AU709882B2 - Use of substituted aryl imidazoles - Google Patents

Description

WO 97/36582 PCT/EP97/01390 -1- Use of substituted aryl-imidazoles The present invention relates to the use of substituted aryl-imidazoles as agents for controlling parasitic protozoa and, in particular, coccidia, and fish parasites and insect parasites.

Aryl-halogenoalkylimidazoles and their use as fungicides and insecticides have already been disclosed (WO 95/17390, WO 95/04724, EP 283 173).

It has been found that aryl-imidazoles of the formula (I) Ar W

Y

A

in which Ar represents optionally substituted aryl, W represents halogenoalkyl, A represents hydrogen or represents CH 2

R,

R represents optionally substituted aryl or represents one of the radicals -OR', -SR' or -N(R 2

)COR

3 and Y represents halogen, trifluoromethyl, nitro, -S(O),R 6 represents CN or -CONR 4

R

or represents optionally substituted aryl, R' represents hydrogen, represents alkyl, cycloalkyl, alkenyl, alkinyl, aryl or aralkyl, each of which is optionally substituted,

R

2 represents hydrogen, alkyl, halogenoalkyl, cycloalkyl or optionally substituted -2aryl,

R

3 represents (X)mR 7

-N-

X represents O, S, or m represents 0 or 1,

R

4

R

5

R

8 independently of one another each represent hydrogen, alkyl or optionally substituted aryl,

R

6 represents alkyl, halogenoalkyl or optionally substituted aryl and

R

7 represents alkyl, halogenoalkyl or represents aryl, aralkyl or hetaryl, each of which is optionally substituted and n represents 0, 1 or 2, are outstandingly suitable for controlling parasitic protozoa.

The formulae (Ib) and (Ic) below

N

SNI Ar W I

A

Ar

W

Y I

A

(Ib)

M

-3- Ar NAr N Y (Ic) W I

A

in which A, Ar, W and Y are each as defined above, represent preferred substitution patterns.

The aryl-imidazoles which can be used according to the invention are known, they are defined in a general way by the formula Preferred substituents or ranges of the radicals listed in the formulae mentioned hereinabove and hereinbelow are illustrated below: Ar preferably represents C 6 -C10-aryl which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, nitro, cyano, C,-C,,-alkyl, C,-C, 2 -alkylthio, C,-Cl2-alkoxy, by optionally substituted, doubly attached dioxyalkylene or by -OCF 2 Z, -S(O),CF 2

Z

or -CFR 9

R'.

W preferably represents C,-C 6 -halogenoalkyl.

A preferably represents hydrogen or CH 2

R.

R preferably represents phenyl which is optionally mono- to trisubstituted by halogen, cyano, nitro, C,-C 6 -alkyl, Cl-C 6 -halogenoalkyl or C,-C 6 -alkoxy or represents one of the radicals -SR 1

-N(R

2

)COR

3 Y preferably represents halogen, trifluoromethyl, nitro, -S(O)nR 6 CN, -CONR 4

R

or represents C 6

-C

10 -aryl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen, cyano, a -4nitro, by optionally substituted doubly attached dioxyalkylene or by -OCF 2

Z,

-S(O),CFR

9

R

1

-CFR

9

R.

R' preferably represents hydrogen, C 1

-C

6 -alkyl, C -C 4 -alkoxy-Ci-C 6 -alkyl, CI-C 6 halogenoalkyl, C 3

-C

6 -cycloalkyl, C 2

-C

6 -alkenyl, C 2

-C

6 -halogenoalkenyl, C2-C 6 alkinyl, C 2

-C

6 -halogenoalkinyl or represents phenyl or benzyl, each of which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen, CI-C 6 -alkyl and C 1

-C

6 -alkoxy.

R

2 preferably represents hydrogen, Ci-C 6 -alkyl, C,-C 6 -halogenoalkyl, C 3

-C

6 -cycloalkyl or represents phenyl which is optionally mono- to trisubstituted by halogen, CI-C 6 -alkyl or C 1

-C

6 -alkoxy.

R

3 preferably represents (X),R 7 X preferably represents O.

m preferably represents 0 or 1.

R

4 and R 5 independently of one another each preferably represent hydrogen, Ci-C 6 alkyl or represent phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen and C,-C6-alkyl

R

6 preferably represents Ci-C 6 -alkyl, Ci-C 6 -halogenoalkyl or represents phenyl which is optionally mono- to trisubstituted by [lacuna] or different substituents selected from the group consisting of halogen, C 1

-C

6 -alkyl and C 1

-C

6 -alkoxy.

R

7 preferably represents Ci-C 6 -alkyl, Cl-C 6 -halogenoalkyl, represents benzyl or phenyl, [lacuna] which is optionally mono- to trisubstituted by halogen, CI-C 6 alkyl, CI-C 6 -alkoxy, trifluoromethyl, cyano or nitro or represents pyridylmethyl or pyridyl, [lacuna] which is optionally mono- to trisubstituted by identical or Sdifferent substituents selected from the group consisting of halogen, C 1

-C

6 -alkyl

IL

and C-C 6 -alkoxy.

R

9 and R' 0 independently of one another each preferably represent hydrogen or halogen.

Z preferably represents hydrogen, halogen or C,-C 6 -halogenoalkyl.

S preferably represents 0, 1 or 2.

n preferably represents 0, 1 or 2.

Ar preferably represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen, nitro; cyano, by optionally halogen-substituted, doubly attached dioxyalkylene having 1 to 4 carbon atoms or up to disubstituted by

-OCF

2 Z, -S(O),CF 2 Z or -CFR 9

R'

0 W particularly preferably represents C,-C 4 -alkyl which is substituted by fluorine or chlorine.

A particularly preferably represents hydrogen or represents CH 2

R.

R particularly preferably represents one of the radicals -N(R 2

)COR

7 or

N(R

2 )CO2R 7 Y particularly preferably represents halogen, trifluoromethyl, nitro represents -S(O)n R6 CN, CONR 4

R

5 or represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen, cyano, nitro or by -OCF 2 Z, -S(O),CFR 9

R

0 or -CFR 9

R'.

R' particularly preferably represents hydrogen, represents C,-C 4 -alkyl which is T P optionally substituted by one to three fluorine and/or chlorine atoms or by r -6methoxy or ethoxy, C 3

-C

6 -cycloalkyl, C 2

-C

4 -alkenyl, C 2

-C

4 -alkinyl, C2-C 4 halogenoalkenyl, C 2

-C

4 -halogenoalkinyl or represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of F, Cl, Br, CI-C 4 -alkyl and C 1

-C

4 -alkoxy.

R

2 particularly preferably represents hydrogen, C 1

-C

4 -alkyl, C-C 4 -halogenoalkyl,

C

3

-C

6 -cycloalkyl or represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, C,-C 4 -alkyl and C 1

-C

4 -alkoxy.

R

4 and R 5 independently of one another each particularly preferably represent hydrogen, C 1

-C

4 -alkyl or represent phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, bromine and C 1

-C

4 -alkyl.

R

6 particularly preferably represents methyl which is mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine and bromine.

R

7 in -N(R 2

)CO

2

R

7 particularly preferably represents C-C 4 -alkyl.

R

7 in -N(R 2

)COR

7 particularly preferably represents C 1

-C

4 -alkyl which is optionally substituted by halogen, represents phenyl or pyridyl, each of which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, Cl-C4-alkyl and C 1

-C

4 -alkoxy.

R

9 and R 10 independently of one another each particularly preferably represent hydrogen, fluorine, chlorine or bromine.

Z particularly preferably represents hydrogen, fluorine, chlorine or represents C -C 4 -alkyl which is mono- or polysubstituted by fluorine and/or chlorine.

1 particularly preferably represents 0 or 1.

-7n particularly preferably represents 0, 1 or 2.

Ar very particularly preferably represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, nitro, cyano, by doubly attached dioxyalkylene which is optionally mono- to tetrasubstituted by fluorine and/or chlorine atoms and has one or two carbon atoms, or up to disubstituted by

-OCF

2 Z, -S(O),CF 2 Z or -CFR 9

R'.

W very particularly preferably represents CF 3 or C 2

F

5 A very particularly preferably represents hydrogen or represents CH 2

R.

R very particularly preferably represents a radical of the formula -SR',

-N(R

2 )C0 2

R

7 or -NHCOR 7 Y very particularly preferably represents chlorine, bromine, trifluoromethyl, nitro or represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, cyano, nitro or by -OCF 2 Z, -S(O)nCFR 9

R'

1 or -CFR 9

R'.

R' very particularly preferably represents ethyl, n- or i-propyl, sec-, i- or t-butyl or methyl, [lacuna] which is optionally substituted by one to three fluorine and/or chlorine atoms or by methoxy, represents cyclopropyl, cyclopentyl, represents 2-propenyl, 2-butenyl, 4-chloro-2-butenyl, 2-propinyl, 4-chloro-2butinyl or represents optionally fluorine-,. chlorine-, bromine-, methoxy- or methyl-substituted phenyl.

R

2 very particularly preferably represents hydrogen, represents ethyl, n- or i-propyl, sec-, i- or t-butyl or methyl, [lacuna] which is optionally substituted by one to three fluorine and/or chlorine atoms, represents cyclopropyl, cyclopentyl or ,represents phenyl which is optionally mono- to trisubstituted by identical or -8different substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and methoxy.

R

7 in -N(R 2

)CO

2

R

7 very particularly preferably represents methyl, ethyl, n- or ipropyl, sec-, i- or t-butyl.

R

7 in -NHCOR 7 very particularly preferably represents ethyl, n- or i-propyl, n-, sec-, i- or t-butyl or methyl, [lacuna] which is optionally substituted by one to three fluorine and/or chlorine atoms, or represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and methoxy.

R

9 and R'O independently of one another each very particularly preferably represent hydrogen, fluorine or chlorine.

Z very particularly preferably represents hydrogen, fluorine, chlorine, difluoromethyl, trifluoromethyl, chlorofluoromethyl or the radical of the formula

-CHFCF

3 1 very particularly preferably represents 0.

n very particularly preferably represents 0 or 1.

The above-mentioned general or preferred radical definitions or illustrations can be combined with each other at will, i.e. including combinations between the range and preferred ranges in question.

Preference is given to using the compounds of the general formula in which there is present a combination of the meanings given above as being preferred (preferable).

Very particular preference is given to using the compounds of the general formula (I) in which there is present a combination of these meanings given above as being very Sparticularly preferred.

-9- In particular, mention may be made of the following arylimidazoles of the general formula (1a): Y 7NAr

A

Ex. A Ar Y W No. 4,5-isomer mixture mixture I H 2,3-Cl, 4-CF 3 Ph Br CF 3 2 CH2,OEt 2,3-Cl 2 4-CF 3 Ph Br CF 3 3 H 2,3-Cl 2 Ph Br CF 3 4 CH2OEt 2,3-C1 2 Ph Br CF 3

CH

2

N(CH

3 )COEt 2,3-Cl 2 Ph Br CF 3 6 H 2,4-Cl 2 Ph Br CF 3 7 CH 2 0Et 2,4-Cl2Ph Br CF 3 8 CH2,OEt 2,4-Cl 2 Ph Cl C F 3 9 CH2OEt 2-Cl, 4-CF 3 Ph Br CF 3 CH2,OEt 2-Cl, 6-FPh Br CF 3 11I H 2-Cl, 4-CF 3 Ph Br CF7 3 12 H 2-Cl, 6-FPh Br CF 3 I I T j.ri ]If.r 1.1 z -Arii Ja -I 14 CH 2 OEt 2-ClPh Br CF 3

CH

2

N(CH

3

)CO

2 Et 2-CiPh Br CF 3 16 H 3,4-Cl 2 Ph Br CF 3 17 H3,4-Cl 2 Ph CF 3

CF

3 10 Ex. A Ar Y W No. 4,5-isomer mixture mixture 18 H 3,4-C1 2 Ph Cl CF 3 19 CH 2 OnBu 3,4-C1 2 Ph Br CF 3

CH

2 OiPr 3,4-C1 2 Ph Br CF 3 21 CH 2 OiPr 3,4-C1 2 Ph CF 3

CF

3 22 CH 2 OEt 3,4-CI 2 Ph Br CF 3 23 CH 2 OEt 3,4-C1 2 Ph CF 3

CF

3 24 CH 2 OEt 3,4-C1 2 Ph Cl CF 3 CH2N(nBU)CO 2 Et 3,4-CI 2 Ph Br CF 3 26 CH2N(iBU)CO 2 Me 3,4-C1 2 Ph Br CF 3 27 CH 2 N(Et)CO2Me 3,4-C1,Ph Br CF 3 28 CH 2

N(CH

3

)CO

2 Et 3,4-CI 2 Ph Br CF 3 29 CH 2

N(CH

3

)CO

2 Et 3,4-C1 2 Ph CF 3

CF

3 H 3,4-OCF 2 OPh Br CF 3 31 CH 2 OEt 3,4-OCF 2 OPh Br CF 3 32 H 3,5-(CF 3 2 Ph Br CF 3 33 CH 2 OEt 3,5-(CH 3 2 Ph Br CF 3 34 CH 2 OnBu 3,5-(CF 3 )Ph Br CF 3 r2U -15r, 4-Ph Dr UP 3 36 H 3-Br, 4-FPh Br CF 3 37 CH 2 OEt 3-CF 3 4-CiPh Br CF 3 38 H 3-CF 3 4-CiPh Br CF 3 39 TH 3-ClPh Br CF 3 11 Ex. A Ar Y W No. 4,5-isomer mixture mixture 1H 3-CIPh

CF

3

CF

3 41 CH 2 OEt 3-CiPh Br CF 3 42 CH2OEt 3-CIPh

CF

3

CF

3 43 H 4-BrPh Br CF 3 44 CH 2 OEt 4-BrPh Br CF 3 H 4-CF 3 Ph Br CF 3 j 46 H 4-CF 3 Ph CF 3

CF

3 47 CH2OiPr 4-CF 3 Ph Br CF 3 48 CH 2 0Et 4-CF 3 Ph Br CF 3 49 CH2OEt 4-CF 3 Ph CF 3

CF

3

CH

2 N(iBU)CO 2 Et 4-CF 3 Ph CF 3

CF

3 51 CH 2

N(CH

3

)CO

2 Et 4-CF 3 Ph CF 3

CF

3 52 H 4-CF 3 Ph CN CF 3 53 CH 2 OEt 4-CF 3 Ph CN CF 3 54 H 4-CIPh Br CF 3 H 4-CiPh

CF

3

CF

3 56 CH 2 OEt 4-CiPh Br CF 3 OLT (Y~t A fli n, I I! 1 58 CH 2

OCH

2

CH(CH

3 2 4-CiPh

CF

3

CF

3 59 H 4-HPh

CF

3

CF

3 H 4-OC 2

F

5 Ph Br CF 3 61 CH 2 OEt 4-OC2F5Ph Br CF 3 12 Ex. A Ar Y W No. 4,5-isomer 4 mixture mixture 62 H 4-OCF 3 Ph Br

CF

3 63 CH2OEt 4-OCF 3 Ph Br

CF

3 64 H 4-SCF 3 Ph Br

CF

3 CH2,OEt 4-SCF 3 Ph Br

CF

3 In particular, mention may be made of the following arylimidazoles of the general formula (Ib): Ar I

A

(1b) Ex. A W Ar

Y

No. 4 ,5-Isomer mixture _______mixture 66 H

CF

3 2,4-Cl 2 Ph Br 67 H CF7 3 2-Cl, 6-FPh Br 68 H

CF

3 3,4-Cl 2 Ph Br 69 H CF7 3 3-B3r, 4-FPh Br H CF7 3 3-NO 2 Ph Br 71 H

CF

3 4-CF 3 Ph Br 72 H

CF

3 4-C]Ph Br 73 H

CF

3 4-OCF 3 Ph Br 74 CH 2 OiPr

CF

3 4-CiPh Br 13 Ex. A W Ar Y No. 4,5-Isomer mixture 4 mixture

CH

2 OEt CF 3 2,3-Cl 2 Ph Br 76 CH 2 OEt CF 3 2,4-C1 2 Ph Br 77 CH,OEt CF 3 2-Cl, 6-FPh Br 78 CH2OEt CF 3 2,4-(OCF2CHFCl 2 )Ph Br 79 CH 2 OEt CF 3 3,4-Cl 2 Ph Br

CH

2 OEt CF 3 3,4-OCFCICFC1OPh Br 81 CH 2 OEt CF 3 3-Br, 4-FPh Br 82 CH 2 OEt CF 3 4-CF 3 Ph Br 83 CH 2 OEt CF 3 4-CiPh Br 84 CH 2 OEt CF 3 4-OCF 3 Ph Br

CH

2

N(CH

3

)CO

2 Et CF 3 3-Br, 4-FPh Br 86 CH 2

N(CH

3

)CO

2 Et CF 3 4-CiPh Br 87 H

CF

3 2,4-Cl2Ph

CF

3 88 H

CF

3 3,4-Cl 2 Ph CF 3 89 H

CF

3 4-CF 3 Ph

CF

3 H

CF

3 4-CiPh

CF

3 91 CH 2 OEt CF 3 24C2P

CF

3 W) £'TT f 71- %?r 2 kr i,-1 l 2 Fhn Cr 3 93 CH 2 OEt CF 3 4-CF 3 Ph CF 3 94 CH 2 OEt CF 3 4-CiPh

CF

3 CH2N(CH 3

)CO

2 Et CF 3 3,4-Cl 2 Ph CF 3 96 H CF 3 2,3-Cl2Ph Cl 14 Ex. A W Ar Y No. 4,5-Isomer mixture 4 mixture 97 H CF 3 3,4-CI 2 Ph Cl 98 H CF 3 3,5-C1 2 Ph Cl 99 H CF 3 4-BrPh Cl 100 H CF 3 4-CF 3 Ph Cl 101 H CF 3 4-CIPh Cl 102 H CF 3 4-NO-,Ph Cl 103 H CF 3 4-OCF 3 Ph Cl 104 CH 2 OnBu CF 3 3,4-CI 2 Ph Cl 105 CH2OnBu CF 3 4-CIPh Cl 106 CH 2 OiPr CF 3 3,4-Cl 2 Ph Cl 107 CH 2 OiPr CF 3 4-CIPh Cl 108 CH 2 OEt CF 3 2,C2P Cl 109 CH2OEt CF 3 2,4-Cl 2 Ph Cl 110 CH 2 OEt CF 3 3,4-Cl 2 Ph Cl 111 CH 2 OEt CF 3 35C2hCl 112 CH 2 OEt CF 3 3-B3r, 4-FPh Cl 113 CH 2 OEt CF 3 3-CIPh Cl I IA I-L(Ynr+ r'~A 1' rl 115 CH 2 OEt CF 3 4-CF 3 Ph CI 116 CH 2 OEt CF 3 4-CIPh Cl 117 CH 2 OEt CF 3 4-NO 2 Ph Cl 18 CH 2 OEt CF 3 4-OCF 3 Ph Cl 15 Ex. A W Ar Y No. 4,5-Isomer mixture mixture 119 CHOCHCCCH 2 C1 CF 3 Ph Cl 120 CH 2

OCH(CH

2

F)

2

CF

3 Ph Cl 121 CH 1

O(CH

2 4 C1 CF 3 4-CIPh Cl 122 CH 2

O(CH

2

)OCH

3

CF

3 Ph Cl 123 CH 2 O(4-CI-Ph) CF 3 Ph Cl 124 CH 2

N(H)COCH

3

CF

3 4-CIPh Cl 125 CH 2

N(CH

3 )CO2Et CF 3 4-BrPh Cl 126 CH 2 (4-CI-Ph) CF 3 4-ClPh Cl 1l27 CH 2 OEt CF 3 3,4-C1 2 -Ph S(O)CF 3 In particular, mention may be formula (1c): made of the following arylimidazoles of the general Ar 117 N- Y Ex. A Y Ar W No. 4,5-Isomer mixture mixture 128 H Br 4-Cl-Ph

C

2 17 129 CH 2 OEt Br 4-Cl-PhC27 130 H Br 3,4-Cl-,Ph CF 3 131 H Br 4-ClPh

CF

3 132 H Br 4-OCF 3 Ph CF 3 Ex. A Y Ar W No. 4,5-Isomer mixture 4 mixture 133 H Br 4-SCF 3 Ph CF 3 134 CH 2 OEt Br 3,4-C1 2 Ph CF 3 135 CH 2 OEt Br 4-ClPh CF 3 136 CH 2 OEt Br 4-OCF 3 Ph CF 3 137 CH 2 OEt Br 4-SCF 3 Ph CF 3 138 CH 2

N(CH

3

)CO

2 Et Br 3,4-Cl2Ph CF 3 139 CH 2

N(CH

3

)CO

2 Et Br 4-OCF 3 Ph CF 3 140 CH 2

N(CH

3

)CO

2 Et Br 4-SCF 3 Ph CF 3 141 H Cl 4-Cl-Ph C 2

F

142 CI-bOEt Cl 4-Cl-Ph C2F 143 H Cl 3,4-C1 2 Ph CF 3 144 H Cl 4-CiPh CF 3 145 H CI 4-OCF 3 Ph CF 3 146 H Cl 4-SCF 3 Ph CF 3 147 CH 2 OEt Cl 3,4-CI 2 Ph CF 3 148 CH 2 OEt Cl 4-CiPh CF 3 149 CH 2 OEt Cl 4-OCF 3 Ph CF 3 151 CH 2

N(CH

3

)CO

2 Et CI 4-OCF 3 Ph CF 3 152 H CN 3,4-C1 2 -Ph CF 3 153 H CN 4-CF 3 -Ph CF 3 154 CH 2 OEt CN 3,4-C l 2 Ph CF 3 17 Ex. A Y Ar W No. 4,5-Isomer mixture 4 mixture 1 CH 2 OEt CN I4-CF 3 -Ph

CF

3 Particularly preferred compounds from the series of the arylimidazoles of the formula (1a) which may be mentioned are: YN A

A

Ex. A Ar Y W No. 4,5- Isomer Isomer mixture mixture 1 H 2,3-Cl 2 4-CF 3 Ph Br CF 3 2 CH 2 OEt 2,3-Cl 2 4-CF 3 Ph Br CF 3 23 CH 2 OEt 3,4-C1 2 Ph CF 3

CF

3 31 CH2OEt 3,4-OCF 2 OPh Br CF 3 32 H 3,5-(CF 3 2 Ph Br CF 3 33 CH 2 OEt 3,5-(CH 3 2 Ph Br CF 3 34 CH 2 OnBu 3,5-(CF 3 2 Ph Br CF 3 37 CH,OEt 3-CF 3 4-CiPh Br CF 3 38 H 3-CF 3 4-CIPh Br CF 3 46 H 4-CF 3 Ph CF 3

CF

3 H 4-CF 3 Ph Br CF 3 47 CH 2 OiPr 4-CF 3 Ph Br CF 3 18 Ex. A Ar Y W No. 4,5- Isomer Isomer mixture mixture 48 CH 2 OEt 4-CF 3 Ph Br CF 3 49 CH 2 OEt 4-CF 3 Ph CF 3

CF

3 64 H 4-SCF 3 Ph Br CF 3

CH

2 OEt 4-SCF 3 Ph Br CF 3 Particularly preferred compounds from the series of the arylimidazoles of the formula (1b) which may be mentioned are: Ar-4 N W

A

Ex. A W Ar Y No. 4,5-Isomer mixture mixture 87 H CF 3 2,4-C1 2 Ph CF 3 88 H CF 3 3,4-CI 2 Ph CF 3 89 H CF 3 4-CF 3 Ph CF 3 H CF 3 4-CIPh CF 3 91 CH 2 OEt CF 3 2,4-Cl 2 Ph CF 3 92 CH 2 Obt CF 3 3,4-CI 2 Ph CF 3 93 CH 2 OEt CF 3 4-CF 3 Ph CF 3 94 CH 2 OEt CF 3 4-CIPh CF 3

CH

2

N(CH

3

)CO

2 Et CF 3 3,4-Cl 2 Ph CF 3 19- Particularly preferred compounds from the series of the arylimidazoles of the formula (Ic) which may be mentioned are: W N Ar4-.

I

N Y

I

A

(Ic) Ex. A Y Ar W No. 4,5-Isomer mixture mixture 133 H Br 4-SCF 3 Ph CF 3 137 CH 2 OEt Br 4-SCF 3 Ph CF 3 145 H Cl 4-OCF 3 Ph CF 3 146 H Cl 4-SCF 3 Ph CF 3 148 CH 2 OEt Cl 4-ClPh CF 3 149 CHO2Et Cl 4-OCF 3 Ph CF 3 150 CHOEt Cl 4-SCF 3 Ph CF 3 The compounds which can be used according to the invention are outstandingly suitable for use in mixtures with synthetic coccidiostats or polyether antibiotics.

Compared with the activity of the individual components, some of these mixtures show considerably increased activity (synergism). In control programmes, they can also advantageously be employed alternating with synthetic coccidiostats or polyether antibiotics.

Suitable polyether antibiotics include maduramycin, lasalocid, monensin, narasin, salinomycin. Suitable synthetic coccidiostats include: 20 1 (-(4-amino-2-n-propyl-5-pyrimidinylmethyl)-2-picolinium chloride 1 (-(4-amino-2-n-propyl-5-pyrimidinylmethyl)-2-picolinium chloride sulfaquinoxaline 1 (-(4-amino-2-n-propyl-5-pyrimidinylmethyl)-2-picolinium chloride sulfaquinoxaline ethopabate 4,4-dinitrocarbanilide 2-hydroxy-4,6-dimethylpyrimidine 3,5-dichloro-2,6-dimethyl-4-pyridinol 3 ,5-dichloro-2,6-dimethyl-4-pyridinol methyl-7-benzyloxy- 6-butyl- 1 ,4-dihydro-4-oxylquinoline-3-carboxylate ethyl 6-n-decyloxy-7-ethoxy-4-hydroxyquinoline-3carboxylate 9-(2-chloro-6-fluorophenylmethyl)-9H-purin-6-amine (±)-2,6-dichloro-alpha-(4-chlorophenyl)-4-(4,5-dihydro-3 ,5dioxo- 1 ,2,4-triazin-2(3H)-yl)-benzeneacetonitrile 1- [3-methyl-4-(4'-trifluoromethylthiophenoxy)-phenyl] -3methyl-I ,3,5-triazine-2,4,6( 1 H,3H4,5H)-trione 4,4-dinitrocarbanilide 2-hydroxy-4,6-dimethylpyrimidine nicarbazin] 7-bromo-6-chloro-febrifugin 3 ,5-dinitro-o-toluamide Amprolium Amprolium sulfaquinoxaline Amprolium sulfaquinoxaline ethopabate Nicarbazin Clopidol Clopidol methylbenzoquate Decoquinate Arprinocid Benzeneacetonitrile, diclazuril Toltrazuril Robenidine Halofuginone Zoalene.

The active compounds are suitable, while having favourable toxicity for warm-blooded species, for controlling parasitic protozoa which occur in livestock management and livestock breeding in useful, breeding, zoo, laboratory, experimental and pet animals.

They are moreover active against all or individual stages of development of the pests and against resistant and normally sensitive strains. The intention of the control of the parasitic protozoa is to reduce disease, deaths and reductions in performance (for -21 example in the production of meat, milk, wool, hides, eggs, honey etc.), so that the use of the active compounds makes more economical and simpler livestock management possible.

The parasitic protozoa include: Mastigophora (Flagellata) such as, for example Trypanosomatidae, for example Trypanosoma b. brucei, T.b. gambiense, T.b. rhodesiense, T. congolense, T. cruzi, T.

evansi, T. equinum, T. lewisi, T. percae, T. simiae, T. vivax, Leishmania brasiliensis, L. donovani, L. tropica, such as, for example Trichomonadidae, for example Trichomonas vaginalis, Tritrichomonas foetus, such as, for example Diplomonadida, for example Giardia lamblia, G. canis.

Sarcomastigophora (Rhizopoda) such as Entamoebidae, for example Entamoeba histolytica, Hartmanellidae, for example Acanthamoeba sp., Hartmanella sp.

Apicomplexa (Sporozoa) such as Eimeridae, for example Eimeria acervulina, E.

adenoides, E. alabahmensis, E. anatis, E. anseris, E. arloingi, E. ashata, E. auburnensis, E. bovis, E. brunetti, E. canis, E. chinchillae, E. clupearum, E. columbae, E. contorta, E. crandalis, E. debliecki, E. dispersa, E. ellipsoidales, E. falciformis, E. faurei, E.

flavescens, E. gallopavonis, E. hagani, E. intestinalis, E. iroquoina, E. irresidua, E.

labbeana, E. leucarti, E. magna, E. maxima, E. media, E. meleagridis, E. meleagrimitis, E. mitis, E. necatrix, E. ninakohlyakimovae, E. ovis, E. parva, E. pavonis, E. perforans, E. phasani, E. piriformis, E. praecox, E. residua, E. scabra, E. spec., E. stiedai, E. suis, E. tenella, E. truncata, E. truttae, E. zuernii, Globidium spec., Isospora belli, I. canis, I. felis, I. ohioensis, I. rivolta, I. spec., I. suis, Cystisospora spec., Cryptosporidium spec. such as Toxoplasmadidae, for example Toxoplasma gondii, such as Sarcocystidae, for example Sarcocystis bovicanis, S. bovihominis, S. ovicanis, S. ovifelis, S. spec., S.

suihominis such as Leucozoidae, for example Leucozytozoon simondi, such as Plasmodiidae, for example Plasmodium berghei, P. falciparum, P. malariae, P. ovale, P. vivax, P. spec., such as Piroplasmea, for example Babesia argentina, B. bovis, B. canis, B.

spec., Theileria parva, Theileria spec., such as Adeleina, for example Hepatozoon canis, H. spec.

22 Furthermore Myxospora and Microspora, for example Glugea spec. Nosema spec.

Furthermore Pneumocystis carinii, and Ciliophora (Cilata) such as, for example Balantidium coli, Ichthiophthirius spec., Trichodina spec., Epistylis spec.

The compounds according to the invention are also active against protozoa occurring as parasites in insects. Examples of these are parasites of the phylum Microsporida, in particular of the genus Nosema. Particular mention may be made of Nosema agis in the case of the honeybee.

Useful and breeding livestock include mammals such as, for example, cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, furbearing livestock such as, for example, mink, chinchillas, raccoons, birds such as, for example, chickens, geese, turkeys, ducks, pigeons, bird species for keeping at home and in zoos. They further include productive and ornamental fish.

Laboratory and experimental animals include mice, rats, guinea pigs, hamsters, dogs and cats.

Pet animals include dogs and cats.

Fish include productive, breeding, aquarium and ornamental fish of all ages, which live in fresh and salt water. Productive and breeding fish include e.g. carp, eel, trout, whitefish, salmon, bream, roach, rudd, chub, sole, plaice, halibut, Japanese yellowtail (Seriola quinqueradiata), Japanese eel (Anguilla japonica), red seabream (Pagurus major), sea bass (Dicentrarchus labrax), grey mullet (Mugilus cephalus), pompano, gilthead seabream (Sparus auratus), Tilapia spp., Chichlidae species such as e.g.

Plagioscion, channel catfish. The compositions according to the invention are particularly suitable for the treatment of fry, e.g. carp of 2 4 cm body length. The compositions are also very highly suitable in eel feeding.

Both prophylactic and therapeutic use are possible.

-23 The active compounds are used directly or in the form of suitable preparations, enterally, parenterally, dermally, nasally.

Enteral use of the active compounds takes place, for example, orally in the form of powders, suppositories, tablets, capsules, pastes, drinks, granules, drenches, boli, medicated feed or drinking water. Dermal use takes place, for example, in the form of dipping, spraying, bathing, washing, pouring on and spotting on, and dusting. Parenteral use takes place, for example, in the form of injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.

Suitable preparations are: solutions such as injection solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, pour-on formulations, gels; emulsions and suspension for oral or dermal use and for injection; semisolid preparations; formulations in which the active compound is incorporated in an ointment base or in an oil-in-water or water-in-oil emulsion base; solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, boli, capsules; aerosols and inhalations, shaped articles containing active compound.

Injection solutions are administered intravenously, intramuscularly and subcutaneously.

Injection solutions are prepared by dissolving the active compound in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives. The solutions are sterilized by filtration and bottled.

Solvents which may be mentioned are: physiologically tolerated solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, hydrocarbons, propylene 24 glycol, polyethylene glycols, N-methylpyrrolidone, and mixtures thereof.

The active compounds can, where appropriate, also be dissolved in physiologically tolerated vegetable or synthetic oils which are suitable for injection.

Solubilizers which may be mentioned are: solvents which promote dissolution of the active compound in the main solvent or prevent its precipitation. Examples are polyvinylpyrrolidone, polyethoxylated castor oil, polyethoxylated sorbitan esters.

Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic esters, n-butanol.

Oral solutions are used directly. Concentrates are used orally after previous dilution to the use concentration. Oral solutions and concentrates are prepared, as described above for injection solutions, it being possible to dispense with sterile operation.

Solutions for use on the skin are spotted on, painted on, rubbed in, applied by spraying or jetting, or applied by dipping, bathing or washing. These solutions are prepared, as described above for the injection solutions.

It may be advantageous to add thickeners during preparation. Thickeners are: inorganic thickeners such as bentonites, colloidal silica, aluminium monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and metacrylates.

Gels are applied or painted onto the skin or introduced into body cavities. Gels are prepared by adding sufficient thickeners to solutions, which have been prepared as described for the injection solutions, to result in a clear composition with an ointmentlike consistency. The thickeners used are the thickeners indicated hereinbefore.

Pour-on formulations are poured onto or sprayed onto limited areas of the skin, in which case the active compound either penetrates the skin and acts systemically or is dispersed on the surface of the body.

25 Pour-on formulations are prepared by dissolving, suspending or emulsifying the active compound in suitable skin-compatible solvents or solvent mixtures. Where appropriate, other auxiliaries such as colorants, absorption-promoting substances, antioxidants, sunscreen agents, adherents are added.

Solvents which may be mentioned are: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenyl ethanol, phenoxy ethanol, esters such as ethyl acetate, butyl acetate, benzylbenzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol monobutyl ether, ketones such as acetone, methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-1,3-dioxolane.

Colorants are all colorants approved for use on livestock, and which can be dissolved or suspended.

Absorption-promoting substances are, for example, DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Antioxidants are sulphites or metabisulphites such as potassium metabisulphite, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol.

Sunscreen agents are, for example, substances from the class of benzophenones or novantisolic acid.

Adherents are, for example, cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.

Emulsions can be used orally, dermally or as injections.

Emulsions are either of the water-in-oil type or of the oil-in-water type.

26- They are prepared by dissolving the active compound either in the hydrophobic or in the hydrophilic phase and homogenizing the latter with the assistance of suitable emulsifiers and, where appropriate, other auxiliaries such as colorants, absorptionpromoting substances, preservatives, antioxidants, sunscreen agents, viscosity-increasing substances, with a solvent of the other phase.

The following may be mentioned as hydrophobic phase (oils): paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic/capric acid biglyceride, triglyceride mixture with vegetable fatty acids of chain length C 8 1 2 or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated, possibly also hydroxyl groupcontaining fatty acids, mono- and diglycerides of C 8 /Co fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length C 16

-C

1 8 isopropyl myristate, isopropyl palmitate, caprylic/capric esters of saturated fatty alcohols of chain length C 12

-C

1 8 isopropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, waxy fatty acid esters such as dibutyl phthalate, diisopropyl adipate, ester mixtures related to the latter, including fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oleyl alcohol.

Fatty acids such as, for example, oleic acid and mixtures thereof.

The following may be mentioned as hydrophilic phase: water, alcohols such as, for example, propylene glycol, glycerol, sorbitol and mixtures thereof.

Emulsifiers which may be mentioned are: nonionic surfactants, for example polyethoxylated castor oil, polyethoxylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether; -27 ampholytic surfactants such as di-Na-N-lauryl-3-iminodipropionate or lecithin; anionic surfactants, such as Na-lauryl sulphate, fatty alcohol ether sulphates, mono/dialkylpolyglycol ether orthophosphoric ester monoethanolamine salt; cationic surfactants such as cetyltrimethylammonium chloride.

Further auxiliaries which may be mentioned are: viscosity-increasing and emulsion-stabilizing substances such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal silica or mixtures of the substances mentioned.

Suspensions can be used orally, dermally or as injection. They are prepared by suspending the active compound in a liquid vehicle, where appropriate with the addition of further auxiliaries such as wetting agents, colorants, absorption-promoting substances, preservatives, antioxidants, sunscreen agents.

Liquid vehicles which may be mentioned are all homogeneous solvents and solvent mixtures.

Wetting agents (dispersants) which may be mentioned are the surfactants indicated hereinbefore.

Further auxiliaries which may be mentioned are those indicated hereinbefore.

Semisolid preparations can be administered orally or dermally. They differ from the suspensions and emulsions described above only by their higher viscosity.

To prepare solid preparations, the active compound is mixed with suitable excipients, where appropriate with the addition of auxiliaries, and converted into the desired shape.

28- Excipients which may be mentioned are all physiologically tolerated solid inert substances. Used as such are inorganic and organic substances. Inorganic substances are, for example, sodium chloride, carbonates such as calcium carbonate, bicarbonates, aluminium oxides, silicas, aluminas, precipitated or colloidal silicon dioxide, phosphates.

Organic substances are, for example, sugars, cellulose, foodstuffs and feedstuffs, such as milk powder, animal meals, cereal meals and coarse meals, starches.

Auxiliaries are preservatives, antioxidants, colorants, which have already been listed hereinbefore.

Further suitable auxiliaries are lubricants and glidants, such as, for example, magnesium stearate, stearic acid, talc, bentonites, disintegration-promoting substances such as starch or crosslinked polyvinylpyrrolidone, binders such as, for example, starch, gelatin or linear polyvinylpyrrolidone, and dry binders such as microcrystalline cellulose.

The active compounds may also be present in the preparations mixed with synergists or with other active compounds.

Preparations ready for use contain the active compound in concentrations of 10 ppm to per cent by weight, preferably from 0.1 to 10 per cent by weight.

Preparations which are diluted before use contain the active compound in concentrations of 0.5 to 90 per cent by weight, preferably from 1 to 50 per cent by weight.

It has in general proved advantageous to administer amounts of about 0.5 to about mg, preferably 1 to 20 mg, of active compound per kg of bodyweight per day to achieve effective results.

The active compounds can also be administered to the livestock together with the feed or drinking water.

29 Feedstuffs and foodstuffs contain 0.01 to 100 ppm, preferably 0.5 to 50 ppm, of the active compound in combination with a suitable edible material.

Such a feedstuff and foodstuff can be used both for curative purposes and for prophylactic purposes.

Such a feedstuff or foodstuff is prepared by mixing a concentrate or a premix which contains 0.5 to 30%, preferably 1 to 20% by weight, of an active compound mixed with an edible organic or inorganic vehicle, with customary feedstuffs. Edible vehicles are, for example, maize meal or maize and soya bean meal or mineral salts, which preferably contain a small amount of an edible dust-preventing oil, for example corn oil or soya oil. The premix obtained in this way can then be added to the complete feedstuff before it is fed to the livestock.

The use for coccidiosis may be mentioned by way of example: For the cure and prophylaxis, for example, of coccidiosis in poultry, in particular in chickens, ducks, geese and turkeys, 0.1 to 100 ppm, preferably 0.5 to 100 ppm, of an active compound are mixed with a suitable edible material, for example a nutritious feedstuff. If required, these amounts can be increased, especially if the active compound is well tolerated by the recipient. Administration via the drinking water can take place correspondingly.

For the treatment of single animals, for example in the case of treatment of coccidiosis in mammals or of toxoplasmosis, preferably amounts of active compound of 0.5 to 100 mg/kg of bodyweight are administered each day in order to achieve the desired results. It may, nevertheless, be necessary on occasions to deviate from the stated amounts, in particular as a function of the bodyweight of the experimental animal or of the nature of the method of administration, but also because of the animal genus and its individual reaction to the active compound or the type of formulation and the time or interval over which administration takes place. Thus, it may suffice in certain cases to make do with less than the above-mentioned minimum amount, whereas in other cases the stated upper limit must be exceeded. On administration of larger amounts, it may be expedient to divide these into several individual administrations over the course of the day.

Fish parasites include, from the subkingdom of the protozoa, species of the phylum of the Ciliata, for example Ichthyophthirius multifiliis, Chilodonella cyprini, Trichodina spp., Glossatella spp., Epistylis spp. of the phylum of the Myxosporidia, for example Myxosoma cerebralis, Myxidium spp., Myxobolus spp., Heneguya spp., Hoferellus spp., from the class of the Microsporidia for example Glugea spp., Thelohania spp., Pleistophora spp., of the phylum of the Plathelminth: trematodes; Monogenea for example Dactylogyrus spp., Gyrodactylus spp., Pseudodactylogyrus spp., Diplozoon spp., cestodes, for example from the groups of the Caryphyllidea (for example Caryophyllaeus laticeps), Pseudophyllidea (for example diphyllobothrium spp.), Tetraphyllidea (for example Phyllobothrium spp.) and Protocephalida (for example species of the genus Proteocephalus) and from the phylum of the Arthropoda various parasitic crustaceans, in particular from the subclasses of the Branchiura (fish lice) and Copepoda (copepods) and from the orders of the Isopoda (isopods) and Amphipoda (beech fleas).

The treatment of the fish is carried out either orally, for example via the feed or by short-term treatment, "medical bath", into which the fish are placed and where they are kept for a certain period of time (minutes up to several hours), for example during transfer from one breeding basin into another.

However, it is also possible to treat the habitat of the fish (for example entire pond systems, aquariums, tanks or basins), where the fish are kept, for a time or permanently.

The active compound is administered in formulations which are adapted to the applications.

The concentration of the active compound, in the formulations is from 1 ppm to by weight.

31 Preferred formulations for the short-term treatment in the application as "medical bath" for example in the treatment during transfer of the fish or for the treatment of the habitat (pond treatment) of the fish are solutions of the active compound in one or more polar solvents which gives an alkaline reaction when diluted with water.

These solutions are prepared by dissolving the active compound in a polar, watersoluble solvent which either gives an alkaline reaction or to which an alkaline watersoluble substance is added. The latter is advantageously also dissolved in the solvent, but may also be suspended in the solvent and only dissolved in the water. The pH of the water after addition of the solution of active compound should be 7-10, but preferably 8-10.

The concentration of the active compound can be in the range from 0.5-50%, but is preferably in the range 1-25%.

Suitable solvents are all water-soluble solvents in which the active compound is soluble in a sufficient concentration and which are physiologically acceptable.

These are ethyl alcohol, isopropyl alcohol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycols, poly(oxoethylene)/poly(oxypropylene)polymers, basic alcohols such as mono-, di and triethanolamine, ketones such as acetone or methyl ethyl ketone, esters such as ethyl lactate furthermore N-methylpyrrolidone, dimethylacetamide, dimethylformamide, furthermore dispersants and emulsifiers such as polyethoxylated castor oil, polyethylene glycol/sorbitan/monooleate, polyethylene glycol stearate, or polyethylene glycol ethers, polyethylene glycol alkylamines.

Bases which are suitable for adjusting the alkaline pH are organic bases such as basic amino acids such as L- or D,L-arginine, L- or D, L-lysine, methylglucosamine, glucosamine, 2-amino-2-hydroxymethylpropane-1,3-diol furthermore such as tetrakis-(2-hydroxypropyl)-ethylenediamine or polyethertetrol based on ethylenediamine 480-420), inorganic bases, such as ammonia or sodium carbonate-if appropriate with addition of water.

I

32 The formulations may also comprise 0.1 to 20% by weight, preferably 0.1-10% by weight of other formulation auxiliaries, such as antioxidants, surfactants, suspension stabilizers and thickeners such as, for example, methylcellulose, alginates, polysaccharides, galactomannanes and colloidal silicic acid. The addition of colorant, flavoring and nutrients for the animal diet is also possible. Acids which together with the base initially charged form a buffer system or which reduce the pH of the solution may also be mentioned in this context.

The use concentration of the active compound depends on the nature and the duration of the treatment, and on the age and the state of the fish treated. In the short-term treatment it is, for example, 2-50 mg of active compound per litre of water preferably 5-10 mg per litre, at a duration of treatment of 3-4 hours. Young carps are treated, for example, with a concentration of 5-10 mg/l and a duration of treatment of approximately 1-4 hours.

Eels are treated with concentrations of approximately 5 mg/l for approximately 4 hours.

If the treatment lasts longer, or for permanent treatment, the concentration may be reduced correspondingly.

For pond treatment, 0.1-5 mg of active compound per litre of water may be employed.

Formulations for use as feed additive have, for example, the following composition: a) active compound of the formula I soya bean protein b) active compound of the formula I benzyl alcohol hydroxypropylmethylcellulose Water 1 10 parts by weight 49 90 parts by weight 0.5 10 parts by weight 0.08 1.4 parts by weight 0 3.5 parts by weight remainder ad 100 33 Formulations for use in "medical baths" and for pond treatment are, for example, composed and prepared as shown below.

c) 2.5 g of active compound of the formula are dissolved with heating in 100 ml of triethanolamine.

d) 2.5 g of active compound of the formula (I) 12.5 g of lactic acid are dissolved with heating and stirring in 100 ml of triethanolamine.

e) 10.0 g of active compound of the formula are dissolved in 100 ml of monoethanolamine.

f) active compound of the formula I propylene glycol sodium carbonate water g) active compound of the formula I monoethanolamine N-methylpyrrolidone h) active compound of the formula I sodium carbonate polyethylene glycol 200 5.0 g 50.0 g 5.0 g ad 100 ml 5.0 g 10 g ad 100 ml 2.5 g 5.0 g ad 100 ml The active compound is dissolved with heating in polyethylene glycol, and sodium carbonate is suspended therein.

A feed containing active compound is prepared with the compounds according to the invention generally in such a way that approximately 0.1 to 5000 ppm, preferably 0.1 to 100 ppm of active compound are thoroughly mixed with an animal feed which is balanced in nutrient terms, for example with the chick feed described in the example -34below.

If a concentrate or a premix is to be prepared and is finally to be diluted in the feed to the figures mentioned above, in general about 1 to 30%, preferably about 10 to 20% by weight of active compound are mixed with an edible organic or inorganic vehicle, for example maize and soya meal or mineral salts, which contain a small amount of an edible anti-dusting oil, for example corn oil or soya bean oil. The premix obtained in this way can then be added to the complete poultry feed before administration.

An example of a suitable composition for use of the substances according to the invention in poultry feed is the following.

52.00% coarse cereal feed meal, in particular: 40% maize, 12% wheat 17.00% extr. coarse soya meal 5.00% maize gluten feed 5.00% wheat feed meal 3.00% fish meal 3.00% mineral mixture 3.00% alfalfa meal 2.50% vitamin premix 2.00% wheatgerms, crushed 2.00% soya oil 2.00% meat and bone meal 1.50% whey powder 1.00% molasses 1.00% brewer's yeast, bound to brewer's grains 100.00% Such a feed contains 18% crude protein, 5% crude fibre, 1% Ca, 0.7% P and, per kg, 1200 I.U. of vitamin A, 1200 I.U. of vitamin D 3 10 mg of vitamin E, 20 mg of zinc bacitracin.

35 The efficacy of the compounds according to the invention is demonstrated by the example below, without limiting the chemical range of its applicability.

36 Example A Cage test on coccidiosis/chicks Male chicken chicks (for example LSL Brinkschulte/Senden) which have been reared coccidia-free and are 8 to 12 days old receive the compounds according to the invention (test substances) in the concentration stated in ppm with the feed from 3 days before (day the infection to 8 days after the infection Three birds are kept in each cage. One or more such groups are used per dosage. The infection takes place using a tube direct into the crop with about 100,000 sporulated oocysts of Eimeria acervulina and with in each case about 5-80,000 sporulated oocysts of E.

maxima and E. tenella. Highly virulent strains of these are used. The exact infection dose is adjusted so that, where possible, one in three untreated experimentally infected chicks dies from the infection. The following criteria are taken into account for assessing the efficacy: weight gain from start of test to end of test, mortality rate from the infection, macroscopic assessment of the faeces with regard to diarrhoea and excretion of blood on days 5 and 7 macroscopic assessment of the intestinal mucosa, especially of the caeca and excretion of oocysts, and the proportion (in of oocysts sporulating within 24 hours. The number of oocysts in the faeces was determined using a McMaster counting chamber (see Engelbrecht and coworkers "Parasitologische Arbeitsmethoden in Medizin und Veterinirmedizin, Akademie-Verlag, Berlin (1965)).

The individual findings are related to the untreated infected and uninfected control groups, and a total score is calculated (cf. A. Haberkorn (1986) pages 263 270 in Research in Avian Coccidiosis ed. L.R. McDougald, L.P. Joyner, P.L. Long Proceedings of the Georgia Coccidiosis Conference Nov, 18. 20. 1995 Athens/Georgia USA).

The efficacy is scored as follows: 2 fully effective; 1 partially effective; 0 not effective.

37 Table 1 Efficacy of exemplary compounds against Coccidia acervulina, E. maxima, E.

tenella) in chicks Eimeria acervulina Efficacy at a dose of ppm in the E. maxima feed Ex. No. E. tenella 25 10 5 137 Eimeria acervulina 2 1 0-1 E. maxima 2 1 0-1 E. tenella 2 1 0-1 146 Eimeria acervulina 2 E. maxima 1 E. tenella 1 64 Eimeria acervulina 2 1 E. maxima 2 1 E. tenella 2 0 29 Eimeria acervulina 1 E. maxima 1 E. tenella I 46 Eimeria acervulina 2 E. maxima 2 E. tenella 2 23 Eimeria acervulina 2 2 E. maxima 2 2 E. tenella 2 1 92 Eimeria acervulina 2 E. maxima 2 E. tenella 2 38 Eimeria acervulina Efficacy at a dose of ppm in the E. maxima feed Ex. No. E. tenella 25 10 5 49 Eimeria acervulina 1 1 E. maxima 1 0 E. tenella 2 1 Eimeria acervulina 2 E. maxima 2 E. tenella 1 93 Eimeria acervulina 1 E. maxima 1 E. tenella 1 32 Eimeria acervulina 2 1-2 E. maxima 2 1-2 E. tenella 1-2 1-2 2 fully effective, 1 partially effective, 0 not effective; tot inf. toxicity

Claims (1)

1. 39- Patent claims 1. Use of aryl-imidazoles of the formula (I) Arf W Y I A in which Ar represents optionally substituted aryl, W represents halogenoalkyl, A represents hydrogen or represents CH 2 R, R represents optionally substituted aryl or represents one of the radicals -SR' or -N(R 2 )COR 3 and Y represents halogen, trifluoromethyl, nitro, -S(O)nR 6 represents CN or -CONR 4 R 5 or represents optionally substituted aryl, R' represents hydrogen, represents alkyl, cycloalkyl, alkenyl, alkinyl, aryl or aralkyl, each of which is optionally substituted, R 2 represents hydrogen, alkyl, halogenoalkyl, cycloalkyl or optionally substituted aryl, R 3 represents (X)mR 7 X represents O, S, -N- 40 m represents 0 or 1, R 4 R 5 R 8 independently of one another each represent hydrogen, alkyl or optionally substituted aryl, R 6 represents alkyl, halogenoalkyl or optionally substituted aryl and R 7 represents alkyl, halogenoalkyl or represents aryl, aralkyl or hetaryl, each of which is optionally substituted and n represents 0, 1 or 2, for preparing compositions for controlling parasitic protozoa in veterinary medicine. 2. Use according to Claim 1, characterized in that aryl-imidazoles of the formulae (Ib) and (Ic) SAr (Ia) W I A Ar N W (Ib) Y I A Ar- I N Y (Ic) W A in which A, Ar, W and Y are each as defined in Claim 1, -41 are employed as active compounds. 3. Method for controlling parasitic protozoa, characterized in that aryl-imidazoles of the formula according to Claim 1 are allowed to act on them and/or their habitat. 4. Methods of treatment involving/containing compounds of the formula substantially as hereinbefore described with reference to the Example. DATED this 30th day of June, 1999 BAYER AKTIENGESELLSCHAFT 1 By its Patent Attorneys 10 DAVIES COLLISON CAVE i *ft