EP0214731A2
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Antiparasitic avermectin and milbemycin derivatives and process for their preparation
Assignee: Pfizer Ltd
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Filing: 1986-07-22
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Granted: —
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Expires: 2006-07-22
Abstract
Abstract The invention provides novel compounds having the formula: wherein the broken line at the 22-23 position represents an optional double bond and wherein R' is H or OH and the double bond is absent, or, the double bond is present and R' is absent; R 2 is an alpha-branched C 3 -C 8 alkyl, alkenyl, alkynyl, alkoxyalkyl or alkylthioalkyl group; a C 3 -C 8 cycloalkyl, C 5 -C 8 cycloalkenyl or C 5 -C 8 cycloalkylalkyl group, any of which may optionally be substituted by methylene or one or more C 1 -C 4 alkyl groups or halo atoms; or a 3 to 6 membered oxygen or sulphur containing heterocyclic ring which may optionally be substituted by one or more C 1 -C 4 alkyl groups or halo atoms; R 3 is hydrogen or methyl; R 4 is H or 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrosyloxy, with the proviso that when R 2 is alkyl it is not isopropyl or sec-butyl, and when R 4 is H, R 1 is OH, and the double bond is absent, R 2 is not 2-buten-2-yl, 2-pentene-2-yl or 4-methyl-2-pentene-2-yl. The compounds are broad spectrum antiparasitic agents having utility as anthelmintics, ectoparasiticides, insecticides and acaricides. The invention also provides a process for producing the novel avermectin and milbemycin derivatives by adding a carboxylic acid or derivative thereof to a fermentation of an avermectin or milbemycin producing organism.
Inventors
- 👤 Stephen Paul Gibson
- 👤 Kelvin Scott Holdom
- 👤 Alexander Crossan Goudie
- 👤 John Desmond Bu'lock
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-05 07:43
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/01; A; A01; A01N; A01N43/00; A01N43/90; A23; A23K; A23K20/00; A23K20/10; A23K20/195; A61; A61P; A61P33/00; A61P33/10; C12; C12N; C12N1/00; C12N1/20; C12N1/205; C12P; C12P17/00; C12P17/18; C12P17/181; C12P19/00; C12P19/44; C12P19/60; C12P19/62; C12R; C12R2001/00; C12R2001/01; C12R2001/465; Y; Y10; Y10S; Y10S435/00; Y10S435/8215; Y10S435/822; Y10S435/886
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
207 words
A compound having the formula: wherein the broken line at the 22-23 position represents an optional double bond and wherein R is H or OH and the double bond is absent, or, the double bond is present and R 1 is absent; R 2 is an alpha-branched C 3 -C 8 alkyl, alkenyl, alkynyl, alkoxyalkyl or alkylthioalkyl group; a C 5 -C 8 cycloalkylalkyl group wherein the alkyl group is an alpha-branched C 2 -C 5 alkyl group; a C 3 -C 8 cycloalkyl or C 5 -C 8 cycloalkenyl group, either of which may optionally be substituted by methylene or one or more C 1 -C 4 alkyl groups or halo atoms; or a 3 to 6 membered oxygen or sulphur containing heterocyclic ring which may be saturated, or fully or partially unsaturated and which may optionally be substituted by one or more C 1 -C 4 alkyl groups or halo atoms; R3 is hydrogen or methyl; R 4 is H or a 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrosyloxy group of the formula: with the proviso that when R 1 is alkyl it is not isopropyl or sec-butyl, and when R 4 is H, R 1 is OH, and the double bond is absent, R 2 is not 2-buten-2-yl,2-penten-2-yl or 4-methyl-2-penten-2-yl.
Claim 2
Dependent Claim
207 words
A compound having the formula: wherein the broken line at the 22-23 position represents an optional double bond and wherein R is H or OH and the double bond is absent, or, the double bond is present and R 1 is absent; R 2 is an alpha-branched C 3 -C 8 alkyl, alkenyl, alkynyl, alkoxyalkyl or alkylthioalkyl group; a C 5 -C 8 cycloalkylalkyl group wherein the alkyl group is an alpha-branched C 2 -C 5 alkyl group; a C 3 -C 8 cycloalkyl or C 5 -C 8 cycloalkenyl group, either of which may optionally be substituted by methylene or one or more C 1 -C 4 alkyl groups or halo atoms; or a 3 to 6 membered oxygen or sulphur containing heterocyclic ring which may be saturated, or fully or partially unsaturated and which may optionally be substituted by one or more C 1 -C 4 alkyl groups or halo atoms; R3 is hydrogen or methyl; R 4 is H or a 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrosyloxy group of the formula: with the proviso that when R 1 is alkyl it is not isopropyl or sec-butyl, and when R 4 is H, R 1 is OH, and the double bond is absent, R 2 is not 2-buten-2-yl,2-penten-2-yl or 4-methyl-2-penten-2-yl.
Claim 3
Dependent Claim
16 words
A compound of the formula I as claimed in claim 1 wherein R 4 is 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrosyloxy.
Claim 4
Dependent Claim
36 words
A compound as claimed in claim 2 wherein R 2 is a C 5 or C 6 cycloalkyl or cycloalkenyl group which may optionally be substituted by one or more C 1 -C 4 alkyl groups.
Claim 5
Dependent Claim
11 words
A compound as claimed in claim 3 wherein R is cyclopentyl.
Claim 6
Dependent Claim
12 words
A compound as claimed in claim 2 wherein R 2 is cyclobutyl.
Claim 7
Dependent Claim
40 words
A compound as claimed in claim 2 wherein R 2 is a 5 or 6 membered oxygen or sulphur containing heterocyclic ring which may optionally be substituted by one or more C 1 -C 4 alkyl groups or halogen atoms.
Claim 8
Dependent Claim
12 words
A compound as claimed in claim 6 wherein R 2 is 3-thienyl.
Claim 9
Dependent Claim
14 words
A compound as claimed in claim 2 wherein R 2 is C3-C8 alkylthioalkyl group.
Claim 10
Dependent Claim
12 words
A compound as claimed in claim 8 wherein R 2 is 1-methylthioethyl.
Claim 11
Dependent Claim
47 words
A process for producing a novel avermectin derivative having an unnatural substituent group at the 25-position which comprises adding a carboxylic acid, or a salt, ester or amide thereof or oxidative precursor therefor, to a fermentation of an avermectin producing organism, and isolating the novel avermectin derivative.
Claim 12
Dependent Claim
47 words
A process for producing a novel avermectin derivative having an unnatural substituent group at the 25-position which comprises adding a carboxylic acid, or a salt, ester or amide thereof or oxidative precursor therefor, to a fermentation of an avermectin producing organism, and isolating the novel avermectin derivative.
Claim 13
Dependent Claim
153 words
A process for producing a compound of the formula (1) as claimed in claim 1 which comprises fermenting an avermectin producing strain of the organism Streptomyces avermitilis in the presence of a carboxylic acid of the formula R 2 CO 2 H wherein R 2 is as defined in claim 1, or a salt, ester or amide thereof or oxidative precursor therefor, and isolating the compound of formula (I) wherein R is OH and the double bond is absent or wherein the double present and R 1 is absent and R 4 is 4'-(alpha-L-oleandrosyl)-alpha-L-oleandrosyloxy and, if desired, reducing the compound wherein the double bond is present and R is absent to obtain the compound of formula (I) wherein R is H and the double bond is absent or, if desired, removing the 4-(alpha-L-oleandrosyl)-alpha-L-oleandrosyloxy group by hydrolysis followed by halogenation and reduction to yield the compound of formula (I) wherein R 4 is H.
Claim 14
Dependent Claim
15 words
A process as claimed in claim 11 wherein the organism is Streptomyces avermitlis NClB 12121.
Claim 15
Dependent Claim
46 words
A composition for the treatment and prevention of parasitic infections in humans and animals, including ectoparasiticicidal, insecticdal, acaricidal and anthelmintic compositions, which comprises a compound of the formula (I) as claimed in any one of claims 1 to 9 together with an inert diluent or carrier.
Claim 16
Dependent Claim
20 words
A composition as claimed in claim 13 in the form of a liquid drench or an oral or injectable formulation.
Claim 17
Dependent Claim
28 words
A composition as claimed in claim 13 in the form of an animal feedstuff or in the form of a premix or supplement for addition to animal feed.
Claim 18
Dependent Claim
41 words
A compound of the formula I as claimed in any one of claims 1 to 9 or a composition thereof as claimed in claims 13 to 15 for use in the treatment or prevention of parasitic infections in humans and animals.
Claim 19
Independent Claim
60 words
A method of combating insect or parasite infections or infestations, including parasitic conditions in humans and animals and agricultural or horticultural pest infestations, which comprises applying an effective amount of a compound of the formula (1) as claimed in any one of claims 1 to 9 to the organism responsible for said infection or infestation or to the location thereof.
References Cited (Backward Citations)
No citation records indexed.
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