# US 8,772,285 B2 · Benzothiazoles having histamine H3 receptor activity

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

- Number: US 8,772,285 B2
- Document ID: US8772285B2
- Status: Granted
- Kind: B2
- Application number: 13/660,045
- Filed: 2012-10-25
- Published: 2013-03-28
- Granted: 2014-07-08
- Earliest claimed: 2006-03-28
- Assignees: High Point Pharmaceuticals, LLC
- Applicants: Florencio Zaragoza Dorwald; Inge Thoger Christensen
- Inventors: Florencio Zaragoza Dorwald; Rolf Hohlweg; Inge Thoger Christensen; Jane Marie Lundbeck; Knud Erik Andersen
- Web page: https://patentgrep.com/patent/US8772285B2

## 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
- A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics
- A61P 1/12: Antidiarrhoeals
- A61P 1/14: Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 5/06: of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A61P 5/10: of the posterior pituitary hormones, e.g. oxytocin, ADH
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/06: Antimigraine agents
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/24: Antidepressants
- 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 35/00: Antineoplastic agents
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 263/58: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D 277/82: Nitrogen atoms
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- 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

Certain novel benzothiazoles and benzoxazoles, e.g., 2-(piperazin-1-yl)benzothiazoles and 2-(piperazin-1-yl)benzoxazoles, optionally substituted in the 3 and/or 4 positions of the piperazine rings, having histamine H3 antagonistic activity can be used in pharmaceutical compositions.

## Claims

### Claim 1

A method of treating obesity comprising administering to a human subject a compound selected from the group consisting of:
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]piperidin-1-ylmethanone,
2-(4-isopropylpiperazin-1-yl)benzothiazole-6-carboxylic acid dimethylamide,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]morpholin-4-ylmethanone,
2-(4-isopropylpiperazin-1-yl)-6-piperidin-1-ylmethylbenzothiazole,
2-(4-isopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(piperidin-1-ylmethyl)benzothiazole,
cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine,
2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-ylmethyl]dimethylamine, and
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-yl]pyrrolidin-1-ylmethanone;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound is 2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound is cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the compound is 2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.

### Claim 5

A method of reducing weight comprising administering to a human subject a compound selected from the group consisting of
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]piperidin-1-ylmethanone,
2-(4-isopropylpiperazin-1-yl)benzothiazole-6-carboxylic acid dimethylamide,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]morpholin-4-ylmethanone,
2-(4-isopropylpiperazin-1-yl)-6-piperidin-1-ylmethylbenzothiazole,
2-(4-isopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(piperidin-1-ylmethyl)benzothiazole,
cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine,
2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-ylmethyl]dimethylamine, and
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-yl]pyrrolidin-1-ylmethanone;
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the compound is 2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 5)

The method of claim 5, wherein the compound is cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 5)

The method of claim 5, wherein the compound is 2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.

### Claim 9

A method of suppressing appetite or inducing satiety comprising administering to a human subject a compound selected from the group consisting of:
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]piperidin-1-ylmethanone,
2-(4-isopropylpiperazin-1-yl)benzothiazole-6-carboxylic acid dimethylamide,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]morpholin-4-ylmethanone,
2-(4-isopropylpiperazin-1-yl)-6-piperidin-1-ylmethylbenzothiazole,
2-(4-isopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(piperidin-1-ylmethyl)benzothiazole,
cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine,
2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-ylmethyl]dimethylamine, and
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-yl]pyrrolidin-1-ylmethanone;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 9)

The method of claim 9, wherein the compound is 2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 9)

The method of claim 9, wherein the compound is cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 9)

The method of claim 9, wherein the compound is 2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.