+

WO1992008454A1 - Use of avermectins and milbemycins for treating parasitic infestations in ruminants - Google Patents

Use of avermectins and milbemycins for treating parasitic infestations in ruminants Download PDF

Info

Publication number
WO1992008454A1
WO1992008454A1 PCT/GB1991/001978 GB9101978W WO9208454A1 WO 1992008454 A1 WO1992008454 A1 WO 1992008454A1 GB 9101978 W GB9101978 W GB 9101978W WO 9208454 A1 WO9208454 A1 WO 9208454A1
Authority
WO
WIPO (PCT)
Prior art keywords
optionally
compound
formula
substituted
treatment
Prior art date
Application number
PCT/GB1991/001978
Other languages
French (fr)
Inventor
Roderick John Dorgan
David Owen Morgan
Peter Robin Shelley
Simon Edward Blanchflower
Geoffrey Harold Baker
Original Assignee
Beecham Group Plc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Beecham Group Plc filed Critical Beecham Group Plc
Publication of WO1992008454A1 publication Critical patent/WO1992008454A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system

Definitions

  • This invention relates to a method of treating parasites in ruminant animals. 5
  • This invention is particularly concerned with the use of certain avermectins and milbemycins described in EP-A-0 421 568 (USSN 525,094) for the treatment or prophylaxis of endo- and ectoparasitic infestations of 10 ruminants, such as cattle and sheep.
  • the compounds used in this invention have parasiticidal properties, for example against nematodes, and are useful for the treatment of helminthiasis in ruminant animals.
  • helminthiasis encompasses diseases of animals caused by infestation with parasitic worms such as Strongyles, Ascarids, hookworms, lungworms, filarial worms and whipworms.
  • the compounds used in this invention are also active against Arthropods.
  • the phylum Arthropoda comprises insects - such as biting flies, lice, bugs, beetles and fleas - and arachnids - such as mites and ticks.
  • the present invention provides the use of a compound of general formula (I) as defined below for the manufacture of a medicament for the treatment or prophylaxis of endo and ectoparasitic infestations, especially helminthiasis and
  • the present invention also provides a method of treatment or prophylaxis of endo- and ectoparasitic infestations, 35 especially helminthiasis and anthropod or nematode infestations, which comprises administering an effective non-toxic amount of a compound of general formula (I) as defined below to a ruminant animal in need thereof.
  • This invention is particularly concerned with the use of a compound of general formula (I) to combat infestations in ruminants of lice, lungworm, Hypoderma (the larval stage of warble fly) and gastrointestinal worms (such as Cooperia, Trichostronqylus, Haemonchus) .
  • the present invention includes prophylatic treatment of healthy animals to prevent infestation, as well as treatment of infected animals.
  • the compounds of general formula (I) may be formulated for administration with carriers and adjuvants in any convenient way for use in veterinary medicine, by analogy with known anthelmintics.
  • the compounds of general formula (I) may be administered to animals orally (as a paste, drench, bolus, capsule or tablet) , parenterally, percutaneously, as a food additive (eg granules, pellets or powder) , topically (as a cream, wash or spray) , or transdermally (as a pour-on) .
  • a food additive eg granules, pellets or powder
  • topically as a cream, wash or spray
  • transdermally as a pour-on
  • the compounds of general formula (I) may be formulated as a mixture with each other and/or with other anthelmintics, insecticides, acaricides or other pharmacologically active substances.
  • the composition consists of sufficient material to provide a dose of from 0.001 to lOOmg of active ingredient per kg of animal body weight per dose, more suitably 0.01 to lOmg/kg per dose.
  • a composition for use in the invention may suitably contain from 0.1% by weight, preferably from 1.0 to 60% by weight, of the compound of general formula (I) (based on the total -3- weight of the composition) , depending on the method of administration.
  • the compound used in this invention is an avermectin or milbemycin selected from avermectins and milbemycins having the general formula (I) :
  • R 1 1 is hydrogen or optionally protected hydroxy
  • R . is alkoxy, optionally protected hydroxy, oxo or optionally 0-substituted oximmo
  • R° is hydrogen, optionally protected 30 hydroxy,or a group 4'- ( ⁇ -L-oleandrosyl)- ⁇ -L-oleandrosyloxy or ⁇ -L- oleandrosyloxy wherein the terminal hydroxy group is optionally protected
  • R , R , R° and R are the same or o different and each is hydrogen or an organic radical
  • R is an optionally substituted amino or imino group such as optionally O-substituted oxyimino, optionally N-substituted hydrazone, or optionally N-substituted semicarbazone; with the proviso that the compound of formula (I) is not a compound of formula (E) or (F)below or a compound disclosed in EP-A-0 307 220.
  • R 3 is in
  • EP-A-0 259 779, EP-A-0 293 549, EP-A-0 307 225 and GB-A-2192630 describe compounds of formula (E) :
  • R 1 is optionally protected hydroxy or methoxy
  • ⁇ is optionally protected hydroxy, oxo, or an imino group such as optionally O-substituted oxyimino, optionally N-substituted hydrazone, or optionally N-substituted semicarbazone
  • R n is methyl, ethyl or isopropyl
  • the dashed line is a double bond or an epoxide group.
  • R° is optionally protected hydroxy or methoxy
  • P is hydrogen or a sugar residue
  • R ⁇ is optionally protected hydroxy, oxo, or an imino group such as optionally O-substituted oxyimino or optionally N-substituted hydrazone
  • R r is isopropyl or sec-butyl.
  • the compound used in the present invention is VS 54396 or VS 55759 disclosed respectively in Example 6 (Z- and E-isomers) and in Example 36 (E-isomer) of EP-A-0 421 568 (U.S. Patent Application serial No. 525,094). 5
  • the preparation of these compounds is illustrated below as Examples 1 and 2.
  • This product (3.35g 5.7 mmol) was dissolved in methanol (25 ml) and a solution of mercuric oxide (56 mg, 0.26 mmol) water (3.5 ml) and concentrated sulphuric acid (0.75 ml, 14 mmol)was added dropwise at 20°C. The mixture was stirred at 20°C for 2 h., water was added and the mixture was extracted with dichloromethane (3 x 100 ml) . The combined organic layers were washed with sodium bicarbonate solution (100 ml), dried (MgS0 4 ) and evaporated to give the title ketone (3.2g)) pure by nmr + tic.
  • Efficacy was determined by monitoring the number of grubs in the animals back weekly. Grub determination were made by palpating the animal's backs weekly until no new grubs appeared. Charts were prepared at each observation period to show the location of each grub. Exiting grubs were observed, if possible, and a determination made as to their viability.
  • the compound under test was applied by sucutaneous injection.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Environmental Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Pest Control & Pesticides (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Agronomy & Crop Science (AREA)
  • Molecular Biology (AREA)
  • Plant Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

Avermectins and milbemycins are useful in the treatment or prophylaxis of endo- and ectoparasitic infestations in ruminants.

Description

Use of avermectins and milbe ycins for treating parasitic infestations in ruminants.
This invention relates to a method of treating parasites in ruminant animals. 5
This invention is particularly concerned with the use of certain avermectins and milbemycins described in EP-A-0 421 568 (USSN 525,094) for the treatment or prophylaxis of endo- and ectoparasitic infestations of 10 ruminants, such as cattle and sheep.
The compounds used in this invention have parasiticidal properties, for example against nematodes, and are useful for the treatment of helminthiasis in ruminant animals.
15
The term helminthiasis encompasses diseases of animals caused by infestation with parasitic worms such as Strongyles, Ascarids, hookworms, lungworms, filarial worms and whipworms.
20
The compounds used in this invention are also active against Arthropods. The phylum Arthropoda comprises insects - such as biting flies, lice, bugs, beetles and fleas - and arachnids - such as mites and ticks.
25
Thus the present invention provides the use of a compound of general formula (I) as defined below for the manufacture of a medicament for the treatment or prophylaxis of endo and ectoparasitic infestations, especially helminthiasis and
30 arthropod or nematode infestations, in ruminant animals, such as sheep and cattle.
The present invention also provides a method of treatment or prophylaxis of endo- and ectoparasitic infestations, 35 especially helminthiasis and anthropod or nematode infestations, which comprises administering an effective non-toxic amount of a compound of general formula (I) as defined below to a ruminant animal in need thereof.
This invention is particularly concerned with the use of a compound of general formula (I) to combat infestations in ruminants of lice, lungworm, Hypoderma (the larval stage of warble fly) and gastrointestinal worms (such as Cooperia, Trichostronqylus, Haemonchus) . As indicated above the present invention includes prophylatic treatment of healthy animals to prevent infestation, as well as treatment of infected animals.
For use according to the invention the compounds of general formula (I) may be formulated for administration with carriers and adjuvants in any convenient way for use in veterinary medicine, by analogy with known anthelmintics.
In suitable formulations the compounds of general formula (I) may be administered to animals orally (as a paste, drench, bolus, capsule or tablet) , parenterally, percutaneously, as a food additive (eg granules, pellets or powder) , topically (as a cream, wash or spray) , or transdermally (as a pour-on) .
The compounds of general formula (I) may be formulated as a mixture with each other and/or with other anthelmintics, insecticides, acaricides or other pharmacologically active substances.
Suitably the composition consists of sufficient material to provide a dose of from 0.001 to lOOmg of active ingredient per kg of animal body weight per dose, more suitably 0.01 to lOmg/kg per dose.
A composition for use in the invention may suitably contain from 0.1% by weight, preferably from 1.0 to 60% by weight, of the compound of general formula (I) (based on the total -3- weight of the composition) , depending on the method of administration.
It will be appreciated that, in some cases, it will be 5 advisable to repeat the dosing of the infected or potentially infected animal with the compound of general formula (I) according to conventional dosage regimes used with anthelmintics:
10 The compound used in this invention is an avermectin or milbemycin selected from avermectins and milbemycins having the general formula (I) :
15
Figure imgf000005_0001
25 (I)
wherein R1 1 is hydrogen or optionally protected hydroxy; R . is alkoxy, optionally protected hydroxy, oxo or optionally 0-substituted oximmo; R° is hydrogen, optionally protected 30 hydroxy,or a group 4'- (α-L-oleandrosyl)-α-L-oleandrosyloxy or α-L- oleandrosyloxy wherein the terminal hydroxy group is optionally protected; R , R , R° and R are the same or o different and each is hydrogen or an organic radical; and R is an optionally substituted amino or imino group such as optionally O-substituted oxyimino, optionally N-substituted hydrazone, or optionally N-substituted semicarbazone; with the proviso that the compound of formula (I) is not a compound of formula (E) or (F)below or a compound disclosed in EP-A-0 307 220. Typically R3 is in the α-configuration. When R3 is in the β-configuration then it is preferably optionally protected hydroxy, and/or R is preferably hydrogen, and/or R^ is preferably methoxy or optionally protected hydroxy.
EP-A-0 259 779, EP-A-0 293 549, EP-A-0 307 225 and GB-A-2192630 describe compounds of formula (E) :
Figure imgf000006_0001
wherein R1 is optionally protected hydroxy or methoxy, ^ is optionally protected hydroxy, oxo, or an imino group such as optionally O-substituted oxyimino, optionally N-substituted hydrazone, or optionally N-substituted semicarbazone, Rn is methyl, ethyl or isopropyl, and the dashed line is a double bond or an epoxide group. EP-A-0 260 536 and EP-A-0 260 537 describe compounds of formula (F) :
Figure imgf000007_0001
(F)
wherein R° is optionally protected hydroxy or methoxy, P is hydrogen or a sugar residue, R^ is optionally protected hydroxy, oxo, or an imino group such as optionally O-substituted oxyimino or optionally N-substituted hydrazone, and Rr is isopropyl or sec-butyl.
The above compounds of general formula (I) form the subject of EP-A-0 421 568 (U.S. Patent Application Serial No. 525,094) which also describes methods of their preparation and indicates preferred substituents.
A corresponding disclosure exists in the following numbered patent applications of the countries indicated:
Australia 55140/90; Canada 2017030; Eire 1785/90; Japan 125638/90; Mexico 21897; New Zealand 233680; Portugal 94075; South Africa 90/3703; South Korea 7054/90; Taiwan (ROC) 79104620.
The disclosure of the above-mentioned patent applications is incorporated herein by reference. Preferably the compound used in the present invention is VS 54396 or VS 55759 disclosed respectively in Example 6 (Z- and E-isomers) and in Example 36 (E-isomer) of EP-A-0 421 568 (U.S. Patent Application serial No. 525,094). 5 The preparation of these compounds is illustrated below as Examples 1 and 2.
Reference Example
1023 Qxo-25 (S)-t-butyl milbemycin x
To a solution of (4S)-5,5-dimethyl-4-triethylsilyloxy- 1-hexyne (8.3 g, 33 mmol) in THF (100 ml) at -78°C under a nitrogen atmosphere was added butyllithium (1.6M in hexane,
1518.9 ml, 30 mmol) dropwise over a period of 5 mins. and the mixture stirred at -78°C for a further 3 H. A solution of VS 48927 prepared as described in Examples 1 to 3 of EP-A- 0319142 (4.8g, 8.6 mmol) in THF (20 ml) was added to the mixture which was stirred at -78°C for a further 15 mins.
20 The reaction was quenched with a cold solution (—20°C) of glacial acetic acid (10 ml) in THF (10 ml) and the mixture was then allowed to warm to 0°C. Brine (100 ml) was added and the mixture was extracted with ether (3 x 100 ml) . The combined organic extracts were washed with water, dried
25 (MgSO^) and evaporated to an approximate volume of 50 ml. Methanol (50 ml) was added and the solution again evaporated to an approximate volume of 50 ml. 4-Toluenesulphonic acid (lg) was added and the mixture stirred at 20°C for 1 h.
30 Sodium bicarbonate (100 ml) was added to the mixture and the whole extracted with dichloromethane (3 x 100 ml) . The combined organic extracts were washed with brine (100 ml) , dried (MgS04) and evaporated. The residue was purified by column chromatography (silica eluted initially with dichloromethane and subsequently gradient eluted with 10-60% ethyl acetate in hexane) to afford the methylacetal (3.35g, 66%) .
This product (3.35g 5.7 mmol) was dissolved in methanol (25 ml) and a solution of mercuric oxide (56 mg, 0.26 mmol) water (3.5 ml) and concentrated sulphuric acid (0.75 ml, 14 mmol)was added dropwise at 20°C. The mixture was stirred at 20°C for 2 h., water was added and the mixture was extracted with dichloromethane (3 x 100 ml) . The combined organic layers were washed with sodium bicarbonate solution (100 ml), dried (MgS04) and evaporated to give the title ketone (3.2g)) pure by nmr + tic.
Example 1
VS 54396 (=Z-isomer)
23-0xo-25(S.)-t-butyl milbemycin X (50 mg, 0.09 mmol) was dissolved in methanol (5 ml) . A solution of methoxylamine hydrochloride (50 mg, 0.60 mmol) in water (2 ml) was added and the mixture stirred at room temperature (Ih) . The reaction mixture was concentrated and then treated with water (30 ml) and extracted with ether (3 x 15 ml) . The combined ethereal extracts were dried (MgSO^) and evaporated. The 1:1 mixture* of Z_ and E_ oximes was separated by silica gel preparative thin layer chromatography with hexane - ethyl acetate, 1:1 as eluant.
The 23 (Z_)-methoxyimino-25 (S.)-t-butyl milbemycin X was obtained as a white solid (yield 16 mg) . M/z (FAB Na+/Noba) 622 [MNa]+ 50% (relative intensity). Hplc retention time = 7.7 min.
The 23 (E)-methoxyimino-25 (S_)-t-butyl milbemycin X was obtained as a white solid (yield 16 mg) . I i (FAB Na+/Noba) 622 [MNa]+ 25% (relative intensity). Hplc retention time = 7.9 min.
Hplc conditions : Dynamax C18 column (25 cm x 4.6 mm id) eluted with methanol - water , 9 : 1 at 1 ml/min monitored at 245 nm.
* Ratio is dependent upon the pH of the reaction mixture
Example 2
VS 55759 (=E-isomer)
To a solution of 23-oxo-25 (S)-t-butyl milbemycin X
(60 mg 0.1 mmol) and sodium acetate (300 mg, 2.2 mmol) in methanol (3 ml) was added 0-t-butylhydroxylamine hydrochloride (50 mg, 0.4 mmol); The mixture was stirred at 20°C for 1 h., water (10 ml) was added and the whole mixture extracted with dichloromethane (3 x 15 ml) . The combined organic extracts were washed with water, dried (MgS04) and evaporated to dryness. Purification by preparative t.l.c, (silica taper plate* (AnaltechR) eluted with ethyl acetate/hexane 2:5) yielded a 4:1 mixture of E:Z oxime isomers (54 mg) . Treatment of a portion of this mixture (30 mg) with methanol (2 ml) and hydrochloric acid (IM, 0.2 ml) gave a 1:1 E:Z ratio of oxime isomers. The two isomers were separated by preparative t.l.c. (silica taperplate eluted four times with chloroform) .
23 (Z)-t-butyloxyimino-25(S)-t-butyl milbemycin X: tic R = 0.5 (Silica eluted three times with chloroform containing 1.5% ethanol) m/z (FAB Na+/Noba) (relative intensity) 664 [MNa]+ (95%)
23 (E)-t-butyloxyimino-25 (S)-t-butyl milbemycin X: tic
Figure imgf000011_0001
(Silica eluted three times with chloroform containing 1.5% ethanol) m/z (FAB Na+/Noba) (relative intensity) 664 [MNa]+ (95%).
Hplc retention times : Dynamax 60A Silica column (25 cm x 4.6 mm id) eluted with chloroform/methanol 99:1 at 1 ml/min monitored at 245 nm. Retention time 23-Z isomer = 14.2 min.
Retention time 23-E isomer = 15.4 min.
Efficacy of VS 55759 against Hypoderma in Cattle
Method
Twenty-five yearling cattle of different sexes weighing between 200 to 330 kilograms were used in the study.
Animals were naturally infested with Hypoderma, and were inspected prior to treatment to determine the number of grubs in the animals back. Animals were ranked according to the number of grubs found in the back and assigned to a treatment group so each treatment group had similar infestation levels. Animals within each treatment group were maintained in the same paddock.
Efficacy was determined by monitoring the number of grubs in the animals back weekly. Grub determination were made by palpating the animal's backs weekly until no new grubs appeared. Charts were prepared at each observation period to show the location of each grub. Exiting grubs were observed, if possible, and a determination made as to their viability.
The compound under test was applied by sucutaneous injection.
Results
Animals treated with 100 mg/kg of VS 55759 failed to produce normal, living, exiting larvae. In treated animals, numerous dead, flaccid grubs were observed partially extruded.
No adverse reactions were observed during study.

Claims

Claims
1. Use of a compound of formula (I): for the manufacture of a medicament for the treatment or prophylaxis of endo and ectoparasitic infestations in ruminant animals.
Figure imgf000013_0001
wherein Rx is hydrogen or optionally protected hydroxy; R is alkoxy, optionally protected hydroxy, oxo or optionally O-substituted oximino; R3 is hydrogen, optionally protected hydroxy,or a group A ' - (α-L-oleandrosyl)-α-L-oleandrosyloxy or α-L- oleandrosyloxy wherein the terminal hydroxy group is optionally protected; R4, R , R° and R are the same or different and each is hydrogen or an organic radical; and R is an optionally substituted amino or imino group such as optionally O-substituted oxyimino, optionally N-substituted hydrazone, or optionally N-substituted semicarbazone; with the proviso that the compound of formula (I) is not a compound of formula (E) or (F) as defined hereinabove or a compound disclosed in EP-A-0 307 220.
2. Use according to claim 1, for combating infestations in ruminants of lice, lungworm, Hypoderma and/or gastrointestinal worms.
3. Use according to claim 1 or 2, for the treatment of cattle or sheep.
4. Use according to any preceding claim, wherein R , R , R4, R and R° are hydrogen, R2 is hydroxy, R7 is t.-butyl and R° is t-butyloxyimmo or methoxyimmo (E- or Z-isomer or a mixture thereof) .
5. A method of treatment or prophylaxis of endo- and ectoparasitic infestations which comprises administering an effective non-toxic amount of a compound of formula (I) as defined in claim 1 to a ruminant animal in need thereof.
6. A pharmaceutical composition for use in the treatment of endo- and ectoparasitic infestations of ruminants, which comprises a compound of formula (I) as defined in claim 1, and a pharmaceutically acceptable carrier.
7. A composition according to claim 6, in the form of an oral formulation.
8. A composition according to claim 6, in-the form of a feed additive.
9. A composition according to claim 6, in the form of an injectable formulation.
10. A composition according to claim 6, in the form of a spray or dip.
11. A composition according to claim 6, in the form of a pour-on formulation.
PCT/GB1991/001978 1990-11-16 1991-11-11 Use of avermectins and milbemycins for treating parasitic infestations in ruminants WO1992008454A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9024926.9 1990-11-16
GB909024926A GB9024926D0 (en) 1990-11-16 1990-11-16 Novel treatment

Publications (1)

Publication Number Publication Date
WO1992008454A1 true WO1992008454A1 (en) 1992-05-29

Family

ID=10685474

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1991/001978 WO1992008454A1 (en) 1990-11-16 1991-11-11 Use of avermectins and milbemycins for treating parasitic infestations in ruminants

Country Status (5)

Country Link
AU (1) AU8875091A (en)
GB (1) GB9024926D0 (en)
IE (1) IE913970A1 (en)
WO (1) WO1992008454A1 (en)
ZA (1) ZA919022B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994027598A1 (en) * 1993-05-26 1994-12-08 Commonwealth Scientific And Industrial Research Organisation Antiparasitic compositions

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0237339A1 (en) * 1986-03-12 1987-09-16 American Cyanamid Company Macrolide compounds
EP0259779A1 (en) * 1986-09-12 1988-03-16 American Cyanamid Company 23-Oxo (Keto) and 23-imino Derivatives of LL-F28249 Compounds
EP0260537A1 (en) * 1986-09-12 1988-03-23 American Cyanamid Company 13-Deoxy-23-oxo(keto) and 23-imino derivatives of 13-deoxy C-076-aglycone compounds
EP0260536A2 (en) * 1986-09-12 1988-03-23 American Cyanamid Company 23-imino derivatives of 23-keto compounds useful as pesticides.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0237339A1 (en) * 1986-03-12 1987-09-16 American Cyanamid Company Macrolide compounds
EP0259779A1 (en) * 1986-09-12 1988-03-16 American Cyanamid Company 23-Oxo (Keto) and 23-imino Derivatives of LL-F28249 Compounds
EP0260537A1 (en) * 1986-09-12 1988-03-23 American Cyanamid Company 13-Deoxy-23-oxo(keto) and 23-imino derivatives of 13-deoxy C-076-aglycone compounds
EP0260536A2 (en) * 1986-09-12 1988-03-23 American Cyanamid Company 23-imino derivatives of 23-keto compounds useful as pesticides.

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994027598A1 (en) * 1993-05-26 1994-12-08 Commonwealth Scientific And Industrial Research Organisation Antiparasitic compositions
US5840324A (en) * 1993-05-26 1998-11-24 Commonwealth Scientific And Industrial Organisation Antiparasitic compositions

Also Published As

Publication number Publication date
IE913970A1 (en) 1992-05-20
ZA919022B (en) 1992-09-30
AU8875091A (en) 1992-06-11
GB9024926D0 (en) 1991-01-02

Similar Documents

Publication Publication Date Title
SI9520021A (en) Antiparasitic agents, compuonds related to the avermectins and milbemycins but having substituents at the 3-position
JP2654028B2 (en) 23-oxo (keto) and 23-imino derivatives of LL-F28249 compounds
JP3135918B2 (en) Alkylthioalkyl avermectins as active antiparasitic agents
AU7073698A (en) Methods for using macrocyclic lactone compounds as multidrug resistance reversing agents in tumor and other cells
JPH10504041A (en) Nodulisporic acid derivative
EP0629202B1 (en) Antiparasitic avermectin and milbemycin derivatives
JP2018531912A (en) Spinosyn derivatives as insecticides
EP0623137B1 (en) Antiparasitic agents
Awasthi et al. Analytical profile of moxidectin
WO1992008352A1 (en) Avermectins and milbemycins to treat parasitic infestations in fish
JP2859372B2 (en) Preparation of new compounds and compounds useful as drugs
CA2168731C (en) Antiparasitic agents
WO1992008454A1 (en) Use of avermectins and milbemycins for treating parasitic infestations in ruminants
AU660429B2 (en) Method for treatment or prophylaxis of endo- and ectoparasitic infestations in dogs
Rock et al. Chemistry, pharmacology and safety: moxidectin
JP2938974B2 (en) Stable solvates of avermectin compounds
US5362862A (en) Process for 4"-EPI-acetylamino-4"-deoxy-5-oximinoavermectin-B1
JP3502103B2 (en) Nodulisporic acid derivatives
JPS63264586A (en) 23-deoxy-27-halo(chloro or bromo) derivative of ll-f28249 compound
WO2025057117A1 (en) Antiparasitic cyclic depsipeptides
WO1993011129A1 (en) Antiparasitic agents
RO111681B1 (en) STABLE SALTS OF 4"-DEOXY-4"-EPIMETHYLAMINO-AVERMECTYN B1a/B1b, MEDICINAL COMPOSITION AND TREATMENT METHOD THEREOF
IE914423A1 (en) Novel compounds

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA JP KR US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LU NL SE

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载