# US 4,397,782 A · Antiinflammatory 17-spiroandrostenes

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- Number: US 4,397,782 A
- Document ID: US4397782A
- Status: Granted
- Kind: A
- Application number: 06/382,891
- Filed: 1982-05-28
- Granted: 1983-08-09
- Earliest claimed: 1982-05-28
- Assignees: E. R. Squibb & Sons, Inc.
- Inventors: Ravi K. Varma
- Web page: https://patentgrep.com/patent/US4397782A

## CPC

- C07J 33/005: {spiro-condensed}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07J 1/0011: {substituted in position 17 by a keto group}
- C07J 21/008: {at position 17}
- C07J 43/006: {spiro-condensed}
- C07J: STEROIDS (seco-steroids C07C)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Topical antiinflammatory activity is exhibited by steroids having the formula ##STR1## and the 1,2-dehydro and 15,16-dehydro derivatives thereof, wherein R.sub.1 is hydrogen, alkyl, carboxyl, or alkoxycarbonyl; R.sub.2 is hydrogen, chlorine, bromine, fluorine, methyl, hydroxyl or a conventional hydrolyzable ester thereof, methoxy, or oxo (.dbd.O); R.sub.3 is carbonyl or .beta.-hydroxymethylene; R.sub.4 is hydrogen or fluorine; R.sub.5 is hydrogen, methyl or fluorine; X and Y are the same or different, and each is S, O, NH, N--CH.sub.3, SO or SO.sub.2 ; and n is 1, 2, 3, 4 or 5.

## Claims

### Claim 1

A steroid having the formula ##STR15## or the 1,2-dehydro and 15,16-dehydro derivatives thereof, wherein R.sub.1 is hydrogen, alkyl, carboxyl, or alkoxycarbonyl;
R.sub.2 is hydrogen, chlorine, bromine, fluorine, methyl, hydroxyl or a conventional hydrolyzable ester thereof, methoxy, or oxo;
R.sub.3 is carbonyl or .beta.-hydroxymethylene;
R.sub.4 is hydrogen or fluorine;
R.sub.5 is hydrogen, methyl or fluorine;
X and Y are the same or different, and each is S, O, NH, N--CH.sub.3, SO or SO.sub.2 ; and
n is 1, 2, 3, 4 or 5; with the proviso that X and Y are not both O.

### Claim 2 (depends on 1)

A steroid in accordance with claim 1 wherein R.sub.1 is hydrogen, R.sub.3 is .beta.-hydroxymethylene, R.sub.4 is fluorine and R.sub.5 is hydrogen.

### Claim 3 (depends on 1)

A steroid in accordance with claim 1 wherein both X and Y are S.

### Claim 4 (depends on 1)

A steroid in accordance with claim 1 wherein one of X and Y is S and the other is O.

### Claim 5 (depends on 1)

A steroid in accordance with claim 1 wherein one of X and Y is SO and the other is O.

### Claim 6 (depends on 1)

A steroid in accordance with claim 1 wherein one of X and Y is SO.sub.2 and the other is O.

### Claim 7 (depends on 1)

A steroid in accordance with claim 1 wherein one of X and Y is S and the other is NH.

### Claim 8 (depends on 1)

A steroid in accordance with claim 1 wherein n is 1 or 2.

### Claim 9 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,16.beta.)-9-fluoro-11-hydroxy-16-methylandrosta-1,4-diene-3,17-d ione, cyclic 17-(1,2-ethanediyl mercaptole).

### Claim 10 (depends on 1)

The steroid in accordance with claim 1 (11.beta.)-9-fluoro-11-hydroxyandrosta-1,4-diene-3,17-dione, cyclic 17-(1,2-ethanediyl mercaptole).

### Claim 11 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,16.beta.)-9-fluoro-11-hydroxy-16-methylandrosta-1,4-diene-3,17-d ione, cyclic 17-(1,3-propanediyl mercaptole).

### Claim 12 (depends on 1)

The steroid in accordance with claim 1 (11.beta.)-9-fluoro-11-hydroxyandrosta-1,4-diene-3,17-dione, cyclic 17-(1,3-propanediyl mercaptole).

### Claim 13 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,16.alpha.)-9-fluoro-11-hydroxy-16-methylandrosta-1,4-diene-3,17- dione,cyclic 17-(1-3-propanediyl mercaptole).

### Claim 14 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,16.alpha.)-9-fluoro-11-hydroxy-16-methylandrosta-1,4-diene-3,17- dione, cyclic 17-(1,2-ethanediyl mecaptole).

### Claim 15 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,17S)-9-fluoro-11-hydroxyandrosta-1,4-diene-3,17-dione, cyclic 17-[(oxyethylene)thio]mixed acetal.

### Claim 16 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,17S)-9-fluoro-11-hydroxyspiro[androsta-1,4-diene-17,2'-[1,3]-oxa thiolane]-3-one, 3',3'-dioxide.

### Claim 17 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,17S)-9-fluoro-11-hydroxyspiro[androsta-1,4-diene-17,2'[1,3]-oxat hiolane]-3-one,3'oxide (Isomer A).

### Claim 18 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,17S)-9-fluoro-11-hydroxyspiro[androsta-1,4-diene-17,2'[1,3]oxath iolane]-3-one,3'-oxide (Isomer B).

### Claim 19 (depends on 1)

The steroid in accordance with claim 1 (11.beta.,17R)-9-fluoro-11-hydroxyandrosta-1,4-diene-3,17-dione, cyclic 17-[(oxyethylene)thio]mixed acetal.

### Claim 20 (depends on 1)

The steroid in accordance with claim 1 (11.beta.)-9-fluoro-11-hydroxyspiro(pregna-1,4-diene-17,2'-thiazolidin)-3- one.

### Claim 21

A steroid having the formula ##STR16## or the 1,2-dehydro and 15,16-dehydro derivatives thereof, wherein R.sub.1 is hydrogen, alkyl, carboxyl, or alkoxycarbonyl;
R.sub.2 is hydrogen, chlorine, bromine, fluorine, methyl, hydroxyl or a conventional hydrolyzable ester thereof, methoxy, or oxo;
R.sub.3 is carbonyl or .beta.-hydroxymethylene;
R.sub.5 is hydrogen, methyl or fluorine;
n is 1, 2, 3, 4 or 5.

### Claim 22 (depends on 21)

The steroid in accordance with claim 21 (11.beta.)-9-fluoro-11-hydroxyandrosta-1,4-diene-3,17-dione, cyclic 17-(1,2-ethanediyl acetal).