formula (I), compositions containing said compounds to inhibit the sodium-proton exchanger of subtype 3 (NHE3) which are useful in the prevention or treatment of various disorders in a patient suffering from a disease state, such as, renal disorders including acute or chronic renal failure, disorders of biliary function and for respiratory disorders such as snoring or sleep apnea or for stroke.

## Claims

### Claim 1

A compound of formula I
wherein,
R1 and R4 are independently H, F, Cl, Br, C1-C4-alkyl or C1-C4-alkoxy, wherein the C1-C4-alkyl and C1-C4-alkoxy are independently optionally substituted by 1, 2, 3, 4, 5, 6, 7, 8 or 9 fluorine atoms;
R2 and R3 are independently H, F, OH, C1-C3-alkyl or C1-C3-alkoxy, wherein the C1-C3-alkyl and C1-C3-alkoxy are independently optionally substituted by 1, 2, 3, 4, 5, 6 or 7 fluorine atoms;
R5 is C2-C4-alkenyl or C3-C5-cycloalkyl, wherein the C2-C4-alkenyl and C3-C5-cycloalkyl are independently optionally substituted by 1, 2, 3, 4, 5, 6, 7, 8 or 9 fluorine atoms; and
R6 and R7 are independently F, Cl, Br, C1-C4-alkyl or C1-C3-alkoxy, wherein the C1-C4-alkyl and C1-C3-alkoxy are independently optionally substituted by 1, 2, 3, 4, 5, 6, 7, 8 or 9 fluorine atoms,
or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof.

### Claim 2

A compound which is:
(1H-benzoimidazol-2-yl)(2,6-dichlorophenyl)methylamine;
(1H-benzoimidazol-2-yl)(2,6-dichlorophenypethylamine;
(2,6-dichlorophenyl)(5-fluoro-1H-benzoimidazol-2-yl)methylamine;
(1H-benzoimidazol-2-yl)(2,6-dichlorophenypisopropylamine;
allyl(1H-benzoimidazol-2-yl)(2,6-dichlorophenyl)amine; or
(1H-benzoimidazol-2-yl)cyclopentyl(2,6-dichlorophenyl)amine;
or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof, and a pharmaceutically acceptable excipient or carrier.

### Claim 4 (depends on 2)

A pharmaceutical composition comprising the compound according to claim 2 or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof, and a pharmaceutically acceptable excipient or carrier.

### Claim 5 (depends on 1)

A method of inhibiting the activity of sodium-proton exchanger of subtype 3 in a patient in need thereof, comprising comprising administering to the patient an inhibitory amount of the compound according to claim 1 or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof

### Claim 6 (depends on 2)

A method of inhibiting the activity of sodium-proton exchanger of subtype 3 in a patient in need thereof, comprising comprising administering to the patient an inhibitory amount of the compound according to claim 2 or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof

### Claim 7 (depends on 1)

A method of treating a disorder of the respiratory drive, a respiratory disorder, a sleep-related respiratory disorder, sleep apnea, snoring, an acute renal disorder, a chronic renal disorder, an acute renal failure, a chronic renal failure, a disorder of an intestinal function, a disorder of high blood pressure, a disorder of essential hypertension, a disorder of the central nervous system, a disorder resulting from central nervous system overexcitability, epilepsy or centrally induced convulsion, a disorder of an anxiety state, depressions or psychoses, an ischemic state of the peripheral or central nervous system, a stroke, a disorder of acute or chronic damage to a peripheral organ or limb caused by an ischemic event, a disorder of a peripheral organ or limb caused by a reperfusion event, a disorder of atherosclerosis, a disorder of lipid metabolism, a disorder of thromboses, a disorder of biliary function, a disorder of infestation by ectoparasites, a disorder resulting from endothelial dysfunction, a protozoal disorder, malaria, for the preservation and storage of a transplant for a surgical procedure, for use in a surgical operation or an organ transplant, shock, diabetes or late damage from diabetes, or a disease in which cellular proliferation represents a primary or secondary cause, or for maintaining health and prolonging life, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof.

### Claim 8 (depends on 2)

A method of treating a disorder of the respiratory drive, a respiratory disorder, a sleep-related respiratory disorder, sleep apnea, snoring, an acute renal disorder, a chronic renal disorder, an acute renal failure, a chronic renal failure, a disorder of an intestinal function, a disorder of high blood pressure, a disorder of essential hypertension, a disorder of the central nervous system, a disorder resulting from central nervous system overexcitability, epilepsy or centrally induced convulsion, a disorder of an anxiety state, depressions or psychoses, an ischemic state of the peripheral or central nervous system, a stroke, a disorder of acute or chronic damage to a peripheral organ or limb caused by an ischemic event, a disorder of a peripheral organ or limb caused by a reperfusion event, a disorder of atherosclerosis, a disorder of lipid metabolism, a disorder of thromboses, a disorder of biliary function, a disorder of infestation by ectoparasites, a disorder resulting from endothelial dysfunction, a protozoal disorder, malaria, for the preservation and storage of a transplant for a surgical procedure, for use in a surgical operation or an organ transplant, shock, diabetes or late damage from diabetes, or a disease in which cellular proliferation represents a primary or secondary cause, or for maintaining health and prolonging life, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 2 or a pharmaceutically acceptable salt or trifluoroacetic acid salt thereof.