# US 7,608,721 B2 · Hexafluoroisopropanol derivatives

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- Number: US 7,608,721 B2
- Document ID: US7608721B2
- Status: Granted
- Kind: B2
- Application number: 11/801,067
- Filed: 2007-05-08
- Published: 2007-09-13
- Granted: 2009-10-27
- Earliest claimed: 2004-06-28
- Assignees: Hoffmann-La Roche Inc.
- Inventors: Henrietta Dehmlow; Bernd Kuhn; Raffaello Masciadri; Narendra Panday; Hasane Ratni; Matthew Blake Wright
- Web page: https://patentgrep.com/patent/US7608721B2

## CPC

- C07C 215/68: having amino groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- 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 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- 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 17/00: Drugs for dermatological disorders
- 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 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/38: having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
- C07D 263/32: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 277/28: Radicals substituted by nitrogen atoms
- C07D 333/58: Radicals substituted by nitrogen atoms
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention is concerned with novel hexafluoroisopropanol derivatives of formula (I) wherein R1 to R6, m and n are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds bind to LXR alpha and LXR beta and can be used as medicaments.

## Claims

### Claim 1

A compound of the formula (I):
wherein:
R1 is hydrogen, halogen, or lower-alkyl;
R2 is lower-alkyl, fluoro-lower-alkyl, cycloalkyl-lower-alkyl, or heterocyclyl-lower-alkyl;
R3 is hydrogen, lower-alkyl, aryl, cycloalkyl, or heterocyclyl;
R4 is hydrogen, hydroxy, lower-alkoxy, aryl-lower-alkoxy, or heterocyclyl-lower-alkoxy;
R5 is hydrogen, lower-alkyl, aryl, or heterocyclyl;
R6 is heterocyclyl;
m is 0 to 3;
n is 0 or 1;
and pharmaceutically acceptable salts and esters thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein R1 is hydrogen or halogen.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein R1 is hydrogen or chlorine.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein R2 is unsubstituted lower-alkyl or fluoro-lower-alkyl.

### Claim 5 (depends on 4)

The compound according to claim 4, wherein R2 is ethyl or 2,2,2-trifluoro-ethyl.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein R3 is hydrogen or aryl.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein R3 is hydrogen or phenyl.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein R3 is hydrogen.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein R4 is hydrogen or hydroxy.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein R5 is hydrogen.

### Claim 11 (depends on 1)

The compound according to claim 1, wherein R6 is pyridinyl, thiazolyl, benzo[b]thiophenyl or chloro-benzo[b]thiophenyl.

### Claim 12 (depends on 1)

The compound according to claim 1, wherein m is 0 to 2.

### Claim 13 (depends on 1)

The compound according to claim 1, wherein m is 0.

### Claim 14 (depends on 1)

The compound according to claim 1, wherein n is 0.

### Claim 15 (depends on 1)

The compound according to claim 1, selected from the group consisting of:
2-{4-[ethyl-(thiazol-4-ylmethyl)-amino]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,
2-{4-[ethyl-(pyridin-2-ylmethyl)-amino]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,
2-{4-[ethyl-(pyridin-3-ylmethyl)-amino]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,
2-{4-[ethyl-(pyridin-4-ylmethyl)-amino]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,
2-{4-[(5-Chloro-benzo[b]thiophen-2-ylmethyl)-(2,2,2-trifluoro-ethyl)-amino]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol, or
2-{3-chloro-4-[ethyl-(thiazol-4-ylmethyl)-amino]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol, and pharmaceutically acceptable salts and esters thereof.

### Claim 16 (depends on 1)

A process for the manufacture of compounds of formula (I) as defined in claim 1, comprising the step of:
a) reacting a compound of formula (II):
with a compound LG-CHR3—(CH2)m—(CR4R5)n—R6, or
b) reacting a compound of formula (III):
with a compound LG-R2,
wherein R1, R2, R3, R4, R5, R6, m and n are as defined in claim 1 and LG is a leaving group.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier and/or adjuvant.