# US 5,710,173 A · Thienyl compounds for inhibition of cell proliferative disorders

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- Number: US 5,710,173 A
- Document ID: US5710173A
- Status: Granted
- Kind: A
- Application number: 08/487,089
- Filed: 1995-06-07
- Granted: 1998-01-20
- Earliest claimed: 1995-06-07
- Assignees: Sugen, Inc.
- Inventors: Peng Cho Tang; Asaad S. Nematalla; Gerald McMahon
- Web page: https://patentgrep.com/patent/US5710173A

## CPC

- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 333/32: Oxygen atoms
- C07D 333/34: Sulfur atoms
- C07D 333/38: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 333/44: attached in position 5
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to molecules capable of modulating tyrosine signal transduction to prevent and treat cell proliferative disorders or cell differentiation disorders associated with particular tyrosine kinases by inhibiting one or more abnormal tyrosine kinase activities.

## Claims

### Claim 1

A compound of the formula ##STR4## or a pharmaceutically acceptable salt thereof, wherein: X is selected from the group consisting of oxygen, CH.sub.2, NH, substituted alkene, and CH.sub.2 CN,
n is selected from the group consisting of 0, 1, 2, and 4,
R.sub.1 is an aryl or heteroaryl 5 or 6 membered ring optionally substituted with one or more member of the group consisting of hydroxy, halo, alkoxy, trihalomethyl, nitro, carboxy, amide, sulfonyl, and sulfonamide; and
R.sub.2, R.sub.3, and R.sub.4 are independently selected from the group consisting of hydroxy, halo, alkoxy, trihalomethyl, nitro, carboxy, amide, sulfonyl, and sulfonamide.

### Claim 2 (depends on 1)

The compound of claim 1 wherein X is CH.sub.2.

### Claim 3 (depends on 1)

The compound of claim 1 wherein X is NH.

### Claim 4 (depends on 1)

The compound of claim 1 wherein X is C.dbd.C.

### Claim 5 (depends on 1)

The compound of claim 1 wherein X is CH.sub.2 CN.

### Claim 6 (depends on 1)

The compound of claim 1 wherein n is 0.

### Claim 7 (depends on 1)

The compound of claim 1 wherein n is 2.

### Claim 8 (depends on 1)

The compound of claim 1 wherein n is 4.

### Claim 9 (depends on 1)

The compound of claim 1 wherein R.sub.1 is aryl.

### Claim 10 (depends on 1)

The compound of claim 1 wherein R.sub.1 is heteroaryl.

### Claim 11 (depends on 1)

The compound of claim 1 wherein said compound is selected from the group consisting of:
(E)-3-(2-nitrothien-5-yl)-2-phenylsulfonylacrylonitrile
(E)-3-(2-nitrothien-5-yl)-2-›(pyridin-2-yl)sulfonyl!acrylonitrile
(E)-3-(3-phenoxythien-2-yl)-2-(phenylsulfonyl)acrylonitrile
(E)-3-(2-methylmercaptothien-5-yl)-2-›(pyridin-2-yl)sulfonyl!acrylonitrile
(E)-2-(benzylaminosulfonyl)-3-(2-nitrothien-5-yl)acrylonitrile
(E)-2-(benzylaminosulfonyl)-3-(3-phenoxythien-2-yl)acrylonitrile
(E)-3-(2-nitrothien-5-yl)-2-›(3-phenyl-n-propyl)aminosulfonyl!acrylonitrile
(E)-3-(2-methylmercaptothien-5-yl)-2-›(3-phenyl-n-propyl)aminosulfonyl!acry lonitrile
(E)-2-›(4-fluorobenzene)sulfonyl!-3-(2-nitrothien-5-yl)acrylonitrile
(E)-3-(2-aminocarbonylthien-5-yl)-2-›(4-fluorobenzene)sulfonyl!acrylonitril
(E)-3-(2-nitrothien-5-yl)-2-›3-(trifluoromethyl)phenylsulfonyl!acrylonitril e
(E)-3-(3-phenoxythien-2-yl)-2-›3-(trifluoromethyl)phenylsulfonyl!acrylonitr ile
(E)-3-(2-nitrothien-5-yl)-2-›4-(trifluoromethyl)phenylsulfonyl!acrylonitril e
(E)-3-(2-methylmercaptothien-5-yl)-2-›4-(trifluoromethyl)phenylsulfonyl!acr ylonitrile
(E)-3-(2-nitrothien-5-yl)-2-›3-(trifluoromethyl)benzylsulfonyl!acrylonitril e
(E)-3-(2-aminocarbonylthien-5-yl)-2-›3-(trifluoromethyl)benzylsulfonyl!acry lonitrile
(E)-3-(2-nitrothien-5-yl)-2-(thien-2-ylsulfonyl)acrylonitrile
(E)-3-(3-phenoxythien-2-yl)-2-(thien-2-ylsulfonyl)acrylonitrile
(E)-3-(2-nitrothien-5-yl)-2-(thien-3-ylsulfonyl)acrylonitrile
(E)-3-(2-methylmercaptothien-5-yl)-2-(thien-3-ylsulfonyl)acrylonitrile
(E)-2-cyanomethylsulfonyl-3-(2-nitrothien-5-yl)acrylonitrile; and
(E,E)-2-››1-cyano-2-(2-nitrothien-5-yl)ethenyl!sulfonyl!-3-(2-nitrothien-5- yl)acrylonitrile.

### Claim 12 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

### Claim 13 (depends on 1)

A method of treating cell proliferation or cell differentation disorders comprising exposing said cell to a compound of claim 1.

### Claim 14

A compound of the formula ##STR5## wherein R.sub.2, R.sub.3, and R.sub.4 are each independently selected from the group consisting of 2-nitro; 3-phenoxy; 2-methylmercapto; 2-aminocarbonyl; and
R.sub.1 is selected from the group consisting of phenyl; 2-pyridine; 4-fluorobenzene; 3-trifluoromethylphenyl; 4-trifluoromethylphenyl; 3-trifluoromethylbenzyl; thien-2-yl; thien-3-yl; cyanomethyl; and 1-cyano-2-(nitrothien-5-yl)ethenyl.

### Claim 15 (depends on 14)

The compound of claim 14 wherein R.sub.2 is 2-nitro.

### Claim 16 (depends on 14)

The compound of claim 14 wherein R.sub.2 is 3-phenoxy.

### Claim 17 (depends on 14)

The compound of claim 14 wherein R.sub.2 is 2-methylmercapto.

### Claim 18 (depends on 14)

The compound of claim 14 wherein R.sub.2 is 2-aminocarbonyl.

### Claim 19 (depends on 14)

The compound of claim 14 wherein R.sub.1 is phenyl.

### Claim 20 (depends on 14)

The compound of claim 14 wherein R.sub.1 is 2-pyridine.

### Claim 21

A compound named (E)-2-(benzylaminosulfonyl)-3-(2-nitrothien-5-yl)acrylonitrile.

### Claim 22

A compound named (E)-2-(benzylaminosulfonyl)-3-(3-phenoxythien-2-yl)acrylonitrile.

### Claim 23

A compound named (E)-3-(2-nitrothien-5-yl)-2-›(3-phenyl-n-propyl)aminosulfonyl!acrylonitril e.

### Claim 24

A compound named (E)-3-(2-methylmercaptothien-5-yl)-2-›(3-phenyl-n-propyl)aminosulfonyl!acr ylonitrile.