# US 7,745,657 B2 · D-homoandrosta-17-yl carbamate derivatives as selective glucocorticoid receptor ligands

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- Number: US 7,745,657 B2
- Document ID: US7745657B2
- Status: Granted
- Kind: B2
- Application number: 11/919,195
- Filed: 2006-05-15
- Published: 2009-12-10
- Granted: 2010-06-29
- Earliest claimed: 2005-05-18
- Assignees: Merck Sharp & Dohme Corp.
- Inventors: Amjad Ali; Mark L. Greenlee; Carol A. McVean; Robert S. Meissner; Gayle E. Taylor
- Web page: https://patentgrep.com/patent/US7745657B2

## CPC

- C07J 63/008: {Expansion of ring D by one atom, e.g. D homo steroids}
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/14: for calcium homeostasis (vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04)
- A61P 5/42: for decreasing, blocking or antagonising the activity of mineralocorticosteroids
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 11/16: Central respiratory analeptics
- A61P 13/12: of the kidneys
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 17/14: for baldness or alopecia
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07J: STEROIDS (seco-steroids C07C)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to D-homoandrosta-17-yl-carbamate derivatives as selective glucocorticoid receptor ligands useful for treating a variety of autoimmune and inflammatory diseases or conditions. Pharmaceutical compositions and methods of use are also included.

## Claims

### Claim 1

A compound of Formula I
or a pharmaceutically acceptable salt thereof, wherein
R1 and R2 are independently selected from the group consisting of: Ra, —C(O)—Ra, and —C(O)—N(Ra)Ra;
R3 and R4 are independently selected from the group consisting of: hydrogen, C1-10alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, aryl, heteroaryl, heterocyclyl, and C1-10fluoroalkyl; and
each Ra is independently selected from the group consisting of: hydrogen, C1-10alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, aryl, heteroaryl, heterocyclyl, and C1-10fluoroalkyl.

### Claim 2 (depends on 1)

The compound according to claim 1 wherein R2 is selected from hydrogen and CH3—C(O)—.

### Claim 3 (depends on 1)

The compound according to claim 1 wherein R1 is selected from hydrogen and CF3—(CO)—.

### Claim 4 (depends on 1)

The compound according to claim 1 wherein R3 is hydrogen.

### Claim 5 (depends on 4)

The compound according to claim 4 wherein R4 is selected from C1-10alkyl and C3-10cycloalkyl.

### Claim 6 (depends on 1)

The compound according to claim 1 wherein:
R1 is selected from hydrogen or CF3—(CO)—;
R2 is selected from hydrogen and CH3—C(O)—;
R3 is hydrogen; and
R4 is selected from C1-10alkyl and C3-10cycloalkyl.

### Claim 7 (depends on 6)

The compound according to claim 6 wherein R4 is C1-6alkyl.

### Claim 8 (depends on 6)

The compound according to claim 6 wherein R4 is selected from: cyclopentyl, cyclohexyl and adamantanyl.

### Claim 9 (depends on 6)

The compound according to claim 6 wherein R1 and R2 are hydrogen.

### Claim 10 (depends on 1)

The compound according to claim 1 selected from the following group:
(11β,16β,17α)-9-fluoro-11-hydroxy-16-methyl-3,17a-dioxo-17-(hydroxymethyl)-D-homoandrosta-1,4-dien-17-yl-(1-adamantyl)carbamate,
(11β,16β,17α)-9-fluoro-11-hydroxy-16-methyl-3,17a-dioxo-17-(hydroxymethyl)-D-homoandrosta-1,4-dien-17-yl-(2-pentyl)carbamate,
(11β,16β,17α)-9-fluoro-11-hydroxy-16-methyl-3,17a-dioxo-17-(hydroxymethyl)-D-homoandrosta-1,4-dien-17-yl-(2-methyl-pentyl)carbamate,
(11β,16β,17α)-9-fluoro-11-hydroxy-16-methyl-3,17a-dioxo-17-(hydroxymethyl)-D-homoandrosta-1,4-dien-17-yl-(3-methyl-2-propyl)carbamate,
(11β,16β,17α)-9-fluoro-11-trifluoroacetoxy-16-methyl-3,17a-dioxo-17-[(acetyloxy)methyl]-D-homoandrosta-1,4-dien-17-yl-(1-adamantyl)carbamate,
(11β,16β,17α)-9-fluoro-11-hydroxy-16-methyl-3,17a-dioxo-17-[(acetyloxy)methyl]-D-homoandrosta-1,4-dien-17-yl-(1-adamantyl)carbamate,
(11β,16β,17α)-9-fluoro-11-trifluoroacetoxy-16-methyl-3,17a-dioxo-17-(hydroxymethyl)-D-homoandrosta-1,4-dien-17-yl-(1-adamantyl)carbamate,
(11β,16β,17α)-9-fluoro-11-hydroxy-16-methyl-3,17a-dioxo-17-(hydroxymethyl)-D-homoandrosta-1,4-dien-17-yl-(cyclopentyl)carbamate,
(11β,16β,17α)-9-fluoro-11-hydroxy-16-methyl-3,17a-dioxo-17-(hydroxymethyl)-D-homoandrosta-1,4-dien-17-yl-(cyclohexyl)carbamate
or a pharmaceutically acceptable salt of any of the above.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 in combination with a pharmaceutically acceptable carrier.