# US 5,707,985 A · Naphthyl-, quinolyl- and isoquinolyl- sulfonamide derivatives as cell adhesion modulators

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- Number: US 5,707,985 A
- Document ID: US5707985A
- Status: Granted
- Kind: A
- Application number: 08/472,645
- Filed: 1995-06-07
- Granted: 1998-01-13
- Earliest claimed: 1995-06-07
- Assignees: Tanabe Seiyaku Co., Ltd.
- Inventors: Thomas Charles McKenzie; Gilbert M. Rishton; Nancy K. Harn; Wolfgang Scholz; James Hu
- Web page: https://patentgrep.com/patent/US5707985A

## CPC

- C07D 241/24: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07C 311/16: having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C 311/18: to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C 311/20: having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C 311/21: having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C 335/26: Y being a hydrogen or a carbon atom, e.g. benzoylthioureas
- C07D 215/36: Sulfur atoms (C07D215/24 takes precedence)
- C07D 221/22: Bridged ring systems
- C07D 221/24: Camphidines
- C07D 295/26: Sulfur atoms
- C07D 311/00: Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 407/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 453/02: containing not further condensed quinuclidine ring systems
- C07D 471/08: Bridged systems
- C07D 487/08: Bridged systems
- C07D 495/04: Ortho-condensed systems
- C07D 495/08: Bridged systems
- C07C 2601/14: The ring being saturated
- C07C 2602/42: the bicyclo ring system containing seven carbon atoms
- C07C 2603/66: containing five-membered rings
- C07C 2603/74: Adamantanes
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

There are disclosed novel substituted naphthyl-, quinolyl- and isoquinolyl- sulfonamide derivatives that are useful in a method of treating immuno-inflammatory diseases in a mammalian patient suffering therefrom. Pharmaceutical compositions containing the sulfonamide compounds are also provided.

## Claims

### Claim 1

A sulfonamide Compound encompassed by the following Formula (I), ##STR6## wherein, W and Q are selected from a carbon and a nitrogen atom, provided that W and Q are not both simultaneously nitrogen atoms;
X and Y may be the same or different and are selected from a hydrogen atom, a halogen atom, a methyl group, an acetyl group,--OR.sup.3, NH.sub.2, --NHR.sup.4 and --NR.sup.5 R.sup.6 ;
(a) and (b) denote ring positions which may be substituted with the sulfonyl moiety (--SO.sub.2 --);
dotted lines denote double bonds which are optional;
R.sup.1 and R.sup.2 may be the same or different and are selected from a hydrogen atom, C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.3-9 cycloalkyl, aminopropyl, phenyl, 1-adamantyl, 2-adamantyl, bornyl, 1-adamantanemethyl, 3-noradamantyl, 3-aminoquinuclidine, 3-adamantane carboxylic acid-1-yl, 2-oxaadamantane-1-yl, 1-azaadamantane-4-yl and 1-hydroxy-3-adamantyl, 1-hydroxy-2-azahomoadamantane-6-yl, or alternatively,
R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a bridged polycyclic moiety selected from the group consisting of 3-azabicyclo-›3.3.2!decane, 3-azabicyclo›3.2.2!nonane, 3-azabicyclo-›3.2.1!octane, 4-azahomoadamantane, 2-azaadamantane, 2-thia-5-azabicyclo›2.2.1!heptane, 2-oxo-5-azabicyclo-›2.2.1!heptane, 2,5-diazabicyclo›2.2.1!heptane, 5-methylformyl-2,5-diazabicyclo›2.2.1!heptane, 1-hydroxy-4-azahomoadamantane, 3-aminoquinuclidine and 3-thia-5-azabicyclo›2.2.1!heptane-2,2 dioxide, or alternatively,
R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a monocyclic moiety selected from the group consisting of 4-benzyloxy-2-pyrrolidine carboxylic acid and 4-benzyloxy-2-methyl-oxycarbonyl pyrrolidine;
R.sup.3 to R.sup.6 may be the same or different and are selected from a hydrogen atom, C.sub.1-8 alkyl, C.sub.3-9 cycloalkyl, acetyl, fluroenylmethyloxycarbonyl, pyridylmethyl, carobymethyl, piperazinylpropyl, (tert-butoxycarbonyl piperzinyl)propyl and dimethylaminoethyl; or a
pharmaceutically acceptable salt thereof;
provided that 3-(2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane is excluded from formula (I).

### Claim 2 (depends on 1)

The sulfonamide compound of claim 1, wherein Q is a carbon atom and W is a nitrogen atom.

### Claim 3 (depends on 1)

The sulfonamide compound of claim 1, wherein Q is a nitrogen atom and W is a carbon atom.

### Claim 4 (depends on 1)

The sulfonamide compound of claim 1, wherein Q and W are each carbon atoms.

### Claim 5 (depends on 1)

The sulfonamide compound of claim 1, wherein Q and W are each carbon atoms, X is a chlorine atom, Y is a hydrogen atom, R.sup.1 is an adamantyl group and R.sup.2 is a hydrogen atom.

### Claim 6 (depends on 1)

The sulfonamide compound of claim 1, wherein Q and W are each carbon atoms, X is a chlorine atom, Y is a hydrogen atom, and R.sup.1 and R.sup.2 and the nitrogen atom to which they are mutually bonded form a bridged polycyclic moiety selected from the group consisting of 4-azahomoadamantane and 3-azabicyclo›3.2.2!nonane.

### Claim 7 (depends on 1)

The sulfonamide compound of claim 1, wherein Q and W are each carbon atoms, X is a hydrogen atom, Y is a 3-pyridinylmethoxy group, and R.sup.1 and R.sup.2 and the nitrogen atom to which they are mutually bonded form a bridged polycyclic moiety selected from the group consisting of 4-azahomoadamantane and 3-azabicyclo-›3.2.2!nonane.

### Claim 8 (depends on 1)

The sulfonamide compound of claim 1, wherein said compound is a 5-chloro-2-naphthalenesulfonamide derivative encompassed by formula (I).

### Claim 9 (depends on 1)

The sulfonamide compound of claim 1, wherein said compound of formula (I) is
N-(1-adamantyl)-5-chloro-2-naphthalenesulfonamide,
4-(5-chloro-2-naphthylsulfonyl)-4-azahomoadamantane,
3-(5-chloro-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
4-›4-(3-pyridinylmethoxy)-2-naphthylsulfonyl)-4-azahomoadamantane,
3-(4-(3-pyridinylmethoxy)-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(1-acetoxy-3-naphthylsulfonyl)-3-azabicyclo-›3.2.2!nonane,
3-(1-hydroxy-3-naphthylsulfonyl)-3-azabicyclo-3.2.2 !nonane,
3-›1-›1-(3-dimethylamino)-3-naphthylsulfonyl!!-3-azabicyclo›3.2.2!nonane,
4-(1-hydroxy-3-naphthylsulfonyl)-4-azahomoadamantane,
4-(1-acetoxy-3-naphthylsulfonyl)-4-azahomoadamantane,
4-(4-methoxy-1-naphthylsulfonyl)-4-azahomoadamantane,
3-(4-methoxy-1-naphthylsulfonyl)-3-azabicyclo-›3.2.2!nonane,
3-(4-chloro-1-naphthylsulfonyl)-3azabicyclo-›3.2.2!nonane,
3-(1,2,3,4-tetrahydro-6-quinolinesulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-acetoxy-2-naphthylsulfonyl)-3-azabicyclo-›3.2.2!nonane,
6-(5-chloro-2-naphthylsulfonyl)-6-amino-1-hydroxy-2-azahomoadamantane,
4-(6-quinolinesulfonyl)-4-azahomoadamantane,
1-(6-quinolinesulfonyl)-1-azahomoadamantane,
3-(6-quinolinesulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-chloro-2-naphthylsulfonyl)-3-aminonoradamantane,
2-(5-chloro-2-naphthylsulfonyl)-2-aminoadamantane,
2-(5-chloro-2-naphthylsulfonyl)-2-(3-aminopropyl)-2-aminoadamantane,
1-(5-chloro-2-naphthylsulfonyl)-1-phenyl-1,3-diaminopropane,
1-(2-naphthylsulfonyl)-1-aminoadamantane,
3-(5-chloro-2-naphthylsulfonyl)-3-azabicyclo-›3.2.1!octane,
5-(5-chloro-2-naphthylsulfonyl)-2-thia-5-azabicyclo›2.2.1!heptane,
4-(2-naphthylsulfonyl)-4-azahomoadamantane,
3-(1-methoxy-4-naphthylsulfonyl)-3-azabicyclo-›3.2.2!nonane,
3-(5-amino-2-naphthylsulfonyl)-3-azabicyclo-›3.2.2!nonane, or
said pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

A method of treating an immuno-inflammatory disease in a mammalian patient in need of said treatment, the method comprising the step of administering to the mammalian patient a pharmaceutically effective amount of a sulfonamide Compound according to claim 1.

### Claim 11 (depends on 10)

The treatment method of claim 10, wherein Q is a carbon atom and W is a nitrogen atom.

### Claim 12 (depends on 10)

The treatment method of claim 10, wherein Q is a nitrogen atom and W is a carbon atom.

### Claim 13 (depends on 10)

The treatment method of claim 10, wherein Q and W are each carbon atoms.

### Claim 14 (depends on 10)

The treatment method of claim 10, wherein Q and W are each carbon atoms, X is a chlorine atom, Y is a hydrogen atom, R.sup.1 is an adamantyl group and R.sup.2 is a hydrogen atom.

### Claim 15 (depends on 10)

The treatment method of claim 10, wherein Q and W are each carbon atoms, X is a chlorine atom, Y is a hydrogen atom, and R.sup.1 and R.sup.2 and the nitrogen atom to which they are mutually bonded form a polycyclic moiety selected from the group consisting of 4-azahomoadamantane and 3-azabicyclo›3.2.2!nonane.

### Claim 16 (depends on 10)

The treatment method of claim 10, wherein Q and W are each carbon atoms, X is a hydrogen atom, Y is a 3-pyridinylmethoxy group, and R.sup.1 and R.sup.2 and the nitrogen atom to which they are mutually bonded form a bridged polycyclic moiety selected from the group consisting of 4-azahomoadamantane and 3-azabicyclo›3.2.2!nonane.

### Claim 17 (depends on 10)

The treatment method of claim 10, wherein said compound is a 5-Chloro-2-naphthalenesulfonamide derivative encompassed by formula (I).

### Claim 18 (depends on 10)

The treatment method of claim 10, wherein said compound of formula (I) is
N-(1-adamantyl)-5-chloro-2-naphthalenesulfonamide,
4-(5-chloro-2-naphthylsulfonyl)-4-azahomoadamantane,
3-(5-chloro-2-naphthylsulfonyl)-3-azabicyclo-›3.2.2!nonane,
4-›4-(3-pyridinylmethoxy)-2-naphthylsulfonyl)-4-azahomoadamantane,
3-(4-(3-pyridinylmethoxy)-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(1-acetoxy-3-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(1-hydroxy-3-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-›1-›1-(3-dimethylamino)-3-naphthylsulfonyl!!-3-azabicyclo›3.2.2!nonane,
4-(1-hydroxy-3-naphthylsulfonyl-(1-azahomoadamantane,
4-(1-acetoxy-3-naphthylsulfonyl)-4-azahomoadamantane,
4-(4-methoxy-1-naphthylsulfonyl)-4-azahomoadamantane,
3-(4-methoxy-1-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(4-chloro-1-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(1,2,3,4-tetrahydro-6-quinolinesulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-acetoxy-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
6-(5-chloro-2-naphthylsulfonyl)-6-amino-1-hydroxy-2-azahomoadamantane,
4-(6-quinolinesulfonyl)-4-azahomoadamantane,
1-(6-quinolinesulfonyl)-1-azahomoadamantane,
3-(6-quinolinesulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-chloro-2-naphthylsulfonyl)-3-aminonoradamantane,
2-(5-chloro-2-naphthylsulfonyl)-2-aminoadamantane,
2-(5-chloro-2-naphthylsulfonyl)-2-(3-aminopropyl)-2-aminoadamantane,
1-(5-chloro-2-naphthylsulfonyl)-1-phenyl-1,3-diaminopropane,
1-(2-naphthylsulfonyl)-1-aminoadamantane,
3-(5-chloro-2-naphthylsulfonyl)-3-azabicyclo›3.2.1!octane,
5-(5-chloro-2-naphthylsulfonyl)-2-thia-5-azabicyclo›2.2.1!heptane,
3-(2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
4-(2-naphthylsulfonyl)-4-azahomoadamantane,
3-(1-methoxy-4-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-amino-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane, or
said pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

A pharmaceutical composition, comprising:
(1) a pharmaceutically effective amount of a sulfonamide Compound according to claim 1,
(2) a pharmaceutically acceptable carrier or diluent therefor.

### Claim 20 (depends on 19)

The pharmaceutical composition of claim 19, wherein Q is a carbon atom and W is a nitrogen atom.

### Claim 21 (depends on 19)

The pharmaceutical composition of claim 19, wherein Q is a nitrogen atom and W is a carbon atom.

### Claim 22 (depends on 19)

The pharmaceutical composition of claim 19, wherein Q and W are each carbon atoms.

### Claim 23 (depends on 19)

The pharmaceutical composition of claim 19, wherein Q and W are each carbon atoms, X is a chlorine atom, Y is a hydrogen atom, R.sup.1 is an adamantyl group and R.sup.2 is a hydrogen atom.

### Claim 24 (depends on 19)

The pharmaceutical composition of claim 19, wherein Q and W are each carbon atoms, X is a chlorine atom, Y is a hydrogen atom, and R.sup.1 and R.sup.2 and the nitrogen atom to which they are mutually bonded form a bridged polycyclic moiety selected from the group consisting of 4-azahomoadamantane and 3-azabicyclo›3.2.2!nonane.

### Claim 25 (depends on 19)

The pharmaceutical composition of claim 19, wherein Q and W are each carbon atoms, X is a hydrogen atom, Y is a 3-pyridinylmethoxy group, and R.sup.1 and R.sup.2 and the nitrogen atom to which they are mutually bonded form a bridged polycyclic moiety selected from the group consisting of 4-azahomoadamantane and 3-azabicyclo›3.2.2!nonane.

### Claim 26 (depends on 19)

The pharmaceutical composition of claim 19, wherein said compound is a 5-Chloro-2-naphthalenesulfonamide derivative encompassed by formula (I).

### Claim 27 (depends on 19)

The pharmaceutical composition of claim 19, wherein said compound of formula (I) is
N-(1-adamantyl)-5-chloro-2-naphthalenesulfonamide,
4-(5-chloro-2-naphthylsulfonyl)-4-azahomoadamantane,
3-(5-chloro-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
4-›4-(3-pyridinylmethoxy)-2-naphnhylsulfonyl)-4-azahomoadamantane,
3-(4-(3-pyridinylmethoxy)-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(1-acetoxy-3-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(1-hydroxy-3-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-›1-›1-(3-dimethylamino)-3-naphthylsulfonyl!!-3-azabicyclo›3.2.2!nonane,
4-(1-hydroxy-3-naphthylsulfonyl)-4-azahomoadamantane,
4-(1-acetoxy-3-naphthylsulfonyl)-4-azahomoadamantane,
4-(4-methoxy-1-naphthylsulfonyl)-4-azahomoadamantane,
3-(4-methoxy-1-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(4-chloro-1-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(1,2,3,4-tetrahydro-6-quinolinesulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-acetoxy-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
6-(5-chloro-2-naphthylsulfonyl)-6-amino-1-hydroxy-2-azahomoadamantane,
4-(6-quinolinesulfonyl)-4-azahomoadamantane,
1-(6-quinolinesulfonyl)-1-azahomoadamantane,
3-(6-quinolinesulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-chloro-2-naphthylsulfonyl)-3-aminonoradamantane,
2-(5-chloro-2-naphthylsulfonyl)-2-aminoadamantane,
2-(5-chloro-2-naphthylsulfonyl)-2-(3-aminopropyl)-2-aminoadamantane,
1-(5-chloro-2-naphthylsulfonyl)-1-phenyl-1,3-diaminopropane,
1-(2-naphthylsulfonyl)-1-aminoadamantane,
3-(5-chloro-2-naphthylsulfonyl)-3-azabicyclo›3.2.1!octane,
5-(5-chloro-2-naphthylsulfonyl)-2-thia-5-azabicyclo›2.2.1!heptane,
3-(2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
4-(2-naphthylsulfonyl)-4-azahomoadamantane,
3-(1-methoxy-4-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane,
3-(5-amino-2-naphthylsulfonyl)-3-azabicyclo›3.2.2!nonane, or
said pharmaceutically acceptable salt thereof.