# US 7,034,038 B2 · Enantiomer (-) of tenatoprazole and the therapeutic use thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,034,038 B2
- Document ID: US7034038B2
- Status: Granted
- Kind: B2
- Application number: 10/507,485
- Filed: 2003-12-16
- Published: 2005-06-02
- Granted: 2006-04-25
- Earliest claimed: 2002-12-16
- Assignees: Sidem Pharma
- Inventors: Avraham Cohen; Suzy Charbit; François Schutze; Hervé Ficheux; Michel Homerin; Alain Taccoen
- Web page: https://patentgrep.com/patent/US7034038B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to enantiomer (−) of tentoprazole. The inventive enantiomer (−) of tenatoprazole, or (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine exhibits improved pharmacokinetic properties which make it possible to use a once a day posology of a drug for relevant indications. Said invention can be used for curing digestive pathologies.

## Claims

### Claim 1

The compound (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine, or one of its salts, substantially free of the (+) enantiomer.

### Claim 2

A pharmaceutical composition comprising (+)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine or a pharmaceutically acceptable salt thereof, substantially free of the (+) enantiomer, and one or more pharmaceutically acceptable excipients or substrates.

### Claim 3 (depends on 2)

The pharmaceutical composition according to claim 2, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine is a pharmaceutically acceptable salt selected from the group consisting of alkaline and earth-alkaline metal salts.

### Claim 4 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine is a pharmaceutically acceptable salt selected from the group consisting of sodium, potassium, lithium, magnesium and calcium salts.

### Claim 5 (depends on 2)

The pharmaceutical composition according to claim 2, comprising a unitary dose comprising from about 10 mg to about 80 mg of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine.

### Claim 6 (depends on 3)

The pharmaceutical composition according to claim 3, comprising a unitary dose comprising from about 10 mg to about 80 mg of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine.

### Claim 7 (depends on 4)

The pharmaceutical composition according to claim 4, comprising a unitary dose comprising from about 10 mg to 80 mg of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine.

### Claim 8

A method of treatment of digestive diseases and conditions comprising administering to a subject in need thereof an effective amount of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer, or a pharmaceutically acceptable salt thereof,
wherein the digestive diseases and conditions are selected from the group consisting of Barrett's syndrome, Zollinger-Ellison syndrome, and atypical and oesophageal symptoms of gastro-oesophageal reflux.

### Claim 9

A method for the treatment of digestive diseases and conditions comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine or a pharmaceutically acceptable salt thereof, substantially free of the (+) enantiomer, and one or more pharmaceutically acceptable excipients or substrates,
wherein the digestive diseases and conditions are selected from the group consisting of Barrett's syndrome, Zollinger-Ellison syndrome, atypical and oesophageal symptoms of gastro-oesophageal reflux.

### Claim 10

A method of treatment of an ulcer resulting from an infection by Helicobacter pylori comprising administering to a subject in need thereof an effective amount of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer, or a pharmaceutically acceptable salt thereof.

### Claim 11

A method of treatment of an ulcer resulting from an infection by Helicobacter pylori comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine or a pharmaceutically acceptable salt thereof, substantially free of the (+) enantiomer, and one or more pharmaceutically acceptable excipients or substrates.

### Claim 12

A method of treating or preventing the relapse of oesophagitis comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine or a pharmaceutically acceptable salt thereof, substantially free of the (+) enantiomer, and one or more pharmaceutically acceptable excipients or substrates.

### Claim 13

A method of treating or preventing the relapse of oesophagitis comprising administering to a subject in need thereof an effective amount of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 8)

A method for the treatment of digestive diseases and conditions according to claim 8, wherein the effective amount of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer exhibits improved pharmacokinetic properties.

### Claim 15 (depends on 8)

The method of claim 8, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer or pharmaceutically acceptable salt thereof is administered orally.

### Claim 16 (depends on 8)

The method of claim 8, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer or pharmaceutically acceptable salt thereof is administered via a parenteral solution.

### Claim 17 (depends on 15)

The method of claim 15, wherein the oral administration is via tablet, capsule or oral suspension or oral emulsion.

### Claim 18 (depends on 16)

The method of claim 16, wherein the parenteral administration is via an intravenous solution.

### Claim 19 (depends on 16)

The method of claim 16, wherein the parenteral solution comprises a tenatoprazole salt and a pharmaceutically acceptable substrate.

### Claim 20 (depends on 15)

The method of claim 15, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer is administered in an amount of about 10 mg to about 120 mg per day.

### Claim 21 (depends on 20)

The method of claim 20, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer is administered in an amount of about 10 mg to about 80 mg per day.

### Claim 22 (depends on 15)

The method of claim 15, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer is administered once per day.

### Claim 23 (depends on 15)

The method of claim 15, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer is administered once per day for a period of about four to about twelve weeks.

### Claim 24 (depends on 15)

The method of claim 15, wherein the (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer is administered first via an intravenous route and subsequently via an oral route.

### Claim 25 (depends on 17)

The method of claim 17, wherein the tablet is administered once per week and wherein the tablet comprises about 60 mg to about 90 mg of (−)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]imidazol[4,5-b]pyridine substantially free of the (+) enantiomer.