# US 7,745,621 B2 · Long acting bronchodilators for the treatment of respiratory diseases

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- Number: US 7,745,621 B2
- Document ID: US7745621B2
- Status: Granted
- Kind: B2
- Application number: 11/125,744
- Filed: 2005-05-10
- Published: 2005-11-17
- Granted: 2010-06-29
- Earliest claimed: 2004-05-14
- Assignees: Boehringer Ingelheim International GmbH
- Inventors: Matthias Grauert; Thierry Bouyssou; Philipp Lustenberger; Steffen Breitfelder; Andreas Schnapp; Michael P. Pieper; Klaus Rudolf; Georg Speck
- Web page: https://patentgrep.com/patent/US7745621B2

## CPC

- C07D 265/36: condensed with one six-membered ring
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention relates to compounds of general formula 1 wherein n, A, B, D, L, R1, R2, R3 and R4 may have the meanings given in the claims and in the specification, processes for preparing them, and their use as pharmaceutical compositions, particularly as pharmaceutical compositions for the treatment of respiratory complaints.

## Claims

### Claim 1

A compound of formula 1
wherein
n denotes 1 or 2;
A denotes O, N or a single bond;
B denotes —CH2—O—;
L denotes a double-bonded group selected from among
—CO—(CH2)m—, —CO—(CH2)m—NH—CO—(CH2)o—, —CO—(CH2)m—CO—NH—(CH2)o—,
—CO—(CH2)m—O—(CH2)p—, —(CH2)p—, —(CH2)p—O—(CH2)r—, —(CH2)2—NH—CO—(CH2)o—
m, o independently of one another denote 1 to 8;
p, r independently of one another denote 2 to 8;
R1, R2, R3 which may be identical or different, denote hydrogen, C1-C4-alkyl, C1-C4-alkyloxy, hydroxy, —CF3, —CHF2, phenyl, benzyl, —COOH, —COOmethyl, —O—CH2—COOH, —O—CH2—COOmethyl, —O—CH2—COOethyl, —O—CH2—CH2—COOH, —O—CH2—CH2—COOmethyl, —O—CH2—CH2—COOethyl, CN, NO2, fluorine, chlorine or bromine;
D denotes a double-bonded group selected from among
—CH2—CH2— and —CH═CH—;
R4 denotes hydrogen, methyl, ethyl, phenyl, benzyl or the group
E denotes a group selected from among
R5 denotes hydrogen, hydroxy, methyl, ethyl, methyloxy, ethyloxy, —CF3, HO—CH2, HO—CH2—CH2 or fluorine;
M and Q which may be identical or different, preferably identical, denote —S or —CH═CH—;
R6, R7, R6′ and R7′, which may be identical or different, denote hydrogen, methyl, methyloxy, —CF3 or fluorine;
Rx and Rx′ which may be identical or different denote hydrogen, methyl, methyloxy, —CF3 or fluorine
or
Rx and Rx′ together denote a single bond or the bridging group —O—, optionally in the form of the individual enantiomers or optionally diastereomers, mixtures of the individual enantiomers or optionally diastereomers or racemates, optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 2 (depends on 1)

The compound of formula 1 according to claim 1, wherein n denotes 1, optionally in the form of the individual enantiomers or optionally diastereomers, mixtures of the individual enantiomers or optionally diastereomers or racemates, optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 3 (depends on 1)

The compound of formula 1 according to claim 1, wherein A denotes O (oxygen) or N (nitrogen), optionally in the form of the individual enantiomers or optionally diastereomers, mixtures of the individual enantiomers or optionally diastereomers or racemates, optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 4 (depends on 1)

The compound of formula 1 according to claim 1, wherein B denotes —CH2—O—, optionally in the form of the individual enantiomers or optionally diastereomers, mixtures of the individual enantiomers or optionally diastereomers or racemates, optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 5 (depends on 1)

The compound of formula 1 according to claim 1, wherein
L denotes a double-bonded group selected from among —CO—(CH2)1-6—, —CO—(CH2)1-6—NH—CO—(CH2)1-4—, —CO—(CH2)1-6—CO—NH—(CH2)1-4—, —CO—(CH2)1-6—O—(CH2)2-6—, —(CH2)2-6—, —(CH2)2-6—O—(CH2)2-6—, —(CH2)2-6—NH—CO—(CH2)1-4—, optionally in the form of the individual enantiomers or optionally diastereomers, mixtures of the individual enantiomers or optionally diastereomers or racemates, optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 6 (depends on 1)

The compound of formula 1 according to claim 1, characterised in that they are in the form of one of the acid addition salts thereof with pharmacologically acceptable acids, which is selected from among the hydrochloride, hydrobromide, hydroiodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrobenzoate, hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.

### Claim 7 (depends on 1)

The compound of formula 1 according to claim 1, characterised in that they are in the form of the R-enantiomers of general formula R-1
optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 8 (depends on 1)

The compound of formula 1 according to claim 1, characterised in that they are in the form of the regioisomers of general formula Regio-1a
optionally in the form of the individual enantiomers or optionally diastereomers, mixtures of the individual enantiomers or optionally diastereomers or racemates, optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 9 (depends on 1)

The compound of formula 1 according to claim 1, characterised in that they are in the form of the regioisomers of general formula Regio-1b
optionally in the form of the individual enantiomers or optionally diastereomers, mixtures of the individual enantiomers or optionally diastereomers or racemates, optionally in the form of the acid addition salts thereof with pharmacologically acceptable acids.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising a compound of formula 1 according to claim 1 and a pharmaceutically acceptable carrier or excipient thereof.

### Claim 11 (depends on 1)

A pharmaceutical formulation, characterised in that it contains a compound of formula 1 according to claim 1.

### Claim 12 (depends on 1)

An intermediate product of formula 7
wherein
X denotes chlorine, bromine, iodine, methanesulphonate, trifluoromethanesulphonate, p-toluenesulphonate, or an amino function protected by a suitable protective group, preferably —NH—Boc, —NH-Cbz, —NH-Fmoc, —NH-Teoc, or —NH-Alloc;
OPG denotes a hydroxy function protected by a protective group PG, preferably —O—C1-C4-alkyl, —O-benzyl or —O—CH2—O—C1-C4-alkyl, preferably —O-methyl, —O-ethyl, —O-benzyl or —O—CH2—O-methyl, particularly preferably —O-ethyl or —O-benzyl, particularly preferably —O-benzyl; and
n, A, L, D, R1, R2 and R3 may have the meanings given in claim 1.