CA1085857A - 1-aryl-5-carboxy-2 pyridones and derivatives thereof - Google Patents
1-aryl-5-carboxy-2 pyridones and derivatives thereofInfo
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- CA1085857A CA1085857A CA306,765A CA306765A CA1085857A CA 1085857 A CA1085857 A CA 1085857A CA 306765 A CA306765 A CA 306765A CA 1085857 A CA1085857 A CA 1085857A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Abstract of the Disclosure Compounds of the formula
Description
5~57 The Disclosure This invention relates to novel coMpounds which show activity as plant growth regulators, particularly as chemical gametocides, to growth regulant compositions which comprise these compounds, and to methods of regulating the growth of plants with these compounds and compositions.
A new class of compounds has now been found which can be used as plant growth regulators, and particularly as chemical gametocides in cereal grains. The compounds of the invention are 2-pyridones having the formula R4 ~ R2 ':
wherein R is an alkyl group, preferably having up to 4 carbon atoms, R is a carboxy group (-COO~) or an agronomically-acceptable salt thereof, or a carbalkoxy group (-COOR, wherein R is an alkyl group, preferably having up to 12 carbon atoms, most preferably up to 4 carbon atoms), R3 is a hydrogen atom or an alkyl group, preferably having up to 4 carbon atoms, R is a hydrogen atom, an alkyl group, preferably having up to 4 carbon atoms, or a halogen atom, preferably a bromine or a chlorine atom, and R is an optionally substituted aryl group, prefer-ably a phenyl group, a substituted phenyl group,
A new class of compounds has now been found which can be used as plant growth regulators, and particularly as chemical gametocides in cereal grains. The compounds of the invention are 2-pyridones having the formula R4 ~ R2 ':
wherein R is an alkyl group, preferably having up to 4 carbon atoms, R is a carboxy group (-COO~) or an agronomically-acceptable salt thereof, or a carbalkoxy group (-COOR, wherein R is an alkyl group, preferably having up to 12 carbon atoms, most preferably up to 4 carbon atoms), R3 is a hydrogen atom or an alkyl group, preferably having up to 4 carbon atoms, R is a hydrogen atom, an alkyl group, preferably having up to 4 carbon atoms, or a halogen atom, preferably a bromine or a chlorine atom, and R is an optionally substituted aryl group, prefer-ably a phenyl group, a substituted phenyl group,
-2 ~
513~i7 a naphthyl group, or a substituted naphthyl group.
In a preferred embodiment of the invention, Rl is a methyl group, R2 is a carboxy group or a salt thereof, R3 is a hydrogen atom or a methyl group, R4 is a hydrogen atom or a halogen atom, and R5 is a substituted phenyl group.
When R2 is a salt of a carboxy group, an alkali metal, alkaline earth metal, or transition metal can provide the cation. The cation can also be ammonium or substituted ammonium. Representative metal salt cations include alkali metal cations, such as sodium, potassium lithium, or the like, alkaline earth metal cations, such as calcium, magnesium, barium, strontium, or the like, or heavy metal cations, such as zinc, manganese, cupric, cuprous, ferric, ferrous, titanium, aluminum, or the like. Among the ammonium salts are those in which the ammonium cation has the formula -NZlZ2Z3Z4, wherein each of zl, z2, z3, and Z4 is individually a hydrogen atom, a hydroxy group, a (Cl-C4)alkoxy group, a ; (Cl-C20)alkyl group, a (C3-C8)alkenyl group, a (C3-C8)-alkynyl group, a (C2-C8)hydroxyalkyl group, a (C2-C8)-alkoxyalkyl group, a (C2-C6)aminoalkyl group, a (C2-C6)halo-alkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenylalkyl group, having up to 4 carbon atoms in the alkyl moiety, an amino or alkyl-substituted amino group, or any two of zl, z2, z3, or Z4 can be taken together to form with the nitrogen atom a 5- or 6*
member heterocyclic ring, optionally having up to one addi-tional hetero oxygen, ni-trogen, or sulfur atom in the ring, and preferably saturated, such as a piperidine, morpholine, pyrrolidine, or piperazine ring, or the like, or any three of zl, z2, z3, or Z4 can be taken together to form ~ith the nitrogen atom a 5- or 6~member aromatic heterocyclic ring, such as a pyrazole or pyridine ring. When the ammonium group contains a substituted alkyl, substituted phenyl or substituted phenylalkyl group, the substituents will generally be selected from halogen atoms, (Cl-C8)alkyl groups, (Cl-C4)alkoxy groups, hydroxy groups, nitro groups, trifluoromethyl groups, cyano groups, amino groups, (Cl-C4)alkylthio groups, and the like.
Such substituted phenyl groups preferably have up to two such substituents. Representative ammonium cations include ammonium, dimethylammonium, 2-ethylhexylammonium, bis(2-hydroxyethyl)-ammonium, tris~2-hydroxyethyl)ammonium, dicyclohexylammonium, t octylammonium, 2-hydroxyethylammonium, morpholinium, piper-idinium, 2-phenethylammoniumlji 2~methylbenzylammonium, n-hexyl- ;
ammonium, triethylammonium, trimethylammonium, tri(n-butyl)-ammonium, methoxyethylammonium, diisopropylammonium, pyridinium, -diallylammonium, pyra~olium, propargylammonium, dimethylhydra-zinium, hydroxyammonium, methoxyammonium, dodecylammonium, octadecylammonium, 4-dichlorophenylammonium, 4-nitrobenzyl~
ammonium, benzyltrimethylammonium, 2-hydroxyethyldimethylocta-decylammonium, 2-hydroxyethyldiethyloctylammonium, decyltri-methylammonium, hexyltriethylammonium, 4-methylbenzyltrimethyl-ammonium, and the like.
Among the subs.ituents which R5 can contain are alkyl groups, preferably having up to 4 carbon atoms, aryl groups, preferably phenyl or substituted phenyl groups, alkyl-oxy groups~ preferably having up to 4 carbon atoms, phenoxy or substituted phe ~ groups, halogen atoms, such as fluorine, chlorine, bromine, and iodine atoms, nitro :
~35~357~
groups, perhaloalkyl groups, such as trifluoromethyl groups, alkoxyalkyl groups, preferably having up to 6 carbon atoms, alkoxyalkoxy groups, preferably having up to 6 carbon atoms, amino groups, alkyl or dialkyl amino groups, preferably having up to 4 carbon atoms in each alkyl substituent, cyano groups, carboxy groups, carbalkoxy groups, preferably having up to 4 carbon atoms in the alkoxy moiety, carbamoyl groups, alkyl or dialkyl carbamoyl groups, preferably having :
up to 4 carbon atoms in each alkyl substituents, sulfo groups, sulfonamido groups, alkylcarbonyl or carboxyalkyl groups, preferably having up to 4 carbon atoms in the alkyl moiety, alkanoyloxy groups, preferably having up to 4 carbon -.:
atoms, haloalkyl groups, alkanoylamido groups, preferably having up to 4 carbon atoms, alkylthio groups, preferably having up to 4 carbon atoms, alkylsulfinyl groups, prefer-ably having up to 4 carbon atoms, alkylsulfonyl groups, preferably having up to 4 carbon atoms, and the like. Gen-erally, R5 will have up to two substituents. The most preferred substituents are halogen atoms~ preferably with at least one in the 4-position, (Cl-C4)alkyl groups, prefer-ably 4-methyl, (Cl-C4)alkoxy groups, preferably 4-methoxy, trifluoromethyl groups, preferably 4-trifluoromethyl, and nitro groups, preferably 4-nitro.
Typical compounds within the scope of this inven-25 tion include: ;
N~(4-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(3-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-bromophenyl)-5 carboxy-4,6-dimethylpyrid-2-one N-(2-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-iodophenyl)-5-carboxy-4,6-dimethylpyrid-2-one ~5~ii~7 N-(2-fluorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-trifluoromethylphenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-methoxyphenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(3-nitrophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-cyanophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-nitrophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-cyanophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(3-ethoxyphenyl)-5-carboxy-6-methylpyrid-2-one N-(4-methylphenyl)-5-carboxy-6-methylpyrid-2-one N-(3,4-dichlorophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-methyl-3-chlorophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-3 a 4,6-trimethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-4,6-diethylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-4,6-diethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-4,6-dipropylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-4-ethyl-6-methylpyrid-2-one N-(4-trifluoromethylphenyl)-5-carboxy-6-ethyl-4-methylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-6-ethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-6-propylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-3,6-dimethylpyrid-2-one N-(4-trifluoromethylphenyl)-5-carboxy-3 9 6-dimethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-6-methylpyrid-2-one N-(3,4-dichlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(2-chloro-4-methylphenyl)-5-carboxy-4,6-dimethylpyrid-2-one
513~i7 a naphthyl group, or a substituted naphthyl group.
In a preferred embodiment of the invention, Rl is a methyl group, R2 is a carboxy group or a salt thereof, R3 is a hydrogen atom or a methyl group, R4 is a hydrogen atom or a halogen atom, and R5 is a substituted phenyl group.
When R2 is a salt of a carboxy group, an alkali metal, alkaline earth metal, or transition metal can provide the cation. The cation can also be ammonium or substituted ammonium. Representative metal salt cations include alkali metal cations, such as sodium, potassium lithium, or the like, alkaline earth metal cations, such as calcium, magnesium, barium, strontium, or the like, or heavy metal cations, such as zinc, manganese, cupric, cuprous, ferric, ferrous, titanium, aluminum, or the like. Among the ammonium salts are those in which the ammonium cation has the formula -NZlZ2Z3Z4, wherein each of zl, z2, z3, and Z4 is individually a hydrogen atom, a hydroxy group, a (Cl-C4)alkoxy group, a ; (Cl-C20)alkyl group, a (C3-C8)alkenyl group, a (C3-C8)-alkynyl group, a (C2-C8)hydroxyalkyl group, a (C2-C8)-alkoxyalkyl group, a (C2-C6)aminoalkyl group, a (C2-C6)halo-alkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenylalkyl group, having up to 4 carbon atoms in the alkyl moiety, an amino or alkyl-substituted amino group, or any two of zl, z2, z3, or Z4 can be taken together to form with the nitrogen atom a 5- or 6*
member heterocyclic ring, optionally having up to one addi-tional hetero oxygen, ni-trogen, or sulfur atom in the ring, and preferably saturated, such as a piperidine, morpholine, pyrrolidine, or piperazine ring, or the like, or any three of zl, z2, z3, or Z4 can be taken together to form ~ith the nitrogen atom a 5- or 6~member aromatic heterocyclic ring, such as a pyrazole or pyridine ring. When the ammonium group contains a substituted alkyl, substituted phenyl or substituted phenylalkyl group, the substituents will generally be selected from halogen atoms, (Cl-C8)alkyl groups, (Cl-C4)alkoxy groups, hydroxy groups, nitro groups, trifluoromethyl groups, cyano groups, amino groups, (Cl-C4)alkylthio groups, and the like.
Such substituted phenyl groups preferably have up to two such substituents. Representative ammonium cations include ammonium, dimethylammonium, 2-ethylhexylammonium, bis(2-hydroxyethyl)-ammonium, tris~2-hydroxyethyl)ammonium, dicyclohexylammonium, t octylammonium, 2-hydroxyethylammonium, morpholinium, piper-idinium, 2-phenethylammoniumlji 2~methylbenzylammonium, n-hexyl- ;
ammonium, triethylammonium, trimethylammonium, tri(n-butyl)-ammonium, methoxyethylammonium, diisopropylammonium, pyridinium, -diallylammonium, pyra~olium, propargylammonium, dimethylhydra-zinium, hydroxyammonium, methoxyammonium, dodecylammonium, octadecylammonium, 4-dichlorophenylammonium, 4-nitrobenzyl~
ammonium, benzyltrimethylammonium, 2-hydroxyethyldimethylocta-decylammonium, 2-hydroxyethyldiethyloctylammonium, decyltri-methylammonium, hexyltriethylammonium, 4-methylbenzyltrimethyl-ammonium, and the like.
Among the subs.ituents which R5 can contain are alkyl groups, preferably having up to 4 carbon atoms, aryl groups, preferably phenyl or substituted phenyl groups, alkyl-oxy groups~ preferably having up to 4 carbon atoms, phenoxy or substituted phe ~ groups, halogen atoms, such as fluorine, chlorine, bromine, and iodine atoms, nitro :
~35~357~
groups, perhaloalkyl groups, such as trifluoromethyl groups, alkoxyalkyl groups, preferably having up to 6 carbon atoms, alkoxyalkoxy groups, preferably having up to 6 carbon atoms, amino groups, alkyl or dialkyl amino groups, preferably having up to 4 carbon atoms in each alkyl substituent, cyano groups, carboxy groups, carbalkoxy groups, preferably having up to 4 carbon atoms in the alkoxy moiety, carbamoyl groups, alkyl or dialkyl carbamoyl groups, preferably having :
up to 4 carbon atoms in each alkyl substituents, sulfo groups, sulfonamido groups, alkylcarbonyl or carboxyalkyl groups, preferably having up to 4 carbon atoms in the alkyl moiety, alkanoyloxy groups, preferably having up to 4 carbon -.:
atoms, haloalkyl groups, alkanoylamido groups, preferably having up to 4 carbon atoms, alkylthio groups, preferably having up to 4 carbon atoms, alkylsulfinyl groups, prefer-ably having up to 4 carbon atoms, alkylsulfonyl groups, preferably having up to 4 carbon atoms, and the like. Gen-erally, R5 will have up to two substituents. The most preferred substituents are halogen atoms~ preferably with at least one in the 4-position, (Cl-C4)alkyl groups, prefer-ably 4-methyl, (Cl-C4)alkoxy groups, preferably 4-methoxy, trifluoromethyl groups, preferably 4-trifluoromethyl, and nitro groups, preferably 4-nitro.
Typical compounds within the scope of this inven-25 tion include: ;
N~(4-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(3-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-bromophenyl)-5 carboxy-4,6-dimethylpyrid-2-one N-(2-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-iodophenyl)-5-carboxy-4,6-dimethylpyrid-2-one ~5~ii~7 N-(2-fluorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-trifluoromethylphenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-methoxyphenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(3-nitrophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-cyanophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-nitrophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-cyanophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(3-ethoxyphenyl)-5-carboxy-6-methylpyrid-2-one N-(4-methylphenyl)-5-carboxy-6-methylpyrid-2-one N-(3,4-dichlorophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-methyl-3-chlorophenyl)-5-carboxy-6-methylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-3 a 4,6-trimethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-4,6-diethylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-4,6-diethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-4,6-dipropylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-4-ethyl-6-methylpyrid-2-one N-(4-trifluoromethylphenyl)-5-carboxy-6-ethyl-4-methylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-6-ethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-6-propylpyrid-2-one N-(4-chlorophenyl)-5-carboxy-3,6-dimethylpyrid-2-one N-(4-trifluoromethylphenyl)-5-carboxy-3 9 6-dimethylpyrid-2-one N-(4-bromophenyl)-5-carboxy-6-methylpyrid-2-one N-(3,4-dichlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one N-(2-chloro-4-methylphenyl)-5-carboxy-4,6-dimethylpyrid-2-one
3-bromo-N-(4-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one 3-bromo-N-(4-fluorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one 3 3-chloro-N-(2,4-dichlorophenyl)-5-carboxy-4,6-dimethylpyrid--2-one 85~
3-fluoro-N-(3-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one 3-brorno-N-(4-trifluoromethylphenyl)-5-carboxy-6-methylpyrid-2-one and agronomically-acceptable salts of the above acids, N-(4-chlorophenyl)-5-carbomethoxy-4,6-dimethylpyrid-2-one N-(4-fluorophenyl)-5-carbethoxy 4,6 dimethylpyrid-2-one N-(3-methylphenyl)-5-carbobutoxy-4,6-dimethylpyrid-2-one N-(3,4-dichlorophenyl)-5-carbethoxy-6-methylpyrid-2-one N-phenyl-5-carbmethoxy-6-methylpyrid-2-one and the like.
The compounds of the invention can be prepared by several convenient preparative routes. In the first method, an acid chloride of the formula (II) H COCl wherein R6 is a hydrogen atom or an alkyl group~ and R3 is as defined above, is condensed with an enamine of the formula R2 C _~Rl ~ (III) ~ :
H NHR -wherein R, R , and R are as defined above, to yield a dihydropyridone of the formula ~~ C 2 (IV) Nl ~ 1 35~
wherein R, Rl, R3, R5, and R6 are as defined above. This reaction is generally carried out in an inert solvent, such as ethyl etherl methylene chloride, benzene, toluene, or the like, at a temperature of about 0 to about 100C. The dihydro-pyridone is then dehydrogenated in the presence of a dehydro-genating agentl such as 2,3-dichloro-5,6-dic~ano-1~-A4~-~enzo-quinone or similar quinone, palladium on charcoal, N-bromo-succinimide, or the like, in an inert solvent, such as benzene, xylene, chlorobenzene, or the like, generally at a temperature of about 50C to about 250 C to form a pyridone of the formula R
R6,~C02R (V) o ¦ R
wherein R, R , R , R5, and R are as defined above. The ester can then be converted to the corresponding acid or salt by a conventional hydrolysis, such as with sodium hydroxide, potassium hydroxide, or the lik~, at ambient or elevated temperature of up to about 100 C.
In a second preparative route to compounds of the invention, a pyrone of the formula ~/C02R :~
~ ~ (VI~
~ \Rl wherein R, Rl, and R are as defined above, is reacted with an amine of the formula .
~8~8~
NH2-R5 (VII) wherein R is as defined above, in the presence of an acid catalyst, such as p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid, or the like, in an inert solvent such as chlorobenzene, toluene, xylene, cumene, or the like, or using 50% aqueous acetic acid as the reaction medium, to form a pyridone of the formula C02R .. ' l ll (VIII) 0~ 1 ~\
wherein R, Rl, R3, and R5 are as defined above. This reaction is generally carried out at a temperature of about 50 C to about 250 C. The free acid and its salts can then be pre-pared by conventional techniques.
The compounds of the invention in which R4 is a halogen atom can be prepared by reacting the corresponding
3-fluoro-N-(3-chlorophenyl)-5-carboxy-4,6-dimethylpyrid-2-one 3-brorno-N-(4-trifluoromethylphenyl)-5-carboxy-6-methylpyrid-2-one and agronomically-acceptable salts of the above acids, N-(4-chlorophenyl)-5-carbomethoxy-4,6-dimethylpyrid-2-one N-(4-fluorophenyl)-5-carbethoxy 4,6 dimethylpyrid-2-one N-(3-methylphenyl)-5-carbobutoxy-4,6-dimethylpyrid-2-one N-(3,4-dichlorophenyl)-5-carbethoxy-6-methylpyrid-2-one N-phenyl-5-carbmethoxy-6-methylpyrid-2-one and the like.
The compounds of the invention can be prepared by several convenient preparative routes. In the first method, an acid chloride of the formula (II) H COCl wherein R6 is a hydrogen atom or an alkyl group~ and R3 is as defined above, is condensed with an enamine of the formula R2 C _~Rl ~ (III) ~ :
H NHR -wherein R, R , and R are as defined above, to yield a dihydropyridone of the formula ~~ C 2 (IV) Nl ~ 1 35~
wherein R, Rl, R3, R5, and R6 are as defined above. This reaction is generally carried out in an inert solvent, such as ethyl etherl methylene chloride, benzene, toluene, or the like, at a temperature of about 0 to about 100C. The dihydro-pyridone is then dehydrogenated in the presence of a dehydro-genating agentl such as 2,3-dichloro-5,6-dic~ano-1~-A4~-~enzo-quinone or similar quinone, palladium on charcoal, N-bromo-succinimide, or the like, in an inert solvent, such as benzene, xylene, chlorobenzene, or the like, generally at a temperature of about 50C to about 250 C to form a pyridone of the formula R
R6,~C02R (V) o ¦ R
wherein R, R , R , R5, and R are as defined above. The ester can then be converted to the corresponding acid or salt by a conventional hydrolysis, such as with sodium hydroxide, potassium hydroxide, or the lik~, at ambient or elevated temperature of up to about 100 C.
In a second preparative route to compounds of the invention, a pyrone of the formula ~/C02R :~
~ ~ (VI~
~ \Rl wherein R, Rl, and R are as defined above, is reacted with an amine of the formula .
~8~8~
NH2-R5 (VII) wherein R is as defined above, in the presence of an acid catalyst, such as p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid, or the like, in an inert solvent such as chlorobenzene, toluene, xylene, cumene, or the like, or using 50% aqueous acetic acid as the reaction medium, to form a pyridone of the formula C02R .. ' l ll (VIII) 0~ 1 ~\
wherein R, Rl, R3, and R5 are as defined above. This reaction is generally carried out at a temperature of about 50 C to about 250 C. The free acid and its salts can then be pre-pared by conventional techniques.
The compounds of the invention in which R4 is a halogen atom can be prepared by reacting the corresponding
4-pyridones in which R4 is a hydrogen atom with one equivalent of a halogenating agent such as bromine, chlorine, sulfuryl bromide, sulfuryl chloride, or the like in a suitable inert -solvent such as ethylene dichloride, methanol, or the like, generally at a temperature of about 0 to about 100C.
The following examples will further illustrate the compounds of the invention and their preparation, but are not intended to limit the invention in any way. All temperatures are in degrees Celsius and parts and percentages are by weight, unless otherwise indicated. Specific illustrative preparations of the compounds of Examples l, l9, 25, and 28 ~8~S7 are provided. Table I lists typical compounds of the invention and their melting points and elemental analyses. 7 _ ~5~35~
TABLE I
Y~C02R
''.
~X ~.' Example No. X Y R MP C _ H N X
1 4-Cl H H 358-9 60.55 4.36 5.o6 12.77 60.85 4.42 4.99 13.07 2 4-Cl H Na >300 56.10 3.70 4.67 11.83 55.29 3.78 4.73 11.65 3 H H H 250-1 69.12 5.39 5.76 -69.57 5.40 5.61 4 H H Na ~300 63.39 4.56 5.28 61.54 4.78 5.18 4-CH3 H H 238-40 70.02 5.88 5.45 -70.14 6.02 5.29 6 4-CH H Na >300 64.51 5.05 5.02 3 63.45 5.18 5.09 7 3,4-diCl H H 276-7 53.87 3.55 4.49 22.72 54.02 3.54 4.32 22.68 8 394-diCl H Na 296-7 50.32 3.02 4.19 21.22 45.25 3.17 4.05 21.40 9 4-~ H H 260-1 64.36 4.63 5.36 7.27 63.89 4.59 5.53 7.7 4-F H Na >300 59.36 3.92 4.95 6.71 58.83 3.88 5.03 4.95 11 3-Cl H H 254-5 60.55 4.36 5.04 12.77 60.03 4.31 5.05 13.63 12 3-Cl H Na >300 56.10 3.70 4.67 11.83 53.57 3.75 4.46 11.45 13 4-CH3,3-Cl H H 247 51 61.75 4.84 4.80 12.16 61.61 4.88 5.27 12.24 TABLE I (con~t'd) Example No. X Y R MP C H N X
14 4-CH ,3-Cl H Na >300 54.29 4.56 4.2210.66 3 54.88 4.23 4.3911.05 4-OCH H H 219-21 65.92 5.53 5.13 3 65.52 5.39 5.18 16 4-oCH3 H Na 295-8 17 4-CF H H 230-2 57.88 3.89 4.5018.31 3 58.31 3.93 4.6618.04 18 4 CF3 H Na >300 19 4-Br H H 244-6 52.19 3.76 4.3524.81 52.67 3.85 4.6024.84 4 Br H Na ~300 21 4-Cl naph-thyl H H 264-6 65.96 4.31 4.27 10.82 65.68 4.27 4.4111.03 22 4-Cl naph-thyl H Na >300 23 4-Cl Br H 243-6 47.14 3.11 3.93 47.65 3.13 4.29 24 4-Cl Br Na >220 4-Br Br H 248-50 41.92 2.77 3.49 39.85 1l2.o6 2.72 3.91 40.33 26 4-Br Br Na 290 27 4-Br H C2H5129-30 54.87 4.61 4.00 22.82 54.97 4.69 3.98 23.33 Y ~ C02R
~X
28 4-Cl H H 271-73 59.21 3.82 5.31 13.45 59.17 3.76 5.71 13.1l9
The following examples will further illustrate the compounds of the invention and their preparation, but are not intended to limit the invention in any way. All temperatures are in degrees Celsius and parts and percentages are by weight, unless otherwise indicated. Specific illustrative preparations of the compounds of Examples l, l9, 25, and 28 ~8~S7 are provided. Table I lists typical compounds of the invention and their melting points and elemental analyses. 7 _ ~5~35~
TABLE I
Y~C02R
''.
~X ~.' Example No. X Y R MP C _ H N X
1 4-Cl H H 358-9 60.55 4.36 5.o6 12.77 60.85 4.42 4.99 13.07 2 4-Cl H Na >300 56.10 3.70 4.67 11.83 55.29 3.78 4.73 11.65 3 H H H 250-1 69.12 5.39 5.76 -69.57 5.40 5.61 4 H H Na ~300 63.39 4.56 5.28 61.54 4.78 5.18 4-CH3 H H 238-40 70.02 5.88 5.45 -70.14 6.02 5.29 6 4-CH H Na >300 64.51 5.05 5.02 3 63.45 5.18 5.09 7 3,4-diCl H H 276-7 53.87 3.55 4.49 22.72 54.02 3.54 4.32 22.68 8 394-diCl H Na 296-7 50.32 3.02 4.19 21.22 45.25 3.17 4.05 21.40 9 4-~ H H 260-1 64.36 4.63 5.36 7.27 63.89 4.59 5.53 7.7 4-F H Na >300 59.36 3.92 4.95 6.71 58.83 3.88 5.03 4.95 11 3-Cl H H 254-5 60.55 4.36 5.04 12.77 60.03 4.31 5.05 13.63 12 3-Cl H Na >300 56.10 3.70 4.67 11.83 53.57 3.75 4.46 11.45 13 4-CH3,3-Cl H H 247 51 61.75 4.84 4.80 12.16 61.61 4.88 5.27 12.24 TABLE I (con~t'd) Example No. X Y R MP C H N X
14 4-CH ,3-Cl H Na >300 54.29 4.56 4.2210.66 3 54.88 4.23 4.3911.05 4-OCH H H 219-21 65.92 5.53 5.13 3 65.52 5.39 5.18 16 4-oCH3 H Na 295-8 17 4-CF H H 230-2 57.88 3.89 4.5018.31 3 58.31 3.93 4.6618.04 18 4 CF3 H Na >300 19 4-Br H H 244-6 52.19 3.76 4.3524.81 52.67 3.85 4.6024.84 4 Br H Na ~300 21 4-Cl naph-thyl H H 264-6 65.96 4.31 4.27 10.82 65.68 4.27 4.4111.03 22 4-Cl naph-thyl H Na >300 23 4-Cl Br H 243-6 47.14 3.11 3.93 47.65 3.13 4.29 24 4-Cl Br Na >220 4-Br Br H 248-50 41.92 2.77 3.49 39.85 1l2.o6 2.72 3.91 40.33 26 4-Br Br Na 290 27 4-Br H C2H5129-30 54.87 4.61 4.00 22.82 54.97 4.69 3.98 23.33 Y ~ C02R
~X
28 4-Cl H H 271-73 59.21 3.82 5.31 13.45 59.17 3.76 5.71 13.1l9
5~
Example 1 Preparation of N-(4-chlorophenyl)-5-carboxy-4,6-dimethyl-pvrid~2-one .~ . . .
(a) 4-Chloroaniline (48.4 g), ~-toluene sulfonic acid (4.7 g) and ethyl isodehydracetate (65 g) are suspended in cumene (260 ml). The reaction mixture is brought to reflux, and water collected in a Dean-Stark trap. After 18 hours, the reaction mixture is cooled and washed with dilute hydrochloric acid to remove excess 4-chloroaniline. The cumene is then ;
removed in vacuo, leaving the crude 5-carbethoxy-N-(4-chloro-phenyl)-4,6 dimethylpyrid-2-one as a dark brown oil.
(b) The crude ester prepared in (a) above is suspended in a solution prepared by mixing methanol (500 ml), water (500 ml) and 50% aqueous sodium hydroxide (50 g). The suspension is refluxed for six hours. The solvent is then removed in vacuo and replaced with water (1000 ml). Insoluble material is filtered off and discarded~ The clear aqueous layer is then acidified with hydrochloric acid and the result-ing precipitate is filtered and dried, to yield ~after - -recrystallization from acetone) 55 g of product, N-(4-chloro-phenyl)-4,6-dimethyl pyrid-2-one-5-carboxylic acid, having a melting point of 258-9 (decomposition~.
Example 19 Preparation of N-(4-bromophenyl)-5-carboxy-4,6-dimethylpyrid-2-one Ethyl dehydracetate (20 g 0.102 mole) and 4-bromo-ani~ine?~(~l9.3 g, 0.112 mole are dissolved in 50% aqueous acetic acid (100 ml). The mixture is refluxed for 12 hours, the solvent removed, and the crude ester isolated as a brownish oil.
The crude ester isolated above is heated for 6 BS~7 hours with 300 g 5% NaOH in 1:1 methanol/water. The mixture is cooled, diluted with water (100 ml) and filtered to remove insolubles. Some of the methanol is removed in vacuo, and an additional portion of water is added. The clear basic solution is then acidified and the resulting precipitate is filtered and dried. Recrystallization from acetonitrile provides pure N-(4-bromophenyl)-5-carboxy-4,6-dimethyl-pyrid-2-one (5.3 g, 16.1 % yield) having a melting point of 244-6 (dec).
Example 25 Preparation of N-(4-bromophenyl)-3-bromo-5-carboxy-4,6-dime'thy'lpyrid'-'2-one' ' ' ' '' Sodium N-(4-bromophenyl)-4,6-dimethylpyrid-2-one-5-carboxylate (285 g, 0.00828 mole) is dissolved in dry t methanol (5O ml). Bromine (1.59 g, 0.00994 moles, 1.2 equivalents) is dissolved in methanol (5O ml) and slowly drop~added to the vigorously stirred salt solution over a period of 15 to 20 minutes. The solvent is then removed and the residue taken up in dilute base.
After filtering off the insoluble material, the clear basic aqueous solution is acidified with hydrochloric acid. The resulting precipitate is filtered and dried, and recrystallized from acetonitrile to yield N-(ll-bromophenyl)-3-bromo-5-carboxy-4,6-dimethyl-pyrid-2-one (2.25 g, 67.8%) having a melting point of 248-250~. ';
Example 28 Preparation of N-(4-chlorophenyl)-5-carboxy-6-methylpyrid-2-one (a) Ethyl ~-anilinocrotonate (23.9 g) is dissolved 3o in dry benzene (200 ml) and placed in a flask under a nitrogen atmosphere. Acryloyl chloride (10 g) is dissolved in additional dry benzene (200 ml) and drop-added via a sidearm additional funnel over the course of 1 1/2 hour.
The reaction mixture is allowed to stand at about 25 for one hour, and then poured into water and extracted with methylene chloride. Evaporation of the solvent yields crude 5-carbethoxy-N-(4-chlorophenyl)-6-methyl-3,4-dihydropyrid-2-one (23.3 g) having a melting point of 124-6 (from hexane/
ether).
(b) The ester (15 g) prepared in (a) above is dissolved in chlorobenzene (500 ml). 2,3-Dichloro-5,6-10 dicyano-1,4-benzoquinone (DDQ) (23.2 g) is added and the mixture refluxed for 3 hours. The reaction mixture is then cooled~ filtered and diluted with an equal volume of methylene chloride and washed exhaustively with dilute aqueous sodium bicarbonate. The solvent is removed in vacuo and the residue of crude product is recrystallized from hexane-ether to yield pure 5-carbethoxy-N-(4-chlorophenyl)-
Example 1 Preparation of N-(4-chlorophenyl)-5-carboxy-4,6-dimethyl-pvrid~2-one .~ . . .
(a) 4-Chloroaniline (48.4 g), ~-toluene sulfonic acid (4.7 g) and ethyl isodehydracetate (65 g) are suspended in cumene (260 ml). The reaction mixture is brought to reflux, and water collected in a Dean-Stark trap. After 18 hours, the reaction mixture is cooled and washed with dilute hydrochloric acid to remove excess 4-chloroaniline. The cumene is then ;
removed in vacuo, leaving the crude 5-carbethoxy-N-(4-chloro-phenyl)-4,6 dimethylpyrid-2-one as a dark brown oil.
(b) The crude ester prepared in (a) above is suspended in a solution prepared by mixing methanol (500 ml), water (500 ml) and 50% aqueous sodium hydroxide (50 g). The suspension is refluxed for six hours. The solvent is then removed in vacuo and replaced with water (1000 ml). Insoluble material is filtered off and discarded~ The clear aqueous layer is then acidified with hydrochloric acid and the result-ing precipitate is filtered and dried, to yield ~after - -recrystallization from acetone) 55 g of product, N-(4-chloro-phenyl)-4,6-dimethyl pyrid-2-one-5-carboxylic acid, having a melting point of 258-9 (decomposition~.
Example 19 Preparation of N-(4-bromophenyl)-5-carboxy-4,6-dimethylpyrid-2-one Ethyl dehydracetate (20 g 0.102 mole) and 4-bromo-ani~ine?~(~l9.3 g, 0.112 mole are dissolved in 50% aqueous acetic acid (100 ml). The mixture is refluxed for 12 hours, the solvent removed, and the crude ester isolated as a brownish oil.
The crude ester isolated above is heated for 6 BS~7 hours with 300 g 5% NaOH in 1:1 methanol/water. The mixture is cooled, diluted with water (100 ml) and filtered to remove insolubles. Some of the methanol is removed in vacuo, and an additional portion of water is added. The clear basic solution is then acidified and the resulting precipitate is filtered and dried. Recrystallization from acetonitrile provides pure N-(4-bromophenyl)-5-carboxy-4,6-dimethyl-pyrid-2-one (5.3 g, 16.1 % yield) having a melting point of 244-6 (dec).
Example 25 Preparation of N-(4-bromophenyl)-3-bromo-5-carboxy-4,6-dime'thy'lpyrid'-'2-one' ' ' ' '' Sodium N-(4-bromophenyl)-4,6-dimethylpyrid-2-one-5-carboxylate (285 g, 0.00828 mole) is dissolved in dry t methanol (5O ml). Bromine (1.59 g, 0.00994 moles, 1.2 equivalents) is dissolved in methanol (5O ml) and slowly drop~added to the vigorously stirred salt solution over a period of 15 to 20 minutes. The solvent is then removed and the residue taken up in dilute base.
After filtering off the insoluble material, the clear basic aqueous solution is acidified with hydrochloric acid. The resulting precipitate is filtered and dried, and recrystallized from acetonitrile to yield N-(ll-bromophenyl)-3-bromo-5-carboxy-4,6-dimethyl-pyrid-2-one (2.25 g, 67.8%) having a melting point of 248-250~. ';
Example 28 Preparation of N-(4-chlorophenyl)-5-carboxy-6-methylpyrid-2-one (a) Ethyl ~-anilinocrotonate (23.9 g) is dissolved 3o in dry benzene (200 ml) and placed in a flask under a nitrogen atmosphere. Acryloyl chloride (10 g) is dissolved in additional dry benzene (200 ml) and drop-added via a sidearm additional funnel over the course of 1 1/2 hour.
The reaction mixture is allowed to stand at about 25 for one hour, and then poured into water and extracted with methylene chloride. Evaporation of the solvent yields crude 5-carbethoxy-N-(4-chlorophenyl)-6-methyl-3,4-dihydropyrid-2-one (23.3 g) having a melting point of 124-6 (from hexane/
ether).
(b) The ester (15 g) prepared in (a) above is dissolved in chlorobenzene (500 ml). 2,3-Dichloro-5,6-10 dicyano-1,4-benzoquinone (DDQ) (23.2 g) is added and the mixture refluxed for 3 hours. The reaction mixture is then cooled~ filtered and diluted with an equal volume of methylene chloride and washed exhaustively with dilute aqueous sodium bicarbonate. The solvent is removed in vacuo and the residue of crude product is recrystallized from hexane-ether to yield pure 5-carbethoxy-N-(4-chlorophenyl)-
6-methylpyrid-2-one (8.3 g) having a melting point of 53-4.
(c) The pyridone (7.0 g) prepared in (b) above is suspended in 5% aqueous sodium hydroxide (200 ml). The mixture is heated on a steambath for one hour, cooled and acidified with aqueous hydrochloric acid to yield N-(4-chlorophenyl)-5 carboxy-6-methylpyrid-2-one (4.0 g) which, when recrystallized from acetonitrile has a melting point of 271-3 with decomposition.
The compounds of the invention are particularly useful as chemical gametocides in cereal crops, such as wheat, barley, corn, rice, sorghum, millets, oats, rye and the like. When used as chemical gametocides, the compounds effectively induce a high degree of sterility in the treated plants, without causing significant growth inhibition of the treated plants. The compounds of the invention also cause other plant growth regulatory responses,~ such as for example, inhibition of seed formation in undesirable monocot species for weed grass control, control of flowering, control of fruiting and inhibition of seed formation in non-cereal species, control of ripening, and other related growth regulatory responses.
When used as plant growth regulators, the com-pounds of the invention are applied in any amount which will be sufficient to effect the desired plant response without causing any undesirable or phytotoxic response. For example, when the compounds of the invention are used as chemical gametocidesg they are generally applied to the plants to be treated as a rate of about 1/32 to about 20 pounds per acre and preferably about 1/8 to about 10 pounds per acre.
The rate of application will vary depending on the plant species being treated, the compound being used for treatment, and related factors.
A preferred method of applying a compound of the invention as a plant growth regulator is by foliar appli-cation. When this method is employed, gametocidal activity is most effectively induced when the compound is applied prior to meiosis, and preferably after flower initiation.
The compounds of the inventions may also be applied as a seed treatment by soaking the seed in a liquid formulation containing the active compound or by coating the seed with the compound. In seed treatment applications, the compounds of the invention will generally be applied at a rate of about 1/4 to about 10 pounds per hundred weight of seed. The compounds of the invention can also be applied to the soil or, in rice crops, to the water surface.
The compounds of the invention can be used as plant growth regulators either individually or in mixtures.
For example, they can be used in combination with other plant growth regulators, such as auxins, gibberellins, morphactins, ethylene-releasing agents such as ethephon, pyridones, cytokinins, maleic hydrazide9 succinic acid 2,2-dimethyl~
hydrazide, choline and its salts, (2-chloroethyl) trimethyl-ammonium chloride, triiodobenzoic acid, tributyl-2,4-di-chlorobenzylphosphonium chloride, polymeric N-vinyl-2-oxazolidinones, tri(dimethylaminoethyl) phosphate and its salts, and N-dimethylamino-1,2,3,6-tetrahydrophthalamic acid and its salts, 2,3-dichloroisobutyric acid and its salts, 3-(4-chlorophenyl)-6-methoxy-s-triazine-2,4-(lH,3H)-dione, and the like, and under some conditions may be usedadvantageously with other agricultural chemicals such as herbicides, fungicides~ insecticides, and plant bactericides.
A compound of the invention can be applied to the growth medium or to plants to be treated either by itself or, as is generally done, as a component in a growth regulant composition or formulation which also comprises an agronomic-ally acceptable carrier. By '!agronomically acceptable carrier" is meant any substance which can be used to dissolve, disperse, or diffuse a compound in the composition without `
impairing the effectiveness of the compound and which by itself has no significant detrimental effect on the soil~
equipment, crops, or agronomic environment. Mixtures of compounds of the invention may also be used in any of these formulations. Compositions of the invention can be either solid or liquid formulations or solutions. For example, the i7 compounds can be formulated as wettable powders, emulsifi-able concentrates, dusts, granular formulations, aerosols, or flowable emulsion concentrates. In such formulations, the compounds are extended with a liquid or solid carrier and, when desired suitable sur~actants are incorporated.
It is usually desirable, particularly in foliar applications, to include adjuvants, such as wetting agents, spreading agents 3 dispersing agents, stickers, adhesives, and the like, in accordance with agricultural practices.
Examples of adjuvants which are commonly used in the art can be found in the John W. McCutcheon, Inc. publication "Detergents and Emulsifiers Annual."
The compounds of the invention can be dissolved in any appropriate solvent. Examples of solvents which are useful in the practice of this invention include water, alcohols, ketones, aromat~c hydrocarbons, halo~enated hydro-carbons 3 dimethylformamide, dioxane, dimethyl sulfoxide, and the like. Mixtures of these solvents can also be used.
The concentration of the solution can vary from about 2% to about 98% by weight with a preferred range being about 20%
to about 75%.
For the preparation of emulsifiable concentrates, the compound can be dissolved in organic solvents, such as benzene, toluene, xylene, methylated naphthalene 3 corn oil, pine oil, o-dichlorobenzene, isophorone, cyclohexanone, methyl oleate, and the like, or in mixtures of these solvents, together with an emulsifying agent or surfactant which permits disperson in water. Suitable emulsifiers include, for example, the ethylene oxide derivatives of alkylphenols or long-chain alcohols, mercaptans, carboxylic acids, and reactive amines and partially esterified polyhydric alcohols.
Solvent-soluble sulfates or sulfonates, such as the alkaline earth salts or amine salts of alkylbenzenesulfonates and the fatty alcohol sodium sulfates, having surface-active properties can be used as emulsifiers either alone or in con~unction with an ethylene oxide reaction product. Flow-able emulsion concentrates are formulated similarly to the emulsifiable concentrates and include, in addition to the above components, water and a stabilizing agent such as a water-soluble cellulose derivative or a water-soluble salt of a polyacrylic acid. The concentration of the active f~
ingredient in emulsifiable concentrates is usually about 10% to 60% by weight and in flowable emulsion concentrates this can be as high as about 75%.
Wettable powders suitable for spraying can be prepared by admixing the compound with a finely divided solid, such as clays, inorganic silicates and carbonates, and silicas and incorporating wetting agents, sticking agents, and/or dispersing agents in such mixtures. The concentration of active ingredients in such formulations ::s usually in the range of about 20% to 98% by weight, prefer-ably about Llo% to 75%. A dispersing agent may generally consititute about 0.5% to about 3% by weight o~ the compo-sition, and a wetting agent may generally constitute from about 0.1% to about 5% by weight of the composition.
Dusts can be prepared by mixing the compounds of the invention with finely divided inert solids which may be organic or inorganic in nature. Materials useful for this purpose include, for example, botanical flours, silicas, silicates, carbonates and clays. One convenient method of , preparing a dus~ is to dilute a wettable powder with a finely divided carrier. Dust concentrates containing about 20% to 80% of the active ingredient are commonly made and are sub-sequently diluted to about 1~ to 10~ by weight use concen-tration.
Granular formulations can be prepared by impreg-nating a solid such as granular fuller's earth, vermiculite, ground corn cobs, seed hulls, including bran or other grain hulls, or similar material. A solution of one or more of the compounds in a volatile organic solvent can be sprayed or mixed with the granular solid and the solvent then removed by evaporation. The granular material can have any suitable size, with a preferable size range of 16 to 60 mesh. The active compound will usually comprise about 2 to about 15% by weight of the granular ~ormulation.
Salts of the compounds of the invention can be formulated and applied as aqueous solutions. The salt will typically aomprise about 0~05 to about 50% by weight, prefer-ably about 0.1% to about 10~, of the solution. These compo-sitions can also be further diluted with water if desiredprior to actual application. In some applications, the activ-ity of these compositions can be enhanced by incorporating into the composition an adjuvant such as glycerin, methylethyl-cellulose, hydroxyethylcellulose, polyoxyethylenesorbitan monooleate, polypropylene glycol, polyacrylic acid, poly- ~
ethylene sodium malate, polyethylene oxide, or the like. The adjuvant will generally comprise about 0.1 to about 5% by weight, preferably about 0.5 to about 2%, of the composition. Such compositions can also optionally include an agronomically-acceptable surfactant.
.. . ...
1~385~357 The compounds of the invention can be applied as sprays by methods commonly employed, such as conventional hydraulic sprays, aerial sprays, and dusts. For low-volume applications a solution of the compound is usually used.
The dilution and volume of application will usually depend upon such factors as the type of equipment employed, the method of application, the area to be treated and the type and stage of development of the crop being treated.
The following exmaples will further illustrate 10 the growth regulatory activity of the compounds of the `~
invention but are not intended to limit the invention in any way.
'Examp'le''29 Che~mic l Gam'et'oc'idal Activity The following procedures are used to evaluate the ~
activity of the compounds of the invention as chemical ,~, gametocides in cereals.
An awned variety (Fielder) and an awnless variety (Mayo-64) of spring wheat are planted at the rate of 6 to 8 ~ , seeds per 6" pot containing a sterile medium of 3 parts ' soil and 1 part humus. The plants are grown under short-day (9 hour) conditions for the first 4 weeks to obtain good vegetative growth before flower initiation. The plants are then moved to long-day (16 hour) conditions which are pro-vided by high intensity lights in the greenhouse. The plants are fertilized at 2, 4, and 8 weeks after planing with a water soluble fertilizer (16-25-16) at the rate of 1 tsp/gal of water, and are frequently sprayed with isotox for aphid control and dusted with sulfur for powdery mildew control.
3o Test ^ompounds are foliarly applied to the awned 3S~35~7 female plants when these plants reach the flag leaf emergence stage (stage 8 on Feekes' scale). All compounds are applied in a carrier volume of 50 gal/A con~aining a surfactant, such as "Triton x-100"*, at the rate of 2 oz/50 gal.
After spike emergence but before anthesis, 4 to 6 spikes per pot are bagged to prevent outcrossing. At the first signs of flower opening, two spikes per pot are cross pollin-ated, using the approach method, with the a~nless male parent.
As soon as the seeds became plainly visible, spike length is 10 measured and seeds per spikelet counted in both bagged and -~
crossed spikes. Male sterility is then calculated as percent inhibition of seed set in bagged spikes of treated plants.
After maturity the seed on crossed spikes can be planted for determination of percent hybridization.
Percent sterility is calculated from the following formula:
% Sterility = C St x 100 ~t C
Sc = seeds/spikelet in bagged spikes of control plants St = seeds/spikelet in bagged spikes of treated plants Table II summarizes typical results obtained in the evaluation of compounds of the invention. A dash indicates that no test at the indicated rate was made.
*Trademark of Rohm and Haas ~om~pany ~or a liquid nonionic - surfactant; it is octylphenoxy polyethoxy ethanol.
. r .
TABLE II
CH3 ~:
Y~ C02R
Jl ;-~ I \ CH3 ' ~:
Rate(lb./A) ~ Sterility X Y R ~ 4 2 1 1/21/4 1/8 4-Cl H H100 100100 96 4-Cl HNa 100100 100100 92 52 H HNa 46 0 13 8 4-CH3 HNa 0 0 0 1411 2 3 3,4-diCl H H 98 93 80 122016 12 3,4-diCl , HNa 96 91 33 222521 4 4-F HNa 0 0 0 2 7 18 15 3-Cl H H 4 0 0 0 3 3 2 3-Cl H Na 0 2 0 4-CH3,3 Cl H H 6 4 0 19 0 4-CH3,3-Cl H Na 0 2 1 0 1 6 -4-oCH3 H H 56 18 2 9 4-oCH3 H Na 54 31 0 3 - - ~ -4 ' H H 15 3 - - - -4-CF3 H Na 0 3 0 0 4-Br H H 100100 100 - - - -4-Br H Na 100100 100100 100100 100 ~3~ 5~t~
TABLE II (cont'd) X Y R 8 4: 2 11/2 1/4 1/8 .
4~C1 naphthyl H H 2 4-Cl naphthyl H Na 14 4 0 0 4-Cl Br H 9 7 9 1613 4-Cl Br Na 15 13 13 2013 4-Br Br H
4-Br Br Na 100 99 89 4325 4-Br H C2H5 100 _ 100 - 100 - 100 Y ~ C02R ':' O ~ N 3 ~X
4-Cl H Na 100 100 90 39 - - -It should be understood that changes and variations may be made without departing from the spirit and scope of the invention as defined by the appended claims.
(c) The pyridone (7.0 g) prepared in (b) above is suspended in 5% aqueous sodium hydroxide (200 ml). The mixture is heated on a steambath for one hour, cooled and acidified with aqueous hydrochloric acid to yield N-(4-chlorophenyl)-5 carboxy-6-methylpyrid-2-one (4.0 g) which, when recrystallized from acetonitrile has a melting point of 271-3 with decomposition.
The compounds of the invention are particularly useful as chemical gametocides in cereal crops, such as wheat, barley, corn, rice, sorghum, millets, oats, rye and the like. When used as chemical gametocides, the compounds effectively induce a high degree of sterility in the treated plants, without causing significant growth inhibition of the treated plants. The compounds of the invention also cause other plant growth regulatory responses,~ such as for example, inhibition of seed formation in undesirable monocot species for weed grass control, control of flowering, control of fruiting and inhibition of seed formation in non-cereal species, control of ripening, and other related growth regulatory responses.
When used as plant growth regulators, the com-pounds of the invention are applied in any amount which will be sufficient to effect the desired plant response without causing any undesirable or phytotoxic response. For example, when the compounds of the invention are used as chemical gametocidesg they are generally applied to the plants to be treated as a rate of about 1/32 to about 20 pounds per acre and preferably about 1/8 to about 10 pounds per acre.
The rate of application will vary depending on the plant species being treated, the compound being used for treatment, and related factors.
A preferred method of applying a compound of the invention as a plant growth regulator is by foliar appli-cation. When this method is employed, gametocidal activity is most effectively induced when the compound is applied prior to meiosis, and preferably after flower initiation.
The compounds of the inventions may also be applied as a seed treatment by soaking the seed in a liquid formulation containing the active compound or by coating the seed with the compound. In seed treatment applications, the compounds of the invention will generally be applied at a rate of about 1/4 to about 10 pounds per hundred weight of seed. The compounds of the invention can also be applied to the soil or, in rice crops, to the water surface.
The compounds of the invention can be used as plant growth regulators either individually or in mixtures.
For example, they can be used in combination with other plant growth regulators, such as auxins, gibberellins, morphactins, ethylene-releasing agents such as ethephon, pyridones, cytokinins, maleic hydrazide9 succinic acid 2,2-dimethyl~
hydrazide, choline and its salts, (2-chloroethyl) trimethyl-ammonium chloride, triiodobenzoic acid, tributyl-2,4-di-chlorobenzylphosphonium chloride, polymeric N-vinyl-2-oxazolidinones, tri(dimethylaminoethyl) phosphate and its salts, and N-dimethylamino-1,2,3,6-tetrahydrophthalamic acid and its salts, 2,3-dichloroisobutyric acid and its salts, 3-(4-chlorophenyl)-6-methoxy-s-triazine-2,4-(lH,3H)-dione, and the like, and under some conditions may be usedadvantageously with other agricultural chemicals such as herbicides, fungicides~ insecticides, and plant bactericides.
A compound of the invention can be applied to the growth medium or to plants to be treated either by itself or, as is generally done, as a component in a growth regulant composition or formulation which also comprises an agronomic-ally acceptable carrier. By '!agronomically acceptable carrier" is meant any substance which can be used to dissolve, disperse, or diffuse a compound in the composition without `
impairing the effectiveness of the compound and which by itself has no significant detrimental effect on the soil~
equipment, crops, or agronomic environment. Mixtures of compounds of the invention may also be used in any of these formulations. Compositions of the invention can be either solid or liquid formulations or solutions. For example, the i7 compounds can be formulated as wettable powders, emulsifi-able concentrates, dusts, granular formulations, aerosols, or flowable emulsion concentrates. In such formulations, the compounds are extended with a liquid or solid carrier and, when desired suitable sur~actants are incorporated.
It is usually desirable, particularly in foliar applications, to include adjuvants, such as wetting agents, spreading agents 3 dispersing agents, stickers, adhesives, and the like, in accordance with agricultural practices.
Examples of adjuvants which are commonly used in the art can be found in the John W. McCutcheon, Inc. publication "Detergents and Emulsifiers Annual."
The compounds of the invention can be dissolved in any appropriate solvent. Examples of solvents which are useful in the practice of this invention include water, alcohols, ketones, aromat~c hydrocarbons, halo~enated hydro-carbons 3 dimethylformamide, dioxane, dimethyl sulfoxide, and the like. Mixtures of these solvents can also be used.
The concentration of the solution can vary from about 2% to about 98% by weight with a preferred range being about 20%
to about 75%.
For the preparation of emulsifiable concentrates, the compound can be dissolved in organic solvents, such as benzene, toluene, xylene, methylated naphthalene 3 corn oil, pine oil, o-dichlorobenzene, isophorone, cyclohexanone, methyl oleate, and the like, or in mixtures of these solvents, together with an emulsifying agent or surfactant which permits disperson in water. Suitable emulsifiers include, for example, the ethylene oxide derivatives of alkylphenols or long-chain alcohols, mercaptans, carboxylic acids, and reactive amines and partially esterified polyhydric alcohols.
Solvent-soluble sulfates or sulfonates, such as the alkaline earth salts or amine salts of alkylbenzenesulfonates and the fatty alcohol sodium sulfates, having surface-active properties can be used as emulsifiers either alone or in con~unction with an ethylene oxide reaction product. Flow-able emulsion concentrates are formulated similarly to the emulsifiable concentrates and include, in addition to the above components, water and a stabilizing agent such as a water-soluble cellulose derivative or a water-soluble salt of a polyacrylic acid. The concentration of the active f~
ingredient in emulsifiable concentrates is usually about 10% to 60% by weight and in flowable emulsion concentrates this can be as high as about 75%.
Wettable powders suitable for spraying can be prepared by admixing the compound with a finely divided solid, such as clays, inorganic silicates and carbonates, and silicas and incorporating wetting agents, sticking agents, and/or dispersing agents in such mixtures. The concentration of active ingredients in such formulations ::s usually in the range of about 20% to 98% by weight, prefer-ably about Llo% to 75%. A dispersing agent may generally consititute about 0.5% to about 3% by weight o~ the compo-sition, and a wetting agent may generally constitute from about 0.1% to about 5% by weight of the composition.
Dusts can be prepared by mixing the compounds of the invention with finely divided inert solids which may be organic or inorganic in nature. Materials useful for this purpose include, for example, botanical flours, silicas, silicates, carbonates and clays. One convenient method of , preparing a dus~ is to dilute a wettable powder with a finely divided carrier. Dust concentrates containing about 20% to 80% of the active ingredient are commonly made and are sub-sequently diluted to about 1~ to 10~ by weight use concen-tration.
Granular formulations can be prepared by impreg-nating a solid such as granular fuller's earth, vermiculite, ground corn cobs, seed hulls, including bran or other grain hulls, or similar material. A solution of one or more of the compounds in a volatile organic solvent can be sprayed or mixed with the granular solid and the solvent then removed by evaporation. The granular material can have any suitable size, with a preferable size range of 16 to 60 mesh. The active compound will usually comprise about 2 to about 15% by weight of the granular ~ormulation.
Salts of the compounds of the invention can be formulated and applied as aqueous solutions. The salt will typically aomprise about 0~05 to about 50% by weight, prefer-ably about 0.1% to about 10~, of the solution. These compo-sitions can also be further diluted with water if desiredprior to actual application. In some applications, the activ-ity of these compositions can be enhanced by incorporating into the composition an adjuvant such as glycerin, methylethyl-cellulose, hydroxyethylcellulose, polyoxyethylenesorbitan monooleate, polypropylene glycol, polyacrylic acid, poly- ~
ethylene sodium malate, polyethylene oxide, or the like. The adjuvant will generally comprise about 0.1 to about 5% by weight, preferably about 0.5 to about 2%, of the composition. Such compositions can also optionally include an agronomically-acceptable surfactant.
.. . ...
1~385~357 The compounds of the invention can be applied as sprays by methods commonly employed, such as conventional hydraulic sprays, aerial sprays, and dusts. For low-volume applications a solution of the compound is usually used.
The dilution and volume of application will usually depend upon such factors as the type of equipment employed, the method of application, the area to be treated and the type and stage of development of the crop being treated.
The following exmaples will further illustrate 10 the growth regulatory activity of the compounds of the `~
invention but are not intended to limit the invention in any way.
'Examp'le''29 Che~mic l Gam'et'oc'idal Activity The following procedures are used to evaluate the ~
activity of the compounds of the invention as chemical ,~, gametocides in cereals.
An awned variety (Fielder) and an awnless variety (Mayo-64) of spring wheat are planted at the rate of 6 to 8 ~ , seeds per 6" pot containing a sterile medium of 3 parts ' soil and 1 part humus. The plants are grown under short-day (9 hour) conditions for the first 4 weeks to obtain good vegetative growth before flower initiation. The plants are then moved to long-day (16 hour) conditions which are pro-vided by high intensity lights in the greenhouse. The plants are fertilized at 2, 4, and 8 weeks after planing with a water soluble fertilizer (16-25-16) at the rate of 1 tsp/gal of water, and are frequently sprayed with isotox for aphid control and dusted with sulfur for powdery mildew control.
3o Test ^ompounds are foliarly applied to the awned 3S~35~7 female plants when these plants reach the flag leaf emergence stage (stage 8 on Feekes' scale). All compounds are applied in a carrier volume of 50 gal/A con~aining a surfactant, such as "Triton x-100"*, at the rate of 2 oz/50 gal.
After spike emergence but before anthesis, 4 to 6 spikes per pot are bagged to prevent outcrossing. At the first signs of flower opening, two spikes per pot are cross pollin-ated, using the approach method, with the a~nless male parent.
As soon as the seeds became plainly visible, spike length is 10 measured and seeds per spikelet counted in both bagged and -~
crossed spikes. Male sterility is then calculated as percent inhibition of seed set in bagged spikes of treated plants.
After maturity the seed on crossed spikes can be planted for determination of percent hybridization.
Percent sterility is calculated from the following formula:
% Sterility = C St x 100 ~t C
Sc = seeds/spikelet in bagged spikes of control plants St = seeds/spikelet in bagged spikes of treated plants Table II summarizes typical results obtained in the evaluation of compounds of the invention. A dash indicates that no test at the indicated rate was made.
*Trademark of Rohm and Haas ~om~pany ~or a liquid nonionic - surfactant; it is octylphenoxy polyethoxy ethanol.
. r .
TABLE II
CH3 ~:
Y~ C02R
Jl ;-~ I \ CH3 ' ~:
Rate(lb./A) ~ Sterility X Y R ~ 4 2 1 1/21/4 1/8 4-Cl H H100 100100 96 4-Cl HNa 100100 100100 92 52 H HNa 46 0 13 8 4-CH3 HNa 0 0 0 1411 2 3 3,4-diCl H H 98 93 80 122016 12 3,4-diCl , HNa 96 91 33 222521 4 4-F HNa 0 0 0 2 7 18 15 3-Cl H H 4 0 0 0 3 3 2 3-Cl H Na 0 2 0 4-CH3,3 Cl H H 6 4 0 19 0 4-CH3,3-Cl H Na 0 2 1 0 1 6 -4-oCH3 H H 56 18 2 9 4-oCH3 H Na 54 31 0 3 - - ~ -4 ' H H 15 3 - - - -4-CF3 H Na 0 3 0 0 4-Br H H 100100 100 - - - -4-Br H Na 100100 100100 100100 100 ~3~ 5~t~
TABLE II (cont'd) X Y R 8 4: 2 11/2 1/4 1/8 .
4~C1 naphthyl H H 2 4-Cl naphthyl H Na 14 4 0 0 4-Cl Br H 9 7 9 1613 4-Cl Br Na 15 13 13 2013 4-Br Br H
4-Br Br Na 100 99 89 4325 4-Br H C2H5 100 _ 100 - 100 - 100 Y ~ C02R ':' O ~ N 3 ~X
4-Cl H Na 100 100 90 39 - - -It should be understood that changes and variations may be made without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (13)
1. A compound of the formula wherein R1 is a (C1-C4)alkyl group, R2 is a carboxy group or an agronomically-acceptable salt thereof, or a carb(C1-C4)alkoxy group, R3 is a hydrogen atom or a (C1-C4)alkyl group, R4 is a hydrogen atom, a (C1-C4)alkyl group, or a halogen atom, and R5 is a phenyl group, a naphthyl group, or a substituted phenyl group having one or two substituents selected from halogen atoms, (C1-C4)alkyl groups, (C1-C4)alkoxy groups, tri-fluoromethyl groups, and nitro groups.
2. The compound of claim 1 wherein R2 is a carboxy group or an agronomically-acceptable salt thereof.
3. The compound of claim 2 wherein R1 is a methyl group and R4 is a hydrogen atom.
4. The compound of claim 3 wherein R3 is a methyl group.
5. The compound of claim 4 wherein R5 is a sub-stituted phenyl group.
6. The compound of claim 5 wherein R5 is a 4-halophenyl group.
7. The compound of claim 3 wherein R3 is a hydrogen atom.
8. The compound of claim 2 wherein R1 is a methyl group and R4 is a halogen atom.
9. The compound of claim 8 wherein R3 is a methyl group.
10. The compound of Claim 9 wherein R4 is a bromine atom.
11. A method of inhibiting plant growth which comprises applying to the plant, the plant seeds, or the plant habitat an effective amount of a compound of claim 1.
12. The method of claim 11 wherein the plant is a cereal grain.
13. The method of claim 12 wherein the compound is applied to the plant prior to meiosis in an amount effective to produce male sterility in the plant.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81605177A | 1977-07-15 | 1977-07-15 | |
| US816,051 | 1977-07-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1085857A true CA1085857A (en) | 1980-09-16 |
Family
ID=25219570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA306,765A Expired CA1085857A (en) | 1977-07-15 | 1978-07-04 | 1-aryl-5-carboxy-2 pyridones and derivatives thereof |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS5452084A (en) |
| AR (1) | AR218070A1 (en) |
| AU (1) | AU521772B2 (en) |
| BE (1) | BE868999A (en) |
| CA (1) | CA1085857A (en) |
| CH (1) | CH635324A5 (en) |
| DE (1) | DE2830700A1 (en) |
| DK (1) | DK158350C (en) |
| ES (1) | ES471780A1 (en) |
| FR (1) | FR2397405A1 (en) |
| GB (1) | GB1596887A (en) |
| HU (1) | HU181943B (en) |
| IL (1) | IL55133A (en) |
| IT (1) | IT1108115B (en) |
| NL (1) | NL188695C (en) |
| NZ (1) | NZ187735A (en) |
| SE (1) | SE436568B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8741936B2 (en) | 2005-05-10 | 2014-06-03 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US8969347B2 (en) | 2008-06-03 | 2015-03-03 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US9359379B2 (en) | 2012-10-02 | 2016-06-07 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10233195B2 (en) | 2014-04-02 | 2019-03-19 | Intermune, Inc. | Anti-fibrotic pyridinones |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4936904A (en) * | 1980-05-12 | 1990-06-26 | Carlson Glenn R | Aryl-4-oxonicotinates useful for inducing male sterility in cereal grain plants |
| US4714492A (en) * | 1980-05-12 | 1987-12-22 | Rohm And Haas Company | Certain 2-phenyl-4-oxo-nicotinates and their use for inducing male sterility in a cereal grain plant |
| US4568751A (en) * | 1983-04-29 | 1986-02-04 | Merrell Dow Pharmaceuticals Inc. | 5-Acyl-2-(1H)-pyridinones |
| CA2416192A1 (en) * | 2000-07-18 | 2003-01-15 | Basf Aktiengesellschaft | 1-aryl-4-alkyl halide-2(1h)-pyridones and their use as herbicides |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1316461A (en) * | 1959-09-23 | 1963-02-01 | Wallace & Tiernan Inc | Improvements in processes for the preparation of 2-pyridone derivatives |
-
1978
- 1978-05-26 GB GB23085/78A patent/GB1596887A/en not_active Expired
- 1978-06-19 SE SE7807006A patent/SE436568B/en not_active IP Right Cessation
- 1978-06-30 NZ NZ187735A patent/NZ187735A/en unknown
- 1978-07-04 AR AR272835A patent/AR218070A1/en active
- 1978-07-04 CA CA306,765A patent/CA1085857A/en not_active Expired
- 1978-07-11 NL NLAANVRAGE7807464,A patent/NL188695C/en not_active IP Right Cessation
- 1978-07-12 FR FR7820803A patent/FR2397405A1/en active Granted
- 1978-07-12 DE DE19782830700 patent/DE2830700A1/en active Granted
- 1978-07-13 CH CH761678A patent/CH635324A5/en not_active IP Right Cessation
- 1978-07-13 IL IL55133A patent/IL55133A/en unknown
- 1978-07-13 AU AU38025/78A patent/AU521772B2/en not_active Expired
- 1978-07-14 IT IT68682/78A patent/IT1108115B/en active
- 1978-07-14 BE BE189285A patent/BE868999A/en not_active IP Right Cessation
- 1978-07-14 DK DK318578A patent/DK158350C/en not_active IP Right Cessation
- 1978-07-14 HU HU78RO989A patent/HU181943B/en unknown
- 1978-07-14 JP JP8599978A patent/JPS5452084A/en active Pending
- 1978-07-15 ES ES471780A patent/ES471780A1/en not_active Expired
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8741936B2 (en) | 2005-05-10 | 2014-06-03 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US9527816B2 (en) | 2005-05-10 | 2016-12-27 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US10010536B2 (en) | 2005-05-10 | 2018-07-03 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US8969347B2 (en) | 2008-06-03 | 2015-03-03 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US9290450B2 (en) | 2008-06-03 | 2016-03-22 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| USRE47142E1 (en) | 2008-06-03 | 2018-11-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US9359379B2 (en) | 2012-10-02 | 2016-06-07 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US9675593B2 (en) | 2012-10-02 | 2017-06-13 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10376497B2 (en) | 2012-10-02 | 2019-08-13 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10898474B2 (en) | 2012-10-02 | 2021-01-26 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10233195B2 (en) | 2014-04-02 | 2019-03-19 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10544161B2 (en) | 2014-04-02 | 2020-01-28 | Intermune, Inc. | Anti-fibrotic pyridinones |
Also Published As
| Publication number | Publication date |
|---|---|
| CH635324A5 (en) | 1983-03-31 |
| FR2397405B1 (en) | 1981-12-24 |
| AR218070A1 (en) | 1980-05-15 |
| IL55133A (en) | 1982-11-30 |
| NL188695C (en) | 1992-09-01 |
| DK158350C (en) | 1990-10-08 |
| FR2397405A1 (en) | 1979-02-09 |
| IT7868682A0 (en) | 1978-07-14 |
| AU521772B2 (en) | 1982-04-29 |
| DK318578A (en) | 1979-01-16 |
| HU181943B (en) | 1983-11-28 |
| DE2830700A1 (en) | 1979-02-01 |
| NL188695B (en) | 1992-04-01 |
| NZ187735A (en) | 1981-03-16 |
| IL55133A0 (en) | 1978-09-29 |
| SE436568B (en) | 1985-01-07 |
| SE7807006L (en) | 1979-01-16 |
| IT1108115B (en) | 1985-12-02 |
| NL7807464A (en) | 1979-01-17 |
| JPS5452084A (en) | 1979-04-24 |
| GB1596887A (en) | 1981-09-03 |
| BE868999A (en) | 1979-01-15 |
| DK158350B (en) | 1990-05-07 |
| DE2830700C2 (en) | 1989-03-16 |
| AU3802578A (en) | 1980-01-17 |
| ES471780A1 (en) | 1979-01-16 |
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