# US 5,707,977 A · Watersoluble azole antifungals

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- Number: US 5,707,977 A
- Document ID: US5707977A
- Status: Granted
- Kind: A
- Application number: 08/666,270
- Filed: 1996-06-20
- Granted: 1998-01-13
- Earliest claimed: 1994-01-24
- Assignees: Janssen Pharmaceutica NV
- Inventors: Jan Heeres; Leo Jacobus Jozef Backx; Luc Alfons Leo Van der Eycken; Frank Christopher Odds; Jean Louis Mesens
- Web page: https://patentgrep.com/patent/US5707977A

## CPC

- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07F 9/65586: {at least one of the hetero rings does not contain nitrogen as ring hetero atom}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

A compound of formula (I), ##STR1## an acid or base addition salt thereof or a stereochemically isomeric form thereof, wherein A and B taken together form --N.dbd.CH--, --CH.dbd.N--, --CH.sub.2 --CH.sub.2, CH.dbd.CH--, --C(.dbd.O)--CH.sub.2 --, --CH.sub.2 --C(.dbd.O); D is a radical of formula ##STR2## L is a radical of formula ##STR3## Alk is a C.sub.1-4 alkanediyl radical; R.sup.1 is halo; R.sup.2 is hydrogen or halo; R.sup.3 is hydrogen, C.sub.1-6 alkyl, phenyl or halophenyl; R.sup.4 is hydrogen, C.sub.1-6 alkyl, phenyl or halophenyl; R.sup.5 is hydrogen or C.sub.1-6 alkyl; R.sup.6 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxycarbonyl, or R.sup.5 and R.sup.6 taken together with the nitrogen atom to which they are attached form a heterocyclic ring. Active intermediates, compositions and methods of preparing compounds, compositions are described.

## Claims

### Claim 1

A compound of formula (I), ##STR28## a pharmaceutically acceptable acid or base addition salt thereof or a stereochemically isomeric form thereof, wherein
A and B taken together form a bivalent radical of formula:
--N.dbd.CH-- (a),
--CH.dbd.N-- (b),
--CH.sub.2 --CH.sub.2 -- (c),
--CH.dbd.CH-- (d),
--C(.dbd.O)--CH.sub.2 -- (e),
--CH.sub.2 --C(.dbd.O)-- (f),
wherein one hydrogen atom in the radicals (a) and (b) may be replaced with a C.sub.1-6 -alkyl-radical and up to two hydrogen atoms in radical (c), (d), (e) or (f) may be replaced by a C.sub.1-6 -alkyl-radical;
D is a radical of formula ##STR29## L is a radical of formula ##STR30## Alk is a C.sub.1-4 alkanediyl radical; R.sup.1 is halo;
R.sup.2 is hydrogen or halo;
R.sup.3 is hydrogen, C.sub.1-6 alkyl, phenyl or halophenyl;
R.sup.4 is hydrogen, C.sub.1-6 alkyl, phenyl or halophenyl;
R.sup.5 is hydrogen or C.sub.1-6 alkyl;
R.sup.6 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxycarbonyl, or
R.sup.5 and R.sup.6 taken together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine, morpholine, piperazine or substituted piperazine ring, said substituted piperazine being a piperazine ring substituted on the 4-position of the piperazine ring with C.sub.1-6 alkyl, hydroxyC.sub.1-6 alkyl, aminoC.sub.1-6 alkyl, mono- or di(C.sub.1-6 alkyl) aminoC.sub.1-6 alkyl.

### Claim 2 (depends on 1)

A compound according to claim 1, wherein D is a radical of formula (D.sub.1) or (D.sub.2).

### Claim 3 (depends on 2)

A compound according to claim 2, wherein D is a radical of formula (D.sub.1), wherein R.sup.1 is chloro or fluoro and R.sup.2 is hydrogen, chloro or fluoro; L is a radical of formula (L.sub.1), wherein R.sup.3 and R.sup.4 each independently are phenyl or hydrogen.

### Claim 4 (depends on 3)

A compound according to claim 3, wherein the compound is (.+-.)-cis-4-›4-›4-›4-››2-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-ylmet hyl)-1,3-dioxolan-4-yl!methoxy!phenyl!-1-piperazinyl!phenyl!-2-›3,3-dimethy l-2-(phosphonooxy)butyl!-2,4-dihydro-3H-1,2,4-triazol-3-one, a stereochemically isomeric form or a base addition salt form thereof.

### Claim 5 (depends on 1)

A composition comprising a pharmaceutically acceptable carrier and as active ingredient an antifungally effective amount of a compound as claimed in claim 1.

### Claim 6 (depends on 2)

A composition comprising a pharmaceutically acceptable carrier and as active ingredient an antifungally effective amount of a compound as claimed in claim 2.

### Claim 7 (depends on 3)

A composition comprising a pharmaceutically acceptable carrier and as active ingredient an antifungally effective amount of a compound as claimed in claim 3.

### Claim 8 (depends on 4)

A composition comprising a pharmaceutically acceptable carrier and as active ingredient an antifungally effective amount of a compound as claimed in claim 4.

### Claim 9 (depends on 1)

A method of inhibiting the development of or eliminating fungi in warm blooded animals suffering from infection by said fungi, which method comprises administering to said warm blooded animals an antifungally effective amount of a compound as claimed in claim 1.

### Claim 10 (depends on 2)

A method of inhibiting the development of or eliminating fungi in warm blooded animals suffering from infection by said fungi, which method comprises administering to said warm blooded animals an antifungally effective amount of a compound as claimed in claim 2.

### Claim 11 (depends on 3)

A method of inhibiting the development of or eliminating fungi in warm blooded animals suffering from infection by said fungi, which method comprises administering to said warm blooded animals an antifungally effective amount of a compound as claimed in claim 3.

### Claim 12 (depends on 4)

A method of inhibiting the development of or eliminating fungi in warm blooded animals suffering from infection by said fungi, which method comprises administering to said warm blooded animals an antifungally effective amount of a compound as claimed in claim 4.