GB2142537A

GB2142537A - <Mammalian ectoparasiticides containing n-phenyloxadiazolinones

Info

Publication number: GB2142537A
Application number: GB08315231A
Authority: GB
Inventors: Michael Pearson
Original assignee: Shell Internationale Research Maatschappij BV
Current assignee: Shell Internationale Research Maatschappij BV
Priority date: 1983-06-03
Filing date: 1983-06-03
Publication date: 1985-01-23
Also published as: GB8315231D0

Abstract

Compositions for use as mammalian ectoparasiticides contain as active ingredient, a compound of general formula I <IMAGE> wherein R represents an alkyl group having 1-4 carbon atoms, R1 represents an alkyl or an alkoxy group having 1-4 carbon atoms, R2 represents an alkyl group having 1-carbon atoms or a halogen group or is hydrogen and R3 represents an alkyl group having 1-4 carbon atoms or is hydrogen, suitably together with an appropriate topical vehicle. The compositions may be dips, sprays, pour-on liquids or ointments, in aqueous, oily, or glycol emulsions or solutions. Further active ingredients may be present, e.g. pyrethroids such as permethrin and cypermethrin.

Description

SPECIFICATION Ectoparasiticides The present invention relates to the use of certain 3-N-phenyloxadiazolinones of which the phenyl group is substituted with one or more substituents, and compositions comprising the latter as animal ectoparasiticides. Ectoparasites are e.g. lice, mites and ticks. The present oxadiazolinones which surprisingly appear to possess ectoparasiticidal activity in particular against ticks are known from UK patent specification 1518042.

In that patent specification it is said that the oxadiazolinones possess besides insecticidal and anthelmintic activity, acaricidal activity as well. However nowhere in UK 1518042 is reference made tithe ectoparasiticidal activity of those compounds.

UK patent specification 1518041 relates to similar oxadiazolinones. However substitution in the phenyl group is restricted to the ortho-place. In UK 1518041 reference is made to the acaricidal activity of these compounds on Tetranychus telarius and its eggs.

Tetranychus telarius is a phytophagous mite, and it was therefore not to be expected that mammalian ectoparasites would also be killed by the oxadiazolinone derivatives known from the above prior art.

Furthermore the present oxadiazolinones appear two be quite acceptable in regard to mammalian toxicity which renders them very suitable for application on animals.

Oxadiazolinone derivatives which are known from European patent application publication 0048040 in the name of Applicant as pesticides were tested for tickicidal activity. Although those compounds did show tickicidal activity they appeared to be not acceptable for such use on toxicity grounds.

Thus the present N-phenyl oxadiazolinones surprisingly appear two combine a suitable mammalian ectoparasiticidal activity with an acceptable mammalian toxicity which renders them very suitable for use as animal ectoparasiticides.

Therefore the present invention relates to the use as an animal ectoparasiticide of a compound of general formula I

wherein R represents an alkyl group having 1-4 carbon atoms, R1 represents an alkyl or an alkoxy group having 1-4 carbon atoms, R2 represents an alkyl group having 1-4 carbon atoms or a halogen group or is hydrogen and R3 represents an alkyl group having 1-4 carbon atoms or is hydrogen.

Preferably R represents a methyl group when R2 and R3 are each hydrogen. According to another preferred embodiment R1 and R2 each represent an alkyl group having 1-4 carbon atoms. Most preferably R, R1 and R2 are each methyl and R3 is hydrogen.

Preferably the compounds of general formula I are used in the form of a composition comprising at least one compound of formula I and a veterinarily acceptable carrier. Compositions according to the present invention may also comprise other active ingredients such as the pyrethroids permethrin and cypermethrin.

Furthermore the present invention relates to a method for combating ectoparasites at a locus which may be any part of an animal body which is effected by ectoparasites using an ectoparasiticidally effective amount of a N-phenyl oxadiazolinone of formula (I). The composition may suitably be applied in the form of a spray or a dipwash and if a more local application is desired in the form of a pour-on formulation or a grease. Preferably the composition comprises 4-1 5%wt of a N-phenyloxadiazolinone according to the invention. Spray formulations are particularly preferred. Preferably they comprise 5-1 0%wt of a N phenyloxadiazolinone. If desired these formulations may be further diluted e.g. with water.

Animals which are suitably treated with compositions comprising N-phenyl oxadiazolinones according to the present invention are cattle in particular. However sheep, goats and domestic animals like dogs, cats and horses may also be suitably treated with the present compositions. Compositions according to the invention may also comprise a glycol such as one selected from the group consisting of ethylene glycol, propylene glycol, polyethylene glycols and polypropylene glycols, ethylene glycol-propylene glycol copolymers and alkyl ethers like preferably diethylene glycol mono-n-butyl ether. The latter glycol alkylether having minimal adverse effect on the skin is most suitable.

Alternatively, the composition may be an aqueous formulation containing a compound of formula I in the form of a suspension or emulsion and comprising suitable surfactants to stabilise the suspension or emulsion, and prevent undue run-off from the body of the animal.

run-off from the body of the animal.

Paraffin oils, vegetable oils, e.g. peanut oil, castor oil, olive oil, can be added as viscosity modifiers and co-solvents.

The present invention will further be illustrated with reference to the following Examples.

EXAMPLE 1 Preparation of 5-methoxy.3-(2,3-dimethyl phen yl)- 1,3,4-oxadiazol-2(3H)-one Methyl 2-(2,3-dimethyl phenyl) hydrazine carboxylate (2,9g,0.015m) was added in one portion to a stirred solution of phosgene (2.2g, 0.022m) in dry benzene (50cm3) at room temperature. The solution was heated at 60 C until gas evolution had ceased (1 hour). Solvent was removed in vacuo to leave a red oil. This was dissolved in methanol (50cm3) and diisopropyl ethyl amine (1.93g,0.015m) added.The solution was heated at reflux for 30 minutes and solvent removed in vacuo. the residue was purified by chromatography, on Merck Kiesel gel 60 (70-230 Mesh) with chloroform as eluent, and by recrystallisation from cyclohexane to give 5-methoxy-3-(2,3-dimethyl phenyl)-1,3,4-oxadiazol-2(3H)-one as a pale yellow solid, m.p. 89-90 C, yield 2.49,73%.

Analysis calculated for: CH12N203 C 60.0 H 5.5 N 12.7 Found: C 60.0 H 5.4 N 12.7 The following Examples describe 1,3,4 oxadiazol-2 (3H)-ones which have been prepared using a process similar two that as described in Example 1.

EXAMPLE2 5 methoxy-3-(2-ethylphenylj- 1,3,4-oxa diazol-2(3H)-one Yellow oil, yield 60%.

Analysis calculated for: CllH12N203 C 60.0 H 5.5 N 12.7 Found: C61.7H5.6N12.8 EXAMPLE3 5-methoxy-3-(2 methoxy-3-chlorophenyl)- 1,3,4-oxadiazol-2(3K)-one Pale yellow solid, mp. 85-86 C, yield 53%.

Analysis calculated for: C1cH9N2O4Cl C46.8 H 3.5 N 10.9 Found: C46.6H3.6N 10.7 EXAMPLE4 5-meth oxy-3-(3,4-dimethylphen yl)- ,3,4-oxadiazol-2f3H)-one Pale yellow solid, m.p. 76-77 C, yield 13%.

Analysis calculated for: CllH12N203 C 60.0 H 5.5 N 12.7 Found: C 59.9 H 5.3 N 12.4 Biological tests The effect of the compounds according to Examples 1-4 on adults of the phytophagous mite Tetranychus urticae (Tu) and adults atid larvae of the cattle tick Boophilus microplus (Bm) was investigated by determining the Toxicity Index (T.l.) reiative to Parathion and the Acute Oral Toxicity on Mouse (A.O.M.).

LC50 of Parathion xlOO LC50 of test comound

TABLE ** T.l.'s relative to Para thion Ex. R R1 R2 R3 Tu- Bm(1) Bm(a) A.O.M LC50 (mg/kg) 1 methyl methyl methyl H > 0.2 150 41 250-500 2 methyl ethyl H H > 0.2 115 23 3 methyl methoxy chloro H 11 120 11 50-250 4 methyl H methyl methyl > 0.2 147 10 5* methyl methoxy H H > 0.2 49 23 250 * no preparation example given.

** Tu-LC50 is the percentage minimum dose of active ingredient necessary to kill 50% of the population of the phytophagous mite Tetranychus urticae (Tu).

N.B. Compounds with a Tu-LC50's > 0.2% are considered to be inactive.

The results of the above table clearly show the lack of miticidal activity of the tested compounds and the existence of quite a surprisingly effect against cattle ticks which latter effect is furthermore parallelled by an unexpectedly acceptable level of mammalian toxicity. Afurthertoxicity test of the compound of Example 1 revealed an acute percutaneous toxicity to mouse of greater than 600mg/kg which provides a further proof of the moderate mammalian toxicity.

Claims

1. The use as a mammalian ectoparasiticide of a compound of general formula

wherein R represents an alkyl group having 1-4 carbon atoms, R1 represents an alkyl or an alkoxy group having 1-4 carbon atoms, R2 represents an alkyl group having 1-4 carbon atoms or a halogen group or is hydrogen and F3 represents an alkyl group having 1-4 carbon atoms or is hydrogen.

2. The use as a mammalian ectoparasiticide of a compound as defined in claim 1, wherein R represents a methyl group.

3. The use as a mammalian ectoparasiticide of a compound as defined in claim 1 or 2 wherein R2 and R3 are each hydrogen.

4. The use as a mammalian ectoparasiticide of a compound as defined in claim 1 or 2 wherein R1 and R2 each represent an alkyl group having 1-4 carbon atoms.

5. The use as a mammalian ectoparasiticide of a compound as defined in claim 4 wherein R, R1 and R2 each are methyl and F3 is hydrogen.

6. The use as a mammalian ectoparasiticide of a composition comprising a compound as defined in any one of the claims 1-5 and a veterinarily acceptable carrier.

7. Method for combating mammalian ectoparasites at a locus by using a composition comprising an ectoparasiticidally effective amount of a compound as defined in any one of the claims 1-5.

8. Method as claimed in claim 7 in which the locus is any part of an animal body which is effected by ectoparasites.

9. Method as claimed in claim 7 or 8 wherein a compound as defined in any one of the claims 1-5 is applied in the form of a spray formulation.

10. Method as claimed in any one of the claims 7-9 in which the composition comprises 4-15% wt of a compound as defined in any one of the claims 1-5.

11. Method as claimed in claim 9 and 10 in which the spray formulation comprises 5-10% wt of a compound as defined in any one of the claims 1-5.

12. Method as claimed in any one of the claims 7-11 in which the mammalian ectoparasite is a tick.