# US 9,040,523 B2 · Antifungal 5,6-dihydro-4H-pyrrolo[1,2-α][1,4]-benzodiazepines and 6H-pyrrolo[1,2-α][1,4]benzodiazepines substituted with benzene derivatives

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- Number: US 9,040,523 B2
- Document ID: US9040523B2
- Status: Granted
- Kind: B2
- Application number: 13/989,233
- Filed: 2011-11-18
- Published: 2013-10-17
- Granted: 2015-05-26
- Earliest claimed: 2010-11-24
- Assignees: Janssen Pharmaceutica NV
- Applicants: Lieven Meerpoel; Louis Jules Roger Marie Maes; Kelly de Wit
- Inventors: Lieven Meerpoel; Louis Jules Roger Marie Maes; Kelly de Wit
- Web page: https://patentgrep.com/patent/US9040523B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 31/10: Antimycotics
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is concerned with novel antifungal 5,6-dihydro-4H-pyrrolo-[1,2-a][1,4]benzodiazepines and 6H-pyrrolo[1,2-a][1,4]benzodiazepines of Formula (I) wherein R1, R2, R3, R4, R5 and R6 have the meaning defined in the claims. The compounds according to the present invention are active mainly against dermatophytes and systemic fungal infections. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

## Claims

### Claim 1

A compound of formula (I)
or a stereoisomeric form thereof, wherein
R1 is hydrogen, halo, C1-4alkyl or C1-4alkyloxy;
R2 is hydrogen or halo;
R3 and R4 are hydrogen;
or R3 and R4 taken together form a bond;
R5 is C1-4alkylcarbonyl, C1-4alkylsulphonyl, C1-4alkylsulphinyl, or C1-4alkyl substituted with one hydroxyl moiety;
R6 is hydrogen or halo;
or a pharmaceutically acceptable addition salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1 wherein
R1 is hydrogen, halo, C1-4alkyl or C1-4alkyloxY;
R2 is hydrogen or halo;
R3 and R4 are hydrogen;
or R3 and R4 taken together form a bond;
R5 is C1-4alkylcarbonyl; C1-4alkylsulphonyl; or C1-4alkyl substituted with one hydroxyl moiety;
R6 is hydrogen or halo;
or a pharmaceutically acceptable addition salt thereof.

### Claim 3 (depends on 1)

The compound according to claim 1 wherein
R1 is chloro or fluoro;
R2 is hydrogen, chloro of fluoro;
R5 is methylcarbonyl, methylsulphonyl or 1-hydroxyethyl;
R6 is hydrogen or fluoro.

### Claim 4 (depends on 1)

The compound according to claim 1 wherein R5 is C1-4alkylcarbonyl.

### Claim 5 (depends on 1)

The compound according to claim 1 wherein R1 is halo.

### Claim 6 (depends on 1)

The compound according to claim 1 wherein the compound is a compound of formula (I-x) or (I-y)

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The compound according to any one of claims 1 to 6 wherein R3 and R4 are taken together to form a bond.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as defined in claim 1.

### Claim 9 (depends on 1)

A method of treating a patient with a fungal infection, said method comprising administering to said patient a therapeutically effective amount of a compound of claim 1.

### Claim 10 (depends on 9)

The method according to claim 9 wherein the fungal infection is caused by one or more of the fungi selected from the group consisting of Candida spp.; Aspergillus spp.; Cryptococcus neoformans; Sporothrix schenckii; Epidermophyton floccosum; Microsporum spp.; Trichophyton spp; Fusarium spp.; Rhizomucor spp.; Mucor circinelloides; Rhizopus spp.; Malassezia furfur; Acremonium spp.; Paecilomyces; Scopulariopsis; Arthrographis spp.; Scytalidium; Scedosporium spp.; Trichoderma spp.; Penicillium spp.; Penicillium marneffei; Blastoschizomyces.

### Claim 11 (depends on 9)

The method according to claim 9 wherein the fungal infection is caused by one or more of the fungi selected from the group consisting of Candida parapsilosis; Aspergillus spp.; Cryptococcus neoformans; Sporothrix schenckii; Epidermophyton floccosum; Microsporum spp.; Trichophyton spp.; Fusarium spp.; Rhizomucor spp.; Mucor circinelloides; Rhizopus spp.; Acremonium spp.; Paecilomyces; Scopulariopsis; Arthrographis spp.; Scytalidium; Scedosporium spp.; Trichoderma spp.; Penicillium spp.; Penicillium marneffei; Blastoschizomyces.

### Claim 12 (depends on 9)

The method according to claim 9 wherein the fungal infection is caused by one or more of the fungi selected from the group consisting of Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum and Aspergillus fumigatus.