Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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I
FILE, l~r! !'l ~,"S A~E~
Use of ~ d ar~ imidazoles T~l l'AN"LArl~N
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, insecticides and herbicides
have already been disclosed (WO 95/17390, WO 95/04724, EP 283 173,
WO 95/33730)-
It has been found that aryl-imidazoles of the formula (I)
Ar~gW
y N (I)
in which
Ar represents optionally substituted aryl,
W represents halogenoalkyl,
A represents hydrogen or represents CH2R,
R represents optionally substituted aryl or represents one of the radicals -OR',
-SR' or-N(R2)COR3 and
Y represents halogen, trifluoromethyl, nitro, -S(O)nR6, represents CN or-CONR4R5
or represents optionally substituted aryl,
R' represents hydrogen, represents alkyl, cycloalkyl, alkenyl, alkinyl, aryl or
aralkyl, each of which is optionally substituted,
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R2 represents hydrogen, alkyl, halogenoalkyl, cycloalkyl or optionally substituted
aryl,
R3 represents (X)mR7,
18
X represents O, S, or N
m represents 0 or 1,
R4, R5, R8 independently of one another each represent hydrogen, alkyl or optionally
substituted aryl,
R6 represents alkyl, halogenoalkyl or optionally substituted aryl and
R7 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 (Ia), (Ib) and (Ic) below
W IA Ar (Ia)
y~NlW (Ib)
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Ar~J~
N y (Ic)
W 1
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 (I).
Preferred substituents or ranges of the radicals listed in the formulae mentioned here-
inabove and hereinbelow are illustrated below:
Ar preferably represents C6-C,0-aryl which is optionally mono- or polysubstituted
by identical or different substituents selected from the group consisting of
halogen, nitro, cyano, C,-C,2-alkyl, C,-C,2-alkylthio, C,-C,2-alkoxy, by
optionally substituted, doubly attached dioxyalkylene or by -OCF2Z, -S(O),CF2Z
or-CFR9R'0.
W preferably represents C,-C6-halogenoalkyl.
A preferably represents hydrogen or CH2R.
R preferably represents phenyl which is optionally mono- to trisubstituted by
halogen, cyano, nitro, C,-C6-alkyl, C,-C6-halogenoalkyl or C,-C6-alkoxy or
represents one of the radicals -OR', -SR', -N(R2)CoR3.
Y preferably represents halogen, trifluoromethyl, nitro, -S(O)nR6, CN, -CoNR4R5
or represents C6-C,0-aryl which is optionally mono- to trisubstituted by identical
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or different substituents selected from the group consisting of halogen, cyano,
nitro, by optionally substituted doubly attached dioxyalkylene or by -OCF2Z,
-S(O)nCFR9R'0, -CFR9R'0.
R' preferably represents hydrogen, Cl-C6-alkyl, C,-C4-alkoxy-C,-C6-alkyl, C,-C6-
halogenoalkyl, C3-Cb-cycloalkyl, C2-C6-alkenyl, C2-C6-halogenoalkenyl, C2-C6-
alkinyl, C2-C6-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, C,-C6-alkyl and C,-C6-alkoxy.
R2 preferably represents hydrogen, C,-C6-alkyl, Cl-C6-halogenoalkyl, C3-C6-cyclo-
alkyl or represents phenyl which is optionally mono- to trisubstituted by
halogen, C~-C6-alkyl or Cl-C6-alkoxy.
R3 preferably represents (X)mR7.
X preferably represents O.
m preferably represents 0 or 1.
R4 and R5 independently of one another each preferably represent hydrogen, Cl-C6-
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.
R6 preferably represents Cl-C6-alkyl, C,-C6-halogenoalkyl or represents phenyl
which is optionally mono- to trisubstituted by identical or different substituents
selected from the group consisting of halogen, C,-C6-alkyl and C,-C6-alkoxy.
R7 preferably represents C,-C6-alkyl, C,-C6-halogenoalkyl, represents phenyl or
benzyl, each of which is optionally mono- to trisubstituted by halogen, C,-C6-
alkyl, C,-C6-alkoxy, trifluoromethyl, cyano or nitro or represents pyridyl or
pyridylmethyl, each of which is optionally mono- to trisubstituted by identical
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or different substituents selected from the group consisting of halogen, C,-C6-
alkyl and Cl-C6-alkoxy.
R9 and R'~ independently of one another each preferably represent hydrogen or
halogen.
Z preferably represents hydrogen, halogen or C,-C6-halogenoalkyl.
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 I to 4 carbon atoms or up to disubstituted by
-OCF2Z, -S(O),CF2Z or -CFR9R'0.
W particularly preferably represents C,-C4-alkyl which is substituted by fluorine or
chlorine.
A particularly preferably represents hydrogen or represents CH2R.
R particularly preferably represents one of the radicals -OR', -SR', -N(R2)CoR7 or
N(R2)co2R7
Y particularly preferably represents halogen, trifluoromethyl, nitro represents
-S(O)nR6, CN, CoNR4R5 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 -OCF2Z, -S(o)nCFR9R'0 or -CFR9R'0.
R' particularly preferably represents hydrogen, represents C,-C4-alkyl which is
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optionally substituted by one to three fluorine and/or chlorine atoms or by
methoxy or ethoxy, C3-C6-cycloalkyl, C2-C4-alkenyl, C2-C4-alkinyl, C2-C4-
halogenoalkenyl, C2-C4-halogenoalkinyl or represents phenyl which is optionally
mono- to trisubstituted by identical or different substituents selected from thegroup consisting of F, Cl, Br, C,-C4-alkyl and C,-C4-alkoxy.
R2 particularly preferably represents hydrogen, C,-C4-alkyl, C,-C4-halogenoalkyl,
C3-C6-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,-C4-alkyl and C~-C4-alkoxy.
R4 and R5 independently of one another each particularly preferably represent hydro-
gen, C,-C4-alkyl or represent phenyl which is optionally mono- to trisubstitutedby identical or different substituents selected from the group consisting of
fluorine, chlorine, bromine and C,-C4-alkyl.
R6 particularly preferably represents methyl which is mono- to trisubstituted byidentical or different substituents selected from the group consisting of fluorine,
chlorine and bromine.
R7 in -N(R2)Co2R7 particularly preferably represents C,-C4-alkyl.
R7 in -N(R2)CoR7 particularly preferably represents C,-C4-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 thegroup consisting of fluorine, chlorine, bromine, C,-C4-alkyl and C,-C4-alkoxy.
R9 and R'~ independently of one another each particularly preferably represent hydro-
gen, fluorine, chlorine or bromine.
Z particularly preferably represents hydrogen, fluorine, chlorine or represents
C,-C4-alkyl which is mono- or polysubstituted by fluorine and/or chlorine.
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panicularly preferably represents 0 or 1.
n 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
-OCF2Z, -S(O)ICF2Z or -CFR9R~0.
W very particularly preferably represents CF3 or C2F5.
A very particularly preferably represents hydrogen or represents CH2R.
R very particularly preferably represents a radical of the formula -OR', -SR',
-N(R2)Co2R7 or -NHCoR7.
Y very particularly preferably represents chlorine, bromine, trifluoromethyl, nitro
or represents phenyl which is optionally mono- to trisubstituted by identical ordifferent substituents selected from the group consisting of fluorine, chlorine,bromine, cyano, nitro or by -OCF2Z, -S(o)nCFR9R'0 or -CFR9R'0.
R' very particularly preferably represents methyl, ethyl, n- or i-propyl, n-, sec-, i-
or t-butyl, each of 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-2-
butinyl or represents optionally fluorine-, chlorine-, bromine-, methoxy- or
methyl-substituted phenyl.
R very panicularly preferably represents hydrogen, represents methyl, ethyl, n- or
i-propyl, n-, sec-, i- or t-butyl. each of which is optionally substituted by one to
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three fluorine and/or chlorine atoms, represents cyclopropyl, cyclopentyl 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.
s
R7 in -N(R2)Co2R7 very particularly preferably represents methyl, ethyl, n- or i-
propyl, n-, sec-, i- or t-butyl.
R7 in -NHCoR7 very particularly preferably represents methyl, ethyl, n- or i-
propyl, n-, sec-, i- or t-butyl, each of which is optionally substituted by one to
three fluorine andlor chlorine atoms, or represents phenyl which is optionally
mono- to trisubstituted by identical or different substituents selected from thegroup consisting of fluorine, chlorine, bromine, methyl and methoxy.
R9 and R'~ independently of one another each very particularly preferably represent
hydrogen, fluorine or chlorine.
Z very particularly preferably represents hydrogen, fluorine, chlorine, difluoro-
methyl, trifluoromethyl, chlorofluoromethyl or the radical of the formula
-CHFCF3.
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 forrnula (I) 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)
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g
in which there is present a combination of these meanings given above as being very
particularly preferred.
In particular, mention may be made of the following arylimidazoles of the general
S formula (Ia):
W A Ar (Ia)
Ex. A Ar Y W
No. 4,5-isomer 4,5-isomer
mixture mixture
H 2,3-CI, 4-CF3Ph Br CF3
2 CH2OEt 2,3-CI2, 4-CF3Ph Br CF3
3 H 2,3-CI2Ph Br CF3
4 CH2OEt 2,3-CI2Ph Br CF3
CH2N(CH3)CO2Et 2,3-CI2Ph Br CF3
6 H 2,4-CI2Ph Br CF3
7 CH2OEt 2,4-CI2Ph Br CF3
8 CH2OEt 2,4-CI2Ph Cl CF3
9 CH2OEt 2-CI, 4-CF3Ph Br CF3
CH2OEt 2-CI, 6-FPh Br CF3
Il H 2-CI, 4-CF3Ph Br CF3
12 H 2-CI, 6-FPh Br CF3
13 H 2-ClPh Br CF3
14 CH2OEt 2-ClPh Br CF3
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Ex. A Ar Y W
No. 4,5-isomer 4,5-isomer
mixture mixture
CH2N(CH3)CO2Et 2-ClPh Br CF3
16 H 3,4-CI2Ph Br CF3
17 H 3,4-CI2Ph CF3 CF3
18 H 3,4-CI2Ph Cl CF3
19 CH2OnBu 3,4-CI2Ph Br CF3
CH2OiPr 3,4-CI2Ph Br CF3
21 CH2OiPr 3,4-CI2Ph CF3 CF3
22 CH2OEt 3,4-CI2Ph Br CF3
23 CH2OEt 3,4-CI2Ph CF3 CF3
24 CH2OEt 3,4-CI2Ph Cl CF3
CH2N(nBu)CO2Et 3,4-CI2Ph Br CF3
26 CH2N(iBu)CO2Me 3,4-CI2Ph Br CF3
27 CH2N(Et)CO2Me 3,4-CI2Ph Br CF3
28 CH2N(CH3)CO2Et 3,4-CI2Ph Br CF3
29 CH2N(CH3)CO2Et 3,4-CI2Ph CF3 CF3
H 3,4-OCF2OPh Br CF3
31 CH2OEt 3,4-OCF2OPh Br CF3
32 H 3,5-(CF3)2Ph Br CF3
33 CH2OEt 3,5-(CH3)2Ph Br CF3
34 CH2OnBu 3,5-(CF3)Ph Br CF3
CH2OEt 3-Br, 4-FPh Br CF3
36 H 3-Br, 4-FPh Br CF3
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Ex. A Ar Y W
No. 4,5-isomer 4,5-isomer
mixture mixture
37 CH2OEt 3-CF3, 4-ClPh Br CF3
38 H 3-CF3, 4-ClPh Br CF3
39 H 3-ClPh Br CF3
H 3-ClPh CF3 CF3
41 CH2OEt 3-ClPh Br CF3
42 CH2OEt 3-ClPh CF3 CF3
43 H 4-BrPh Br CF3
44 CH2OEt 4-BrPh Br CF3
H 4-CF3Ph Br CF3
46 H 4-CF3Ph CF3 CF3
47 CH2OiPr 4-CF3Ph Br CF3
48 CH2OEt 4-CF3Ph Br CF3
49 CH2OEt 4-CF3Ph CF3 CF3
CH2N(iBu)CO2Et 4-CF3Ph CF3 CF3
51 CH2N(CH3)CO2Et 4-CF3Ph CF3 CF3
52 H 4-CF3Ph CN CF3
53 CH2OEt 4-CF3Ph CN CF3
54 H 4-ClPh Br CF3
H 4-ClPh CF3 CF3
56 CH2OEt 4-ClPh Br CF3
57 CH2OEt 4-ClPh CF3 CF3
58 CH2OCH2CH(CH3)2 4-ClPh CF3 CF3
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Ex. A Ar Y W
No. 4,5-isomer 4,5-isomer
mixture mixture
59 H 4-HPh CF3 CF3
H 4-OC2F5Ph Br CF3
61 CH2OEt 4-OC2F5Ph Br CF3
62 H 4-OCF3Ph Br CF3
63 CH2OEt 4-OCF3Ph Br CF3
64 H 4-SCF3Ph Br CF3
CH2OEt 4-SCF3Ph Br CF3
In particular, mention may be made of the following arylimidazoles of the general
formula (Ib):
Ar ~
Y A W (Ib)
Ex. A W Ar Y
No. 4,5-Isomer mixture 4,5-Isomer
mixture
66 H CF3 2,4-CI2Ph Br
67 H CF3 2-CI, 6-FPh Br
68 H CF3 3,4-CI2Ph Br
69 H CF3 3-Br, 4-FPh Br
H CF3 3-NO2Ph Br
71 H CF3 4-CF3Ph Br
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Ex. A W Ar Y
No. 4,5-Isomer mixture 4,5-Isomer
mixture
72 H CF3 4-ClPh Br
73 H CF3 4-OCF3Ph Br
74 CH2OiPr CF3 4-ClPh Br
CH2OEt CF3 2,3-CI2Ph Br
76 CH2OEt CF3 2,4-CI2Ph Br
77 CH2OEt CF3 2-CI, 6-FPh Br
78 CH2OEt CF3 2,4-(OCF2CHFCI2)Ph Br
79 CH2OEt CF3 3,4-Cl2Ph Br
CH2OEt CF3 3,4-OCFClCFClOPh Br
81 CH2OEt CF3 3-Br, 4-FPh Br
82 CH2OEt CF3 4-CF3Ph Br
83 CH2OEt CF3 4-ClPh Br
84 CH2OEt CF3 4-OCF3Ph Br
CH2N(CH3)CO2Et CF3 3-Br, 4-FPh Br
86 CH2N(CH3)CO2Et CF3 4-ClPh Br
87 H CF3 2,4-CI2Ph CF3
88 H CF3 3,4-CI2Ph CF3
89 H CF3 4-CF3Ph CF3
H CF3 4-ClPh CF3
91 CH2OEt CF3 2,4-CI2Ph CF3
92 CH2OEt CF3 3,4-CI2Ph CF3
93 CH2OEt CF3 4-CF3Ph CF3
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Ex. A W Ar Y
No. 4,5-Isomer mixture 4,5-Isomer
mixture
94 CH2OEt CF3 4-ClPh CF3
CH2N(CH3)CO2Et CF3 3,4-CI2Ph CF3
96 H CF3 2,3-CI2Ph Cl
97 H CF3 3,4-CI2Ph Cl
98 H CF3 3,5-CI2Ph Cl
99 H CF3 4-BrPh Cl
100 H CF3 4-CF3Ph Cl
101 H CF3 4-ClPh Cl
102 H CF3 4-NO2Ph Cl
103 H CF3 4-OCF3Ph Cl
104 CH2OnBu CF3 3,4-CI2Ph Cl
105 CH2OnBu CF3 4-ClPh Cl
106 CH2OiPr CF3 3,4-CI2Ph Cl
107 CH2OiPr CF3 4-ClPh Cl
108 CH2OEt CF3 2,3-CI2Ph Cl
109 CH2OEt CF3 2,4-CI2Ph Cl
11 0 CH2OEt CF3 3,4-CI2Ph Cl
111 CH2OEt CF3 3,5-CI2Ph Cl
112 CH2OEt CF3 3-Br, 4-FPh Cl
1 13 CH~OEt CF3 3-ClPh Cl
11 4 CH2OEt CF3 4-BrPh Cl
I l5 CH2OEt CF3 4-CF3Ph Cl
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Ex. A W Ar Y
No. 4,5-Isomer mixture 4,5-Isomer
mixture
116 CH2OEt CF3 4-ClPh Cl
117 CH2OEt CF3 4-NO2Ph Cl
118 CH2OEt CF3 4-OCF3Ph Cl
119 CH2OCH2CCCH2CI CF3 Ph Cl
120 CH2OCH(CH2F)2 CF3 Ph Cl
121 CHIO(CH2)4Cl CF3 4-ClPh Cl
122 CH2O(CH2)OCH3 CF3 Ph Cl
123 CH2O(4-CI-Ph) CF3 Ph Cl
124 CH2N(H)COCH3 CF3 4-ClPh Cl
125 CH2N(CH3)CO2Et CF3 4-BrPh Cl
126 CH2(4-CI-Ph) CF3 4-ClPh Cl
127 CH2OEt CF3 3,4-CI2-Ph S(O)CF3
In particular, mention may be made of the following arylimidazoles of the general
formula (Ic):
W~N
N 1 y (Ic)
Ex. A Y Ar W
No. 4,5-Isomer mixture 4,5-Isomer
mixture
128 H Br 4-CI-Ph C2F5
129 CH2OEt Br 4-CI-Ph C2F5
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Ex. A Y Ar W
No. 4,5-Isomer mixture 4,5-Isomer
mixture
130 H Br 3,4-CI2Ph CF3
131 H Br 4-ClPh CF3
132 H Br 4-OCF3Ph CF3
133 H Br 4-SCF3Ph CF3
134 CH2OEt Br 3,4-CI2Ph CF3
135 CH2OEt Br 4-ClPh CF3
136 CH2OEt Br 4-OCF3Ph CF3
137 CH2OEt Br 4-SCF3Ph CF3
138 CH2N(CH3)CO2Et Br 3,4-CI2Ph CF3
139 CH2N(CH3)CO2Et Br 4-OCF3Ph CF3
140 CH2N(CH3)CO2Et Br 4-SCF3Ph CF3
141 H Cl 4-CI-Ph C2F5
142 CH2OEt Cl 4-CI-Ph C2F5
143 H Cl 3,4-CI2Ph CF3
144 H Cl 4-ClPh CF3
145 H Cl 4-OCF3Ph CF3
146 H Cl 4-SCF3Ph CF3
147 CH2OEt Cl 3,4-CI2Ph CF3
148 CH2OEt Cl 4-ClPh CF3
149 CH2OEt Cl 4-OCF3Ph CF3
150 CH2OEt Cl 4-SCF3Ph CF3
151 CH2N(CH3)CO2Et Cl 4-OCF~Ph CF3
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Ex. A Y Ar W
No. 4,5-Isomer mixture 4,5-Isomer
mixture
152 H CN 3,4-CI2-Ph CF3
153 H CN 4-CF3-Ph CF3
154 CH2OEt CN 3,4-CI2Ph CF3
155 CH2OEt CN 4-CF3-Ph CF3
Particularly preferred compounds from the series of the arylimidazoles of the formula
(Ia) which may be mentioned are:
~N
W A Ar (Ia)
Ex. A Ar Y W
No. 4,5- 4,5-
Isomer Isomer
mixture mixture
H 2,3-CI2, 4-CF3Ph Br CF3
2 CH2OEt 2,3-CI2, 4-CF3Ph Br CF3
23 CH2OEt 3,4-CI2Ph CF3 CF3
31 CH2OEt 3,4-OCF2OPh Br CF3
32 H 3,5-(CF3)2Ph Br CF3
33 CH2OEt 3,5-(CH3)2Ph Br CF3
34 CH2OnBu 3,5-(CFl)2Ph Br CF3
37 CH2OEt 3-CF3, 4-ClPh Br CF3
38 H 3-CF3, 4-ClPh Br CF3
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Ex. A Ar Y W
No. 4,5- 4,5-
Isomer Isomer
mixture mixture
46 H 4-CF3Ph CF3 CF3
H 4-CF3Ph Br CF3
47 CH2OiPr 4-CF3Ph Br CF3
48 CH2OEt 4-CF3Ph Br CF3
49 CH2OEt 4-CF3Ph CF3 CF3
64 H 4-SCF3Ph Br CF3
CH2OEt 4-SCF3Ph Br CF3
Particularly preferred compounds from the series of the arylimidazoles of the formula
(Ib) which may be mentioned are:
N W (Ib)
Ex. A W Ar Y
No. 4,5-Isomer 4,5-Isomer
mixture mixture
87 H CF3 2,4-CI2Ph CF3
88 H CF3 3,4-CI2Ph CF3
89 H CF3 4-CF3Ph CF3
H CF3 4-ClPh CF3
91 CH2OEt CF3 2,4-CI2Ph CF3
92 CH2OEt CF3 3,4-CI2Ph CF3
93 CH OEt CF3 4-CF3Ph CF3
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Ex. A W Ar Y
No. 4,5-Isomer 4,5-Isomer
mixture mixture
94 CH2OEt CF3 4-ClPh CF3
CH2N(CH3)CO2Et CF3 3,4-CI2Ph CF3
Particularly preferred compounds from the series of the arylimidazoles of the formula
(Ic) which may be mentioned are:
W~N
N 1 y (Ic)
Ex. A Y Ar W
No. 4,5-Isomer 4,5-Isomer
mixture mixture
133 H Br 4-SCF3Ph CF3
137 CH2OEt Br 4-SCF3Ph CF3
145 H Cl 4-OCF3Ph CF3
146 H Cl 4-SCF3Ph CF3
148 CH2OEt Cl 4-ClPh CF3
149 CH2OEt Cl 4-OCF3Ph CF3
150 CH2OEt Cl 4-SCF3Ph CF3
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
5 advantageously be employed alternating with synthetic coccidiostats or polyether
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antibiotics.
Suitable polyether antibiotics include maduramycin, lasalocid, monensin, narasin,
salinomycin, semduramycin. Suitable synthetic coccidiostats include:
I (-(4-amino-2-n-propyl-5-pyrimidinylmethyl)-2-picolinium Amprolium
chloride
I (-(4-amino-2-n-propyl-5-pyrimidinylmethyl)-2-picolinium Amprolium +
chloride + sulfaquinoxaline sulfaquinoxaline
I (-(4-amino-2-n-propyl-5-pyrimidinylmethyl)-2-picolinium Amprolium +
chloride + sulfaquinoxaline + ethopabate sulfaquinoxaline +
ethopabate
4,4-dinitrocarbanilide + 2-hydroxy-4,6-dimethylpyrimidine Nicarbazin
3,5-dichloro-2,6-dimethyl-4-pyridinol Clopidol
3,5-dichloro-2,6-dimethyl-4-pyridinol + methyl-7-benzyloxy- Clopidol +
6-butyl- 1 ,4-dihydro-4-oxylquinoline-3-carboxylate methylbenzoquate
ethyl 6-n-decyloxy-7-ethoxy-4-hydroxyquinoline-3- Decoquinate
1 5 carboxylate
9-(2-chloro-6-fluorophenylmethyl)-9H-purin-6-amine Arprinocid
(+)-2,6-dichloro-alpha-(4-chlorophenyl)-4-(4,5-dihydro-3,5- Benzeneacetonitrile,
dioxo- I ,2,4-triazin-2(3H)-yl)-benzeneacetonitrile diclazuril
1-[3-methyl-4-(4'-trifluoromethylthiophenoxy)-phenyl]-3- Toltrazuril
methyl- I ,3,5-triazine-2,4,6( I H,3H,SH)-trione
4,4-dinitrocarbanilide + 2-hydroxy-4,6-dimethylpyrimidine Robenidine
[= nicarbazin]
7-bromo-6-chloro-febrifugin Halofuginone
3,5-dinitro-o-toluamide Zoalene.
25 The active compounds are suitable, while having favourable toxicity for warm-blooded
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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
5 parasitic protozoa is to reduce disease, deaths and reductions in performance (for
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:
10 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. Iewisi, T. percae, T. simiae, T. vivax, Lei.chm~nia brasiliensis,
L. donovani, L. tropica, such as, for example Trichomonadidae, for example
Trichomonas vagin~1is, Tritrichomonas foetus, such as, for example Diplomonadida, for
15 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,
20 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.
Iabbeana, E. Ieucarti, E. magna, E. maxima, E. media, E. meleagridis, E. meleagrimitis,
E. mitis, E. necatrix, E. ninakohlyakimovae, E. ovis, E. parva, E. pavonis, E. perforans,
25 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.
30 suihominis such as Leucozoidae, for example Leucozytozoon simondi, such as Plasmo-
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diidae, 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.
5 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
10 particular of the genus Nosema. Particular mention may be made of Nosema agis in the
case of the honeybee.
Useful and breeding livestock include m~mm~lc such as, for example, cattle, horses,
sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur-
bearing livestock such as, for example, mink, chinchillas, raccoons, birds such as, for
15 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 ~nim~l~ include mice, rats, guinea pigs, hamsters, dogs
and cats.
Pet animals include dogs and cats.
20 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,
25 gilthead seabream (Sparus auratus), Tilapia spp., Chichlidae species such as e.g.
Plagioscion, channel catfish. The compositions according to the invention are particu-
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larly suitable for the treatment of fry, e.g. carp of 2 - 4 cm body length. The composi-
tions are also very highly suitable in eel feeding.
Both prophylactic and therapeutic use are possible.
The active compounds are used directly or in the form of suitable preparations,
5 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
10 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 ~-lmini.ctration
after dilution, solutions for use on the skin or in body cavities, pour-on formulations,
1 5 gels;
emulsions and suspension for oral or dermal use and for injection; semisolid prepara-
tions;
formulations in which the active compound is incorporated in an ointment base or in
an oil-in-water or water-in-oil emulsion base;
20 solid preparations such as powders, premixes or concentrates, granules, pellets, tablets,
boli, capsules; aerosols and inhalations, shaped articles containing active compound.
Injection solutions are ~-~ministered intravenously, intramuscularly and subcutaneously.
Injection solutions are prepared by dissolving the active compound in a suitable solvent
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and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxi-
dants, 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
5 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 poly-
10 vinylpyrrolidone, 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.
15 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, organic20 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 ointment-
25 like consistency. The thickeners used are the thickeners indicated hereinbefore.
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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.
Pour-on formulations are prepared by dissolving, suspending or emulsifying the active
S compound in suitable skin-compatible solvents or solvent mixtures. Where ~pp-op,iate,
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
10 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, dimethyl-
acetamide, N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-1,3-dioxolane.
15 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.
20 Antioxidants are sulphites or metabisulphites such as potassium metabisulphite, ascor-
bic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol.
Sunscreen agents are, for example, substances from the class of benzophenones ornovantisolic acid.
Adherents are, for example, cellulose derivatives, starch derivatives, polyacrylates,
25 natural polymers such as alginates, gelatin.
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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.
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
5 emulsifiers and, where appropriate, other auxiliaries such as colorants, absorption-
promoting 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
10 triglycerides such as caprylic/capric acid biglyceride, triglyceride mixture with veg-
etable fatty acids of chain length C8 ,2 or other specially selected natural fatty acids,
partial glyceride mixtures of saturated or unsaturated, possibly also hydroxyl group-
containing fatty acids, mono- and diglycerides of C8/C,0 fatty acids.
Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene
15 glycol pelargonate, esters of a branched fatty acid of medium chain length with satu-
rated fatty alcohols of chain length C,6-C,8, isopropyl myristate, isopropyl palmitate,
caprylic/capric esters of saturated fatty alcohols of chain length C,2-C,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,
20 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
25 thereof.
Emulsifiers which may be mentioned are:
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nonionic surfactants, for example polyethoxylated castor oil, polyethoxylated sorbitan
monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate,alkylphenol polyglycol ether;
ampholytic surfactants such as di-Na-N-lauryl-,B-iminodipropionate or lecithin;
5 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 carboxymethyl-
10 cellulose, 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 sus-
15 pending the active compound in a liquid vehicle, where appropriate with the addition
of further auxiliaries such as wetting agents, colorants, absorption-promoting sub-
stances, preservatives, antioxidants, sunscreen agents.
Liquid vehicles which may be mentioned are all homogeneous solvents and solvent
mixtures.
20 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.
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To prepare solid preparations, the active compound is mixed with suitable excipients,
where apl)lopliate with the addition of auxiliaries, and converted into the desired shape.
Excipients which may be mentioned are all physiologically tolerated solid inert sub-
S stances. 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, phos-
phates.
Organic substances are, for example, sugars, cellulose, foodstuffs and feedstuffs, such
10 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, mag-
nesium stearate, stearic acid, talc, bentonites, disintegration-promoting substances such
15 as starch or crosslinked polyvinylpyrrolidone, binders such as, for example, starch,
gelatin or linear polyvinylpyrrolidone, and dry binders such as microcrystalline cellu-
lose.
The active compounds may also be present in the preparations mixed with synergists
or with other active compounds.
20 Preparations ready for use contain the active compound in concentrations of 10 ppm to
20 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 concentra-
tions of 0.5 to 90 per cent by weight, preferably from I to 50 per cent by weight.
It has in general proved advantageous to administer amounts of about 0.5 to about
25 50 mg, preferably I tO 20 mg, of active compound per kg of bodyweight per day to
achieve effective results.
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The active compounds can also be ~-lmini~tered to the livestock together with the feed
or drinking water.
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.
5 Such a feedstuff and foodstuff can be used both for curative purposes and for prophy-
lactic purposes.
Such a feedstuff or foodstuff is prepared by mixing a concentrate or a premix which
contains 0.5 to 30%, preferably I to 20% by weight, of an active compound mixed
with an edible organic or inorganic vehicle, with customary feedstuffs. Edible vehicles
10 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:
15 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 com-
pound is well tolerated by the recipient. Administration via the drinking water can take
20 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
25 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
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or interval over which ~ministration 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 atlmini.~trations over the course
5 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.,
10 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., Diplozoonspp., cestodes, for example from the groups of the Caryphyllidea (for example Caryo-
phyllaeus laticeps), Pseudophyllidea (for example diphyllobothrium spp.), Tetra-
15 phyllidea (for example Phyllobothrium spp.) and Protocephalida (for example speciesof the genus Proteocephalus) and from the phylum of the Arthropoda various parasitic
crustaceans, in particular from the subclasses of the Branchiura (fish lice) andCopepoda (copepods) and from the orders of the Isopoda (isopods) and Amphipoda
(beech fleas).
20 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
25 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 applica-
tions.
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The concentration of the active compound, in the formulations is from I ppm to 10%
by weight.
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
5 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, water-
soluble solvent which either gives an alkaline reaction or to which an alkaline water-
soluble substance is added. The latter is advantageously also dissolved in the solvent,
10 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 prefer-
ably 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%.
15 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,
20 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
25 amino acids such as L- or D,L-arginine, L- or D, L-lysine, methylglucosamine, glucos-
amine, 2-amino-2-hydroxymethylpropane- 1 ,3-diol furthermore, N,N,N',N'-tetrakis-
(2-hydroxypropyl)-ethylenediamine or polyethertetrol based on ethylenediamine
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(M.W. 480-420), inorganic bases, such as ammonia or sodium carbonate - if appropri-
ate with addition of water.
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
5 stabilizers and thickeners such as, for example, methylcellulose, alginates, poly-
saccharides, 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.
10 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 approximate-
15 ly 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.
20 Formulations for use as feed additive have, for example, the following composition:
a) active compound of the
formula I I - 10 parts by weight
soya bean protein 49 - 90 parts by weight
b) active compound of the
formula I 0.5 - 10 parts by weight
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benzyl alcohol 0.08 - 1.4 parts by weight
hydroxypropylmethylcellulose 0 - 3.5 parts by weight
Water remainder ad 100
Formulations for use in "medical baths" and for pond treatment are, for example,5 composed and prepared as shown below.
c) 2.5 g of active compound of the formula (I) 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 tri-
I 0 ethanolamine.
e) 10.0 g of active compound of the formula (I) are dissolved in 100 ml of mono- ethanolamine.
f) active compound of the formula I 5.0 g
propylene glycol 50 0 g
sodium carbonate 5.0 g
water ad 100 ml
g) active compound of the formula I 5.0 g
monoethanolamine 10 g
N-methylpyrrolidone ad 100 ml
h) active compound of the formula I 2.5 g
sodium carbonate 5.0 g
polyethylene glycol 200 ad 100 ml
The active compound is dissolved with heating in polyethylene glycol, and sodiumcarbonate is suspended therein.
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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
below.
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 I 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 an10 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 ~iministration.
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
l.OO~o brewer's yeast, bound to brewer's grains
I 00.00%
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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 D3, lO mg of vitamin E, 20 mg of zinc
bacitracin.
The efficacy of the compounds according to the invention is demonstrated by the
S example below, without limiting the chemical range of its applicability.
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Example A
Cage test on coccidiosis/chicks
Male chicken chicks (for example LSL Brinkschulte/Senden) which have been rearedcoccidia-free and are 8 to 12 days old receive the compounds according to the inven-
5 tion (test substances) in the concentration stated in ppm with the feed from 3 daysbefore (day -3) the infection (= a.i.) to 8 (9) days after the infection (= p.i.). Three
birds are kept in each cage. One or more such groups are used per dosage. The infec-
tion 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.
10 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 assess-
ing 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
15 of blood on days 5 and 7 p.i., 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 Veterinarmedizin, Akademie-Verlag, Berlin (1965)).
20 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 Proceed-
ings of the Georgia Coccidiosis Conference Nov, 18. - 20. 1995 Athens/Georgia USA).
The efficacy is scored as follows: 2 = fully effective; I = partially effective; 0 = not
25 effective.
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Table 1
Efficacy of exemplary compounds against Coceidia (E. acervulina, E. maxima, E.
tenella) in ehieks
Eimeria aeervulina Effieaey at a dose of ppm in the
E. maxima feed
Ex. No. E. tenella 25 10 5 2.5
137 Eimeria aeervulina 2 1 0-1
E. maxima 2 1 0-1
E. tenella 2 1 0-1
146 Eimeria aeervulina 2
E. maxima
E. tenella
64 Eimeria acervulina 2
E. maxima 2
E. tenella 2 0
29 Eimeria acervulina
E. maxima
E. tenella
46 Eimeria acervulina 2
E. maxima 2
E. tenella 2
23 Eimeria acervulina 2 2
E. maxima 2 2
E. tenella 2
92 Eimeria acervulina 2
E. maxima 2
E. tenella 2
CA 022~0~07 1998-09-29
Le A 31 607-Foreign countries
- 38 -
Eimeria acervulina Efficacy at a dose of ppm in the
E. maxima feed
Ex. No. E. tenella 25 10 5 2.5
49 Eimeria acervulina
E. maxima 1 0
E. tenella 2
Eimeria acervulina 2
E. maxima 2
E. tenella
93 Eimeria acervulina
E. maxima
E. tenella
32 Eimeria acervulina 2 1-2
E. maxima 2 1-2
E. tenella 1-2 1-2
5 2 = fully effective, I = partially effective, 0 = not effective; + = tot inf. toxicity
