Patent Application
20190090486
The present invention relates to microbiocidal oxadiazole derivatives, e.g., as active ingredients, which have microbiocidal activity, in particular fungicidal activity. The invention also relates to agrochemical compositions which comprise at least one of the oxadiazole derivatives, to the preparation of these compositions and to the use of the oxadiazole derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular, fungi.
Phenyl oxadiazole derivatives are known as pharmaceutically-active agents from, eg, WO 2013/008162. WO 2015/185485 discloses the use of substituted oxadiazoles for combating phytopathogenic fungi.
According to the invention, there is provided a compound of formula (I):
wherein
R1 is hydrogen;
R2 is halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl; and
R4 represents R4A, R4B, R4C, R4D or R4E; wherein
R4A represents heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, optionally substituted by 1, 2 or 3 substitutents, which may be the same or different, selected from R5A;
R5A represents C1-4alkyl, C1-4alkoxy, C1-4alkoxycarbonyl, phenylC0-2alkyl;
R4B represents C3-8cycloalkylC0-6alkyl optionally substituted by 1, 2, 3 or 4 substitutents, which may be the same or different, selected from R5B;
R5B represents cyano, halogen, C1-4alkyl, C2-4alkynyl, C1-4alkoxycarbonyl, C3-6cycloalkylC0-2alkyl, phenylC0-2alkyl, and wherein any of said cycloalkyl or phenyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6B; and
R6B represents methyl, methoxy or halogen;
R4C represents C1-6alkyl, C2-6alkenyl or C2-6alkynyl, wherein C1-6alkyl is optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R5C;
R5C represents halogen, C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, hydroxyl, C1-4alkylaminocarbonyl;
R4D represents a phenylC0-6alkyl optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R5D;
R5D represents cyano, halogen, hydroxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl, C1-4alkoxycarbonylamino, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R6D; and
R6D represents methyl, methoxy or halogen; and
R4E represents heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-6alkyl moiety is optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R5E;
R5E represents cyano, amino, halogen, hydroxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkylamino, diC1-4alkylamino, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl, C1-4alkoxycarbonylamino, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R6E; and
R6E represents methyl, methoxy or halogen;
or a salt or an N-oxide thereof; wherein
when R4 is R4A, the compound according to Formula (I) is not:
when R4 is R4C, the compound according to Formula (I) is not:
when R4 is R4E, the compound according to Formula (I) is not:
Surprisingly, it has been found that the novel compounds of formula (I) have, for practical purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.
According to the invention, there is provided an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I) optionally, further comprising at least one additional active ingredient and/or an agrochemically-acceptable diluent or carrier.
According to the invention, there is provided method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I), or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
According to the invention, there is provided the use of a compound of formula (I) as a fungicide.
Where substituents are indicated as being optionally substituted, this means that they may or may not carry one or more identical or different substituents.
Cyano refers to a —CN group.
Hydroxy refers to a —OH group
Halogen (halo) refers to fluorine, chlorine, bromine or iodine.
Amino refers to an —NH2 group.
As used herein, the term “C1-6alkyl” refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond. The term “C1-4alkyl” is to be construed accordingly. Examples of C1-6alkyl include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (iso-propyl), n-butyl, n-pentyl and 1,1-dimethylethyl (t-butyl).
As used herein, the term “C2-6alkenyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or (Z)-configuration, having from two to six carbon atoms, which is attached to the rest of the molecule by a single bond. The term “C2-4alkenyl” is to be construed accordingly. Examples of C2-6alkenyl include, but are not limited to, ethenyl, prop-1-enyl, but-1-enyl.
As used herein, the term “C2-6alkynyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to six carbon atoms, and which is attached to the rest of the molecule by a single bond. The term “C2-4alkynyl” is to be construed accordingly. Examples of C2-6alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, but-1-ynyl.
As used herein, the term “haloC1-4alkyl” refers to a C1-4alkyl radical, as defined above, substituted by one or more halo radicals, as defined above. Examples of haloC1-4alkyl include, but are not limited to, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, 3-bromo-2-fluoropropyl and 1-bromomethyl-2-bromoethyl.
As used herein, the term “C1-4alkoxy” refers to a radical of the formula —ORa where Ra is a C1-4alkyl radical as generally defined above. Examples of C1-4alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy, n-butoxy.
As used herein, the term “C1-4alkylamino” refers to a radical of the formula —NH—Ra where Ra is a C1-4alkyl radical as defined above.
As used herein, the term “di-C1-4alkylamino” refers to a radical of the formula —N(Ra)(Rb) where Ra and Rb independently can be the same or a different C1-4alkyl radical as defined above.
As used herein, the term “C1-4alkylcarbonyl” refers to a radical of the formula —C(O)—Ra where Ra is a C1-4alkyl radical as defined above.
As used herein, the term “C1-4alkoxycarbonyl” refers to a radical of the formula —C(O)—O—Ra where Ra is a C1-4alkyl radical as defined above.
As used herein, the term “C1-4alkoxycarbonylamino” refers to a radical of the formula —NH—C(O)—O—Ra where Ra is a C1-4alkyl radical as defined above.
As used herein, the term “aminocarbonyl” refers to a radical of the formula —C(O)—NH2.
As used herein, the term “C1-4alkylaminocarbonyl” refers to a radical of the formula —C(O)—NH—Ra where Ra is a C1-4alkyl radical as defined above.
As used herein, the term “diC1-4alkylaminocarbonyl” refers to a radical of the formula —C(O)—N(Ra)—Ra where each Ra is a C1-4alkyl radical, which may be the same or different, as defined above.
As used herein, the term “C3-8cycloalkylC0-6alkyl” refers to a stable, non-aromatic, monocyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, the cycloalkyl group having from three to eight carbon atoms, and which is saturated or partially unsaturated and attached to the rest of the molecule by a single bond or by a C1-6alkyl radical as defined above. The terms “C3-6cycloalkylC0-2alkyl” and “C3-4cycloalkylC0-2alkyl” are to be construed accordingly. Examples of C3-8cycloalkylC0-6alkyl include, but are not limited to, cyclopropyl, cyclopropyl-methyl, cyclobutyl, cyclobutyl-ethyl, cyclopentyl, cyclopentyl-propyl, cyclohexyl, cyclohepty and cyclooctyl.
As used herein, the term “phenylC0-6alkyl” refers to a phenyl ring attached to the rest of the molecule by a single bond or by a C1-6alkyl radical as defined above. The term “phenylC0-2alkyl” should be construed accordingly. Examples of phenylC0-6alkyl include, but are not limited to, phenyl and benzyl.
As used herein, the term “heterocyclyl” or “heterocyclic” refers to a stable 5- or 6-membered non-aromatic monocyclic ring radical which comprises 1, 2, or 3, heteroatoms individually selected from nitrogen, oxygen and sulfur. The heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heterocyclyl include, but are not limited to pyrrolinyl, pyrrolidyl, tetrahydrofuryl, tetrahydrothienyl, piperidyl, piperazinyl, tetrahydropyranyl, morpholinyl or perhydroazepinyl.
As used herein, the term “heterocyclylC0-6alkyl” refers to a heterocyclic ring as defined above which is attached to the rest of the molecule by a single bond or by a C1-6alkyl radical as defined above. The term “heterocyclylC0-2alkyl” should be construed accordingly.
As used herein, the term “heteroaryl” refers to a 5- or 6-membered aromatic monocyclic ring radical which comprises 1, 2, 3 or 4 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heteroaryl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heteroaryl include, but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl or pyridyl.
As used herein, the term “heteroarylC0-6alkyl” refers to a heteroaryl ring as defined above which is attached to the rest of the molecule by a single bond or by a C1-6alkyl radical as defined above. Likewise, the terms “heteroarylC0-2alkyl” and “heteroarylC0-1alkyl” are to be construed accordingly.
The presence of one or more possible asymmetric carbon atoms in a compound of formula (I) means that the compounds may occur in optically isomeric forms, i.e., enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond. Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of Formula (I). Likewise, Formula (I) is intended to include all possible tautomers. The present invention includes all possible tautomeric forms for a compound of Formula (I).
In each case, the compounds of Formula (I) according to the invention are in free form, in oxidized form as an N-oxide, in covalently hydrated form, or in salt form, e.g., an agrochemically acceptable salt form.
N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
The following list provides definitions, including preferred definitions, for substituents R1, R2, R3, R4 (ie, R4A, R4B, R4C, R4D, R4E), R5 (ie, R5A, R5B, R5C, R5D, R5E) and R6 (ie, R6B, R6D, R6E) with reference to compounds of formula (I). For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
R1 is hydrogen.
R2 is halogen, methyl or methoxy. Preferably, R2 is halogen. More preferably, R2 is chlorine or fluorine. Most preferably, R2 is fluorine.
R3 represents hydrogen or C1-4alkyl. Preferably, R3 is hydrogen or methyl. Most preferably, R3 is hydrogen.
R4 represents R4A, R4B, R4C, R4D or R4E.
In one embodiment of the invention, R4 is R4A. In another embodiment of the invention, R4 is R4B. In another embodiment of the invention, R4 is R4C. In another embodiment of the invention, R4 is R4D. In another embodiment of the invention, R4 is R4E.
R4A represents heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, optionally substituted by 1, 2 or 3 substitutents, which may be the same or different, selected from R5A.
Preferably, R4A represents heterocyclylC0-2alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein the heterocyclylC0-2alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5A. More preferably, R4A represents heterocyclylC0-1alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, and wherein the heterocyclylC0-1alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5A. Even more preferably, R4A represents heterocyclylC0-1alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein the heterocyclylC0-1alkyl moiety is optionally substituted by 1 substitutent, selected from R5A.
In certain embodiments, R4A may be a pyrrolidinyl, piperidinyl, (pyrrolidinyl)methyl, (piperidinyl)methyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxanyl, (tetrahydrofuranyl)methyl, (tetrahydropyranyl)methyl, (1,4-dioxanyl)methyl, 1,3-dioxolanyl, (1,3-dioxolanyl)methyl, tetrahydrothienyl, tetrahydropyranyl, (tetrahydrothienyl)methyl or (tetrahydropyranyl)methyl, which is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5A.
R4B represents C3-8cycloalkylC0-6alkyl optionally substituted by 1, 2, 3 or 4 substitutents, which may be the same or different, selected from R5B.
Preferably, R4B represents C3-6cycloalkylC0-2alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5B. More preferably, R4B represents C3-4cycloalkylC0-2alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5B. Preferably, R4B is cyclopropyl, (cyclopropyl)methyl, 1-(cyclopropyl)ethyl, cyclobutyl, (cyclobutyl)methyl, cyclopentyl, (cyclopentyl)methyl, cyclohexyl, 1-(cyclohexyl)ethyl or cyclooctyl, optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5B.
R4C represents C1-6alkyl, C2-6alkenyl or C2-6alkynyl, wherein C1-6alkyl is optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R5C.
Preferably, R4C represents C1-6alkyl, C2-6alkenyl or C2-6alkynyl, wherein C1-6alkyl is optionally substituted by 1 or 2 substituents which may be the same or different, selected from R5C, wherein R5C represents C1-4alkoxy or hydroxyl. More preferably, R4C represents C1-6alkyl, C2-6alkenyl or C2-6alkynyl, wherein C1-6alkyl is optionally substituted by 1 substituent selected from R5C, wherein R5C represents C1-4alkoxy or hydroxyl. Even more preferably, R4C represents C1-6alkyl optionally substituted by 1 substituent selected from R5C, wherein R5C represents hydroxyl; or R4C represents C2-6alkenyl or C2-6alkynyl.
R4D represents a phenylC0-6alkyl optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R5D.
Preferably, R4D represents phenylC0-6alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5D. More preferably, R4D represents phenylC0-2alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5D.
R4E represents heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-6alkyl moiety is optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R5E.
Preferably, R4E represents heteroarylC0-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring comprising 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-2alkyl moiety is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5E. More preferably, R4E represents heteroarylC0-2alkyl, wherein the heteroaryl moiety of R4E is a 5-membered aromatic ring comprising 1 or 2 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-2alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5E. In some embodiments of the invention, R4E comprises at least one heteroatom which is sulfur, such as a thienyl moiety, in particular, a 2-thienyl moiety. In some embodiments of the invention, R4E may be pyridinyl, pyrazolyl, furanyl, triazolyl, imidazolyl, thiazolyl. In some embodiments of the invention, R4E is unsubstituted.
R5A represents C1-4alkyl, C1-4alkoxy, C1-4alkoxycarbonyl, phenylC0-2alkyl. Preferably, R5A represents methyl, methoxy, methoxycarbonyl, tert-butyloyxcarbonyl or benzyl.
R5B represents cyano, halogen, C1-4alkyl, C2-4alkynyl, C1-4alkoxycarbonyl, C3-6cycloalkylC0-2alkyl, phenylC0-2alkyl, and wherein any of said cycloalkyl or phenyl moieties is optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6B.
Preferably, R5B represents cyano, fluoro, methyl, ethynyl, cyclopropyl, phenyl or benzyl, wherein cyclopropyl and phenyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6B.
R5C represents halogen, C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, hydroxyl, C1-4alkylaminocarbonyl. In certain embodiments, R5C may also be haloC1-4alkoxy.
R5D represents cyano, halogen, hydroxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl, C1-4alkoxycarbonylamino, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R6D.
Preferably, R5D represents halogen, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S. More preferably, R5D represents halogen, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy or heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S. Even more preferably, R5D is selected from fluoro, chloro, methoxy, methyl, ethyl, trifluoromethyl and N-morpholinyl, in particular, when there are 1 or 2 R5D substitutents, which may be the same or different, these are phenyl ring substituents.
R5E represents cyano, amino, halogen, hydroxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkylamino, diC1-4alkylamino, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl, C1-4alkoxycarbonylamino, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl is optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R6E.
Preferably, R5E represents amino, cyano, halogen, hydroxy, C1-4alkyl, C2-3alkenyl, C2-3alkynyl, haloC1-2alkyl, C1-2alkoxy, C1-2alkylcarbonyl, C1-2alkoxycarbonyl, aminocarbonyl, C1-2alkylaminocarbonyl, diC1-2alkylaminocarbonyl, C1-2alkoxycarbonylamino, C3-8cycloalkylC0-2alkyl, phenylC0-2alkyl, heteroarylC0-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-2alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R6E. More preferably, R5E represents amino, cyano, halogen, C1-4alkyl, haloC1-2alkyl, C1-2alkoxy, C1-2alkylcarbonyl, C1-2alkoxycarbonyl, aminocarbonyl, C1-2alkylaminocarbonyl, diC1-2alkylaminocarbonyl, C1-2alkoxycarbonylamino, C3-8cycloalkylC0-2alkyl wherein any of said moieties is optionally substituted by 1, 2, or 3 substituents, which may be the same or different, selected from R6E. Even more preferably, R5E represents amino, cyano, halogen, C1-4alkyl, haloC1-2alkyl, C1-2alkoxy, aminocarbonyl, wherein any of said moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6E. Most preferably, R5E is selected from amino, cyano, halogen, C1-4alkyl, haloC1-2alkyl or C1-2alkoxy.
R6B represents methyl, methoxy or halogen. Preferably, R6B represents chloro.
R6D represents methyl, methoxy or halogen. Preferably, R6 represents methyl, methoxy, fluoro or chloro.
R6E represents methyl, methoxy or halogen. Preferably, R6E represents methyl, methoxy, fluoro or chloro.
Preferably, R1 is hydrogen and R2 is fluoro;
Preferably, R1 is hydrogen and R2 is halogen (preferably fluorine);
Preferably, R1 is hydrogen and R2 is halogen;
Even more preferably, R1 is hydrogen and R2 is fluorine;
Still further preferably, R1 is hydrogen and R2 is fluorine;
Preferably, R1 is hydrogen and and R2 is fluoro;
More preferably, R1 is hydrogen and and R2 is fluoro;
Preferably, R1 is hydrogen and and R2 is fluoro;
Also, in accordance with this disclosure, there is provided a method of controlling or preventing infestation of a useful plant by phytopathogenic microorganisms, which comprises applying to the plant, to a part thereof or the locus thereof, a fungicidally effective amount of a compound of formula (I):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl, halogenC1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkylcarbonylC1-6alkyl, C1-6alkoxycarbonylC1-6alkyl, hydroxylC1-6alkyl, aminoC1-6alkyl, C1-4alkylaminoC1-6alkyl, diC1-4alkylaminoC1-6alkyl, aminocarbonylC1-6alkyl, C1-4alkylaminocarbonylC1-6alkyl, diC1-4alkylaminocarbonylC1-6alkyl, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, phenylC0-6alkylaminoC1-6alkyl, phenylC0-6alkylamino(C1-4alkyl)C1-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R5;
R5 represents cyano, amino, halogen, hydroxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, halogenC1-4 alkyl, C1-4alkoxy, C1-4alkylamino, diC1-4alkylamino, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl, C1-4alkoxycarbonylamino, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R6; and
R6 represents methyl, methoxy or halogen;
or a salt or an N-oxide thereof.
The following list provides definitions, including preferred definitions, for substituents R1, R2, R3, R4, R5 and R6 with reference to compounds of formula (I) for use in the method of controlling or preventing infestation of a useful plant by phytopathogenic microorganisms. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
Preferably, R1 and R2 independently represent hydrogen or halogen. More preferably, R1 and R2 independently represent hydrogen, fluorine or chlorine. Most preferably, R1 and R2 are hydrogen or R1 is hydrogen and R2 is fluorine.
Preferably, R3 represents hydrogen or methyl. Most preferably, R3 represents hydrogen.
Preferably, R4 represents (i) heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S; (ii) C3-8cycloalkylC0-6alkyl; (iii) C1-6alkyl wherein C1-6alkyl is optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R5, which is C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, hydroxyl, amino, C1-4alkylamino, diC1-4alkylamino, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl; (iv) C2-6alkenyl; (v) C2-6alkynyl; (vi) phenylC0-6alkyl; or (vii) heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R5. More preferably, said heterocyclyl, cycloalkyl, phenyl or heteroaryl moieties are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5.
Even more preferably, R4 represents (i) pyrrolidinyl, piperidinyl, (pyrrolidinyl)methyl, (piperidinyl)methyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxanyl, (tetrahydrofuranyl)methyl, (tetrahydropyranyl)methyl, (1,4-dioxanyl)methyl, 1,3-dioxolanyl, (1,3-dioxolanyl)methyl, tetrahydrothienyl, tetrahydropyranyl, (tetrahydrothienyl)methyl or (tetrahydropyranyl)methyl, which is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5; (ii) cyclopropyl, (cyclopropyl)methyl, 1-(cyclopropyl)ethyl, cyclobutyl, (cyclobutyl)methyl, cyclopentyl, (cyclopentyl)methyl, cyclohexyl, 1-(cyclohexyl)ethyl or cyclooctyl, optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5; (iii) C1-6alkyl optionally substituted by 1 or 2 substituents which may be the same or different, selected from R5, which is C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, hydroxyl, amino, C1-4alkylamino, diC1-4alkylamino, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl; (iv) C2-6alkenyl; (v) C2-6alkynyl; (vi) phenylC0-6alkyl optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5; or (vii) heteroarylC0-2alkyl, wherein the heteroaryl moiety of R4 is a 5-membered ring comprising 1 or 2 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-2alkyl moiety is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5.
Most preferably, R4 represents pyrrolidinyl, piperidinyl, (pyrrolidinyl)methyl, (piperidinyl)methyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxanyl, (tetrahydrofuranyl)methyl, (tetrahydropyranyl)methyl, (1,4-dioxanyl)methyl, 1,3-dioxolanyl, (1,3-dioxolanyl)methyl, tetrahydrothienyl, tetrahydropyranyl, (tetrahydrothienyl)methyl or (tetrahydropyranyl)methyl, which is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5 wherein R5 represents methyl, ethyl, methoxy, methoxycarbonyl, ethoxycarbonyl, tert-butyloyxcarbonyl or benzyl; or
cyclopropyl, (cyclopropyl)methyl, 1-(cyclopropyl)ethyl, cyclobutyl, (cyclobutyl)methyl, cyclopentyl, (cyclopentyl)methyl, cyclohexyl, 1-(cyclohexyl)ethyl or cyclooctyl, optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5 wherein R5 represents cyano, fluoro, methyl, cyclopropyl, phenyl or benzyl; or
C1-6alkyl optionally substituted by 1 or 2 substituents which may be the same or different, selected from R5 wherein R5 represents C1-4alkoxy or hydroxyl; or
C2-6alkenyl, C2-6alkynyl; or
phenylC0-6alkyl optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5 wherein R5 represents fluoro, chloro, methyl, methoxy, ethoxy or trifluoromethyl; or
heteroarylC0-2alkyl, wherein the heteroaryl moiety of R4 is a 5-membered ring comprising 1 or 2 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-2alkyl moiety is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5 wherein R5 represents cyano, amino, chloro, bromo, methyl, t-butyl, methoxy or trifluoromethyl.
Preferably, R5 represents cyano, amino, halogen, hydroxyl, C1-4alkyl, C2-4alkynyl, haloC1-4alkyl, C1-4alkoxy, C1-6alkylcarbonyl, C1-4alkoxycarbonyl, C1-4alkylaminocarbonyl, C3-6cycloalkylC0-2alkyl, phenylC0-2alkyl, heterocyclylC0-6alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl and heterocyclyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6.
Preferably, R1 and R2 independently represent hydrogen or halogen;
More preferably, R1 and R2 independently represent hydrogen or halogen;
Also, in accordance with this disclosure, there is provided a compound of formula (IA):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, optionally substituted by 1, 2 or 3 substitutents, which may be the same or different, selected from R5;
R5 represents C1-4alkyl, C1-4alkoxy, C1-4alkoxycarbonyl, phenylC0-2alkyl;
or a salt or an N-oxide thereof;
wherein the compound of formula (IA) is not a compound wherein R1 is hydrogen and R2, R3 and R4 are as follows:
Also, in accordance with this disclosure, there is provided a compound of formula (IB):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents C3-8cycloalkylC0-6alkyl optionally substituted by 1, 2, 3 or 4 substitutents, which may be the same or different, selected from R5;
R5 represents cyano, halogen, C1-4alkyl, C2-4alkynyl, C1-4alkoxycarbonyl, C3-6cycloalkylC0-2alkyl, phenylC0-2alkyl, and wherein any of said cycloalkyl or phenyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6; and
R6 represents methyl, methoxy or halogen;
or a salt or an N-oxide thereof, and
wherein the compound according to Formula (IB) is not a compound wherein R1 and R2 are both hydrogen and R3 and R4 are as follows:
Also, in accordance with this disclosure, there is provided a compound of formula (IC):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents C1-6alkyl, C2-6alkenyl or C2-6alkynyl, wherein C1-6alkyl is optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R5;
R5 represents halogen, C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, hydroxyl, C1-4alkylaminocarbonyl;
or a salt or an N-oxide thereof, and
wherein the compound according to Formula (IC) is not a compound where R1 and R2 are both hydrogen and R3 and R4 are as follows:
or is not a compound according to Formula (IC) wherein R1 is hydrogen, R2 is fluorine, R3 is hydrogen, and R4 is —CH(CH3)CH2OH.
Also, in accordance with this disclosure, there is provided a compound of formula (ID):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents a phenylC0-6alkyl optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R5;
R5 represents cyano, halogen, hydroxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl, C1-4alkoxycarbonylamino, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R6; and
R6 represents methyl, methoxy or halogen;
or a salt or an N-oxide thereof, and
wherein the compound according to Formula (I) is not a compound where together R1 and R2 are hydrogen and R3 and R4 are as follows:
Also, in accordance with this disclosure, there is provided a compound of formula (IE):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-6alkyl moiety is optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R5;
R5 represents cyano, amino, halogen, hydroxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkylamino, diC1-4alkylamino, C1-4alkylcarbonyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, diC1-4alkylaminocarbonyl, C1-4alkoxycarbonylamino, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 substitutents, which may be the same or different, selected from R6; and
R6 represents methyl, methoxy or halogen;
or a salt or a N-oxide thereof;
wherein the compound of formula (I) is not a compound wherein R1 is hydrogen and R2, R3 and R4 are as follows.
Further according to this disclosure, there may be provided a compound of formula (ID):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents a phenylC0-6alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5;
R5 represents halogen, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy or heterocyclylC0-6alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein said heterocyclyl moiety is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R6; and
R6 represents methyl, methoxy or halogen;
or a salt or an N-oxide thereof, and
wherein the compound according to Formula (ID) is not a compound wherein R1 and R2 are both hydrogen and R3 and R4 are as follows:
Further according to this disclosure, there may be provided a compound of formula (IE):
wherein
R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl;
R4 represents heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-6alkyl moiety is optionally substituted by 1, 2 or 3 substitutents, which may be the same or different, selected from R5;
R5 represents cyano, amino, halogen, C1-4alkyl, haloC1-2alkyl or C1-2alkoxy; or a salt or a N-oxide thereof;
wherein the compound of formula (IE) is not a compound wherein R1 is hydrogen and R2, R3 and R4 are as follows:
In accordance with this disclosure as far as it relates to a compound of Formula (IA), (IB), (IC), (ID) or (IE), the following list provides definitions, including preferred definitions, for substituents R1, R2, R3, R4, R5 and R6. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
In accordance with a compound of Formula (IA), preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy. More preferably, R1 is hydrogen and R2 is halogen (preferably fluorine), methyl or methoxy. In a preferred embodiment, R2 is a halogen, in particular, fluorine.
Preferably, R3 represents hydrogen or methyl, and more preferably hydrogen.
Preferably, R4 represents heterocyclylC0-2alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein the heterocyclylC0-2alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5. More preferably, R4 represents heterocyclylC0-1alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, and wherein the heterocyclylC0-1alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5. Even more preferably, R4 represents heterocyclylC0-1alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein the heterocyclylC0-1alkyl moiety is optionally substituted by 1 substitutent, which may be the same or different, selected from R5.
In certain embodiments, R4 may be a pyrrolidinyl, piperidinyl, (pyrrolidinyl)methyl, (piperidinyl)methyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxanyl, (tetrahydrofuranyl)methyl, (tetrahydropyranyl)methyl, (1,4-dioxanyl)methyl, 1,3-dioxolanyl, (1,3-dioxolanyl)methyl, tetrahydrothienyl, tetrahydropyranyl, (tetrahydrothienyl)methyl or (tetrahydropyranyl)methyl, which is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5.
Preferably, R5 represents methyl, methoxy, methoxycarbonyl, tert-butyloyxcarbonyl or benzyl.
Preferably, R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl; and
R4 represents heterocyclylC0-2alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein the heterocyclylC0-2alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, wherein R5 is selected from C1-4alkyl, C1-4alkoxy, C1-4alkoxycarbonyl.
More preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy;
R3 represents hydrogen, methyl, ethyl or n-propyl; and
R4 represents heterocyclylC0-1alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein the heterocyclylC0-1alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, wherein R5 is selected from C1-4alkyl, C1-4alkoxy, C1-4alkoxycarbonyl.
Even more preferably, R1 and R2 independently represent hydrogen or fluoro;
R3 represents hydrogen, methyl, ethyl or n-propyl; and
R4 represents a heterocyclylC0-1alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N and O, and wherein the heterocyclylC0-1alkyl moiety is optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, wherein R5 is selected from methyl, methoxy, methoxycarbonyl or tert-butyloxycarbonyl.
Most preferably, R1 represents hydrogen and R2 represents hydrogen or fluoro;
R3 represents hydrogen, methyl, ethyl or n-propyl; and
R4 represents pyrrolidinyl, piperidinyl, (pyrrolidinyl)methyl, (piperidinyl)methyl, tetrahydrofuranyl, (tetrahydrofuranyl)methyl, (tetrahydropyranyl)methyl, (1,4-dioxanyl)methyl, (1,3-dioxolanyl)methyl, tetrahydrothienyl or tetrahydrothiopyranyl optionally substituted by 1 or 2 substituents which may be the same or different, selected from R5, wherein R5 is selected from methyl, methoxy, methoxycarbonyl or tert-butyloxycarbonyl.
In accordance with a compound of Formula (IB), preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy. More preferably, R1 is hydrogen and R2 is halogen (preferably fluorine), methyl or methoxy. In a preferred embodiment, R2 is a halogen, in particular, fluorine.
Preferably, R3 represents hydrogen, methyl or ethyl, and more preferably hydrogen.
Preferably, R4 is cyclopropyl, (cyclopropyl)methyl, 1-(cyclopropyl)ethyl, cyclobutyl, (cyclobutyl)methyl, cyclopentyl, (cyclopentyl)methyl, cyclohexyl, 1-(cyclohexyl)ethyl or cyclooctyl, optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5.
Preferably, R5 represents cyano, fluoro, methyl, ethynyl, cyclopropyl, phenyl or benzyl, wherein cyclopropyl and phenyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6.
Preferably, R6 represents chloro.
Preferably, R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl; and
R4 represents C3-6cycloalkylC0-2alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, wherein R5 represents cyano, fluoro, methyl, ethynyl, cyclopropyl, phenyl or benzyl wherein cyclopropyl and phenyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6, wherein R6 represents chloro.
More preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy;
R3 represents hydrogen, methyl or ethyl or n-propyl; and
R4 represents cyclopropyl, (cyclopropyl)methyl, 1-(cyclopropyl)ethyl, cyclobutyl, (cyclobutyl)methyl, cyclopentyl, (cyclopentyl)methyl, cyclohexyl, 1-(cyclohexyl)ethyl or cyclooctyl, optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, R5 represents cyano, fluoro, methyl, ethynyl, cyclopropyl, phenyl or benzyl wherein cyclopropyl and phenyl moieties are optionally substituted by 1 substituent selected from R6, wherein R6 represents chloro.
Even more preferably, R1 and R2 independently represent hydrogen or fluoro;
R3 represents hydrogen, methyl, ethyl or n-propyl; and
R4 represents C3-6cycloalkylC0-2alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, wherein R5 represents cyano, fluoro, methyl, ethynyl, cyclopropyl, phenyl or benzyl wherein cyclopropyl and phenyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6, wherein R6 represents chloro.
Most preferably, R1 is hydrogen and R2 is halogen (preferably fluorine),
R3 represents hydrogen; and
R4 represents cyclopropyl, (cyclopropyl)methyl, 1-(cyclopropyl)ethyl, cyclobutyl, (cyclobutyl)methyl, cyclopentyl, (cyclopentyl)methyl, cyclohexyl, 1-(cyclohexyl)ethyl or cyclooctyl, optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, R5 represents cyano, fluoro, methyl, ethynyl, cyclopropyl, phenyl or benzyl wherein cyclopropyl and phenyl moieties are optionally substituted by 1 substituent selected from R6, wherein R6 represents chloro.
In accordance with a compound of Formula (IC), preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy. More preferably, R1 is hydrogen and R2 is hydrogen, halogen (preferably fluorine), methyl or methoxy. In a preferred embodiment, R1 is hydrogen and R2 is a halogen, in particular, fluorine, or R1 and R2 are hydrogen.
Preferably, R3 represents hydrogen, methyl, ethyl, iso-propyl, and more preferably hydrogen.
Preferably, R4 represents C1-6alkyl, C2-6alkenyl or C2-6alkynyl, wherein C1-6alkyl is optionally substituted by 1 or 2 substituents which may be the same or different, selected from R5, wherein R5 represents C1-4alkoxy or hydroxyl. More preferably, R4 represents C1-6alkyl, C2-6alkenyl or C2-6alkynyl, wherein C1-6alkyl is optionally substituted by 1 substituent selected from R5, wherein R5 represents C1-4alkoxy or hydroxyl. Even more preferably, R4 represents C1-6alkyl optionally substituted by 1 substituent selected from R5, wherein R5 represents hydroxyl; or R4 represents C2-6alkenyl or C2-6alkynyl.
Preferably, R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
R3 represents hydrogen or C1-4alkyl; and
R4 represents C2-6alkenyl, C2-6alkynyl or C1-6alkyl optionally substituted by 1 or 2 substituents which may be the same or different, selected from R5, wherein R5 represents C1-4alkoxy or hydroxyl.
More preferably, R1 is hydrogen and R2 is halogen;
R3 represents hydrogen, methyl or ethyl;
R4 represents C2-6alkenyl, C2-6alkynyl or C1-6alkyl optionally substituted by 1 or 2 substituents which may be the same or different, selected from R5, wherein R5 represents C1-4alkoxy or hydroxyl.
Even more preferably, R1 and R2 are hydrogen, or R1 is hydrogen and R2 is fluorine;
R3 represents hydrogen or methyl;
R4 represents C2-6alkenyl, C2-6alkynyl or C1-6alkyl optionally substituted by 1 substituent selected from R5, wherein R5 represents C1-4alkoxy or hydroxyl.
Most preferably, R1 and R2 are hydrogen, or R1 is hydrogen and R2 is fluorine;
R3 represents hydrogen;
R4 represents C2-6alkenyl, C2-6alkynyl or C1-6alkyl optionally substituted by 1 substituent selected from R5, wherein R5 represents C1-4alkoxy or hydroxyl.
In accordance with a compound of Formula (ID), preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy. More preferably, R1 and R2 independently represent hydrogen and fluoro. Even more preferably, R1 is hydrogen and R2 is halogen (preferably fluorine), methyl or methoxy. In a preferred embodiment, R2 is a halogen, in particular fluorine.
Preferably, R3 represents hydrogen or methyl.
Preferably, R4 represents a phenylC0-2alkyl optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R5. More preferably, R4 represents a phenylC0-1alkyl optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R5. Even more preferably, R4 represents a phenylC0-6alkyl optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5. Further more preferably, R4 represents phenylC0-2alkyl optionally substituted by 1 or 2 substitutents, which may be the same or different, selected from R5, which is preferably selected from fluoro, chloro, methoxy, methyl, ethyl, trifluoromethyl or N-morpholinyl, wherein preferably the 1 or 2 substitutents which may be the same or different, selected from R5, are phenyl ring substituents.
Preferably, R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
More preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy;
Even more preferably, R1 and R2 independently represent hydrogen and fluoro;
Most preferably, R1 and R2 independently represent hydrogen and fluoro;
Preferably, R5 represents cyano, halogen, hydroxy, C1-4alkyl, C2-3alkenyl, C2-3alkynyl, haloC1-2alkyl, C1-2alkoxy, C1-2alkylcarbonyl, C1-2alkoxycarbonyl, aminocarbonyl, C1-2alkylaminocarbonyl, diC1-2alkylaminocarbonyl, C1-2alkoxycarbonylamino, C3-8cycloalkylC0-2alkyl, phenylC0-2alkyl, heteroarylC0-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-2alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R6.
More preferably, R5 represents cyano, halogen, C1-4alkyl, haloC1-2alkyl, C1-2alkoxy, C1-2alkylcarbonyl, C1-2alkoxycarbonyl, aminocarbonyl, C1-2alkylaminocarbonyl, diC1-2alkylaminocarbonyl, C1-2alkoxycarbonylamino, C3-8cycloalkylC0-2alkyl, phenylC0-2alkyl, heteroarylC0-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-2alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6.
Even more preferably, R5 represents cyano, halogen, C1-4alkyl, haloC1-2alkyl, C1-2alkoxy, C1-2alkylcarbonyl, C1-2alkoxycarbonyl, aminocarbonyl, C1-2alkylaminocarbonyl, diC1-2alkylaminocarbonyl, C1-2alkoxycarbonylamino, C3-8cycloalkylC0-2alkyl wherein any of said moieties is optionally substituted by 1, 2, or 3 substituents, which may be the same or different, selected from R6.
Most preferably, R5 represents cyano, halogen, C1-4alkyl, haloC1-2alkyl, C1-2alkoxy, aminocarbonyl, wherein any of said moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6.
Preferably, R6 represents methyl, methoxy, fluoro or chloro.
In certain embodiments of this disclosure, it is preferred that R5 represents halogen, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C3-8cycloalkylC0-6alkyl, phenylC0-6alkyl, heteroarylC0-6alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties is optionally substituted by a substituent selected from R6, wherein R6 represents methyl, methoxy or halogen.
More preferably in accordance with this embodiment, R5 represents halogen, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy or heterocyclylC0-6alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S.
In accordance with a compound of Formula (IE), preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy. More preferably, R1 is hydrogen and R2 is halogen (preferably fluorine), methyl or methoxy. In a preferred embodiment, R2 is a halogen, in particular, fluorine.
Preferably, R3 represents hydrogen or methyl, and more preferably hydrogen.
Preferably, R4 represents heteroarylC0-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered ring comprising 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-2alkyl moiety is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5. In some embodiments, R4 is not a 4-pyridyl substituent.
In another embodiment, R4 represents heteroarylC0-2alkyl, wherein the heteroaryl moiety of R4 is a 5-membered ring comprising 1 or 2 heteroatoms individually selected from N, O and S, and wherein the heteroarylC0-2alkyl moiety is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R5. According to this embodiment, preferably, at least one heteroatom is S, and more preferably, R4 is a thienyl derivative, in particular, a 2-thienyl derivative.
In other embodiments of the invention, R4 is unsubstituted.
Preferably, R5 represents amino, cyano, halogen, hydroxy, C1-4alkyl, C2-3alkenyl, C2-3alkynyl, haloC1-2alkyl, C1-2alkoxy, C1-2alkylcarbonyl, C1-2alkoxycarbonyl, aminocarbonyl, C1-2alkylaminocarbonyl, diC1-2alkylaminocarbonyl, C1-2alkoxycarbonylamino, C3-8cycloalkylC0-2alkyl, phenylC0-2alkyl, heteroarylC0-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclylC0-2alkyl wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, heteroaryl and heterocyclyl moieties are optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R6.
More preferably, R5 represents amino, cyano, halogen, C1-4alkyl, haloC1-2alkyl, C1-2alkoxy, C1-2alkylcarbonyl, C1-2alkoxycarbonyl, aminocarbonyl, C1-2alkylaminocarbonyl, diC1-2alkylaminocarbonyl, C1-2alkoxycarbonylamino, C3-8cycloalkylC0-2alkyl wherein any of said moieties are optionally substituted by 1, 2, or 3 substituents, which may be the same or different, selected from R6.
Even more preferably, R5 represents amino, cyano, halogen, C1-4alkyl, haloC1-2alkyl, C1-2alkoxy, aminocarbonyl, wherein any of said moieties are optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R6. Most preferably, R5 is selected from amino, cyano, halogen, C1-4alkyl, haloC1-2alkyl or C1-2alkoxy.
Preferably, R6 represents methyl, methoxy, fluoro or chloro.
Preferably, R1 and R2 independently represent hydrogen, halogen, methyl or methoxy;
More preferably, R1 and R2 independently represent hydrogen, fluoro, chloro, methyl or methoxy;
Even more preferably, R1 and R2 independently represent hydrogen or fluoro;
Most preferably, R1 and R2 independently represent hydrogen and fluoro;
In accordance with the definition of R4 for compounds of Formula (IE), preferred heteroaryl fragments in the definition of heteroarylC0-6alkyl, heteroarylC0-2alkyl, heteroarylC0-1alkyl, etc, include thienyl, pyrazolyl, pyridyl, triazolyl, furanyl and thiazolyl moieties.
It is understood that when in aqueous media, the compounds of formula (I) according to the invention may be present in a reversible equilibrium with the corresponding covalently hydrated forms (ie, the compounds of formula (I-I) and formula (I-II) as shown below) at the CF3-oxadiazole motif. This dynamic equilibrium may be important for the biological activity of the compounds of Formula (I). The designations of R1, R2, R3, R4 (including, R4A, R4B, R4C, R4D, R4E), R5 (including, R5A, R5B, R5C, R5D, R5E) and R6 (including, R6B, R6D, R6E), with reference to the compounds of formula (I) of the present invention apply generally to the compounds of Formula (I-I) and Formula (I-I), as do the specific disclosures of combinations of R1, R2, R3, R4 (including, R4A, R4B, R4C, R4D, R4E), R5 (including, R5AR5B, R5C, R5D, R5E) and R6 (including, R6B, R6D, R6E) as represented for the individual compounds disclosed in Tables 1A to 30A, 1B to 29B, 1C to 33C, 1D to 27D or 1E to 27E (below), or the individual compounds disclosed in Tables T1a, T1b, T2a, T2b, T3a, T3b, T4a, T4b, T5a or T5b (below).
Compounds of the present invention can be made as shown in the following schemes, in which, unless otherwise stated, the definition of each variable is as defined above for a compound of formula (I).
The compounds of formula (I) can be obtained by an amide coupling transformation with compounds of formula (A) and compounds of formula (B) by activating the carboxylic acid function of the compounds of formula (A), a process that usually takes place by converting the —OH of the carboxylic acid into a good leaving group, such as a chloride group, for example by using (COCl)2 or SOCl2, prior to treatment with the compounds of formula (B), preferably in a suitable solvent (eg, dimethylformamide, dichloromethane or tetrahydrofuran), preferably at a temperature of between 25° C. and 100° C., and optionally in the presence of a base such as triethyl amine or N,N-diisopropylethylamine, or under conditions described in the literature for an amide coupling. This reaction is shown in Scheme 1 below. For examples, see Valeur, E.; Bradley, M. Chem. Soc. Rev. (2009), 38, 606 and Chinchilla, R., Najera, C. Chem. Soc. Rev. (2011), 40, 5084. Compounds of formula (A) can be made by known methods from known compounds or are commercially available. For examples, see: Liu, K. et al. J. Med. Chem. (2008), 51, 7843 and WO 2013/008162 A1. Compounds of formula (B) are known compounds or are commercially available.
Alternatively, compounds of formula (I) can be prepared from compounds of formula (C) by treatment with trifluoroacetic anhydride (TFAA) in a suitable solvent, such as tetrahydrofuran, at a temperature between 0° C. and 25° C. For related examples, see Kitamura, S. et al. Chem. Pharm. Bull. (2001), 49, 268. This reaction is shown in Scheme 2.
Compounds of formula (C) can be prepared from compounds of formula (D) by treating them with a hydroxylamine hydrochloride salt in the presence of a base, such as sodium carbonate, in a suitable solvent, such as methanol, at a temperature between 0° C. and 100° C. For related examples, see Kitamura, S. et al. Chem. Pharm. Bull. (2001), 49, 268. This reaction is shown in Scheme 3.
Compounds of formula (D) are known or may be made by known methods from known compounds. See for examples Chobanian, H. R. et al Tet. Lett. (2006), 47, 3303; or Makovec, F. et al J. Med. Chem. (1992), 35, 3633.
Surprisingly, it has now been found that the compounds of formula (I) have, for practical purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.
The compounds of formula (I) can be used in the agricultural sector and related fields of use, e.g., as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man. The novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants. The compounds of formula (I) can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later, e.g., from phytopathogenic microorganisms.
The present invention further relates to a method for controlling or preventing infestation of plants or plant propagation material and/or harvested food crops susceptible to microbial attack by treating plants or plant propagation material and/or harvested food crops wherein an effective amount a compound of formula (I) is applied to the plants, to parts thereof or the locus thereof.
The present invention also relates to the use of the compounds of formula (I) as a fungicide. The term “fungicide” as used herein means a compound that controls, modifies, or prevents the growth of fungi. The term “fungicidally effective amount” in accordance with present invention means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
It is also possible to use the compounds of formula (I) as dressing agents for the treatment of plant propagation material, e.g., seed, such as fruits, tubers or grains, or plant cuttings (eg, rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil. The propagation material can be treated with a composition comprising a compound of formula (I) before planting: seed, for example, can be dressed before being sown. The active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
Furthermore, the compounds of formula (I) can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood-related technical products, in food storage, in hygiene management.
In addition, the compounds of formula (I) may be used to protect non-living materials from fungal attack, e.g., lumber, wall boards and paint.
The compounds of formula (I) are for example, effective against fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses. These fungi and fungal vectors of disease, as well as phytopathogenic bacteria and viruses are for example:
Absidia corymbifera, Alternaria spp, Aphanomyces spp, Ascochyta spp, Aspergillus spp. including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terrus, Aureobasidium spp. including A. pullulans, Blastomyces dermatitidis, Blumeria graminis, Bremia lactucae, Botryosphaeria spp. including B. dothidea, B. obtusa, Botrytis spp. including B. cinerea, Candida spp. including C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. tropicalis, Cephaloascus fragrans, Ceratocystis spp, Cercospora spp. including C. arachidicola, Cercosporidium personatum, Cladosporium spp, Claviceps purpurea, Coccidioides immitis, Cochliobolus spp, Colletotrichum spp. including C. musae, Cryptococcus neoformans, Diaporthe spp, Didymella spp, Drechslera spp, Elsinoe spp, Epidermophyton spp, Erwinia amylovora, Erysiphe spp. including E. cichoracearum, Eutypa lata, Fusarium spp. including F. culmorum, F. graminearum, F. langsethiae, F. moniliforme, F. oxysporum, F. proliferatum, F. subglutinans, F. solani, Gaeumannomyces graminis, Gibberella fujikuroi, Gloeodes pomigena, Gloeosporium musarum, Glomerella cingulate, Guignardia bidwellii, Gymnosporangium juniperi-virginianae, Helminthosporium spp, Hemileia spp, Histoplasma spp. including H. capsulatum, Laetisaria fuciformis, Leptographium lindbergi, Leveillula taurica, Lophodermium seditiosum, Microdochium nivale, Microsporum spp, Monilinia spp, Mucor spp, Mycosphaerella spp. including M. graminicola, M. pomi, Oncobasidium theobromaeon, Ophiostoma piceae, Paracoccidioides spp, Penicillium spp. including P. digitatum, P. italicum, Petriellidium spp, Peronosclerospora spp. Including P. maydis, P. philippinensis and P. sorghi, Peronospora spp, Phaeosphaeria nodorum, Phakopsora pachyrhizi, Phellinus igniarus, Phialophora spp, Phoma spp, Phomopsis viticola, Phytophthora spp. including P. infestans, Plasmopara spp. including P. halstedii, P. viticola, Pleospora spp., Podosphaera spp. including P. leucotricha, Polymyxa graminis, Polymyxa betae, Pseudocercosporella herpotrichoides, Pseudomonas spp, Pseudoperonospora spp. including P. cubensis, P. humuli, Pseudopeziza tracheiphila, Puccinia Spp. including P. hordei, P. recondita, P. striiformis, P. triticina, Pyrenopeziza spp, Pyrenophora spp, Pyricularia spp. including P. oryzae, Pythium spp. including P. ultimum, Ramularia spp, Rhizoctonia spp, Rhizomucor pusillus, Rhizopus arrhizus, Rhynchosporium spp, Scedosporium spp. including S. apiospermum and S. prolificans, Schizothyrium pomi, Sclerotinia spp, Sclerotium spp, Septoria spp, including S. nodorum, S. tritici, Sphaerotheca macularis, Sphaerotheca fusca (Sphaerotheca fuliginea), Sporothorix spp, Stagonospora nodorum, Stemphylium spp, Stereum hirsutum, Thanatephorus cucumeris, Thielaviopsis basicola, Tilletia spp, Trichoderma spp. including T. harzianum, T. pseudokoningii, T. viride, Trichophyton spp, Typhula spp, Uncinula necator, Urocystis spp, Ustilago spp, Venturia spp. including V. inaequalis, Verticillium spp, and Xanthomonas spp.
Within the scope of present invention, target crops and/or useful plants to be protected typically comprise perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St. Augustine grass and Zoysia grass; herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber; vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
The term “useful plants” is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.
The term “useful plants” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Examples of such plants are: YieldGard® (maize variety that expresses a CryIA(b) toxin); YieldGard Rootworm® (maize variety that expresses a CryIIIB(b1) toxin); YieldGard Plus® (maize variety that expresses a CryIA(b) and a CryIIIB(b1) toxin); Starlink® (maize variety that expresses a Cry9(c) toxin); Herculex I® (maize variety that expresses a CryIF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CryIA(c) toxin); Bollgard I® (cotton variety that expresses a CryIA(c) toxin); Bollgard II® (cotton variety that expresses a CryIA(c) and a CryIIA(b) toxin); VIPCOT® (cotton variety that expresses a VIP toxin); NewLeaf® (potato variety that expresses a CryIIIA toxin); NatureGard® Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait), Agrisure® RW (corn rootworm trait) and Protecta®.
The term “crops” is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as 8-endotoxins, e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases.
In the context of the present invention there are to be understood by 8-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a Cry1Ab toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a Cry1Ac toxin); Bollgard I® (cotton variety that expresses a Cry1Ac toxin); Bollgard II® (cotton variety that expresses a Cry1Ac and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a Cry1Ab toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); NatureGard®, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta®.
Further examples of such transgenic crops are:
1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a Cry1Ab toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects.
5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein CryIF for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603×MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603×MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
The term “locus” as used herein means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
The term “plants” refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
The term “plant propagation material” is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably, “plant propagation material” is understood to denote seeds.
The compounds of formula (I) may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations, e.g., in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
Suitable carriers and adjuvants, e.g., for agricultural use, can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended. Such formulations include anti-settling agents and dispersing agents and may further include a wetting agent to enhance activity as well an anti-foam and a crystal growth inhibitor. In use, these concentrates are diluted in water and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller's earth, kaolin clays, silicas and other readily wet organic or inorganic solids. Wettable powders normally contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent.
Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
Granular formulations include both extrudates and relatively coarse particles and are usually applied without dilution to the area in which treatment is required. Typical carriers for granular formulations include sand, fuller's earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugars, sodium chloride, sodium sulphate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other organic or inorganic materials which absorb or which can be coated with the active compound. Granular formulations normally contain 5% to 25% of active ingredients which may include surface-active agents such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils; and/or stickers such as dextrins, glue or synthetic resins.
Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers.
Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates. Encapsulated droplets are typically 1 to 50 microns in diameter. The enclosed liquid typically constitutes 50 to 95% of the weight of the capsule and may include solvent in addition to the active compound. Encapsulated granules are generally porous granules with porous membranes sealing the granule pore openings, retaining the active species in liquid form inside the granule pores. Granules typically range from 1 millimetre to 1 centimetre and preferably 1 to 2 millimetres in diameter. Granules are formed by extrusion, agglomeration or prilling, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.
Other useful formulations for agrochemical applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurised sprayers, wherein the active ingredient is dispersed in finely-divided form as a result of vaporisation of a low boiling dispersant solvent carrier, may also be used.
Suitable agricultural adjuvants and carriers that are useful in formulating the compositions of the invention in the formulation types described above are well known to those skilled in the art.
Liquid carriers that can be employed include, for example, water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octyl amine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc., ethylene glycol, propylene glycol, glycerine and N-methyl-2-pyrrolidinone. Water is generally the carrier of choice for the dilution of concentrates.
Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay, fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour and lignin.
A broad range of surface-active agents are advantageously employed in both said liquid and solid compositions, especially those designed to be diluted with carrier before application. These agents, when used, normally comprise from 0.1% to 15% by weight of the formulation. They can be anionic, cationic, non-ionic or polymeric in character and can be employed as emulsifying agents, wetting agents, suspending agents or for other purposes. Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C.sub. 18 ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C.sub. 16 ethoxylate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono and dialkyl phosphate esters.
Other adjuvants commonly utilized in agricultural compositions include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, anti-foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralising agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents.
In addition, further, other biocidally active ingredients or compositions may be combined with the compositions of the invention and used in the methods of the invention and applied simultaneously or sequentially with the compositions of the invention. When applied simultaneously, these further active ingredients may be formulated together with the compositions of the invention or mixed in, for example, the spray tank. These further biocidally active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and/or plant growth regulators.
Pesticidal agents are referred to herein using their common name are known, for example, from “The Pesticide Manual”, 15th Ed., British Crop Protection Council 2009.
In addition, the compositions of the invention may also be applied with one or more systemically acquired resistance inducers (“SAR” inducer). SAR inducers are known and described in, for example, U.S. Pat. No. 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl.
The compounds of formula (I) are normally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants. They can also be selective herbicides or non-selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
The compounds of formula (I) may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula (I) or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.
The invention, in particular as it relates to the compounds of Formula (I) (including Formulae (IA), (IB), (IC), (ID) and (IE)), provides a composition, preferably a fungicidal composition, comprising at least one compound formula (I), an agriculturally acceptable carrier and optionally an adjuvant. An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art. Preferably, said composition may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula (I).
The compound of formula (I) may be the sole active ingredient of a composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may, in some cases, result in unexpected synergistic activities.
Examples of suitable additional active ingredients include the following acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorous fungicides, organotin fungicides, oxathiin fungicides, oxazole fungicides, phenylsulfamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.
Examples of suitable additional active ingredients also include the following: 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid methoxy-[1-methyl-2-(2,4,6-trichlorophenyl)-ethyl]-amide, 1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-1-methyl-indan-4-yl)-amide (1072957-71-1), 1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid (4′-methylsulfanyl-biphenyl-2-yl)-amide, 1-methyl-3-difluoromethyl-4H-pyrazole-4-carboxylic acid [2-(2,4-dichloro-phenyl)-2-methoxy-1-methyl-ethyl]-amide, (5-Chloro-2,4-dimethyl-pyridin-3-yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, (5-Bromo-4-chloro-2-methoxy-pyridin-3-yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, 2-{2-[(E)-3-(2,6-Dichloro-phenyl)-1-methyl-prop-2-en-(E)-ylideneaminooxymethyl]-phenyl}-2-[(Z)-methoxyimino]-N-methyl-acetamide, 3-[5-(4-Chloro-phenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine, (E)-N-methyl-2-[2-(2, 5-dimethylphenoxymethyl) phenyl]-2-methoxy-iminoacetamide, 4-bromo-2-cyano-N, N-dimethyl-6-trifluoromethylbenzimidazole-1-sulphonamide, a-[N-(3-chloro-2, 6-xylyl)-2-methoxyacetamido]-y-butyrolactone, 4-chloro-2-cyano-N,-dimethyl-5-p-tolylimidazole-1-sulfonamide, N-allyl-4, 5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide, N-(I-cyano-1, 2-dimethylpropyl)-2-(2, 4-dichlorophenoxy) propionamide, N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, (.+-.)-cis-1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)-cycloheptanol, 2-(1-tert-butyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ol, 2′,6′-dibromo-2-methyl-4-trifluoromethoxy-4′-trifluoromethyl-1,3-thiazole-5-carboxanilide, 1-imidazolyl-1-(4′-chlorophenoxy)-3,3-dimethylbutan-2-one, methyl (E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl]3-methoxyacrylate, methyl (E)-2-[2-[6-(2-thioamidophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2-fluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2,6-difluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(pyrimidin-2-yloxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(5-methylpyrimidin-2-yloxy)-phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(phenyl-sulphonyloxy)phenoxy]phenyl-3-methoxyacrylate, methyl (E)-2-[2-[3-(4-nitrophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-phenoxyphenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3,5-dimethyl-benzoyl)pyrrol-1-yl]-3-methoxyacrylate, methyl (E)-2-[2-(3-methoxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2[2-(2-phenylethen-1-yl)-phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3,5-dichlorophenoxy)pyridin-3-yl]-3-methoxyacrylate, methyl (E)-2-(2-(3-(1,1,2,2-tetrafluoroethoxy)phenoxy)phenyl)-3-methoxyacrylate, methyl (E)-2-(2-[3-(alpha-hydroxybenzyl)phenoxy]phenyl)-3-methoxyacrylate, methyl (E)-2-(2-(4-phenoxypyridin-2-yloxy)phenyl)-3-methoxyacrylate, methyl (E)-2-[2-(3-n-propyloxy-phenoxy)phenyl]3-methoxyacrylate, methyl (E)-2-[2-(3-isopropyloxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(2-fluorophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3-ethoxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(4-tert-butyl-pyridin-2-yloxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(3-cyanophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[(3-methyl-pyridin-2-yloxymethyl)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2-methyl-phenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(5-bromo-pyridin-2-yloxymethyl)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3-(3-iodopyridin-2-yloxy)phenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2-chloropyridin-3-yloxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E),(E)-2-[2-(5,6-dimethyl pyrazin-2-ylmethyloximinomethyl)phenyl]-3-methoxyacrylate, methyl (E)-2-{2-[6-(6-methylpyridin-2-yloxy)pyrimidin-4-yloxy]phenyl}-3-methoxy-acrylate, methyl (E),(E)-2-{2-(3-methoxyphenyl)methyloximinomethyl]-phenyl}-3-methoxyacrylate, methyl (E)-2-{2-(6-(2-azidophenoxy)-pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[6-phenylpyrimidin-4-yl)-methyloximinomethyl]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[(4-chlorophenyl)-methyloximinomethyl]-phenyl}-3-methoxyacrylate, methyl (E)-2-{2-[6-(2-n-propylphenoxy)-1,3,5-triazin-4-yloxy]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[(3-nitrophenyl)methyloximinomethyl]phenyl}-3-methoxyacrylate, 3-chloro-7-(2-aza-2,7,7-trimethyl-oct-3-en-5-ine), 2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide, 3-iodo-2-propinyl alcohol, 4-chlorophenyl-3-iodopropargyl formal, 3-bromo-2,3-diiodo-2-propenyl ethylcarbamate, 2,3,3-triiodoallyl alcohol, 3-bromo-2,3-diiodo-2-propenyl alcohol, 3-iodo-2-propinyl n-butylcarbamate, 3-iodo-2-propinyl n-hexylcarbamate, 3-iodo-2-propinyl cyclohexyl-carbamate, 3-iodo-2-propinyl phenylcarbamate; phenol derivatives, such as tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3,5-dimethyl-4-chlorophenol, phenoxyethanol, dichlorophene, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2-benzyl-4-chlorophenol, 5-hydroxy-2-(5H)-furanone; 4,5-dichlorodithiazolinone, 4,5-benzodithiazolinone, 4,5-trimethylenedithiazolinone, 4,5-dichloro-(3H)-1,2-dithiol-3-one, 3,5-dimethyl-tetrahydro-1,3,5-thiadiazine-2-thione, N-(2-p-chlorobenzoylethyl)-hexaminium chloride, acibenzolar, acypetacs, alanycarb, albendazole, aldimorph, allicin, allyl alcohol, ametoctradin, amisulbrom, amobam, ampropylfos, anilazine, asomate, aureofungin, azaconazole, azafendin, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthiazole, benzalkonium chloride, benzamacril, benzamorf, benzohydroxamic acid, berberine, bethoxazin, biloxazol, binapacryl, biphenyl, bitertanol, bithionol, bixafen, blasticidin-S, boscalid, bromothalonil, bromuconazole, bupirimate, buthiobate, butylamine calcium polysulfide, captafol, captan, carbamorph, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chitosan, chlobenthiazone, chloraniformethan, chloranil, chlorfenazole, chloroneb, chloropicrin, chlorothalonil, chlorozolinate, chlozolinate, climbazole, clotrimazole, clozylacon, copper containing compounds such as copper acetate, copper carbonate, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper oxyquinolate, copper silicate, copper sulphate, copper tallate, copper zinc chromate and Bordeaux mixture, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cypendazole, cyproconazole, cyprodinil, dazomet, debacarb, decafentin, dehydroacetic acid, di-2-pyridyl disulphide 1, 1′-dioxide, dichlofluanid, diclomezine, dichlone, dicloran, dichlorophen, dichlozoline, diclobutrazol, diclocymet, diethofencarb, difenoconazole, difenzoquat, diflumetorim, O, O-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetachlone, dimetconazole, dimethomorph, dimethirimol, diniconazole, diniconazole-M, dinobuton, dinocap, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine, dipyrithione, disulfiram, ditalimfos, dithianon, dithioether, dodecyl dimethyl ammonium chloride, dodemorph, dodicin, dodine, doguadine, drazoxolon, edifenphos, enestroburin, epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin, ethilicin, ethyl (Z)-N-benzyl-N ([methyl (methyl-thioethylideneamino-oxycarbonyl) amino] thio)-β-alaninate, etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, flupicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutanil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fuberidazole, furalaxyl, furametpyr, furcarbanil, furconazole, furfural, furmecyclox, furophanate, glyodin, griseofulvin, guazatine, halacrinate, hexa chlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexylthiofos, hydrargaphen, hydroxyisoxazole, hymexazole, imazalil, imazalil sulphate, imibenconazole, iminoctadine, iminoctadine triacetate, inezin, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isopropanyl butyl carbamate, isoprothiolane, isopyrazam, isotianil, isovaledione, izopamfos, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY248908, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, mefenoxam, mepanipyrim, mepronil, mercuric chloride, mercurous chloride, meptyldinocap, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, methasulfocarb, methfuroxam, methyl bromide, methyl iodide, methyl isothiocyanate, metiram, metiram-zinc, metominostrobin, metrafenone, metsulfovax, milneb, moroxydine, myclobutanil, myclozolin, nabam, natamycin, neoasozin, nickel dimethyldithiocarbamate, nitrostyrene, nitrothal-iso-propyl, nuarimol, octhilinone, ofurace, organomercury compounds, orysastrobin, osthol, oxadixyl, oxasulfuron, oxine-copper, oxolinic acid, oxpoconazole, oxycarboxin, parinol, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, penthiopyrad, phenamacril, phenazin oxide, phosdiphen, phosetyl-AI, phosphorus acids, phthalide, picoxystrobin, piperalin, polycarbamate, polyoxin D, polyoxrim, polyram, probenazole, prochloraz, procymidone, propamidine, propamocarb, propiconazole, propineb, propionic acid, proquinazid, prothiocarb, prothioconazole, pyracarbolid, pyraclostrobin, pyrametrostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinacetol, quinazamid, quinconazole, quinomethionate, quinoxyfen, quintozene, rabenzazole, santonin, sedaxane, silthiofam, simeconazole, sipconazole, sodium pentachlorophenate, solatenol, spiroxamine, streptomycin, sulphur, sultropen, tebuconazole, tebfloquin, tecloftalam, tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor, thicyofen, thifluzamide, 2-(thiocyanomethylthio) benzothiazole, thiophanate-methyl, thioquinox, thiram, tiadinil, timibenconazole, tioxymid, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumazole, triforine, triflumizole, triticonazole, uniconazole, urbacide, validamycin, valifenalate, vapam, vinclozolin, zarilamid, zineb, ziram, and zoxamide.
The compounds of the invention may also be used in combination with anthelmintic agents. Such anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP-357460, EP-444964 and EP-594291. Additional anthelmintic agents include semisynthetic and biosynthetic avermectin/milbemycin derivatives such as those described in U.S. Pat. No. 5,015,630, WO-9415944 and WO-9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel. Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
The compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in U.S. Pat. Nos. 5,478,855, 4,639,771 and DE-19520936.
The compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO 96/15121 and also with anthelmintic active cyclic depsipeptides such as those described in WO 96/11945, WO 93/19053, WO 93/25543, EP 626375, EP 382173, WO 94/19334, EP 382173, and EP 503538.
The compounds of the invention may be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid and the like.
The compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers WO 95/19363 or WO 04/72086, particularly the compounds disclosed therein.
Other examples of such biologically active compounds that the compounds of the invention may be used in combination with include but are not restricted to the following:
Organophosphates: acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, methacriphos, methamidophos, methidathion, methyl-parathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, paraoxon, parathion, parathion-methyl, phenthoate, phosalone, phosfolan, phosphocarb, phosmet, phosphamidon, phorate, phoxim, pirimiphos, pirimiphos-methyl, profenofos, propaphos, proetamphos, prothiofos, pyraclofos, pyridapenthion, quinalphos, sulprophos, temephos, terbufos, tebupirimfos, tetrachlorvinphos, thimeton, triazophos, trichlorfon, vamidothion.
Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb, HCN-801, isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
Pyrethroids: acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, bifenthrin, beta-cyfluthrin, cyfluthrin, a-cypermethrin, beta-cypermethrin, bioallethrin, bioallethrin((S)-cyclopentylisomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, ethofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D-isomer), imiprothrin, cyhalothrin, lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins (natural products), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluofen, t-fluvalinate, tefluthrin, tralomethrin, Zeta-cypermethrin.
Arthropod growth regulators: a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-118, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine, diacloden, diafenthiuron, DBI-3204, dinactin, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI-800, fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox, fluproxyfen, halofenprox, hydramethylnon, IKI-220, kanemite, NC-196, neem guard, nidinorterfuran, nitenpyram, SD-35651, WL-108477, pirydaryl, propargite, protrifenbute, pymethrozine, pyridaben, pyrimidifen, NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301.
Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
Bactericides: chlortetracycline, oxytetracycline, streptomycin.
Other biological agents: enrofloxacin, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, carprofen, metaflumizone, praziquarantel, triclabendazole.
The following mixtures of the compounds of formula (I) with active ingredients are preferred (the abbreviation “TX” means “one compound selected from the group consisting of the compounds described in Tables 1A to 30A, 1B to 29B, 1C to 33C, 1D to 27D or 1E to 27E (below), or Tables T1a, T1b, T2a, T2b, T3a, T3b, T4a, T4b, T5a or T5b (below)”).
an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628)+TX,
an acaricide selected from the group of substances consisting of 1,1-bis(4-chlorophenyl)-2-ethoxyethanol (IUPAC name) (910)+TX, 2,4-dichlorophenyl benzenesulfonate (IUPAC/Chemical Abstracts name) (1059)+TX, 2-fluoro-N-methyl-N-1-naphthylacetamide (IUPAC name) (1295)+TX, 4-chlorophenyl phenyl sulfone (IUPAC name) (981)+TX, abamectin (1)+TX, acequinocyl (3)+TX, acetoprole [CCN]+TX, acrinathrin (9)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, alpha-cypermethrin (202)+TX, amidithion (870)+TX, amidoflumet [CCN]+TX, amidothioate (872)+TX, amiton (875)+TX, amiton hydrogen oxalate (875)+TX, amitraz (24)+TX, aramite (881)+TX, arsenous oxide (882)+TX, AVI 382 (compound code)+TX, AZ 60541 (compound code)+TX, azinphos-ethyl (44)+TX, azinphos-methyl (45)+TX, azobenzene (IUPAC name) (888)+TX, azocyclotin (46)+TX, azothoate (889)+TX, benomyl (62)+TX, benoxafos (alternative name) [CCN]+TX, benzoximate (71)+TX, benzyl benzoate (IUPAC name) [CCN]+TX, bifenazate (74)+TX, bifenthrin (76)+TX, binapacryl (907)+TX, brofenvalerate (alternative name)+TX, bromocyclen (918)+TX, bromophos (920)+TX, bromophos-ethyl (921)+TX, bromopropylate (94)+TX, buprofezin (99)+TX, butocarboxim (103)+TX, butoxycarboxim (104)+TX, butylpyridaben (alternative name)+TX, calcium polysulfide (IUPAC name) (111)+TX, camphechlor (941)+TX, carbanolate (943)+TX, carbaryl (115)+TX, carbofuran (118)+TX, carbophenothion (947)+TX, CGA 50′439 (development code) (125)+TX, chinomethionat (126)+TX, chlorbenside (959)+TX, chlordimeform (964)+TX, chlordimeform hydrochloride (964)+TX, chlorfenapyr (130)+TX, chlorfenethol (968)+TX, chlorfenson (970)+TX, chlorfensulfide (971)+TX, chlorfenvinphos (131)+TX, chlorobenzilate (975)+TX, chloromebuform (977)+TX, chloromethiuron (978)+TX, chloropropylate (983)+TX, chlorpyrifos (145)+TX, chlorpyrifos-methyl (146)+TX, chlorthiophos (994)+TX, cinerin 1 (696)+TX, cinerin II (696)+TX, cinerins (696)+TX, clofentezine (158)+TX, closantel (alternative name) [CCN]+TX, coumaphos (174)+TX, crotamiton (alternative name) [CCN]+TX, crotoxyphos (1010)+TX, cufraneb (1013)+TX, cyanthoate (1020)+TX, cyflumetofen (CAS Reg. No.: 400882-07-7)+TX, cyhalothrin (196)+TX, cyhexatin (199)+TX, cypermethrin (201)+TX, DCPM (1032)+TX, DDT (219)+TX, demephion (1037)+TX, demephion-O (1037)+TX, demephion-S (1037)+TX, demeton (1038)+TX, demeton-methyl (224)+TX, demeton-O (1038)+TX, demeton-O-methyl (224)+TX, demeton-S (1038)+TX, demeton-S-methyl (224)+TX, demeton-S-methylsulfon (1039)+TX, diafenthiuron (226)+TX, dialifos (1042)+TX, diazinon (227)+TX, dichlofluanid (230)+TX, dichlorvos (236)+TX, dicliphos (alternative name)+TX, dicofol (242)+TX, dicrotophos (243)+TX, dienochlor (1071)+TX, dimefox (1081)+TX, dimethoate (262)+TX, dinactin (alternative name) (653)+TX, dinex (1089)+TX, dinex-diclexine (1089)+TX, dinobuton (269)+TX, dinocap (270)+TX, dinocap-4 [CCN]+TX, dinocap-6 [CCN]+TX, dinocton (1090)+TX, dinopenton (1092)+TX, dinosulfon (1097)+TX, dinoterbon (1098)+TX, dioxathion (1102)+TX, diphenyl sulfone (IUPAC name) (1103)+TX, disulfiram (alternative name) [CCN]+TX, disulfoton (278)+TX, DNOC (282)+TX, dofenapyn (1113)+TX, doramectin (alternative name) [CCN]+TX, endosulfan (294)+TX, endothion (1121)+TX, EPN (297)+TX, eprinomectin (alternative name) [CCN]+TX, ethion (309)+TX, ethoate-methyl (1134)+TX, etoxazole (320)+TX, etrimfos (1142)+TX, fenazaflor (1147)+TX, fenazaquin (328)+TX, fenbutatin oxide (330)+TX, fenothiocarb (337)+TX, fenpropathrin (342)+TX, fenpyrad (alternative name)+TX, fenpyroximate (345)+TX, fenson (1157)+TX, fentrifanil (1161)+TX, fenvalerate (349)+TX, fipronil (354)+TX, fluacrypyrim (360)+TX, fluazuron (1166)+TX, flubenzimine (1167)+TX, flucycloxuron (366)+TX, flucythrinate (367)+TX, fluenetil (1169)+TX, flufenoxuron (370)+TX, flumethrin (372)+TX, fluorbenside (1174)+TX, fluvalinate (1184)+TX, FMC 1137 (development code) (1185)+TX, formetanate (405)+TX, formetanate hydrochloride (405)+TX, formothion (1192)+TX, formparanate (1193)+TX, gamma-HCH (430)+TX, glyodin (1205)+TX, halfenprox (424)+TX, heptenophos (432)+TX, hexadecyl cyclopropanecarboxylate (IUPAC/Chemical Abstracts name) (1216)+TX, hexythiazox (441)+TX, iodomethane (IUPAC name) (542)+TX, isocarbophos (alternative name) (473)+TX, isopropyl O-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473)+TX, ivermectin (alternative name) [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX, jodfenphos (1248)+TX, lindane (430)+TX, lufenuron (490)+TX, malathion (492)+TX, malonoben (1254)+TX, mecarbam (502)+TX, mephosfolan (1261)+TX, mesulfen (alternative name) [CCN]+TX, methacrifos (1266)+TX, methamidophos (527)+TX, methidathion (529)+TX, methiocarb (530)+TX, methomyl (531)+TX, methyl bromide (537)+TX, metolcarb (550)+TX, mevinphos (556)+TX, mexacarbate (1290)+TX, milbemectin (557)+TX, milbemycin oxime (alternative name) [CCN]+TX, mipafox (1293)+TX, monocrotophos (561)+TX, morphothion (1300)+TX, moxidectin (alternative name) [CCN]+TX, naled (567)+TX, NC-184 (compound code)+TX, NC-512 (compound code)+TX, nifluridide (1309)+TX, nikkomycins (alternative name) [CCN]+TX, nitrilacarb (1313)+TX, nitrilacarb 1:1 zinc chloride complex (1313)+TX, NNI-0101 (compound code)+TX, NNI-0250 (compound code)+TX, omethoate (594)+TX, oxamyl (602)+TX, oxydeprofos (1324)+TX, oxydisulfoton (1325)+TX, pp′-DDT (219)+TX, parathion (615)+TX, permethrin (626)+TX, petroleum oils (alternative name) (628)+TX, phenkapton (1330)+TX, phenthoate (631)+TX, phorate (636)+TX, phosalone (637)+TX, phosfolan (1338)+TX, phosmet (638)+TX, phosphamidon (639)+TX, phoxim (642)+TX, pirimiphos-methyl (652)+TX, polychloroterpenes (traditional name) (1347)+TX, polynactins (alternative name) (653)+TX, proclonol (1350)+TX, profenofos (662)+TX, promacyl (1354)+TX, propargite (671)+TX, propetamphos (673)+TX, propoxur (678)+TX, prothidathion (1360)+TX, prothoate (1362)+TX, pyrethrin I (696)+TX, pyrethrin II (696)+TX, pyrethrins (696)+TX, pyridaben (699)+TX, pyridaphenthion (701)+TX, pyrimidifen (706)+TX, pyrimitate (1370)+TX, quinalphos (711)+TX, quintiofos (1381)+TX, R-1492 (development code) (1382)+TX, RA-17 (development code) (1383)+TX, rotenone (722)+TX, schradan (1389)+TX, sebufos (alternative name)+TX, selamectin (alternative name) [CCN]+TX, SI-0009 (compound code)+TX, sophamide (1402)+TX, spirodiclofen (738)+TX, spiromesifen (739)+TX, SSI-121 (development code) (1404)+TX, sulfiram (alternative name) [CCN]+TX, sulfluramid (750)+TX, sulfotep (753)+TX, sulfur (754)+TX, SZI-121 (development code) (757)+TX, tau-fluvalinate (398)+TX, tebufenpyrad (763)+TX, TEPP (1417)+TX, terbam (alternative name)+TX, tetrachlorvinphos (777)+TX, tetradifon (786)+TX, tetranactin (alternative name) (653)+TX, tetrasul (1425)+TX, thiafenox (alternative name)+TX, thiocarboxime (1431)+TX, thiofanox (800)+TX, thiometon (801)+TX, thioquinox (1436)+TX, thuringiensin (alternative name) [CCN]+TX, triamiphos (1441)+TX, triarathene (1443)+TX, triazophos (820)+TX, triazuron (alternative name)+TX, trichlorfon (824)+TX, trifenofos (1455)+TX, trinactin (alternative name) (653)+TX, vamidothion (847)+TX, vaniliprole [CCN] and YI-5302 (compound code)+TX,
an algicide selected from the group of substances consisting of bethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX, copper sulfate (172)+TX, cybutryne [CCN]+TX, dichlone (1052)+TX, dichlorophen (232)+TX, endothal (295)+TX, fentin (347)+TX, hydrated lime [CCN]+TX, nabam (566)+TX, quinoclamine (714)+TX, quinonamid (1379)+TX, simazine (730)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX,
an anthelmintic selected from the group of substances consisting of abamectin (1)+TX, crufomate (1011)+TX, doramectin (alternative name) [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin (alternative name) [CCN]+TX, ivermectin (alternative name) [CCN]+TX, milbemycin oxime (alternative name) [CCN]+TX, moxidectin (alternative name) [CCN]+TX, piperazine [CCN]+TX, selamectin (alternative name) [CCN]+TX, spinosad (737) and thiophanate (1435)+TX,
an avicide selected from the group of substances consisting of chloralose (127)+TX, endrin (1122)+TX, fenthion (346)+TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745)+TX,
a bactericide selected from the group of substances consisting of 1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222)+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, 8-hydroxyquinoline sulfate (446)+TX, bronopol (97)+TX, copper dioctanoate (IUPAC name) (170)+TX, copper hydroxide (IUPAC name) (169)+TX, cresol [CCN]+TX, dichlorophen (232)+TX, dipyrithione (1105)+TX, dodicin (1112)+TX, fenaminosulf (1144)+TX, formaldehyde (404)+TX, hydrargaphen (alternative name) [CCN]+TX, kasugamycin (483)+TX, kasugamycin hydrochloride hydrate (483)+TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308)+TX, nitrapyrin (580)+TX, octhilinone (590)+TX, oxolinic acid (606)+TX, oxytetracycline (611)+TX, potassium hydroxyquinoline sulfate (446)+TX, probenazole (658)+TX, streptomycin (744)+TX, streptomycin sesquisulfate (744)+TX, tecloftalam (766)+TX, and thiomersal (alternative name) [CCN]+TX,
a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12)+TX, Agrobacterium radiobacter (alternative name) (13)+TX, Amblyseius spp. (alternative name) (19)+TX, Anagrapha falcifera NPV (alternative name) (28)+TX, Anagrus atomus (alternative name) (29)+TX, Aphelinus abdominalis (alternative name) (33)+TX, Aphidius colemani (alternative name) (34)+TX, Aphidoletes aphidimyza (alternative name) (35)+TX, Autographa californica NPV (alternative name) (38)+TX, Bacillus firmus (alternative name) (48)+TX, Bacillus sphaericus Neide (scientific name) (49)+TX, Bacillus thuringiensis Berliner (scientific name) (51)+TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51)+TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51)+TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51)+TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51)+TX, Bacillus thuringiensis subsp. tenebrionis (scientific name) (51)+TX, Beauveria bassiana (alternative name) (53)+TX, Beauveria brongniartii (alternative name) (54)+TX, Chrysoperla carnea (alternative name) (151)+TX, Cryptolaemus montrouzieri (alternative name) (178)+TX, Cydia pomonella GV (alternative name) (191)+TX, Dacnusa sibirica (alternative name) (212)+TX, Diglyphus isaea (alternative name) (254)+TX, Encarsia formosa (scientific name) (293)+TX, Eretmocerus eremicus (alternative name) (300)+TX, Helicoverpa zea NPV (alternative name) (431)+TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433)+TX, Hippodamia convergens (alternative name) (442)+TX, Leptomastix dactylopii (alternative name) (488)+TX, Macrolophus caliginosus (alternative name) (491)+TX, Mamestra brassicae NPV (alternative name) (494)+TX, Metaphycus helvolus (alternative name) (522)+TX, Metarhizium anisopliae var. acridum (scientific name) (523)+TX, Metarhizium anisopliae var. anisopliae (scientific name) (523)+TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575)+TX, Orius spp. (alternative name) (596)+TX, Paecilomyces fumosoroseus (alternative name) (613)+TX, Phytoseiulus persimilis (alternative name) (644)+TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741)+TX, Steinernema bibionis (alternative name) (742)+TX, Steinernema carpocapsae (alternative name) (742)+TX, Steinernema feltiae (alternative name) (742)+TX, Steinernema glaseri (alternative name) (742)+TX, Steinernema riobrave (alternative name) (742)+TX, Steinernema riobravis (alternative name) (742)+TX, Steinernema scapterisci (alternative name) (742)+TX, Steinernema spp. (alternative name) (742)+TX, Trichogramma spp. (alternative name) (826)+TX, Typhlodromus occidentalis (alternative name) (844) and Verticillium lecanii (alternative name) (848)+TX,
a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537)+TX,
a chemosterilant selected from the group of substances consisting of apholate [CCN]+TX, bisazir (alternative name) [CCN]+TX, busulfan (alternative name) [CCN]+TX, diflubenzuron (250)+TX, dimatif (alternative name) [CCN]+TX, hemel [CCN]+TX, hempa [CCN]+TX, metepa [CCN]+TX, methiotepa [CCN]+TX, methyl apholate [CCN]+TX, morzid [CCN]+TX, penfluron (alternative name) [CCN]+TX, tepa [CCN]+TX, thiohempa (alternative name) [CCN]+TX, thiotepa (alternative name) [CCN]+TX, tretamine (alternative name) [CCN] and uredepa (alternative name) [CCN]+TX,
an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (IUPAC name) (222)+TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829)+TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541)+TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate (IUPAC name) (779)+TX, (Z)-dodec-7-en-1-yl acetate (IUPAC name) (285)+TX, (Z)-hexadec-11-enal (IUPAC name) (436)+TX, (Z)-hexadec-11-en-1-yl acetate (IUPAC name) (437)+TX, (Z)-hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438)+TX, (Z)-icos-13-en-10-one (IUPAC name) (448)+TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782)+TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783)+TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283)+TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780)+TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781)+TX, 14-methyloctadec-1-ene (IUPAC name) (545)+TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (IUPAC name) (544)+TX, alpha-multistriatin (alternative name) [CCN]+TX, brevicomin (alternative name) [CCN]+TX, codlelure (alternative name) [CCN]+TX, codlemone (alternative name) (167)+TX, cuelure (alternative name) (179)+TX, disparlure (277)+TX, dodec-8-en-1-yl acetate (IUPAC name) (286)+TX, dodec-9-en-1-yl acetate (IUPAC name) (287)+TX, dodeca-8+TX, 10-dien-1-yl acetate (IUPAC name) (284)+TX, dominicalure (alternative name) [CCN]+TX, ethyl 4-methyloctanoate (IUPAC name) (317)+TX, eugenol (alternative name) [CCN]+TX, frontalin (alternative name) [CCN]+TX, gossyplure (alternative name) (420)+TX, grandlure (421)+TX, grandlure I (alternative name) (421)+TX, grandlure II (alternative name) (421)+TX, grandlure III (alternative name) (421)+TX, grandlure IV (alternative name) (421)+TX, hexalure [CCN]+TX, ipsdienol (alternative name) [CCN]+TX, ipsenol (alternative name) [CCN]+TX, japonilure (alternative name) (481)+TX, lineatin (alternative name) [CCN]+TX, litlure (alternative name) [CCN]+TX, looplure (alternative name) [CCN]+TX, medlure [CCN]+TX, megatomoic acid (alternative name) [CCN]+TX, methyl eugenol (alternative name) (540)+TX, muscalure (563)+TX, octadeca-2,13-dien-1-yl acetate (IUPAC name) (588)+TX, octadeca-3,13-dien-1-yl acetate (IUPAC name) (589)+TX, orfralure (alternative name) [CCN]+TX, oryctalure (alternative name) (317)+TX, ostramone (alternative name) [CCN]+TX, siglure [CCN]+TX, sordidin (alternative name) (736)+TX, sulcatol (alternative name) [CCN]+TX, tetradec-11-en-1-yl acetate (IUPAC name) (785)+TX, trimedlure (839)+TX, trimedlure A (alternative name) (839)+TX, trimedlure B1 (alternative name) (839)+TX, trimedlure B2 (alternative name) (839)+TX, trimedlure C (alternative name) (839) and trunc-call (alternative name) [CCN]+TX,
an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591)+TX, butopyronoxyl (933)+TX, butoxy(polypropylene glycol) (936)+TX, dibutyl adipate (IUPAC name) (1046)+TX, dibutyl phthalate (1047)+TX, dibutyl succinate (IUPAC name) (1048)+TX, diethyltoluamide [CCN]+TX, dimethyl carbate [CCN]+TX, dimethyl phthalate [CCN]+TX, ethyl hexanediol (1137)+TX, hexamide [CCN]+TX, methoquin-butyl (1276)+TX, methylneodecanamide [CCN]+TX, oxamate [CCN] and picaridin [CCN]+TX,
an insecticide selected from the group of substances consisting of 1-dichloro-1-nitroethane (IUPAC/Chemical Abstracts name) (1058)+TX, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (IUPAC name) (1056), +TX, 1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062)+TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063)+TX, 1-bromo-2-chloroethane (IUPAC/Chemical Abstracts name) (916)+TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate (IUPAC name) (1451)+TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate (IUPAC name) (1066)+TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate (IUPAC/Chemical Abstracts name) (1109)+TX, 2-(2-butoxyethoxy)ethyl thiocyanate (IUPAC/Chemical Abstracts name) (935)+TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate (IUPAC/Chemical Abstracts name) (1084)+TX, 2-(4-chloro-3,5-xylyloxy)ethanol (IUPAC name) (986)+TX, 2-chlorovinyl diethyl phosphate (IUPAC name) (984)+TX, 2-imidazolidone (IUPAC name) (1225)+TX, 2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate (IUPAC name) (1284)+TX, 2-thiocyanatoethyl laurate (IUPAC name) (1433)+TX, 3-bromo-1-chloroprop-1-ene (IUPAC name) (917)+TX, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate (IUPAC name) (1283)+TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate (IUPAC name) (1285)+TX, 5,5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate (IUPAC name) (1085)+TX, abamectin (1)+TX, acephate (2)+TX, acetamiprid (4)+TX, acethion (alternative name) [CCN]+TX, acetoprole [CCN]+TX, acrinathrin (9)+TX, acrylonitrile (IUPAC name) (861)+TX, alanycarb (15)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, aldrin (864)+TX, allethrin (17)+TX, allosamidin (alternative name) [CCN]+TX, allyxycarb (866)+TX, alpha-cypermethrin (202)+TX, alpha-ecdysone (alternative name) [CCN]+TX, aluminium phosphide (640)+TX, amidithion (870)+TX, amidothioate (872)+TX, aminocarb (873)+TX, amiton (875)+TX, amiton hydrogen oxalate (875)+TX, amitraz (24)+TX, anabasine (877)+TX, athidathion (883)+TX, AVI 382 (compound code)+TX, AZ 60541 (compound code)+TX, azadirachtin (alternative name) (41)+TX, azamethiphos (42)+TX, azinphos-ethyl (44)+TX, azinphos-methyl (45)+TX, azothoate (889)+TX, Bacillus thuringiensis delta endotoxins (alternative name) (52)+TX, barium hexafluorosilicate (alternative name) [CCN]+TX, barium polysulfide (IUPAC/Chemical Abstracts name) (892)+TX, barthrin [CCN]+TX, Bayer 22/190 (development code) (893)+TX, Bayer 22408 (development code) (894)+TX, bendiocarb (58)+TX, benfuracarb (60)+TX, bensultap (66)+TX, benzovindiflupyr+TX, beta-cyfluthrin (194)+TX, beta-cypermethrin (203)+TX, bifenthrin (76)+TX, bioallethrin (78)+TX, bioallethrin S-cyclopentenyl isomer (alternative name) (79)+TX, bioethanomethrin [CCN]+TX, biopermethrin (908)+TX, bioresmethrin (80)+TX, bis(2-chloroethyl) ether (IUPAC name) (909)+TX, bistrifluron (83)+TX, borax (86)+TX, brofenvalerate (alternative name)+TX, bromfenvinfos (914)+TX, bromocyclen (918)+TX, bromo-DDT (alternative name) [CCN]+TX, bromophos (920)+TX, bromophos-ethyl (921)+TX, bufencarb (924)+TX, buprofezin (99)+TX, butacarb (926)+TX, butathiofos (927)+TX, butocarboxim (103)+TX, butonate (932)+TX, butoxycarboxim (104)+TX, butylpyridaben (alternative name)+TX, cadusafos (109)+TX, calcium arsenate [CCN]+TX, calcium cyanide (444)+TX, calcium polysulfide (IUPAC name) (111)+TX, camphechlor (941)+TX, carbanolate (943)+TX, carbaryl (115)+TX, carbofuran (118)+TX, carbon disulfide (IUPAC/Chemical Abstracts name) (945)+TX, carbon tetrachloride (IUPAC name) (946)+TX, carbophenothion (947)+TX, carbosulfan (119)+TX, cartap (123)+TX, cartap hydrochloride (123)+TX, cevadine (alternative name) (725)+TX, chlorbicyclen (960)+TX, chlordane (128)+TX, chlordecone (963)+TX, chlordimeform (964)+TX, chlordimeform hydrochloride (964)+TX, chlorethoxyfos (129)+TX, chlorfenapyr (130)+TX, chlorfenvinphos (131)+TX, chlorfluazuron (132)+TX, chlormephos (136)+TX, chloroform [CCN]+TX, chloropicrin (141)+TX, chlorphoxim (989)+TX, chlorprazophos (990)+TX, chlorpyrifos (145)+TX, chlorpyrifos-methyl (146)+TX, chlorthiophos (994)+TX, chromafenozide (150)+TX, cinerin 1 (696)+TX, cinerin II (696)+TX, cinerins (696)+TX, cis-resmethrin (alternative name)+TX, cismethrin (80)+TX, clocythrin (alternative name)+TX, cloethocarb (999)+TX, closantel (alternative name) [CCN]+TX, clothianidin (165)+TX, copper acetoarsenite [CCN]+TX, copper arsenate [CCN]+TX, copper oleate [CCN]+TX, coumaphos (174)+TX, coumithoate (1006)+TX, crotamiton (alternative name) [CCN]+TX, crotoxyphos (1010)+TX, crufomate (1011)+TX, cryolite (alternative name) (177)+TX, CS 708 (development code) (1012)+TX, cyanofenphos (1019)+TX, cyanophos (184)+TX, cyanthoate (1020)+TX, cyclethrin [CCN]+TX, cycloprothrin (188)+TX, cyfluthrin (193)+TX, cyhalothrin (196)+TX, cypermethrin (201)+TX, cyphenothrin (206)+TX, cyromazine (209)+TX, cythioate (alternative name) [CCN]+TX, d-limonene (alternative name) [CCN]+TX, d-tetramethrin (alternative name) (788)+TX, DAEP (1031)+TX, dazomet (216)+TX, DDT (219)+TX, decarbofuran (1034)+TX, deltamethrin (223)+TX, demephion (1037)+TX, demephion-O (1037)+TX, demephion-S (1037)+TX, demeton (1038)+TX, demeton-methyl (224)+TX, demeton-O (1038)+TX, demeton-O-methyl (224)+TX, demeton-S (1038)+TX, demeton-S-methyl (224)+TX, demeton-S-methylsulphon (1039)+TX, diafenthiuron (226)+TX, dialifos (1042)+TX, diamidafos (1044)+TX, diazinon (227)+TX, dicapthon (1050)+TX, dichlofenthion (1051)+TX, dichlorvos (236)+TX, dicliphos (alternative name)+TX, dicresyl (alternative name) [CCN]+TX, dicrotophos (243)+TX, dicyclanil (244)+TX, dieldrin (1070)+TX, diethyl 5-methylpyrazol-3-yl phosphate (IUPAC name) (1076)+TX, diflubenzuron (250)+TX, dilor (alternative name) [CCN]+TX, dimefluthrin [CCN]+TX, dimefox (1081)+TX, dimetan (1085)+TX, dimethoate (262)+TX, dimethrin (1083)+TX, dimethylvinphos (265)+TX, dimetilan (1086)+TX, dinex (1089)+TX, dinex-diclexine (1089)+TX, dinoprop (1093)+TX, dinosam (1094)+TX, dinoseb (1095)+TX, dinotefuran (271)+TX, diofenolan (1099)+TX, dioxabenzofos (1100)+TX, dioxacarb (1101)+TX, dioxathion (1102)+TX, disulfoton (278)+TX, dithicrofos (1108)+TX, DNOC (282)+TX, doramectin (alternative name) [CCN]+TX, DSP (1115)+TX, ecdysterone (alternative name) [CCN]+TX, EI 1642 (development code) (1118)+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, EMPC (1120)+TX, empenthrin (292)+TX, endosulfan (294)+TX, endothion (1121)+TX, endrin (1122)+TX, EPBP (1123)+TX, EPN (297)+TX, epofenonane (1124)+TX, eprinomectin (alternative name) [CCN]+TX, esfenvalerate (302)+TX, etaphos (alternative name) [CCN]+TX, ethiofencarb (308)+TX, ethion (309)+TX, ethiprole (310)+TX, ethoate-methyl (1134)+TX, ethoprophos (312)+TX, ethyl formate (IUPAC name) [CCN]+TX, ethyl-DDD (alternative name) (1056)+TX, ethylene dibromide (316)+TX, ethylene dichloride (chemical name) (1136)+TX, ethylene oxide [CCN]+TX, etofenprox (319)+TX, etrimfos (1142)+TX, EXD (1143)+TX, famphur (323)+TX, fenamiphos (326)+TX, fenazaflor (1147)+TX, fenchlorphos (1148)+TX, fenethacarb (1149)+TX, fenfluthrin (1150)+TX, fenitrothion (335)+TX, fenobucarb (336)+TX, fenoxacrim (1153)+TX, fenoxycarb (340)+TX, fenpirithrin (1155)+TX, fenpropathrin (342)+TX, fenpyrad (alternative name)+TX, fensulfothion (1158)+TX, fenthion (346)+TX, fenthion-ethyl [CCN]+TX, fenvalerate (349)+TX, fipronil (354)+TX, flonicamid (358)+TX, flubendiamide (CAS. Reg. No.: 272451-65-7)+TX, flucofuron (1168)+TX, flucycloxuron (366)+TX, flucythrinate (367)+TX, fluenetil (1169)+TX, flufenerim [CCN]+TX, flufenoxuron (370)+TX, flufenprox (1171)+TX, flumethrin (372)+TX, fluvalinate (1184)+TX, FMC 1137 (development code) (1185)+TX, fonofos (1191)+TX, formetanate (405)+TX, formetanate hydrochloride (405)+TX, formothion (1192)+TX, formparanate (1193)+TX, fosmethilan (1194)+TX, fospirate (1195)+TX, fosthiazate (408)+TX, fosthietan (1196)+TX, furathiocarb (412)+TX, furethrin (1200)+TX, gamma-cyhalothrin (197)+TX, gamma-HCH (430)+TX, guazatine (422)+TX, guazatine acetates (422)+TX, GY-81 (development code) (423)+TX, halfenprox (424)+TX, halofenozide (425)+TX, HCH (430)+TX, HEOD (1070)+TX, heptachlor (1211)+TX, heptenophos (432)+TX, heterophos [CCN]+TX, hexaflumuron (439)+TX, HHDN (864)+TX, hydramethylnon (443)+TX, hydrogen cyanide (444)+TX, hydroprene (445)+TX, hyquincarb (1223)+TX, imidacloprid (458)+TX, imiprothrin (460)+TX, indoxacarb (465)+TX, iodomethane (IUPAC name) (542)+TX, IPSP (1229)+TX, isazofos (1231)+TX, isobenzan (1232)+TX, isocarbophos (alternative name) (473)+TX, isodrin (1235)+TX, isofenphos (1236)+TX, isolane (1237)+TX, isoprocarb (472)+TX, isopropyl O-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473)+TX, isoprothiolane (474)+TX, isothioate (1244)+TX, isoxathion (480)+TX, ivermectin (alternative name) [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX, jodfenphos (1248)+TX, juvenile hormone I (alternative name) [CCN]+TX, juvenile hormone II (alternative name) [CCN]+TX, juvenile hormone Ill (alternative name) [CCN]+TX, kelevan (1249)+TX, kinoprene (484)+TX, lambda-cyhalothrin (198)+TX, lead arsenate [CCN]+TX, lepimectin (CCN)+TX, leptophos (1250)+TX, lindane (430)+TX, lirimfos (1251)+TX, lufenuron (490)+TX, lythidathion (1253)+TX, m-cumenyl methylcarbamate (IUPAC name) (1014)+TX, magnesium phosphide (IUPAC name) (640)+TX, malathion (492)+TX, malonoben (1254)+TX, mazidox (1255)+TX, mecarbam (502)+TX, mecarphon (1258)+TX, menazon (1260)+TX, mephosfolan (1261)+TX, mercurous chloride (513)+TX, mesulfenfos (1263)+TX, metaflumizone (CCN)+TX, metam (519)+TX, metam-potassium (alternative name) (519)+TX, metam-sodium (519)+TX, methacrifos (1266)+TX, methamidophos (527)+TX, methanesulfonyl fluoride (IUPAC/Chemical Abstracts name) (1268)+TX, methidathion (529)+TX, methiocarb (530)+TX, methocrotophos (1273)+TX, methomyl (531)+TX, methoprene (532)+TX, methoquin-butyl (1276)+TX, methothrin (alternative name) (533)+TX, methoxychlor (534)+TX, methoxyfenozide (535)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, methylchloroform (alternative name) [CCN]+TX, methylene chloride [CCN]+TX, metofluthrin [CCN]+TX, metolcarb (550)+TX, metoxadiazone (1288)+TX, mevinphos (556)+TX, mexacarbate (1290)+TX, milbemectin (557)+TX, milbemycin oxime (alternative name) [CCN]+TX, mipafox (1293)+TX, mirex (1294)+TX, monocrotophos (561)+TX, morphothion (1300)+TX, moxidectin (alternative name) [CCN]+TX, naftalofos (alternative name) [CCN]+TX, naled (567)+TX, naphthalene (IUPAC/Chemical Abstracts name) (1303)+TX, NC-170 (development code) (1306)+TX, NC-184 (compound code)+TX, nicotine (578)+TX, nicotine sulfate (578)+TX, nifluridide (1309)+TX, nitenpyram (579)+TX, nithiazine (1311)+TX, nitrilacarb (1313)+TX, nitrilacarb 1:1 zinc chloride complex (1313)+TX, NNI-0101 (compound code)+TX, NNI-0250 (compound code)+TX, nornicotine (traditional name) (1319)+TX, novaluron (585)+TX, noviflumuron (586)+TX, 0-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate (IUPAC name) (1057)+TX, O,O-diethyl O-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate (IUPAC name) (1074)+TX, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate (IUPAC name) (1075)+TX, O,O,O′,O′-tetrapropyl dithiopyrophosphate (IUPAC name) (1424)+TX, oleic acid (IUPAC name) (593)+TX, omethoate (594)+TX, oxamyl (602)+TX, oxydemeton-methyl (609)+TX, oxydeprofos (1324)+TX, oxydisulfoton (1325)+TX, pp′-DDT (219)+TX, para-dichlorobenzene [CCN]+TX, parathion (615)+TX, parathion-methyl (616)+TX, penfluron (alternative name) [CCN]+TX, pentachlorophenol (623)+TX, pentachlorophenyl laurate (IUPAC name) (623)+TX, permethrin (626)+TX, petroleum oils (alternative name) (628)+TX, PH 60-38 (development code) (1328)+TX, phenkapton (1330)+TX, phenothrin (630)+TX, phenthoate (631)+TX, phorate (636)+TX, phosalone (637)+TX, phosfolan (1338)+TX, phosmet (638)+TX, phosnichlor (1339)+TX, phosphamidon (639)+TX, phosphine (IUPAC name) (640)+TX, phoxim (642)+TX, phoxim-methyl (1340)+TX, pirimetaphos (1344)+TX, pirimicarb (651)+TX, pirimiphos-ethyl (1345)+TX, pirimiphos-methyl (652)+TX, polychlorodicyclopentadiene isomers (IUPAC name) (1346)+TX, polychloroterpenes (traditional name) (1347)+TX, potassium arsenite [CCN]+TX, potassium thiocyanate [CCN]+TX, prallethrin (655)+TX, precocene I (alternative name) [CCN]+TX, precocene II (alternative name) [CCN]+TX, precocene III (alternative name) [CCN]+TX, primidophos (1349)+TX, profenofos (662)+TX, profluthrin [CCN]+TX, promacyl (1354)+TX, promecarb (1355)+TX, propaphos (1356)+TX, propetamphos (673)+TX, propoxur (678)+TX, prothidathion (1360)+TX, prothiofos (686)+TX, prothoate (1362)+TX, protrifenbute [CCN]+TX, pymetrozine (688)+TX, pyraclofos (689)+TX, pyrazophos (693)+TX, pyresmethrin (1367)+TX, pyrethrin I (696)+TX, pyrethrin II (696)+TX, pyrethrins (696)+TX, pyridaben (699)+TX, pyridalyl (700)+TX, pyridaphenthion (701)+TX, pyrimidifen (706)+TX, pyrimitate (1370)+TX, pyriproxyfen (708)+TX, quassia (alternative name) [CCN]+TX, quinalphos (711)+TX, quinalphos-methyl (1376)+TX, quinothion (1380)+TX, quintiofos (1381)+TX, R-1492 (development code) (1382)+TX, rafoxanide (alternative name) [CCN]+TX, resmethrin (719)+TX, rotenone (722)+TX, RU 15525 (development code) (723)+TX, RU 25475 (development code) (1386)+TX, ryania (alternative name) (1387)+TX, ryanodine (traditional name) (1387)+TX, sabadilla (alternative name) (725)+TX, schradan (1389)+TX, sebufos (alternative name)+TX, selamectin (alternative name) [CCN]+TX, SI-0009 (compound code)+TX, SI-0205 (compound code)+TX, SI-0404 (compound code)+TX, SI-0405 (compound code)+TX, silafluofen (728)+TX, SN 72129 (development code) (1397)+TX, sodium arsenite [CCN]+TX, sodium cyanide (444)+TX, sodium fluoride (IUPAC/Chemical Abstracts name) (1399)+TX, sodium hexafluorosilicate (1400)+TX, sodium pentachlorophenoxide (623)+TX, sodium selenate (IUPAC name) (1401)+TX, sodium thiocyanate [CCN]+TX, sophamide (1402)+TX, spinosad (737)+TX, spiromesifen (739)+TX, spirotetrmat (CCN)+TX, sulcofuron (746)+TX, sulcofuron-sodium (746)+TX, sulfluramid (750)+TX, sulfotep (753)+TX, sulfuryl fluoride (756)+TX, sulprofos (1408)+TX, tar oils (alternative name) (758)+TX, tau-fluvalinate (398)+TX, tazimcarb (1412)+TX, TDE (1414)+TX, tebufenozide (762)+TX, tebufenpyrad (763)+TX, tebupirimfos (764)+TX, teflubenzuron (768)+TX, tefluthrin (769)+TX, temephos (770)+TX, TEPP (1417)+TX, terallethrin (1418)+TX, terbam (alternative name)+TX, terbufos (773)+TX, tetrachloroethane [CCN]+TX, tetrachlorvinphos (777)+TX, tetramethrin (787)+TX, theta-cypermethrin (204)+TX, thiacloprid (791)+TX, thiafenox (alternative name)+TX, thiamethoxam (792)+TX, thicrofos (1428)+TX, thiocarboxime (1431)+TX, thiocyclam (798)+TX, thiocyclam hydrogen oxalate (798)+TX, thiodicarb (799)+TX, thiofanox (800)+TX, thiometon (801)+TX, thionazin (1434)+TX, thiosultap (803)+TX, thiosultap-sodium (803)+TX, thuringiensin (alternative name) [CCN]+TX, tolfenpyrad (809)+TX, tralomethrin (812)+TX, transfluthrin (813)+TX, transpermethrin (1440)+TX, triamiphos (1441)+TX, triazamate (818)+TX, triazophos (820)+TX, triazuron (alternative name)+TX, trichlorfon (824)+TX, trichlormetaphos-3 (alternative name) [CCN]+TX, trichloronat (1452)+TX, trifenofos (1455)+TX, triflumuron (835)+TX, trimethacarb (840)+TX, triprene (1459)+TX, vamidothion (847)+TX, vaniliprole [CCN]+TX, veratridine (alternative name) (725)+TX, veratrine (alternative name) (725)+TX, XMC (853)+TX, xylylcarb (854)+TX, YI-5302 (compound code)+TX, zeta-cypermethrin (205)+TX, zetamethrin (alternative name)+TX, zinc phosphide (640)+TX, zolaprofos (1469) and ZXI 8901 (development code) (858)+TX, cyantraniliprole [736994-63-19+TX, chlorantraniliprole [500008-45-7]+TX, cyenopyrafen [560121-52-0]+TX, cyflumetofen [400882-07-7]+TX, pyrifluquinazon [337458-27-2]+TX, spinetoram [187166-40-1+187166-15-0]+TX, spirotetramat [203313-25-1]+TX, sulfoxaflor [946578-00-3]+TX, flufiprole [704886-18-0]+TX, meperfluthrin [915288-13-0]+TX, tetramethylfluthrin [84937-88-2]+TX, triflumezopyrim (disclosed in WO 2012/092115)+TX,
a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913)+TX, bromoacetamide [CCN]+TX, calcium arsenate [CCN]+TX, cloethocarb (999)+TX, copper acetoarsenite [CCN]+TX, copper sulfate (172)+TX, fentin (347)+TX, ferric phosphate (IUPAC name) (352)+TX, metaldehyde (518)+TX, methiocarb (530)+TX, niclosamide (576)+TX, niclosamide-olamine (576)+TX, pentachlorophenol (623)+TX, sodium pentachlorophenoxide (623)+TX, tazimcarb (1412)+TX, thiodicarb (799)+TX, tributyltin oxide (913)+TX, trifenmorph (1454)+TX, trimethacarb (840)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX, pyriprole [394730-71-3]+TX,
a nematicide selected from the group of substances consisting of AKD-3088 (compound code)+TX, 1,2-dibromo-3-chloropropane (IUPAC/Chemical Abstracts name) (1045)+TX, 1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062)+TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063)+TX, 1,3-dichloropropene (233)+TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC/Chemical Abstracts name) (1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPAC name) (1286)+TX, 6-isopentenylaminopurine (alternative name) (210)+TX, abamectin (1)+TX, acetoprole [CCN]+TX, alanycarb (15)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, AZ 60541 (compound code)+TX, benclothiaz [CCN]+TX, benomyl (62)+TX, butylpyridaben (alternative name)+TX, cadusafos (109)+TX, carbofuran (118)+TX, carbon disulfide (945)+TX, carbosulfan (119)+TX, chloropicrin (141)+TX, chlorpyrifos (145)+TX, cloethocarb (999)+TX, cytokinins (alternative name) (210)+TX, dazomet (216)+TX, DBCP (1045)+TX, DCIP (218)+TX, diamidafos (1044)+TX, dichlofenthion (1051)+TX, dicliphos (alternative name)+TX, dimethoate (262)+TX, doramectin (alternative name) [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin (alternative name) [CCN]+TX, ethoprophos (312)+TX, ethylene dibromide (316)+TX, fenamiphos (326)+TX, fenpyrad (alternative name)+TX, fensulfothion (1158)+TX, fosthiazate (408)+TX, fosthietan (1196)+TX, furfural (alternative name) [CCN]+TX, GY-81 (development code) (423)+TX, heterophos [CCN]+TX, iodomethane (IUPAC name) (542)+TX, isamidofos (1230)+TX, isazofos (1231)+TX, ivermectin (alternative name) [CCN]+TX, kinetin (alternative name) (210)+TX, mecarphon (1258)+TX, metam (519)+TX, metam-potassium (alternative name) (519)+TX, metam-sodium (519)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, milbemycin oxime (alternative name) [CCN]+TX, moxidectin (alternative name) [CCN]+TX, Myrothecium verrucaria composition (alternative name) (565)+TX, NC-184 (compound code)+TX, oxamyl (602)+TX, phorate (636)+TX, phosphamidon (639)+TX, phosphocarb [CCN]+TX, sebufos (alternative name)+TX, selamectin (alternative name) [CCN]+TX, spinosad (737)+TX, terbam (alternative name)+TX, terbufos (773)+TX, tetrachlorothiophene (IUPAC/Chemical Abstracts name) (1422)+TX, thiafenox (alternative name)+TX, thionazin (1434)+TX, triazophos (820)+TX, triazuron (alternative name)+TX, xylenols [CCN]+TX, YI-5302 (compound code) and zeatin (alternative name) (210)+TX, fluensulfone [318290-98-1]+TX,
a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580)+TX,
a plant activator selected from the group of substances consisting of acibenzolar (6)+TX, acibenzolar-S-methyl (6)+TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720)+TX,
a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, alpha-chlorohydrin [CCN]+TX, aluminium phosphide (640)+TX, antu (880)+TX, arsenous oxide (882)+TX, barium carbonate (891)+TX, bisthiosemi (912)+TX, brodifacoum (89)+TX, bromadiolone (91)+TX, bromethalin (92)+TX, calcium cyanide (444)+TX, chloralose (127)+TX, chlorophacinone (140)+TX, cholecalciferol (alternative name) (850)+TX, coumachlor (1004)+TX, coumafuryl (1005)+TX, coumatetralyl (175)+TX, crimidine (1009)+TX, difenacoum (246)+TX, difethialone (249)+TX, diphacinone (273)+TX, ergocalciferol (301)+TX, flocoumafen (357)+TX, fluoroacetamide (379)+TX, flupropadine (1183)+TX, flupropadine hydrochloride (1183)+TX, gamma-HCH (430)+TX, HCH (430)+TX, hydrogen cyanide (444)+TX, iodomethane (IUPAC name) (542)+TX, lindane (430)+TX, magnesium phosphide (IUPAC name) (640)+TX, methyl bromide (537)+TX, norbormide (1318)+TX, phosacetim (1336)+TX, phosphine (IUPAC name) (640)+TX, phosphorus [CCN]+TX, pindone (1341)+TX, potassium arsenite [CCN]+TX, pyrinuron (1371)+TX, scilliroside (1390)+TX, sodium arsenite [CCN]+TX, sodium cyanide (444)+TX, sodium fluoro-acetate (735)+TX, strychnine (745)+TX, thallium sulfate [CCN]+TX, warfarin (851) and zinc phosphide (640)+TX,
a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934)+TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903)+TX, farnesol with nerolidol (alternative name) (324)+TX, MB-599 (development code) (498)+TX, MGK 264 (development code) (296)+TX, piperonyl butoxide (649)+TX, piprotal (1343)+TX, propyl isomer (1358)+TX, S421 (development code) (724)+TX, sesamex (1393)+TX, sesasmolin (1394) and sulfoxide (1406)+TX,
an animal repellent selected from the group of substances consisting of anthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX, copper oxychloride (171)+TX, diazinon (227)+TX, dicyclopentadiene (chemical name) (1069)+TX, guazatine (422)+TX, guazatine acetates (422)+TX, methiocarb (530)+TX, pyridin-4-amine (IUPAC name) (23)+TX, thiram (804)+TX, trimethacarb (840)+TX, zinc naphthenate [CCN] and ziram (856)+TX,
a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN]+TX,
a wound protectant selected from the group of substances consisting of mercuric oxide (512)+TX, octhilinone (590) and thiophanate-methyl (802)+TX,
and biologically active compounds selected from the group consisting of azaconazole (60207-31-0]+TX, bitertanol [70585-36-3]+TX, bromuconazole [116255-48-2]+TX, cyproconazole [94361-06-5]+TX, difenoconazole [119446-68-3]+TX, diniconazole [83657-24-3]+TX, epoxiconazole [106325-08-0]+TX, fenbuconazole [114369-43-6]+TX, fluquinconazole [136426-54-5]+TX, flusilazole [85509-19-9]+TX, flutriafol [76674-21-0]+TX, hexaconazole [79983-71-4]+TX, imazalil [35554-44-0]+TX, imibenconazole [86598-92-7]+TX, ipconazole [125225-28-7]+TX, metconazole [125116-23-6]+TX, myclobutanil [88671-89-0]+TX, pefurazoate [101903-30-4]+TX, penconazole [66246-88-6]+TX, prothioconazole [178928-70-6]+TX, pyrifenox [88283-41-4]+TX, prochloraz [67747-09-5]+TX, propiconazole [60207-90-1]+TX, simeconazole [149508-90-7]+TX, tebuconazole [107534-96-3]+TX, tetraconazole [112281-77-3]+TX, triadimefon [43121-43-3]+TX, triadimenol [55219-65-3]+TX, triflumizole [99387-89-0]+TX, triticonazole [131983-72-7]+TX, ancymidol [12771-68-5]+TX, fenarimol [60168-88-9]+TX, nuarimol [63284-71-9]+TX, bupirimate [41483-43-6]+TX, dimethirimol [5221-53-4]+TX, ethirimol [23947-60-6]+TX, dodemorph [1593-77-7]+TX, fenpropidine [67306-00-7]+TX, fenpropimorph [67564-91-4]+TX, spiroxamine [118134-30-8]+TX, tridemorph [81412-43-3]+TX, cyprodinil [121552-61-2]+TX, mepanipyrim [110235-47-7]+TX, pyrimethanil [53112-28-0]+TX, fenpiclonil [74738-17-3]+TX, fludioxonil [131341-86-1]+TX, benalaxyl [71626-11-4]+TX, furalaxyl [57646-30-7]+TX, metalaxyl [57837-19-1]+TX, R-metalaxyl [70630-17-0]+TX, ofurace [58810-48-3]+TX, oxadixyl [77732-09-3]+TX, benomyl [17804-35-2]+TX, carbendazim [10605-21-7]+TX, debacarb [62732-91-6]+TX, fuberidazole [3878-19-1]+TX, thiabendazole [148-79-8]+TX, chlozolinate [84332-86-5]+TX, dichlozoline [24201-58-9]+TX, iprodione [36734-19-7]+TX, myclozoline [54864-61-8]+TX, procymidone [32809-16-8]+TX, vinclozoline [50471-44-8]+TX, boscalid [188425-85-6]+TX, carboxin [5234-68-4]+TX, fenfuram [24691-80-3]+TX, flutolanil [66332-96-5]+TX, mepronil [55814-41-0]+TX, oxycarboxin [5259-88-1]+TX, penthiopyrad [183675-82-3]+TX, thifluzamide [130000-40-7]+TX, guazatine [108173-90-6]+TX, dodine [2439-10-3] [112-65-2] (free base)+TX, iminoctadine [13516-27-3]+TX, azoxystrobin [131860-33-8]+TX, dimoxystrobin [149961-52-4]+TX, enestroburin {Proc. BCPC, Int. Congr., Glasgow, 2003, 1, 93}+TX, fluoxastrobin [361377-29-9]+TX, kresoxim-methyl [143390-89-0]+TX, metominostrobin [133408-50-1]+TX, trifloxystrobin [141517-21-7]+TX, orysastrobin [248593-16-0]+TX, picoxystrobin [117428-22-5]+TX, pyraclostrobin [175013-18-0]+TX, ferbam [14484-64-1]+TX, mancozeb [8018-01-7]+TX, maneb [12427-38-2]+TX, metiram [9006-42-2]+TX, propineb [12071-83-9]+TX, thiram [137-26-8]+TX, zineb [12122-67-7]+TX, ziram [137-30-4]+TX, captafol [2425-06-1]+TX, captan [133-06-2]+TX, dichlofluanid [1085-98-9]+TX, fluoroimide [41205-21-4]+TX, folpet [133-07-3]+TX, tolylfluanid [731-27-1]+TX, bordeaux mixture [8011-63-0]+TX, copperhydroxid [20427-59-2]+TX, copperoxychlorid [1332-40-7]+TX, coppersulfat [7758-98-7]+TX, copperoxid [1317-39-1]+TX, mancopper [53988-93-5]+TX, oxine-copper [10380-28-6]+TX, dinocap [131-72-6]+TX, nitrothal-isopropyl [10552-74-6]+TX, edifenphos [17109-49-8]+TX, iprobenphos [26087-47-8]+TX, isoprothiolane [50512-35-1]+TX, phosdiphen [36519-00-3]+TX, pyrazophos [13457-18-6]+TX, tolclofos-methyl [57018-04-9]+TX, acibenzolar-S-methyl [135158-54-2]+TX, anilazine [101-05-3]+TX, benthiavalicarb [413615-35-7]+TX, blasticidin-S [2079-00-7]+TX, chinomethionat [2439-01-2]+TX, chloroneb [2675-77-6]+TX, chlorothalonil [1897-45-6]+TX, cyflufenamid [180409-60-3]+TX, cymoxanil [57966-95-7]+TX, dichlone [117-80-6]+TX, diclocymet [139920-32-4]+TX, diclomezine [62865-36-5]+TX, dicloran [99-30-9]+TX, diethofencarb [87130-20-9]+TX, dimethomorph [110488-70-5]+TX, SYP-LI90 (Flumorph) [211867-47-9]+TX, dithianon [3347-22-6]+TX, ethaboxam [162650-77-3]+TX, etridiazole [2593-15-9]+TX, famoxadone [131807-57-3]+TX, fenamidone [161326-34-7]+TX, fenoxanil [115852-48-7]+TX, fentin [668-34-8]+TX, ferimzone [89269-64-7]+TX, fluazinam [79622-59-6]+TX, fluopicolide [239110-15-7]+TX, flusulfamide [106917-52-6]+TX, fenhexamid [126833-17-8]+TX, fosetyl-aluminium [39148-24-8]+TX, hymexazol [10004-44-1]+TX, iprovalicarb [140923-17-7]+TX, IKF-916 (Cyazofamid) [120116-88-3]+TX, kasugamycin [6980-18-3]+TX, methasulfocarb [66952-49-6]+TX, metrafenone [220899-03-6]+TX, pencycuron [66063-05-6]+TX, phthalide [27355-22-2]+TX, polyoxins [11113-80-7]+TX, probenazole [27605-76-1]+TX, propamocarb [25606-41-1]+TX, proquinazid [189278-12-4]+TX, pyroquilon [57369-32-1]+TX, quinoxyfen [124495-18-7]+TX, quintozene [82-68-8]+TX, sulfur [7704-34-9]+TX, tiadinil [223580-51-6]+TX, triazoxide [72459-58-6]+TX, tricyclazole [41814-78-2]+TX, triforine [26644-46-2]+TX, validamycin [37248-47-8]+TX, zoxamide (RH7281) [156052-68-5]+TX, mandipropamid [374726-62-2]+TX, isopyrazam [881685-58-1]+TX, sedaxane [874967-67-6]+TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide (dislosed in WO 2007/048556)+TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3′,4′,5′-trifluoro-biphenyl-2-yl)-amide (disclosed in WO 2006/087343)+TX, [(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a, 12b-trimethyl-11-oxo-9-(3-pyridinyl)-2H,11Hnaphtho[2,1-b]pyrano[3,4-e]pyran-4-yl]methyl-cyclopropanecarboxylate [915972-17-7]+TX and 1,3,5-trimethyl-N-(2-methyl-1-oxopropyl)-N-[3-(2-methylpropyl)-4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole-4-carboxamide [926914-55-8]+TX.
The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in “The Pesticide Manual” [The Pesticide Manual—A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound “abamectin” is described under entry number (1). Where “[CCN]” is added hereinabove to the particular compound, the compound in question is included in the “Compendium of Pesticide Common Names”, which is accessible on the internet [A. Wood; Compendium of Pesticide Common Names, Copyright © 1995-2004]; for example, the compound “acetoprole” is described under the internet address http://www.alanwood.net/pesticides/acetoprole.html.
Most of the active ingredients described above are referred to hereinabove by a so-called “common name”, the relevant “ISO common name” or another “common name” being used in individual cases. If the designation is not a “common name”, the nature of the designation used instead is given in round brackets for the particular compound; in that case, the IUPAC name, the IUPAC/Chemical Abstracts name, a “chemical name”, a “traditional name”, a “compound name” or a “develoment code” is used or, if neither one of those designations nor a “common name” is used, an “alternative name” is employed. “CAS Reg. No” means the Chemical Abstracts Registry Number.
The active ingredient mixture of the compounds of formula (I) selected from a compound described in one of Tables 1A to 30A, 1B to 29B, 1C to 33C, 1D to 27D or 1E to 27E (below), or one of Tables T1a, T1b, T2a, T2b, T3a, T3b, T4a, T4b, T5a or T5b (below) and an active ingredient as described above are preferably in a mixing ratio of from 100:1 to 1:6000, especially from 50:1 to 1:50, more especially in a ratio of from 20:1 to 1:20, even more especially from 10:1 to 1:10, very especially from 5:1 and 1:5, special preference being given to a ratio of from 2:1 to 1:2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750. Those mixing ratios are by weight.
The mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
The mixtures comprising a compound of formula (I) selected from one of Tables 1A to 30A, 1B to 29B, 1C to 33C, 1D to 27D or 1E to 27E (below), or one of Tables T1a, T1b, T2a, T2b, T3a, T3b, T4a, T4b, T5a or T5b (below) and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the compounds of formula (I) selected from Tables 1A to 30A, 1B to 29B, 1C to 33C, 1D to 27D or 1E to 27E (below), or Tables T1a, T1b, T2a, T2b, T3a, T3b, T4a, T4b, T5a or T5b (below), and the active ingredient(s) as described above, is not essential for working the present invention.
The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries). These processes for the preparation of the compositions and the use of the compounds (I) for the preparation of these compositions are also a subject of the invention.
Another aspect of invention is related to the use of a compound of formula (I) or of a preferred individual compound according to these general formulae as defined herein, of a composition comprising at least one compound of formula (I) or at least one preferred individual compound as defined herein, or of a fungicidal or insecticidal mixture comprising at least one compound of formula (I) or at least one preferred individual compound as defined herein, in admixture with other fungicides or insecticides as described above, for controlling or preventing infestation of plants (eg, useful plants such as crop plants), propagation material thereof (eg, seeds), harvested crops (e.g., harvested food crops), or non-living materials by insects or by phytopathogenic microorganisms, preferably fungal organisms.
A further aspect of invention is related to a method of controlling or preventing an infestation of plants, (e.g., useful plants such as crop plants), propagation material thereof (e.g., seeds), harvested crops, (e.g., harvested food crops), or of non-living materials by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula (I) or of a preferred individual compound as defined herein as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.
Controlling or preventing means of reducing infestation by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
A preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, or insects which comprises the application of a compound of formula (I), or an agrochemical composition which contains at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen or insect. However, the compounds of formula (I) can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula (I) may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, e.g., a composition containing the compound of formula (I), and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula (I), may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active compounds (surfactants).
Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha, most preferably from 20 g to 600 g a.i./ha. When used as seed drenching agent, convenient dosages are from 10 mg to 1 g of active substance per kg of seeds.
When the combinations of the present invention are used for treating seed, rates of 0.001 to 50 g of a compound of formula (I) per kg of seed, preferably from 0.01 to 10 g per kg of seed are generally sufficient.
The compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
Such compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects). Also conventional slow release formulations may be employed where long lasting efficacy is intended. Particularly formulations to be applied in spraying forms, such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g. the ondensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.
A seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.
In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula (I) together with component (B) and (C), and optionally other active agents, particularly microbiocides or conservatives or the like. Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations
The examples which follow serve to illustrate the invention. The compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm or 0.8 ppm.
Compounds of Formula (I) (including those according to the invention) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
This example illustrates the preparation of 2-fluoro-N-(tetrahydropyran-4-ylmethyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (Compound 1 b. 18 of Table T1 b below)
A solution of hydroxylamine hydrochloride (3.0 g) in water (20 mL) was added at room temperature to a stirred solution of 4-cyano-2-fluorobenzoic acid (3.52 g, 21.3 mmol) in ethanol (35 mL), followed by dropwise addition of potassium carbonate (1.60 g). Then 8-hydroxyquinoline (0.04 g, 0.28 mmol) was added and the resulting thick suspension was heated to reflux for 3 hours to obtain a yellow solution. After removal of ethanol under reduced pressure the residue was acidified with 2N HCl to pH 3. The white precipitate was filtered, washed with water, and dried under reduced pressure at 50° C. to yield 2-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid as a beige solid. Mp: >250° C. 1H NMR (400 MHz, DMSO-d6) δ ppm: 13.22 (s, 1H), 10.00 (s, 1H), 7.85 (t, 1H), 7.63 (m, 1H), 7.54-7.61 (m, 1H).
Trifluoroacetic anhydride (4.1 mL) was added dropwise at 10 to 15° C. to a stirred suspension of 2-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid (3.80 g, 19.0 mmol) in THF (77 mL). The beige suspension was warmed to room temperature and stirred overnight. After evaporation, the crude product was stirred with heptane/ethyl acetate (95:5), filtered and dried under reduced pressure at 50° C. to yield 2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid as a yellow solid. Mp: 175-177° C. 1H NMR (400 MHz, DMSO-d6) δ ppm: 13.55 (s, 1H), 8.12 (t, 1H), 8.00 (d, 1H), 7.94 (d, 1H).
To a white suspension consisting of 2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (3.6 g, 13.0 mmol) and CH2Cl2 (130 mL) at room temperature was added thionyl chloride (1.51 mL) dropwise. The resulting suspension was heated to reflux and stirred for 3 hours, to obtain a yellow solution. The solvent was evaporated under reduced pressure at 30° C. to yield 2-fluoro-4-(5-(trifluoromethyl)-[1,2,4]oxadiazol-3-yl)-benzoyl chloride as a yellowish solid that was used directly without purification. 1H NMR (400 MHz, CDCl3) δ ppm: 8.26 (t, 1H), 8.07 (m, 1H), 7.99 (m, 1H).
To a screw-cap vial containing 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride (0.13 g) suspended in CH2Cl2 (12 mL) cooled to 0° C. was added tetrahydropyran-4-ylmethanamine (0.05 g) as a CH2Cl2 (1 mL) solution. Then triethylamine (0.12 mL) was slowly introduced and the resultant yellow solution was stirred overnight. The reaction contents were then poured into a separatory funnel and diluted with CH2Cl2 and water. The organic layer was separated and then washed with 1N HCl, 1N NaOH, brine, and then dried over sodium sulfate. The solvent was removed under reduced pressure and the crude residue was purified by flash chromatography over silica gel (heptane:ethyl acetate gradient) to give the title compound as a white solid (melting point: 134-136° C.), LC/MS retention time=0.96 minutes, 374.4 (M+H).
This example illustrates the preparation of N-(1-cyano-1-cyclopropyl-ethyl)-2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (Compound 2b.9 of Table T2b below)
To a screw-cap vial containing 2-amino-2-cyclopropyl-propanenitrile (0.05 g) suspended in CH2Cl2 (12 mL) cooled to 0° C. was slowly introduced triethylamine (0.12 mL). Then, 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride (0.13 g) was added in one portion and the resultant yellow solution was stirred overnight. The solvent was removed under reduced pressure and the resultant crude residue was purified by flash chromatography over silica gel (heptane:ethyl acetate eluent gradient) to give the title compound as a yellow oil. LC/MS retention time=1.04 minutes, 369.4 (M+H).
This example illustrates the preparation of N-allyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (Compound 3a.1 of Table T3a below)
To a stirred solution of 4-5-trifluoromethyl-1,2,4-oxadiazol-3-yl benzoic acid (0.08 g) in dry DMF (1.2 ml) under an atmosphere of nitrogen was added N-ethyl-N-isopropylpropan-2-amine (0.14 mL), HATU (0.13 g) and allylamine (0.02 g). The reaction mixture was stirred at room temperature for 2 hours and then ethyl acetate and water were added. The resultant mixture was shaken and the layers were separated. The aqueous layer was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, and filtered. Isolut was added to the filtrate and the resulting mixture was evaporated to dryness and then purified by column chromatography (cyclohexane:ethyl acetate eluent gradient). The title compound was obtained as a white solid (melting point: 135-136° C.), LC/MS retention time=0.95 minutes, 298.2 (M+H).
This example illustrates the preparation of 2-fluoro-N-[(2-fluorophenyl)methyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (Compound 4b.1 of Table T4b below)
A solution of hydroxylamine hydrochloride (3.0 g) in water (20 mL) was added at room temperature to a stirred solution of 4-cyano-2-fluorobenzoic acid (3.52 g, 21.3 mmol) in ethanol (35 mL), followed by dropwise addition of potassium carbonate (1.60 g). Then 8-hydroxyquinoline (0.041 g, 0.28 mmol) was added and the resulting thick suspension was heated to reflux for 3 hours to obtain a yellow solution. After removal of ethanol under reduced pressure the residue was acidified with 2N HCl to pH 3. The white precipitate was filtered, washed with water, and dried under reduced pressure at 50° C. to yield 2-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid as a beige solid. Mp: >250° C. 1H NMR (400 MHz, DMSO-d6) δ ppm: 13.22 (s, 1H), 10.00 (s, 1H), 7.85 (t, 1H), 7.63 (m, 1H), 7.54-7.61 (m, 1H).
Trifluoroacetic anhydride (4.1 mL) was added dropwise at 10 to 15° C. to a stirred suspension of 2-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid (3.80 g, 19.0 mmol) in THF (77 mL). The beige suspension was warmed to room temperature and stirred overnight. After evaporation, the crude product was stirred with heptane/ethyl acetate (95:5), filtered and dried under reduced pressure at 50° C. to yield 2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid as a yellow solid. Mp: 175-177° C. 1H NMR (400 MHz, DMSO-d6) δ ppm: 13.55 (s, 1H), 8.12 (t, 1H), 8.00 (d, 1H), 7.94 (d, 1H).
To a white suspension consisting of 2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (3.6 g, 13.0 mmol) and CH2Cl2 (130 mL) at room temperature was added thionyl chloride (1.51 mL) dropwise. The resulting suspension was heated to reflux and stirred for 3 hours, to obtain a yellow solution. The solvent was evaporated under reduced pressure at 30° C. to yield 2-fluoro-4-(5-(trifluoromethyl)-[1,2,4]oxadiazol-3-yl)-benzoyl chloride as a yellowish solid that was used directly without purification. 1H NMR (400 MHz, CDCl3) δ ppm: 8.26 (t, 1H), 8.07 (m, 1H), 7.99 (m, 1H).
To a screw-cap vial containing 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride (0.13 g) suspended in CH2Cl2 (1.2 mL) cooled to 0° C. was added (2-fluorophenyl)methanamine (0.60 g) as a CH2Cl2 (1 mL) solution. Then triethylamine (0.12 mL) was slowly introduced and the resultant yellow solution was stirred for 4 hours. The reaction contents were then poured into a seporatory funnel and diluted with CH2Cl2 and water. The organic layer was separated and then washed with 1N HCl, 1N NaOH, and brine. The solvent was removed under reduced pressure and the crude residue was purified by flash chromatography over silica gel (cyclohexane:ethyl acetate gradient) to give the title compound as a white solid (mp: 132-136° C.). LC/MS retention time=1.08 minutes, 384 (M+H).
This example illustrates the preparation of N-(p-tolylmethyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (Compound 4a.1 of Table T4a)
To a stirred solution of 4-5-trifluoromethyl-1,2,4-oxadiazol-3-yl benzoic acid (0.08 g, 0.31 mmol) in dry DMF (1.2 ml) under an atmosphere of nitrogen was added N-ethyl-N-isopropylpropan-2-amine (0.11 g, 0.77 mmol), HATU (0.13 g, 0.34 mmol) and 4-methylbenzylamine (0.04 g, 0.31 mmol). The reaction mixture was stirred at room temperature for 2 hours and then ethyl acetate and water were added. The resultant mixture was shaken and the layers were separated. The aqueous layer was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate and filtered. Isolut was added to the filtrate and the resulting mixture was evaporated to dryness and then purified by column chromatography (eluent cyclohexane-ethyl acetate mixture mixtures). The title compound was obtained as a white solid, (m.p. 198-203° C.), LC/MS retention time=1.09 minutes, 362 (M+H).
This example illustrates the preparation of 2-fluoro-N-methyl-N-[(3-methyl-2-thienyl)methyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (Compound 5b.3 of Table T5b below)
A solution of hydroxylamine hydrochloride (3.0 g) in water (20 mL) was added at room temperature to a stirred solution of 4-cyano-2-fluorobenzoic acid (3.52 g, 21.3 mmol) in ethanol (35 mL), followed by dropwise addition of potassium carbonate (1.60 g). Then 8-hydroxyquinoline (0.04 g, 0.28 mmol) was added and the resulting thick suspension was heated to reflux for 3 hours to obtain a yellow solution. After removal of ethanol under reduced pressure the residue was acidified with 2N HCl to pH 3. The white precipitate was filtered, washed with water, and dried under reduced pressure at 50° C. to yield 2-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid as a beige solid. Mp: >250° C. 1H NMR (400 MHz, DMSO-d6) δ ppm: 13.22 (s, 1H), 10.00 (s, 1H), 7.85 (t, 1H), 7.63 (m, 1H), 7.54-7.61 (m, 1H).
Trifluoroacetic anhydride (4.1 mL) was added dropwise at 10 to 15° C. to a stirred suspension of 2-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid (3.80 g, 19.0 mmol) in THF (77 mL). The beige suspension was warmed to room temperature and stirred overnight. After evaporation, the crude product was stirred with heptane/ethyl acetate (95:5), filtered and dried under reduced pressure at 50° C. to yield 2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid as a yellow solid. Mp: 175-177° C. 1H NMR (400 MHz, DMSO-d6) δ ppm: 13.55 (s, 1H), 8.12 (t, 1H), 8.00 (d, 1H), 7.94 (d, 1H).
To a white suspension consisting of 2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (3.6 g, 13.0 mmol) and CH2Cl2 (130 mL) at room temperature was added thionyl chloride (1.51 mL) dropwise. The resulting suspension was heated to reflux and stirred for 3 hours, to obtain a yellow solution. The solvent was evaporated under reduced pressure at 30° C. to yield 2-fluoro-4-(5-(trifluoromethyl)-[1,2,4]oxadiazol-3-yl)-benzoyl chloride as a yellowish solid that was used directly without purification. 1H NMR (400 MHz, CDCl3) δ ppm: 8.26 (t, 1H), 8.07 (m, 1H), 7.99 (m, 1H).
To a screw-cap vial containing 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride (0.13 g) suspended in CH2Cl2 (1.2 mL) cooled to 0° C. was added N-methyl-1-(3-methyl-2-thienyl)methanamine hydrochloride (0.08 g) as a CH2Cl2 (1 mL) solution. Then triethylamine (0.25 mL) was slowly introduced and the resultant yellow solution was stirred for 14 hours. The reaction contents were then poured into a separatory funnel and diluted with CH2Cl2 and water. The organic layer was separated and then washed with 1N HCl, 1N NaOH, and brine. The solvent was removed under reduced pressure and the crude residue was purified by flash chromatography over silica gel (cyclohexane:ethyl acetate gradient) to give the title compound as a yellow oil. LC/MS retention time=1.13 minutes, 400.4 (M+H).
HATU=1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid-hexafluorophosphate
wherein R1 and R3 are hydrogen, R2 is fluorine and R4 or R4A (when R4 is R4A) is as defined below in the table
Table 2A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is fluorine, R3 is methyl and R4A is as defined above in Table 1A.
Table 3A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is fluorine, R3 is ethyl and R4A is as defined above in Table 1A.
Table 4A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is fluorine, R3 is ethyl and R4A is as defined above in Table 1A.
Table 5A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R3 are hydrogen, R2 is chlorine and R4A is as defined above in Table 1A.
Table 6A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is chlorine, R3 is methyl and R4A is as defined above in Table 1A.
Table 7A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is chlorine, R3 is ethyl and R4A is as defined above in Table 1A.
Table 8A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R3 are hydrogen, R2 is methyl and R4A is as defined above in Table 1A.
Table 9A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is methyl, R3 is methyl and R4A is as defined above in Table 1A.
Table 10A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is methyl, R3 is ethyl and R4A is as defined above in Table 1A.
Table 11A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R3 are hydrogen, R2 is methoxy and R4A is as defined above in Table 1A.
Table 12A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is methoxy, R3 is methyl and R4A is as defined above in Table 1A.
Table 13A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is methoxy, R3 is ethyl and R4A is as defined above in Table 1A.
Table 14A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 is hydrogen, R2 is fluorine, R3 is isopropyl and R4A is as defined above in Table 1A.
Table 15A: This table discloses 78 specific compounds of formula (T-1A) wherein R1, R2 and R3 are hydrogen and R4 is as defined above in Table 1A.
Table 16A: This table discloses 78 specific compounds of formula (T-1A) wherein R1, R2 are hydrogen, R3 is methyl and R4 is as defined above in Table 1A.
Table 17A: This table discloses 78 specific compounds of formula (T-1A) wherein R1, R2 are hydrogen, R3 is ethyl and R4 is as defined above in Table 1A.
Table 18A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are fluorine, R3 is hydrogen and R4 is as defined above in Table 1A.
Table 19A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are fluorine, R3 is methyl and R4 is as defined above in Table 1A.
Table 20A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are fluorine, R3 is ethyl and R4 is as defined above in Table 1A.
Table 21A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are chlorine, R3 are hydrogen and R4 is as defined above in Table 1A.
Table 22A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are chlorine, R3 is methyl and R4 is as defined above in Table 1A.
Table 23A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are chlorine, R3 is ethyl and R4 is as defined above in Table 1A.
Table 24A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are methyl, R3 is hydrogen and R4 is as defined above in Table 1A.
Table 25A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are methyl, R3 is methyl and R4 is as defined above in Table 1A.
Table 26A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are methyl, R3 is ethyl and R4 is as defined above in Table 1A.
Table 27A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are methoxy, R3 is hydrogen and R4 is as defined above in Table 1A.
Table 28A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are methoxy, R3 is methyl and R4 is as defined above in Table 1A.
Table 29A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are methoxy, R3 is ethyl and R4 is as defined above in Table 1A.
Table 30A: This table discloses 78 specific compounds of formula (T-1A) wherein R1 and R2 are hydrogen, R3 is isopropyl and R4 is as defined above in Table 1A.
Table 2B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is fluorine, R3 is methyl and R4B is as defined above in Table 1B.
Table 3B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is fluorine, R3 is ethyl and R4B is as defined above in Table 1B.
Table 4B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R3 are hydrogen, R2 is chlorine and R4B is as defined above in Table 1B.
Table 5B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is chlorine, R3 is methyl and R4B is as defined above in Table 1B.
Table 6B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is chlorine, R3 is ethyl and R4B is as defined above in Table 1B.
Table 7B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R3 are hydrogen, R2 is methyl and R4B is as defined above in Table 1B.
Table 8B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is methyl, R3 is methyl and R4B is as defined above in Table 1B.
Table 9B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is methyl, R3 is ethyl and R4B is as defined above in Table 1B.
Table 10B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R3 are hydrogen, R2 is methoxy and R4B is as defined above in Table 1B.
Table 11B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is methoxy, R3 is methyl and R4B is as defined above in Table 1B.
Table 12B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is methoxy, R3 is ethyl and R4B is as defined above in Table 1B.
Table 13B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 is hydrogen, R2 is fluorine, R3 is isopropyl and R4B is as defined above in Table 1B.
Table 14B: This table discloses 43 specific compounds of formula (T-1B) wherein R1, R2 and R3 are hydrogen and R4 is as defined above in the table in Table 1B.
Table 15B: This table discloses 43 specific compounds of formula (T-1B) wherein R1, R2 are hydrogen, R3 is methyl and R4 is as defined above in Table 1B.
Table 16B: This table discloses 43 specific compounds of formula (T-1B) wherein R1, R2 are hydrogen, R3 is ethyl and R4 is as defined above in Table 1B.
Table 17B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are fluorine, R3 is hydrogen and R4 is as defined above in Table 1B.
Table 18B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are fluorine, R3 is methyl and R4 is as defined above in Table 1B.
Table 19B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are fluorine, R3 is ethyl and R4 is as defined above in Table 1B.
Table 20B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are chlorine, R3 is hydrogen and R4 is as defined above in Table 1B.
Table 21B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are chlorine, R3 is methyl and R4 is as defined above in Table 1B.
Table 22B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are chlorine, R3 is ethyl and R4 is as defined above in Table 1B.
Table 23B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are methyl, R3 is hydrogen and R4 is as defined above in Table 1B.
Table 24B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are methyl, R3 is methyl and R4 is as defined above in Table 1B.
Table 25B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are methyl, R3 is ethyl and R4 is as defined above in Table 1B.
Table 26B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are methoxy, R3 is hydrogen and R4 is as defined above in Table 1B.
Table 27B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are methoxy, R3 is methyl and R4 is as defined above in Table 1B.
Table 28B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are methoxy, R3 is ethyl and R4 is as defined above in Table 1B.
Table 29B: This table discloses 43 specific compounds of formula (T-1B) wherein R1 and R2 are hydrogen, R3 is an isopropyl and R4 is as defined above in Table 1B.
Table 2C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is fluorine, R3 is methyl and R4C is as defined above in Table 1C.
Table 3C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is fluorine, R3 is ethyl and R4C is as defined above in Table 1C.
Table 4C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R3 are hydrogen, R2 is chlorine and R4C is as defined above in Table 1C.
Table 5C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is chlorine, R3 is methyl and R4C is as defined above in Table 1C.
Table 9C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is chlorine, R3 is ethyl and R4C is as defined above in Table 1C.
Table 10C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R3 are hydrogen, R2 is methyl and R4C is as defined above in Table 1C.
Table 11C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is methyl, R3 is methyl and R4C is as defined above in Table 1C.
Table 12C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is methyl, R3 is ethyl and R4C is as defined above in Table 1C.
Table 13C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R3 are hydrogen, R2 is methoxy and R4C is as defined above in Table 1C.
Table 14C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is methoxy, R3 is methyl and R4C is as defined above in Table 1C.
Table 15C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is methoxy, R3 is ethyl and R4C is as defined above in Table 1C.
Table 16C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is fluorine, R3 is isopropyl and R4C is as defined above in Table 1C.
Table 17C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 is hydrogen, R2 is chlorine, R3 is isopropyl and R4C is as defined above in Table 1C.
Table 18C: This table discloses 113 specific compounds of formula (T-1C) wherein R1, R2 and R3 are hydrogen and R4 is as defined above in the table in Table 1C.
Table 19C: This table discloses 113 specific compounds of formula (T-1C) wherein R1, R2 are hydrogen, R3 is methyl and R4 is as defined above in Table 1C.
Table 20C: This table discloses 113 specific compounds of formula (T-1C) wherein R1, R2 are hydrogen, R3 is ethyl and R4 is as defined above in Table 1C.
Table 21C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are fluorine, R3 is hydrogen and R4 is as defined above in Table 1C.
Table 22C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are fluorine, R3 is methyl and R4 is as defined above in Table 1C.
Table 23C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are fluorine, R3 is ethyl and R4 is as defined above in Table 1C.
Table 24C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are chlorine, R3 is hydrogen and R4 is as defined above in Table 1C.
Table 25C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are chlorine, R3 is methyl and R4 is as defined above in Table 1C.
Table 26C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are chlorine, R3 is ethyl and R4 is as defined above in Table 1C.
Table 27C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are methyl, R3 is hydrogen and R4 is as defined above in Table 1C.
Table 28C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are methyl, R3 is methyl and R4 is as defined above in Table 1C.
Table 29C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are methyl, R3 is ethyl and R4 is as defined above in Table 1C.
Table 30C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are methoxy, R3 is hydrogen and R4 is as defined above in Table 1C.
Table 31C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are methoxy, R3 is methyl and R4 is as defined above in Table 1C.
Table 32C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are methoxy, R3 is ethyl and R4 is as defined above in Table 1C.
Table 33C: This table discloses 113 specific compounds of formula (T-1C) wherein R1 and R2 are hydrogen, R3 is isopropyl and R4 is as defined above in Table 1C.
Table 2D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 is hydrogen, R2 is fluorine, R3 is methyl and R4D is as defined above in Table 1D.
Table 3D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 is hydrogen, R2 is fluorine, R3 is ethyl and R4D is as defined above in Table 1D.
Table 4D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R3 are hydrogen, R2 is chlorine and R4D is as defined above in Table 1D.
Table 5D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 is hydrogen, R2 is chlorine, R3 is methyl and R4D is as defined above in Table 1D.
Table 6D: This table discloses 174 specific compounds of formula (T-1D) wherein R is hydrogen, R2 is chlorine, R3 is ethyl and R4D is as defined above in Table 1D.
Table 7D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 is hydrogen, R2 is methyl, R3 is hydrogen and R4D is as defined above in Table 1D.
Table 8D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 is hydrogen, R2 is methyl, R3 is methyl and R4D is as defined above in Table 1D.
Table 9D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 is hydrogen, R2 is methyl, R3 is ethyl and R4D is as defined above in Table 1D.
Table 10D: This table discloses 174 specific compounds of formula (T-1 D) wherein R1 is hydrogen, R2 is methoxy, R3 are hydrogen and R4D is as defined above in Table 1D.
Table 11D: This table discloses 174 specific compounds of formula (T-1 D) wherein R1 is hydrogen, R2 is methoxy, R3 is methyl and R4D is as defined above in Table 1D.
Table 12D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 is hydrogen, R2 is methoxy, R3 is ethyl and R4D is as defined above in Table 1D.
Table 13D: This table discloses 174 specific compounds of formula (T-1D) wherein R1, R2 and R3 are hydrogen and R4 is as defined above in Table 1D.
Table 14D: This table discloses 174 specific compounds of formula (T-1D) wherein R1, R2 are hydrogen, R3 is methyl and R4 is as defined above in Table 1D.
Table 15D: This table discloses 174 specific compounds of formula (T-1D) wherein R1, R2 are hydrogen, R3 is ethyl and R4 is as defined above in Table 1D.
Table 16D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are fluorine, R3 is hydrogen and R4 is as defined above in Table 1D.
Table 17D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are fluorine, R3 is methyl and R4 is as defined above in Table 1D.
Table 18D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are fluorine, R3 is ethyl and R4 is as defined above in Table 1D.
Table 19D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are chlorine, R3 is hydrogen and R4 is as defined above in Table 1D.
Table 20D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are chlorine, R3 is methyl and R4 is as defined above in Table 1D.
Table 21D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are chlorine, R3 is ethyl and R4 is as defined above in Table 1D.
Table 22D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are methyl, R3 is hydrogen and R4 is as defined above in Table 1D.
Table 23D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are methyl, R3 is methyl and R4 is as defined above in Table 1D.
Table 24D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are methyl, R3 is ethyl and R4 is as defined above in Table 1D.
Table 25D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are methoxy, R3 is hydrogen and R4 is as defined above in Table 1D.
Table 26D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are methoxy, R3 is methyl and R4 is as defined above in Table 1D.
Table 27D: This table discloses 174 specific compounds of formula (T-1D) wherein R1 and R2 are methoxy, R3 is ethyl and R4 is as defined above in Table 1D.
Table 2E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is fluorine, R3 is methyl and R4E is as defined above in Table 1E.
Table 3E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is fluorine, R3 is ethyl and R4E is as defined above in Table 1E.
Table 4E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is chlorine, R3 is hydrogen and R4E is as defined above in Table 1E.
Table 5E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is chlorine, R3 is methyl and R4E is as defined above in Table 1E.
Table 6E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is chlorine, R3 is ethyl and R4E is as defined above in Table 1E.
Table 7E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is methyl, R3 is hydrogen and R4E is as defined above in Table 1E.
Table 8E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is methyl, R3 is methyl and R4E is as defined above in Table 1E.
Table 9E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is methyl, R3 is ethyl and R4E is as defined above in Table 1E.
Table 10E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is methoxy, R3 is hydrogen and R4E is as defined above in Table 1E.
Table 11E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is methoxy, R3 is methyl and R4E is as defined above in Table 1E.
Table 12E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 is hydrogen, R2 is methoxy, R3 is ethyl and R4E is as defined above in Table 1E.
Table 13E: This table discloses 219 specific compounds of formula (T-1E) wherein R1, R2 and R3 are hydrogen and R4 is as defined above in Table 1E.
Table 14E: This table discloses 219 specific compounds of formula (T-1E) wherein R1, R2 are hydrogen, R3 is methyl and R4 is as defined above in Table 1E Table 15E: This table discloses 219 specific compounds of formula (T-1E) wherein R1, R2 are hydrogen, R3 is ethyl and R4 is as defined above in Table 1E.
Table 16E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are fluorine, R3 is hydrogen and R4 is as defined above in Table 1E.
Table 17E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are fluorine, R3 is methyl and R4 is as defined above in Table 1E.
Table 18E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are fluorine, R3 is ethyl and R4 is as defined above in Table 1E.
Table 19E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are chlorine, R3 is hydrogen and R4 is as defined above in Table 1E.
Table 20E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are chlorine, R3 is methyl and R4 is as defined above in Table 1E.
Table 21E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are chlorine, R3 is ethyl and R4 is as defined above in Table 1E.
Table 22E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are methyl, R3 is hydrogen and R4 is as defined above in Table 1E.
Table 23E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are methyl, R3 is methyl and R4 is as defined above in Table 1E.
Table 24E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are methyl, R3 is ethyl and R4 is as defined above in Table 1E.
Table 25E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are methoxy, R3 is hydrogen and R4 is as defined above in Table 1E.
Table 26E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are methoxy, R3 is methyl and R4 is as defined above in Table 1E.
Table 27E: This table discloses 219 specific compounds of formula (T-1E) wherein R1 and R2 are methoxy, R3 is ethyl and R4 is as defined above in Table 1E.
Throughout this description, temperatures are given in degrees Celsius (° C.) and “m.p.” means melting point. LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the methods (A and B) used for LC/MS analysis are given below.
The description of the apparatus and the method A is:
SQ Detector 2 from Waters
Ionisation method: Electrospray
Polarity: positive and negative ions
Mass range: 100 to 900 Da
DAD Wavelength range (nm): 210 to 500
Method Waters ACQUITY UPLC with the following HPLC gradient conditions
(Solvent A: Water/Methanol 20:1+0.05% formic acid and Solvent B: Acetonitrile+0.05% formic acid)
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60° C.
The description of the apparatus and the method B is:
SQ Detector 2 from Waters
Ionisation method: Electrospray
Polarity: positive ions
Mass range: 140 to 800 Da
DAD Wavelength range (nm): 210 to 400
Method Waters ACQUITY UPLC with the following HPLC gradient conditions
(Solvent A: Water/Methanol 9:1+0.1% formic acid and Solvent B: Acetonitrile+0.1% formic acid)
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60° C.
Where necessary, enantiomerically pure final compounds may be obtained from racemic materials as appropriate via standard physical separation techniques, such as reverse phase chiral chromatography, or through stereoselective synthetic techniques, eg, by using chiral starting materials.
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
28 parts of a combination of the compound of formula (I) are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
General examples of leaf disk tests in well plates: Leaf disks or leaf segments of various plant species are cut from plants grown in a greenhouse. The cut leaf disks or segments are placed in multiwell plates (24-well format) onto water agar. The leaf disks are sprayed with a test solution before (preventative) or after (curative) inoculation. Compounds to be tested are prepared as DMSO solutions (max. 10 mg/ml) which are diluted to the appropriate concentration with 0.025% Tween20 just before spraying. The inoculated leaf disks or segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the respective test system. A single evaluation of disease level is carried out 3 to 14 days after inoculation, depending on the pathosystem. Percent disease control relative to the untreated check leaf disks or segments is then calculated.
Mycelia fragments or conidia suspensions of a fungus prepared either freshly from liquid cultures of the fungus or from cryogenic storage, are directly mixed into nutrient broth. DMSO solutions of the test compound (max. 10 mg/ml) are diluted with 0.025% Tween20 by a factor of 50 and 10 μl of this solution is pipetted into a microtiter plate (96-well format). The nutrient broth containing the fungal spores/mycelia fragments is then added to give an end concentration of the tested compound. The test plates are incubated in the dark at 24° C. and 96% relative humidity. The inhibition of fungal growth is determined photometrically after 2 to 7 days, depending on the pathosystem, and percent antifungal activity relative to the untreated check is calculated.
Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19° C. and 75% relative humidity (rh) under a light regime of 12 hours light/12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 to 9 days after application).
The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Compounds (from Table T1a) 1a.1, 1a.2, 1a.3, 1a.4, 1a.6, 1a.7, 1a.10, and 1a.11
Compounds (from Table T1b) 1b.1, 1b.2, 1b.3, 1b.4, 1b.5, 1b.6, 1b.8, 1b.9, 1b.11, 1b.13, 1b.14, 1b.15, 1b.16, 1b.17, and 1b.18.
Compounds (from Table T2a) 2a.3, 2a.4, 2a.6, 2a.7, and 2a.9.
Compounds (from Table T2b) 2b.1, 2b.3, 2b.4, 2b.5, 2b.9, 2b.10, 2b.11, 2b.12, 2b.13, 2b.14, 2b.15, 2b.16, and 2b.17.
Compounds (from Table T3a) 3a.1, 3a.2, 3a.3, 3a.4, 3a.5, 3a.7, 3a.9, 3a.10, 3a.11, 3a.12, 3a.13, 3a.14, 3a.16, 3a.17, 3a.20, 3a.22, 3a.24, 3a.26, 3a.27, 3a.28, 3a.30, 3a.31, 3a.32, 3a.33, 3a.34, 3a.35, 3a.36, 3a.37, 3a.38, 3a.40, 3a.41, 3a.43, 3a.44, and 3a.45.
Compounds (from Table T3b) 3b.1, 3b.2, 3b.3, 3b.4, 3b.5, 3b.6, 3b.7, 3b.8, 3b.10, 3b.11, 3b.12, 3b.14, 3b.15, 3b.16, 3b.19, 3b.20, 3b.21, 3b.22, 3b.24, 3b.26, 3b.27, 3b.28, 3b.29, 3b.30, 3b.32, 3b.33, 3b.34, 3b.35, 3b.36, 3b.37, 3b.38, 3b.39, 3b.40, 3b.41, 3b.43, and 3b.44.
Compounds (from Table T4a) 4a.2, 4a.3, 4a.4, 4a.5, and 4a.13.
Compounds (from Table T4b) 4b.1, 4b.2, 4b.3, 4b.4, 4b.5, 4b.6, 4b.7, 4b.8, 4b.9, 4b.11, 4b.13, and 4b.14.
Compounds (from Table T5a) 5a.5, 5a.6, 5a.7, 5a.8, 5a.9, and 5a.10.
Compounds (from Table T5b) 5b.1, 5b.2, 5b.7, 5b.9, 5b.10, 5b.11, 5b.13, 5b.14, 5b.15, 5b.16, 5b.17, 5b.18, 5b.19, and 5b.20.
Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are then inoculated with a spore suspension of the fungus. Plates were stored in darkness at 19° C. and 75% relative humidity. The formulated test compound diluted in water was applied 1 day after inoculation. The leaf segments were incubated at 19° C. and 75% relative humidity under a light regime of 12 hours light/12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (6 to 8 days after application).
The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Compounds (from Table T1a) 1a.2, 1a.3, 1a.4, 1a.5, 1a.7, 1a.8, and 1a.9.
Compounds (from Table T1b) 1b.2, 1b.5, 1b.6, 1b.7, 1b.9, 1b.10, 1b.12, 1b.13, 1b.15, 1b.16, 1b.17, and 1b.18.
Compounds (from Table T2a) 2a.3, 2a.4, and 2a.9.
Compounds (from Table T2b) 2b.1, 2b.3, 2b.4, 2b.5, 2b.9, 2b.11, 2b.12, 2b.13, and 2b.17.
Compounds (from Table T3a) 3a.1, 3a.2, 3a.3, 3a.5, 3a.6, 3a.7, 3a.9, 3a.10, 3a.11, 3a.12, 3a.13, 3a.14, 3a.15, 3a.16, 3a.17, 3a.18, 3a.20, 3a.21, 3a.22, 3a.24, 3a.27, 3a.28, 3a.30, 3a.31, 3a.32, 3a.33, 3a.34, 3a.35, 3a.36, 3a.37, 3a.38, 3a.40, 3a.41, 3a.43, 3a.44, and 3a.45.
Compounds (from Table T3b) 3b.1, 3b.2, 3b.3, 3b.4, 3b.5, 3b.6, 3b.8, 3b.9, 3b.10, 3b.11, 3b.12, 3b.14, 3b.15, 3b.16, 3b.17, 3b.18, 3b.19, 3b.20, 3b.21, 3b.22, 3b.23, 3b.24, 3b.27, 3b.28, 3b.29, 3b.30, 3b.31, 3b.32, 3b.33, 3b.34, 3b.35, 3b.36, 3b.37, 3b.38, 3b.39, 3b.40, 3b.41, 3b.43, and 3b.44.
Compounds (from Table T4a) 4a.4, 4a.5, and 4a.13.
Compounds (from Table T4b) 4b.6, and 4b.9.
Compounds (from Table T5a) 5a.4, 5a.5, 5a.6, 5a.8, 5a.9, and 5a.10.
Compounds (from Table T5b) 5b.1, 5b.2, 5b.3, 5b.9, 5b.11, 5b.13, 5b.14, 5b.15, 5b.16, 5b.17, 5b.19, and 5b.20.
Soybean leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. One day after application leaf discs are inoculated by spraying a spore suspension on the lower leaf surface. After an incubation period in a climate cabinet of 24-36 hours in darkness at 20° C. and 75% rh leaf disc are kept at 20° C. with 12 h light/day and 75% rh. The activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (12 to 14 days after application).
The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Compounds (from Table T1a) 1a.1 and 1a.2.
Compounds (from Table T1b) 1b.1, 1b.2, 1b.3, 1b.5, 1b.6, 1b.9, 1b.14, 1b.15, 1b.16, 1b.17, and 1b.18.
Compounds (from Table T2a) 2a.1, 2a.2, 2a.3, 2a.4, 2a.5, 2a.6, 2a.7, 2a.8, and 2a.9
Compounds (from Table T2b) 2b.1, 2b.2, 2b.3, 2b.4, 2b.5, 2b.6, 2b.7, 2b.8, 2b.9, 2b.11, 2b.12, 2b.13, 2b.15, and 2b.17.
Compounds (from Table T3a) 3a.1, 3a.2, 3a.3, 3a.4, 3a.5, 3a.6, 3a.7, 3a.8, 3a.9, 3a.10, 3a.11, 3a.12, 3a.13, 3a.14, 3a.15, 3a.16, 3a.18, 3a.19, 3a.20, 3a.21, 3a.22, 3a.23, 3a.24, 3a.25, 3a.26, 3a.27, 3a.28, 3a.29, 3a.30, 3a.31, 3a.32, 3a.33, 3a.34, 3a.35, 3a.36, 3a.37, 3a.38, 3a.39, 3a.40, 3a.41, 3a.42, 3a.43, 3a.44, and 3a.45.
Compounds (from Table T3b) 3b.1, 3b.2, 3b.3, 3b.4, 3b.5, 3b.6, 3b.7, 3b.8, 3b.9, 3b.10, 3b.11, 3b.12, 3b.13, 3b.14, 3b.15, 3b.16, 3b.17, 3b.19, 3b.20, 3b.21, 3b.22, 3b.23, 3b.24, 3b.25, 3b.26, 3b.27, 3b.29, 3b.30, 3b.31, 3b.32, 3b.33, 3b.34, 3b.35, 3b.36, 3b.37, 3b.38, 3b.39, 3b.40, 3b.41, 3b.42, 3b.43, and 3b.44.
Compounds (from Table T4a) 4a.1, 4a.2, 4a.3, 4a.4, 4a.5, 4a.6, 4a.7, 4a.8, 4a.9, 4a.10, 4a.11, 4a.12, 4a.13.
Compounds (from Table T4b) 4b.1, 4b.2, 4b.3, 4b.4, 4b.5, 4b.6, 4b.7, 4b.8, 4b.9, 4b.10, and 4b.12.
Compounds (from Table T5a) 5a.1, 5a.2, 5a.3, 5a.4, 5a.5, 5a.6, 5a.7, 5a.8, 5a.9, and 5a.10.
Compounds (from Table T5b) 5b.1, 5b.2, 5b.3, 5b.4, 5b.5, 5b.6, 5b.7, 5b.8, 5b.9, 5b.11, 5b.12, 5b.13, 5b.14, 5b.15, 5b.16, 5b.17, 5b.19, and 5b.20.
Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB-potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24° C. and the inhibition of growth is measured photometrically 3 to 4 days after application.
The following compounds at 20 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control under the same conditions, which show extensive disease development.
Compounds (from Table T1a) 1a 1, 1a.2, 1a.3, 1a.4, and 1a.5.
Compounds (from Table T1b) 1b.5, 1b.9, 1b.14, 1b.15, 1b.16, 1b.17, and 1b.18.
Compounds (from Table T2a) 2a.1 and 2a.9.
Compounds (from Table T2b) 2b.1, 2b.2, 2b.3, 2b.4, 2b.5, 2b.6, 2b.8, and 2b.13.
Compounds (from Table T3a) 3a.1, 3a.2, 3a.3, 3a.4, 3a.7, 3a.8, 3a.9, 3a.10, 3a.11, 3a.12, 3a.13, 3a.14, 3a.16, 3a.17, 3a.18, 3a.20, 3a.22, 3a.23, 3a.24, 3a.25, 3a.26, 3a.27, 3a.28, 3a.29, 3a.30, 3a.31, 3a.32, 3a.33, 3a.34, 3a.35, 3a.36, 3a.37, 3a.38, 3a.39, 3a.40, 3a.41, 3a.43, 3a.44, and 3a.45.
Compounds (from Table T3b) 3b.1, 3b.2, 3b.3, 3b.4, 3b.5, 3b.6, 3b.7, 3b.8, 3b.10, 3b.11, 3b.12, 3b.13, 3b.14, 3b.15, 3b.16, 3b.18, 3b.19, 3b.20, 3b.21, 3b.22, 3b.23, 3b.24, 3b.26, 3b.27, 3b.28, 3b.29, 3b.30, 3b.31, 3b.32, 3b.33, 3b.34, 3b.35, 3b.36, 3b.37, 3b.38, 3b.39, 3b.40, 3b.41, 3b.43, and 3b.44.
Compounds (from Table T4a) 4a.1, 4a.2, 4a.3, 4a.4, 4a.5, and 4a.13.
Compounds (from Table T4b) 4b.1, 4b.2, 4b.5, 4b.7, 4b.8, 4b.9, 4b.10, and 4b.11.
Compounds (from Table T5a) 5a.4, 5a.5, 5a.6, 5a.7, 5a.8, 5a.9, and 5a.10.
Compounds (from Table T5b) 5b.2, 5b.3, 5b.7, 5b.9, 5b.10, 5b.11, 5b.13, 5b.14, 5b.15, 5b.16, 5b.17, 5b.18, 5b.19, and 5b.20.
Field bean leaf discs are placed on water agar in multiwell plates (96-well format) and 10 μl of the formulated test compound diluted in acetone and a spreader pipetted onto the leaf disc. Two hours after application leaf discs are inoculated by spraying a spore suspension on the lower leaf surface. The leaf discs are incubated in a climate cabinet at 22° C. with 18 hour day and 70% relative humidity. The activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (12 days after application).
The following compounds at 100 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf discs under the same conditions, which show extensive disease development.
Compounds (from Table T1a) 1a.2, 1a.3, 1a.4, 1a.5, 1a.6, 1a.7, 1a.8, 1a.9, 1a.10, and 1a.11.
Compounds (from Table T1b) 1b.1, 1b.2, 1b.3, 1b.4, 1b.5, 1b.6, 1b.7, 1b.8, 1b.9, 1b.10, 1b.11, 1b.12, 1b.13, 1b.14, 1b.15, 1b.16, 1b.17, and 1b.18.
Compounds (from Table T2a) 2a.2, 2a.3, 2a.4, 2a.5, 2a.6, 2a.7, 2a.8, 2a.9.
Compounds (from Table T2b) 2b.1, 2b.2, 2b.3, 2b.4, 2b.5, 2b.6, 2b.7, 2b.8, 2b.10, 2b.11, 2b.12, 2b.14, 2b.15, 2b.16, and 2b.17.
Compounds (from Table T3a) 3a.1, 3a.2, 3a.3, 3a.4, 3a.5, and 3a.17.
Compounds (from Table T3b) 3b.1, 3b.2, 3b.3, 3b.4, 3b.5, 3b.6, 3b.7, and 3b.8.
Compounds (from Table T4a) 4a.1, 4a.2, 4a.3, 4a.4, 4a.5, 4a.6, 4a.7, 4a.8, 4a.9, 4a.10, 4a.11, 4a.12, and 4a.13.
Compounds (from Table T4b) 4b.1, 4b.2, 4b.3, 4b.4, 4b.5, 4b.6, 4b.7, 4b.8, 4b.9, 4b.10, 4b.11, 4b.12, 4b.13, and 4b.14.
Compounds (from Table T5a) 5a.2, 5a.5, 5a.7, 5a.9, and 5a.10.
Compounds (from Table T5b) 5b.1, 5b.2, 5b.3, 5b.4, 5b.5, 5b.6, 5b.7, 5b.9, 5b.10, 5b.11, 5b.12, 5b.13, 5b.14, 5b.15, 5b.16, 5b.17, 5b.18, 5b.19, and 5b.20.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2016/057845 | 4/8/2016 | WO | 00 |
