# US 5,346,914 A · (4-alkoxypyran-4-yl) substituted arylalkylaryl-, arylalkenylaryl-, and arylalkynylarylurea inhibitors of 5-lipoxygenase

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- Number: US 5,346,914 A
- Document ID: US5346914A
- Status: Granted
- Kind: A
- Application number: 08/061,988
- Filed: 1993-05-14
- Granted: 1994-09-13
- Earliest claimed: 1993-05-14
- Assignees: Abbott Laboratories
- Inventors: Joseph F. Dellaria; Anwer Basha; Lawrence A. Black; Linda J. Dorn; Wendy Lee
- Web page: https://patentgrep.com/patent/US5346914A

## CPC

- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 309/12: only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds of the structure ##STR1## wherein W is selected from ##STR2## where Q is oxygen or sulfur, R.sup.6 and R.sup.7 are hydrogen or alkyl, or R.sup.6 and R.sup.7, together with the nitrogen atoms to which they are attached, define a radical of formula ##STR3## R.sup.8 is selected from hydrogen, alkyl, haloalkyl, optionally substituted phenyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, (alkoxycarbonyl)alkyl, and (alkylaminocarbonyl)alkyl; Z is --CH.sub.2 --, oxygen, sulfur, or --NR.sup.9 where R.sup.9 is hydrogen or alkyl, L.sup.1 and L.sup.2 are selected from a valence bond, alkylene, propenylene, and propynylene, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from alkyl, haloalkyl, halogen, cyano, amino, alkoxycarbonyl, and dialkylaminocarbonyl, Y is selected from oxygen, --NR.sup.10, where R.sup.10 is hydrogen or alkyl, and ##STR4## where n=0, 1, or 2, and R.sup.5 is alkyl, inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

## Claims

### Claim 1

A compound of the formula: ##STR59## or a pharmaceutically acceptable salt thereof wherein W is selected from the group consisting of ##STR60## wherein Q is oxygen or sulfur,
R.sup.6 and R.sup.7 are independently selected from the group consisting of hydrogen and alkyl of one to four carbon atoms, provided that when L.sup.1 is a valence bond, R.sup.6 is alkyl of one to four carbon atoms, or
R.sup.6 and R.sup.7, taken together with the nitrogen atoms to which they are attached, define a radical of the formula ##STR61## R.sup.8 is selected from the group consisting of hydrogen,
alkyl of one to four carbon atoms,
haloalkyl of one to four carbon atoms,
unsubstituted phenyl,
phenyl substituted with
alkyl of one to four carbon atoms,
alkoxy of one to four carbon atoms,
haloalkyl, or
halogen,
hydroxyalkyl of from one to four carbon atoms,
aminoalkyl of from one to four carbon atoms,
carboxyalkyl of from one to four carbon atoms,
(alkoxycarbonyl)alkyl where the alkyl and alkoxy portions each are of one to four carbon atoms,
(alkylaminocarbonyl)alkyl, where the alkyl and aminoalkyl portions each are of one to four carbon atoms; and
Z is --CH2--, oxygen, sulfur, or --NR9 wherein R9 is hydrogen or alkyl of one to four carbon atoms;
L.sup.1 is a valence bond or is selected from alkylene of one to three carbon atoms, propenylene, and propynylene;
R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from the group consisting of
alkyl of one to four carbon atoms,
alkoxy of one to four carbon atoms,
haloalkyl,
halogen,
cyano,
amino,
alkoxycarbonyl of one to four carbon atoms, and
dialkylaminocarbonyl where the alkyl portions are each of one to four carbon atoms;
L.sup.2 is a valence bond or is selected from alkylene of one to three carbon atoms, propenylene, and propynylene;
Y is selected from the group consisting of
oxygen,
>NR10, where R10 is hydrogen or alkyl of one to four carbon atoms, and
where n=0, 1, or 2; and
R.sup.5 is alkyl of one to four carbon atoms.

### Claim 2 (depends on 1)

A compound as defined by claim 1 of the formula: ##STR62## or a pharmaceutically acceptable salt thereof wherein W, L.sup.2, y, R.sup.4, and R.sup.5 are defined therein.

### Claim 3 (depends on 2)

A compound as defined by claim 2 wherein L.sup.2 is methylene.

### Claim 4 (depends on 1)

A compound as defined by claim 1 of the formula: ##STR63## or a pharmaceutically acceptable salt thereof wherein W, Y, R.sup.4, and R.sup.5 are defined therein.

### Claim 5 (depends on 4)

A compound or pharmaceutically acceptable salt thereof as defined in claim 4 wherein Y is oxygen.

### Claim 6 (depends on 4)

A compound of pharmaceutically acceptable salt thereof as defined in claim 4 wherein Y is >NR.sup.10 wherein R.sup.10 is hydrogen or alkyl of one to four carbon atoms.

### Claim 7 (depends on 4)

A compound of pharmaceutically acceptable salt thereof as defined in claim 4 wherein Y is ##STR64## where n=0, 1, or 2.

### Claim 8 (depends on 1)

A compound as defined by claim 1 of the formula: ##STR65## or a pharmaceutically acceptable salt thereof wherein W, Y, R.sup.4, and R.sup.5 are defined therein.

### Claim 9 (depends on 8)

A compound of pharmaceutically acceptable salt thereof as defined in claim 8 wherein Y is oxygen.

### Claim 10 (depends on 8)

A compound of pharmaceutically acceptable salt thereof as defined in claim 8 wherein Y is >NR.sup.10 wherein R.sup.10 is hydrogen or alkyl of one to four carbon atoms.

### Claim 11 (depends on 8)

A compound or pharmaceutically acceptable salt thereof as defined in claim 8 wherein Y is ##STR66## where n=0, 1, or 2.

### Claim 12 (depends on 1)

A compound as defined by claim 1 of the formula: ##STR67## or a pharmaceutically acceptable salt thereof wherein W, n, R.sup.4, and R.sup.5 are defined therein.

### Claim 13 (depends on 12)

A compound or pharmaceutically acceptable salt thereof as defined in claim 12 wherein n=0.

### Claim 14

A compound selected from the group consisting of
4-{3-[4-((N',N'-dimethylaminocarbonyl)-N-methylamino)benzyloxy]-5-fluorophe nyl}-4-methoxytetrahydropyran,
4-{3-[4-((N',N'-dimethylaminocarbonyl)-N-methylamino)phenylthio]phenyl}-4-m ethoxytetrahydropyran,
4-{3-[4-((N',N'-dimethylaminocarbonyl)aminomethyl)benzyloxy]-5-fluorophenyl }-4-methoxytetrahydropyran,
4-{3-[4-(imidazolidin-2-on-1-ylmethyl)benzyloxy]-5-fluorophenyl}-4-methoxyt etrahydropyran, and
4-{3-[3-((N',N'-dimethylaminocarbonyl)-N-methylamino)benzyloxy]-5-fluorophe nyl}-4-methoxytetrahydropyran or
a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

A pharmaceutically composition comprising a therapeutically effective amount of a compound as defined by claim 1 in combination with a pharmaceutically acceptable carrier.

### Claim 16 (depends on 1)

A method of inhibiting 5-lipoxygenase enzyme activity in a mammal in need of such treatment comprising administering an effective amount of a compound as defined in claim 1.