# US 4,391,805 A · 1-(1,3-Dioxolan-2-ylmethyl)-azoles, their salts and their use

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- Number: US 4,391,805 A
- Document ID: US4391805A
- Status: Granted
- Kind: A
- Application number: 06/311,184
- Filed: 1981-10-14
- Granted: 1983-07-05
- Earliest claimed: 1980-10-16
- Assignees: Hoechst Aktiengesellschaft
- Inventors: Ernst Blume; Wolfgang Schaper; Wolfgang Raether; Walter Dittmar
- Web page: https://patentgrep.com/patent/US4391805A

## CPC

- C07D 295/185: from aliphatic carboxylic acids
- C07D 217/04: with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- 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
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 295/096: with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D 295/26: Sulfur atoms
- C07D 317/20: Free hydroxyl or mercaptan
- C07D 317/22: etherified
- C07D 317/24: esterified
- C07D 333/28: Halogen atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

1-(1,3-Dioxolan-2-ylmethyl)-azoles of the general formula ##STR1## and their stereoisomers and their salts with physiologically acceptable acids, the preparation of these compounds, pharmaceutical formulations containing the latter and their use against mycoses, protozoa and Gram-positive and Gram-negative bacteria are described.

## Claims

### Claim 1

A 1-(1,3-dioxolan-2-ylmethyl)-azole of the formula (I) ##STR284## and its stereoisomers and its salts with a physiologically acceptable acid, in which D denotes a 1-(1,3-dioxolan-2-ylmethyl)-azole radical of the following structure ##STR285## in which A denotes nitrogen or methine and X denotes naphthyl, thienyl, halogenothienyl or a phenyl group optionally carrying 1, 2 or 3 substituents, the substituents being identical or different and denoting halogen, trifluoromethyl, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy, and, in formula (I) further, the R.sub.n 's, independently of one another, denote halogen, trifluoromethyl, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.5 alkenyl, C.sub.1 -C.sub.4 alkoxycarbonyl, carboxyl, di-(C.sub.1 -C.sub.4)alkylaminomethyl or nitro, n is 0, 1, 2 or 3, or, in the event that n is 2, R.sub.n denotes a C.sub.4 H.sub.4 radical which, together with the phenyl ring, forms a naphthyl ring, or, in the event that n is 1, R.sub.n represents a phenoxy group optionally carrying 1 or 2 substituents, the substituents being identical or different and denoting halogen, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkoxy, R.sub.1 denotes hydrogen, C.sub.1 -C.sub.4 alkyl or a phenyl group optionally carrying 1 or 2 substituents, the substituents being identical or different and denoting halogen, trifluoromethyl, nitro, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy, m denotes 0, 1 or 2, and Z denotes either
(a) an amino radical of the formula Z(a) ##STR286## in which R.sub.2 and R.sub.3 are identical or different and each denotes hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.5 alkenyl, C.sub.3 -C.sub.8 cycloalkyl or a phenyl or benzyl group optionally carrying 1, 2 or 3 substituents, the substituents being identical or different and each denoting halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or trifluoromethyl, or one of the two radicals R.sub.2 or R.sub.3 denotes C.sub.1 -C.sub.5 alkanoyl or C.sub.1 -C.sub.4 alkoxycarbonyl, or
(b) a radical of the formula Z(b) ##STR287## in which R.sub.4 denotes hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.5 alkenyl, hydroxy-(C.sub.2 -C.sub.3)-alkyl, C.sub.1 -C.sub.4 -alkoxy-(C.sub.2 -C.sub.3)-alkyl, C.sub.1 -C.sub.5 alkanoyl, C.sub.2 -C.sub.5 alkanoylmethyl, C.sub.1 -C.sub.4 alkylsulfonyl, C.sub.1 -C.sub.4 alkyloxycarbonyl, C.sub.1 -C.sub.4 alkyloxycarbonylmethyl, mono-(C.sub.1 -C.sub.4)-alkylaminocarbonylmethyl, di-(C.sub.1 -C.sub.4)-alkylaminocarbonylmethyl, aminocarbonylmethyl-, mono-(C.sub.1 -C.sub.4)alkylaminocarbonyl, di-(C.sub.1 -C.sub.4)-alkylaminocarbonyl, C.sub.1 -C.sub.4 -alkylaminothiocarbonyl, C.sub.1 -C.sub.4 -alkylthiothiocarbonyl, aminocarbonyl, C.sub.3 -C.sub.5 -alkenylaminocarbonyl, or C.sub.3 -C.sub.5 -alkenylaminothiocarbonyl, or R.sub.4 denotes a phenyl, phenylmethyl, phenylaminocarbonyl or benzoyl group, each of the phenyl groups optionally carring 1 or 2 substituents which are identical or different and denote halogen, trifluoromethyl, C.sub.1 -C.sub.4 -alkyl, or C.sub.1 -C.sub.4 -alkoxy, or
(c) a 1-H-imidazol-1-yl, 1H-1,2,4-triazol-1-yl, pyrazol-1-yl-, pyrrolidin-1-yl-, piperidin-1-yl-, morpholin-4-yl, thiomorpholin-4-yl, 2,6-dimethylmorpholin-4-yl, 2,6-dimethylthiomorpholin-4-yl, 1,2,3,4-tetrahydroquinolin-1-yl or 1,2,3,4-tetrahydroisoquinolin-2-yl radical, or
(d) an isocyano group of the formula Z(d)
--N.dbd.C Z(d)
or
(e) an isothiocyano group of the formula Z(e)
--N.dbd.C.dbd.S Z(e)
or
(f) a radical of the general formula Z(f) ##STR288## in which Y represents oxygen or sulfur, G represents oxygen or an NH group, r represents 0 or 1 and R.sub.5 represents hydrogen, C.sub.1 -C.sub.4 -alkyl, monohalogenomethyl, dihalogenomethyl, trihalogenomethyl or a phenyl group optionally carrying 1 or 2 substituents, the substituents being identical or different and each denoting halogen, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkoxy, subject to the proviso that, in the event that Y represents a sulfur atom, G denotes an NH group and r denotes the number 1, that, in the event that G represents an oxygen atom and r represents the number 1, R.sub.5 does not denote hydrogen, and that, in the event that R.sub.5 represents monohalogenomethyl, dihalogenomethyl or trihalogenomethyl, r denotes 0 and Y denotes oxygen.

### Claim 2 (depends on 1)

A 1-(1,3-dioxolan-2-ylmethyl)-azole of the formula (I) as claimed in claim 1 and its stereoisomers and its salts with physiologically acceptable acids, in which D denotes a 1-(1,3-dioxolan-2-ylmethyl)-azole radical as given in claim 1, in which A denotes methine and X denotes 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethyl or 2,4-dichlorophenyl and, in formula (I) further, the R.sub.n 's, independently of one another, denote halogen, C.sub.1 -C.sub.4 -alkyl, methoxy, allyl, n is 0 or 2, R.sub.1 denotes hydrogen, m denotes 0 and Z denotes either
(a) an amino radical of the formula Z(a) ##STR289## in which R.sub.2 and R.sub.3 are identical or different and denote hydrogen, C.sub.1 -C.sub.8 -alkyl, allyl, C.sub.3 -C.sub.8 -cycloalkyl or a phenyl or benzyl group optionally carrying 1 or 2 substituents, the substituents being identical or different and each denoting halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy or trifluoromethyl, or one of the two radicals R.sub.2 or R.sub.3 denotes C.sub.1 -C.sub.5 -alkanoyl, or
(b) a radical of the formula Z(b) ##STR290## in which R.sub.4 denotes hydrogen, C.sub.1 -C.sub.4 -alkyl, allyl, C.sub.1 -C.sub.5 -alkanoyl, methylsulfonyl, methoxycarbonyl, or C.sub.1 -C.sub.4 -alkylaminocarbonyl or R.sub.4 denotes a phenyl, phenylmethyl, or benzoyl group, each of the phenyl groups optionally carrying 1 or 2 substituents which are identical or different and denote halogen, trifluoromethyl, C.sub.1 -C.sub.4 -alkyl, or C.sub.1 -C.sub.4 -alkoxy, or
(c) a piperidin-1-yl-, morpholin-4-yl,2,6-dimethylmorpholin-4-yl, thiomorpholin-4-yl-, 2,6-dimethylthiomorpholin,
(d) a radical of the formula Z(f) ##STR291## in which Y represents oxygen, r represents 0, and R.sub.5 represents C.sub.1 -C.sub.4 -alkyl, or a phenyl group optionally carrying 1 or 2 substituents, the substituents being identical or different and each denoting halogen, trifluoromethyl, C.sub.1 -C.sub.4 -alkyl, or C.sub.1 -C.sub.4 -alkoxy.

### Claim 3

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[4-(4-chlorobenzoylaminomethyl)-2,6-dimethylphenoxymethyl]-1,3-dioxola n.

### Claim 4

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[4-(morpholin-4-ylmethyl)-phenoxymethyl]-1,3-dioxolan.

### Claim 5

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[4-(N-octylaminomethyl)-phenoxymethyl]-1,3-dioxolan.

### Claim 6

2-S, (R)-(2,4-dichlorophenyl)-(2-imidazol-1-ylmethyl)-4-R, (S)-[4-(4-acetylpiperazin-1-ylmethyl)-phenoxymethyl]-1,3-dioxolan.

### Claim 7

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[2,6-dimethyl-4-(N,N-dimethylaminomethyl)-phenoxymethyl]-1,3-dioxolan.

### Claim 8

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[2,6-dimethyl-4-(2,6-dimethylmorpholin-4-ylmethyl)-phenoxymethyl]-1,3- dioxolan.

### Claim 9

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[2-chloro-4-(2,6-dimethylmorpholin-4-ylmethyl)-6-methyl-phenoxymethyl] -1,3-dioxolan.

### Claim 10

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[2,6-dimethyl-4-(2,6-dimethylthiomorpholin-4-ylmethyl)-phenoxymethyl]- 1,3-dioxolan.

### Claim 11

2-S, (R)-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-R, (S)-[2,6-dimethyl-4-(n-octylaminomethyl)-phenoxymethyl]-1,3-dioxolan.

### Claim 12 (depends on 1)

A pharmaceutical composition which contains a compound according to claim 1 in admixture or conjunction with a pharmaceutically acceptable carrier.

### Claim 13 (depends on 1)

Method of treating patients suffering from mycoses, protozoa, Gram-positive or Gram-negative bacteria by administering an effective amount of a compound of formula I as claimed in claim 1.