5-Oxime derivatives of milbemycins and veterinary and agricultural use thereof

Claim 2

A compound of the formula (II): ##STR6## in which R 1 represents methyl, ethyl or isopropyl and R 2 represents hydrogen, a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro or a group of formula --CH 2 COOR 3 , in which R 3 represents hydrogen or a C 1 -C 6 alkyl group; and, when R 2 represents hydrogen, a veterinary or an agriculturally acceptable salt or ester thereof.

Claim 3

The compound as claimed in claim 1, wherein R 2 represents hydrogen, a C 1 -C 6 alkyl group, benzyl or carboxymethyl.

Claim 4

The compound as claimed in claim 1, wherein R 2 represents a hydrogen atom and said salts and esters thereof.

Claim 5

The compound as claimed in claim 2 or claim 3, wherein R 1 represents an ethyl or isopropyl group.

Claim 6

A compound of formula (IIa): ##STR7## wherein: R 1 represents methyl, ethyl or isopropyl; and R 2a represents: a group of formula --COR 4 , in which R 4 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, phenyl, phenyl substituted with at least one C 1 -C 6 alkyl, halogen, nitro, carboxy or C 2 -C 7 alkoxycarbonyl substituents or a group of formula --(CH 2 ) n COOR 5 , wherein n is an integer from 1 to 3 and R 5 represnts a hydrogen atom or a C 1 -C 6 alkyl group; a group of formula --CO.NR 6 R 7 , wherein R 6 represents hydrogen or a C 1 -C 6 alkyl group and R 7 represents hydrogen, a C 1 -C 6 alkyl group, a phenyl group or a group of formula --CH(R 8 ).COOR 9 (wherein R 8 and R 9 are the same or different and each represents hydrogen at a C 1 -C 6 alkyl group); a group of formula --COOR 10 , wherein R 10 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, a phenyl group or a sugar alcohol from which an omega-hydroxy group has been removed, said sugar alcohol is selected from the group consisting of glycerol, erythritol, threitol, arabinitol, adonitol, xylitol, sorbitol, mannitol and dulcitol; said sugar alcohol may be substituted with at least one protecting group selected from the group consisting of formyl, acetyl, tetrahydro-2-furanyl, tetrahydro-2-pyranyl groups, 1-methoxyethyl, 1-ethoxyethyl, trimethylsilyl, triethylsilyl and dimethyl-t-butylsilyl, and the paired hydroxy groups at the 1- and 2-positions or at the 1- and 3-positions may be joined by replacing the terminal hydrogens of respective paired hydroxy groups with a bridging methylene, ethylene, isopropylidene, benzylidene or cyclohexyline group; a group of formula --SO 2 R 11 , wherein R 11 represents a C 1 -C 6 alkyl group or a phenyl group; or a group of formula --(Y 1 ═)P(--Y 2 --R 12 ) 2 , in which Y 1 and Y 2 , which may be the same or different, each represents oxygen or sulphur and the two atoms represented by Y 2 may be the same or different, and each of the groups represented by R 12 , which may be the same or different, is a C 1 -C 6 alkyl group.

Claim 7

A compound of formula (IIa): ##STR7## wherein: R 1 represents methyl, ethyl or isopropyl; and R 2a represents: a group of formula --COR 4 , in which R 4 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, phenyl, phenyl substituted with at least one C 1 -C 6 alkyl, halogen, nitro, carboxy or C 2 -C 7 alkoxycarbonyl substituents or a group of formula --(CH 2 ) n COOR 5 , wherein n is an integer from 1 to 3 and R 5 represnts a hydrogen atom or a C 1 -C 6 alkyl group; a group of formula --CO.NR 6 R 7 , wherein R 6 represents hydrogen or a C 1 -C 6 alkyl group and R 7 represents hydrogen, a C 1 -C 6 alkyl group, a phenyl group or a group of formula --CH(R 8 ).COOR 9 (wherein R 8 and R 9 are the same or different and each represents hydrogen at a C 1 -C 6 alkyl group); a group of formula --COOR 10 , wherein R 10 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, a phenyl group or a sugar alcohol from which an omega-hydroxy group has been removed, said sugar alcohol is selected from the group consisting of glycerol, erythritol, threitol, arabinitol, adonitol, xylitol, sorbitol, mannitol and dulcitol; said sugar alcohol may be substituted with at least one protecting group selected from the group consisting of formyl, acetyl, tetrahydro-2-furanyl, tetrahydro-2-pyranyl groups, 1-methoxyethyl, 1-ethoxyethyl, trimethylsilyl, triethylsilyl and dimethyl-t-butylsilyl, and the paired hydroxy groups at the 1- and 2-positions or at the 1- and 3-positions may be joined by replacing the terminal hydrogens of respective paired hydroxy groups with a bridging methylene, ethylene, isopropylidene, benzylidene or cyclohexyline group; a group of formula --SO 2 R 11 , wherein R 11 represents a C 1 -C 6 alkyl group or a phenyl group; or a group of formula --(Y 1 ═)P(--Y 2 --R 12 ) 2 , in which Y 1 and Y 2 , which may be the same or different, each represents oxygen or sulphur and the two atoms represented by Y 2 may be the same or different, and each of the groups represented by R 12 , which may be the same or different, is a C 1 -C 6 alkyl group.

Claim 8

The compound as claimed in claim 5, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a (C 1 -C 6 alkoxy)carbonylmethylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group, a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group, a C 1 -C 6 alkanesulphonyl group, a benzenesulphonyl group, a di(C 1 -C 6 alkoxy)phosphinyl group or a (C 1 -C 6 alkoxy)-(C 1 -C 6 alkylthio)phosphinyl group.

Claim 9

The compound as claimed in claim 5, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group or a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group.

Claim 10

The compound as claimed in claim 6 or claim 7, wherein R 1 represents an ethyl or isopropyl group.

Claim 11

The compound as claimed in any one of claims 1, 2 and 3, wherein the salt is selected from sodium and potassium salts.

Claim 12

The compound as claimed in claim 9, wherein R 1 represents ethyl or isopropyl.

Claim 13

An anthelmintic, acaricidal and insecticidal composition comprising an effective amount of an anthelmintic, acaricidal and insecticidal compound in admixture with a pharmaceutically, agriculturally or horticulturally acceptable carrier or diluent, wherein said compound is selected from compounds of formula (II): ##STR8## in which R 1 represents methyl, ethyl or isopropyl and R 2 represents hydrogen, a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro or a group of formula --CH 2 COOR 3 , in which R 3 represents hydrogen or a C 1 -C 6 alkyl group; and, when R 2 represents hydrogen, pharmaceutically, agriculturally or horticulturally acceptable salt or ester thereof.

Claim 14

An anthelmintic, acaricidal and insecticidal composition comprising an effective amount of an anthelmintic, acaricidal and insecticidal compound in admixture with a pharmaceutically, agriculturally or horticulturally acceptable carrier or diluent, wherein said compound is selected from compounds of formula (II): ##STR8## in which R 1 represents methyl, ethyl or isopropyl and R 2 represents hydrogen, a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro or a group of formula --CH 2 COOR 3 , in which R 3 represents hydrogen or a C 1 -C 6 alkyl group; and, when R 2 represents hydrogen, pharmaceutically, agriculturally or horticulturally acceptable salt or ester thereof.

Claim 15

A composition as claimed in claim 11, wherein R 2 represents hydrogen, a C 1 -C 6 alkyl group, benzyl or carboxymethyl.

Claim 16

A composition as claimed in claim 11, wherein said compound is selected from compounds in which R 2 represents a hydrogen atom and salts and esters thereof.

Claim 17

A composition as claimed in claim 12 or claim 13, wherein R 1 represents an ethyl or isopropyl group.

Claim 18

A composition as claimed in claim 11, wherein said compound is selected from compounds of formula (IIa): ##STR9## wherein: R 1 represents methyl, ethyl or isopropyl; and R 2a represents: a group of formula --COR 4 , in which R 4 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, phenyl, phenyl substituted with at least one C 1 -C 6 alkyl, halogen, nitro, carboxy or C 2 -C 7 alkoxycarbonyl substituents or a group of formula --(CH 2 ) n COOR 5 , wherein n is an integer from 1 to 3 and R 5 represents a hydrogen atom or a C 1 -C 6 alkyl group; a group of formula --CO.NR 6 R 7 , wherein R 6 represents hydrogen or a C 1 -C 6 alkyl group and R 7 represents hydrogen, a C 1 -C 6 alkyl group, a phenyl group or a group of formula --CH(R 8 ).COOR 9 (wherein R 8 and R 9 are the same or different and each represents hydrogen or a C 1 -C 6 alkyl group); a group of formula --COOR 10 , wherein R 10 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, a phenyl group or a sugar alcohol from which an omega-hydroxy group has been removed, said sugar alcohol is selected from the group consisting of glycerol, erythritol, threitol, arabinitol, adonitol, xylitol, sorbitol, mannitol and dulcitol; said sugar alcohol may be substituted wih at least one protecting group selected from the group consisting of formyl, acetyl, tetrahydro-2-furanyl, tetrahydro-2-pyranyl groups, 1-methoxyethyl, 1-ethoxyethyl, trimethylsilyl, triethylsilyl and dimethyl-t-butylsilyl, and the paired hydroxy groups at the 1- and 2-positions or at the 1- and 3-positions may be joined by replacing the terminal hydrogens of respective paired hydroxy groups with a bridging methylene, ethylene, isopropylidene, benzylidene or cyclohexyline group; a group of formula --SO 2 R 11 , wherein R 11 represents a C 1 -C 6 alkyl group or a phenyl group; or a group of formula --(Y 1 ═)P(--Y 2 --R 12 ) 2 , in which Y 1 and Y 2 , which may be the same or different, each represents oxygen or sulphur and the two atoms represented by Y 2 may be the same or different, and each of the groups represented by R 12 , which may be the same or different, is a C 1 -C 6 alkyl group.

Claim 19

A composition as claimed in claim 15, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a (C 1 -C 6 alkoxy)carbonylmethylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group, a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group, a C 1 -C 6 alkanesulphonyl group, a benzenesulphonyl group, a di(C 1 -C 6 alkoxy)phosphinyl group or a (C 1 -C 6 alkoxy)-(C 1 -C 6 alkylthio)phosphinyl group.

Claim 20

A composition as claimed in claim 15, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group or a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group.

Claim 21

A composition as claimed in claim 16 or claim 17, wherein R 1 represents an ethyl or isopropyl group.

Claim 22

A composition as claimed in any one of claims 11, 12 and 13, wherein said compound is selected from sodium and potassium salts.

Claim 23

A composition as claimed in claim 19, wherein R 1 represents ethyl or isopropyl.

Claim 26

The method as claimed in claim 21, wherein R 2 represents hydrogen, a C 1 -C 6 alkyl group, benzyl or carboxymethyl.

Claim 27

The method as claimed in claim 21, wherein said compound is selected from compounds in which R 2 represents a hydrogen atom and salts and esters thereof.

Claim 28

The method as claimed in claim 22 or claim 23, wherein R 1 represents an ethyl or isopropyl group.

Claim 29

A method as claimed in claim 21, wherein said compound is selected from compounds of formula (IIa): ##STR11## wherein: R 1 represents methyl, ethyl or isopropyl; and R 2a represents: a group of formula --COR 4 , in which R 4 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, phenyl, phenyl substituted with at least one C 1 -C 6 alkyl, halogen, nitro, carboxy or C 2 -C 7 alkoxycarbonyl substituents or a group of formula --(CH 2 ) n COOR 5 , wherein n is an integer from 1 to 3 and R 5 represnts a hydrogen atom or a C 1 -C 6 alkyl group; a group of formula --CO.NR 6 R 7 , wherein R 6 represents hydrogen or a C 1 -C 6 alkyl group and R 7 represents hydrogen, a C 1 -C 6 alkyl group, a phenyl group or a group of formula --CH(R 8 ).COOR 9 (wherein R 8 and R 9 are the same or different and each represents hydrogen or a C 1 -C 6 alkyl group); a group of formula --COOR 10 , wherein R 10 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, a phenyl group or a sugar alcohol from which an omega-hydroxy group has been removed, said sugar alcohol is selected from the group consisting of glycerol, erythritol, threitol, arabinitol, adonitol, xylitol, sorbitol, mannitol and dulcitol; said sugar alcohol may be substituted with at least one protecting group selected from the group consisting of formyl, acetyl, tetrahydro-2-furanyl, tetrahydro-2-pyranyl groups, 1-methoxyethyl, 1-ethoxyethyl, trimethylsilyl, triethylsilyl and dimethyl-t-butylsilyl, and the paired hydroxy groups at the 1- and 2-positions or at the 1- and 3-positions may be joined by replacing the terminal hydrogens of respective paired hydroxy groups with a bridging methylene, ethylene, isopropylidene, benzylidene or cyclohexyline group; a group of formula --SO 2 R 11 , wherein R 11 represents a C 1 -C 6 alkyl group or a phenyl group; or a group of formula --(Y 1 ═)P(--Y 2 --R 12 ) 2 , in which Y 1 and Y 2 , which may be the same or different, each represents oxygen or sulphur and the two atoms represented by Y 2 may be the same or different, and each of the groups represented by R 12 , which may be the same or different, is a C 1 -C 6 alkyl group.

Claim 30

The method as claimed in claim 25, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a (C 1 -C 6 alkoxy)carbonylmethylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group, a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group, a C 1 -C 6 alkanesulphonyl group, a benzenesulphonyl group, a di(C 1 -C 6 alkoxy)phosphinyl group or a (C 1 -C 6 alkoxy)-(C 1 -C 6 alkylthio)phosphinyl group.

Claim 31

The method as claimed in claim 25, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group or a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group.

Claim 32

The method as claimed in claim 26 or claim 27, wherein R 1 represents an ethyl or isopropyl group.

Claim 34

The method as claimed in claim 29, wherein R 1 represents ethyl or isopropyl.

Claim 37

The method as claimed in claim 31, wherein R 2 represents hydrogen, a C 1 -C 6 alkyl group, benzyl or carboxymethyl.

Claim 38

The method as claimed in claim 31, wherein said compound is selected from compounds in which R 2 represents a hydrogen atom and salts and esters thereof.

Claim 39

A method as claimed in claim 32 or claim 33, wherein R 1 represents an ethyl or isopropyl group.

Claim 40

A method as claimed in claim 31, wherein said compound is selected from compounds of formula (IIa): ##STR13## wherein: R 1 represents methyl, ethyl or isopropyl; and R 2a represents: a group of formula --COR 4 , in which R 4 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, phenyl, phenyl substituted with at least one C 1 -C 6 alkyl, halogen, nitro, carboxy or C 2 -C 7 alkoxycarbonyl substituents or a group of formula --(CH 2 ) n COOR 5 , wherein n is an integer from 1 to 3 and R 5 represnts a hydrogen atom or a C 1 -C 6 alkyl group; a group of formula --CO.NR 6 R 7 , wherein R 6 represents hydrogen or a C 1 -C 6 alkyl group and R 7 represents hydrogen, a C 1 -C 6 alkyl group, a phenyl group or a group of formula --CH(R 8 ).COOR 9 (wherein R 8 and R 9 are the same or different and each represents hydrogen or a C 1 -C 6 alkyl group); a group of formula --COOR 10 , wherein R 10 represents a C 1 -C 6 alkyl group, benzyl, benzyl substituted with one C 1 -C 6 alkyl, halogen or nitro, a phenyl group or a sugar alcohol from which an omega-hydroxy group has been removed, said sugar alcohol is selected from the group consisting of glycerol, erythritol, threitol, arabinitol, adonitol, xylitol, sorbitol, mannitol and dulcitol; said sugar alcohol may be substituted with at least one protecting group selected from the group consisting of formyl, acetyl, tetrahydro-2-furanyl, tetrahydro-2-pyranyl groups, 1-methoxyethyl, 1-ethoxyethyl, trimethylsilyl, triethylsilyl and dimethyl-t-butylsilyl, and the paired hydroxy groups at the 1- and 2-positions or at the 1- and 3-positions may be joined by replacing the terminal hydrogens of respective paired hydroxy groups with a bridging methylene, ethylene, isopropylidene, benzylidene or cyclohexyline group; a group of formula --SO 2 R 11 , wherein R 11 represents a C 1 -C 6 alkyl group or a phenyl group; or a group of formula --(Y 1 ═)P(--Y 2 --R 12 ) 2 , in which Y 1 and Y 2 , which may be the same or different, each represents oxygen or sulphur and the two atoms represented by Y 2 may be the same or different, and each of the groups represented by R 12 , which may be the same or different, is a C 1 -C 6 alkyl group.

Claim 41

The method as claimed in claim 35, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a (C 1 -C 6 alkoxy)carbonylmethylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group, a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group, a C 1 -C 6 alkanesulphonyl group, a benzenesulphonyl group, a di(C 1 -C 6 alkoxy)phosphinyl group or a (C 1 -C 6 alkoxy)-(C 1 -C 6 alkylthio)phosphinyl group.

Claim 42

The method as claimed in claim 35, wherein R 2a represents a C 2 -C 7 alkanoyl group, a C 2 -C 7 alkylcarbamoyl group, a C 2 -C 7 alkoxycarbonyl group or a 2,2-dimethyl-1,3-dioxolan-4-ylmethoxycarbonyl group.

Claim 43

The method as claimed in claim 36 or claim 37, wherein R 1 represents an ethyl or isopropyl group.

Claim 45

A method as claimed in claim 39, wherein R 1 represents ethyl or isopropyl.