# US 8,541,618 B2 · Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation

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- Number: US 8,541,618 B2
- Document ID: US8541618B2
- Status: Granted
- Kind: B2
- Application number: 13/035,625
- Filed: 2011-02-25
- Published: 2011-06-23
- Granted: 2013-09-24
- Earliest claimed: 2001-07-27
- Assignees: Bayer HealthCare LLC
- Applicants: Derek B. Lowe; Philip L. Wickens; Xin Ma; Mingbao Zhang; William H. Bullock; Philip D. G. Coish; Ingo A. Mugge; Andreas Stolle; Ming Wang; Yamin Wang; Chengzhi Zhang; Hai-Jun Zhang; Lei Zhu; Manami Tsutsumi; James N. Livingston
- Inventors: Derek B. Lowe; Philip L. Wickens; Xin Ma; Mingbao Zhang; William H. Bullock; Philip D. G. Coish; Ingo A. Mugge; Andreas Stolle; Ming Wang; Yamin Wang; Chengzhi Zhang; Hai-Jun Zhang; Lei Zhu; Manami Tsutsumi; James N. Livingston
- Web page: https://patentgrep.com/patent/US8541618B2

## CPC

- C07D 277/32: 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 to ring carbon atoms
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/12: Antihypertensives
- A61P 17/00: Drugs for dermatological disorders
- A61P 35/00: Antineoplastic agents
- C07C 51/412: {by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part}
- C07C 51/44: by distillation
- C07C 59/72: containing six-membered aromatic rings and other rings
- C07C 69/732: of unsaturated hydroxy carboxylic acids
- C07C 69/734: Ethers
- C07C 69/738: Esters of keto-carboxylic acids {or aldehydo-carboxylic acids}
- C07D 263/32: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 277/24: Radicals substituted by oxygen atoms
- C07D 277/40: Unsubstituted amino or imino radicals
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/10: linked by a carbon chain containing aromatic rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07B 2200/07: Optical isomers
- C07C 2602/08: the other ring being five-membered, e.g. indane
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

This invention relates to novel indane acetic acid derivatives which are useful in the treatment of diseases such as diabetes, obesity, hyperlipidemia, and atherosclerotic diseases. The invention also relates to intermediates useful in preparation of indane acetic derivatives and to methods of preparation.

## Claims

### Claim 1

A compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein c-1′ is in the S configuration or the R configuration.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein the compound has the following structure:

### Claim 4 (depends on 1)

The compound according to claim 1, wherein the compound is a pharmaceutically acceptable salt of the following structure:
and the salt is selected from the group consisting of an alkali metal salt, an alkaline earth metal salt, a quatemized ammonium salt with an organic base, a salt of basic nitrogen containing groups in the conjugate base which is quatemized by a substituent selected from the group consisting of lower alkyl halide, dialkyl sulfate, diamyl sulfate, alkyl halide and aralkyl halide.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein the compound is a N-Methyl-D-glucamine, potassium or sodium salt of the following structure:

### Claim 6 (depends on 1)

The compound according to claim 1, wherein the compound is a sodium salt of the following structure:

### Claim 7

A pharmaceutical composition comprising an effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.

### Claim 8 (depends on 7)

The pharmaceutical composition according to claim 7, wherein the compound has the following structure:

### Claim 9 (depends on 7)

The pharmaceutical composition according to claim 7, wherein the compound is a sodium salt of the following structure:

### Claim 10 (depends on 7)

The pharmaceutical composition according to claim 7, further comprising at least one hypoglycemic agent.

### Claim 11 (depends on 10)

The pharmaceutical composition according to claim 10, wherein said hypoglycemic agent is selected from the group consisting of insulins, biguanidines, sulfonylureas, insulin secretagogues, α-glycosidase inhibitors, and β3-adrenoreceptor agonists.

### Claim 12 (depends on 7)

The pharmaceutical composition according to claim 7 further comprising at least one agent selected from the group consisting of a HMG CoA reductase inhibitor, a bile acid binding agent, a fibric acid derivative, an agent that regulates hypertension, and an agent that regulates body weight.

### Claim 13

A method of treating diabetes comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the compound has the following structure:

### Claim 15 (depends on 13)

The method according to claim 13, wherein the compound is a sodium salt of the following structure:

### Claim 16

A method of treating Syndrome X comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 16)

The method according to claim 16, wherein the compound has the following structure:

### Claim 18 (depends on 16)

The method according to claim 16, wherein the compound is a sodium salt of the following structure:

### Claim 19

A method of treating diabetes-related disorders comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 19)

The method of claim 19, wherein said diabetes-related disorder is selected from the group consisting of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired fasting glucose, dyslipidemia, hypertriglyceridemia, and insulin resistance.

### Claim 21 (depends on 19)

The method according to claim 19, wherein the compound has the following structure:

### Claim 22 (depends on 19)

The method according to claim 19, wherein the compound is a sodium salt of the following structure:

### Claim 23

A method of treating obesity comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 23)

The method according to claim 23, wherein the compound has the following structure:

### Claim 25 (depends on 23)

The method according to claim 23, wherein the compound is a sodium salt of the following structure:

### Claim 26

A method of treating cardiovascular disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 26)

The method of claim 26, wherein said cardiovascular disease is selected from the group consisting of atherosclerotic disease, dyslipidemia, hypercholesterolemia, decreased HDL levels, hypertension, coronary heart disease, and coronary artery disease.

### Claim 28 (depends on 26)

The method according to claim 26, wherein the compound has the following structure:

### Claim 29 (depends on 26)

The method according to claim 26, wherein the compound is a sodium salt of the following structure:

### Claim 30

A method of treating cerebrovascular disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 31 (depends on 30)

The method according to claim 30 wherein the compound has the following structure:

### Claim 32 (depends on 30)

The method according to claim 30, wherein the compound is a sodium salt of the following structure:

### Claim 33

A method of treating peripheral vessel disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 34 (depends on 33)

The method according to claim 33, wherein the compound has the following structure:

### Claim 35 (depends on 33)

The method according to claim 33, wherein the compound is a sodium salt of the following structure:

### Claim 36

A method of treating lupus comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 37 (depends on 36)

The method according to claim 36, wherein the compound has the following structure:

### Claim 38 (depends on 36)

The method according to claim 36, wherein the compound is a sodium salt of the following structure:

### Claim 39

A method of treating polycystic ovary disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 40 (depends on 39)

The method according to claim 39, wherein the compound has the following structure:

### Claim 41 (depends on 39)

The method according to claim 39, wherein the compound is a sodium salt of the following structure:

### Claim 42

A method of treating carcinogenesis and hyperplasia comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof.

### Claim 43 (depends on 42)

The method according to claim 42, wherein the compound has the following structure

### Claim 44 (depends on 42)

The method according to claim 42, wherein the compound is a sodium salt of the following structure: