WO2010046215A2 - Dérivés de diazaindole et leur emploi en tant que fongicides - Google Patents

Dérivés de diazaindole et leur emploi en tant que fongicides Download PDF

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WO2010046215A2
WO2010046215A2 PCT/EP2009/062673 EP2009062673W WO2010046215A2 WO 2010046215 A2 WO2010046215 A2 WO 2010046215A2 EP 2009062673 W EP2009062673 W EP 2009062673W WO 2010046215 A2 WO2010046215 A2 WO 2010046215A2
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optionally substituted
hydrogen
alkyl
halogen
alkenyl
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PCT/EP2009/062673
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WO2010046215A3 (fr
Inventor
Patrice Selles
Nityakalyani Srinivas
Raphael Dumeunier
Frederik Cederbaum
Jayant Umarye
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Syngenta Participations Ag
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention relates to novel fungicidally active diaza-indoles, compositions comprising these novel compounds and their use in methods for the control and/or prevention of fungal infection in plants.
  • the invention relates to processes for preparing the novel compounds of the invention.
  • the present invention provides a method of preventing and/or controlling a fungal infection in a plant and/or plant propagation material, comprising applying to the plant or plant propagation material a compound of formula (I):
  • any one of G 1 , G 2 and G 3 is N and the other two of G 1 , G 2 and G 3 are CR 8 , CR 1 or CR 2 , such that when G 1 is not N, G 1 is CR 8 ; when G 2 is not N, G 2 is CR 1 ; when G 3 is not N, G 3 is CR 2 ;
  • X 1 is N or CH
  • X 2 is N or CR 5 ;
  • R 1 Is:
  • R 2 is:
  • R 3 is:
  • R 4 is:
  • R 5 is: (i) hydrogen, halogen, hydro xyl, cyano or nitro,
  • R 6 is:
  • R 7 is:
  • R 8 is:
  • R 10 , R 11 , R 14 , R 15 , R 16 and R 17 are, independently: (i) hydrogen, halogen, hydroxyl, cyano or nitro; (ii) optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl or optionally substituted alkynyl, or (iii) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl;
  • R 12 and R 13 are, independently:
  • R 18 and R 19 are, independently: (i) hydrogen, (ii) optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl,
  • R 20 is: (i) hydroxyl
  • R 21 and R 22 are, independently: (i) hydrogen,
  • R 23 and R 24 are, independently:
  • R 25 is optionally susbstituted alkyl, optionally susbstituted alkenyl or optionally susbstituted alkynyl;
  • R 1 and R 2 optionally: independently, (i) R 1 and R 2 , (ii) R 1 and R 3 (iii) R 2 and R 3 , (iv) R 3 and R 5 , (v) R 5 : and R 6 , (vi) R 5 and R 18 , (vii) R 5 and R 19 , (viii) R 14 and R 15 and/or (ix) R 18 and R 19 form an optionally substituted aryl, optionally susbstituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl containing from 5 to 18 ring atoms;
  • Alkyl means a linear saturated monovalent hydrocarbon radical of one to eight carbon atoms or a branched saturated monovalent hydrocarbon radical of three to eight carbon atoms, e.g. methyl, ethyl, n-propyl, ⁇ o-propyl, n-butyl, sec-butyl, ⁇ o-butyl, tert- butyl, n-pentyl, n-hexyl and the like.
  • linear alkyl groups contain one to six carbon atoms, more preferably one to four carbon atoms and most preferably are selected from methyl, ethyl or n-propyl.
  • branched alkyl groups contain three to six carbon atoms and more preferably are selected from ⁇ o-propyl, sec-butyl, ⁇ o-butyl or tert- butyl.
  • alkenyl means a linear monovalent hydrocarbon radical of two to eight carbon atoms, or a branched monovalent hydrocarbon radical of three to eight carbon atoms containing at least one double bond, e.g. ethenyl, propenyl and the like. Where appropriate, an alkenyl group can be of either the (E)- or (Z)-configuration.
  • linear alkenyl groups contain two to six carbon atoms and more preferably are selected from ethenyl, prop- 1-enyl, prop-2-enyl, prop-l,2-dienyl, but-1-enyl, but-2-enyl, but-3-enyl, but-l,2-dienyl and but-l,3-dienyl.
  • branched alkenyl groups contain three to six carbon atoms and more preferably are selected from 1-methylethenyl, 1-methylprop- 1-enyl, l-methylprop-2- enyl, 2-methylprop- 1-enyl and 2-methylprop-2-enyl.
  • an alkenyl group may contain at least two double bonds between three contiguous carbon atoms, e.g. prop- 1,2 dienyl, penta-1,2 dienyl, penta-2,3 dienyl, hexa-l,2-dienyl and the like.
  • such an alkenyl group can be of either the (R)- or ( ⁇ -configuration.
  • Preferred is prop- 1,2- dienyl.
  • Alkynyl means a linear monovalent hydrocarbon radical of two to eight carbon atoms, or a branched monovalent hydrocarbon radical of four to eight carbon atoms, containing at least one triple bond, e.g. ethynyl, propynyl and the like.
  • linear alkynyl groups contain two to six carbon atoms and more preferably are selected from ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl and but-3-ynyl.
  • branched alkynyl groups contain four to six carbon atoms and more preferably are selected from l-methylprop-2-ynyl, 3-methylbut-l-ynyl, l-methylbut-2-ynyl, l-methylbut-3-ynyl and 2-methylbut-3 -ynyl.
  • Alkylene means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or a branched saturated divalent hydrocarbon radical or three to six carbon atoms, e.g. methylene, ethylene, propylene, 2-methylpropylene and the like.
  • Preferred alkylene groups are the divalent radicals of the alkyl groups defined above.
  • alkenylene means a linear divalent hydrocarbon radical of two to six carbon atoms or a branched divalent hydrocarbon radical of three to six carbon atoms, containing at least one double bond, e.g. ethenylene, propenylene and the like.
  • Preferred alkenylene groups are the divalent radicals of the alkenyl groups defined above.
  • Cycloalkyl means a saturated monovalent cyclic hydrocarbon radical of three to eight ring carbons.
  • cycloalkyl groups contain three to six ring carbons, more preferably they are selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • Cycloalkenyl means a monovalent cyclic mono- or di-unsaturated hyrodcarbon radical of three to eight ring carbons, preferably four to six ring carbons, e.g. cyclobutenyl, cyclopentenyl and cyclohexenyl.
  • Heterocycloalkyl means a monovalent cyclic radical of three to eight ring atoms, preferably 3-6 or 4-6 ring atoms, containing one, two or three ring heteroatoms independently selected from N, O and S(O) n (where n is an integer from 0 to 2), the remaining ring atoms being carbon where one or two carbon atoms may be a carbonyl group, in which there are no double or triple double bonds linking the ring atoms.
  • rings include, but are not limited to, oxirane, oxetane, tetrahydrofuran, tetrahydropyran, 1,3- dioxolane, 1 ,4-dioxane, aziridine, azetidine, pyrrolidine, piperidine, oxazinane, morpholine, thiomorpholine, imidazolidine, pyrazolidine and piperazine. More preferably, the heterocycloalkyl group contains three to five ring atoms including one O and/or one N ring atom.
  • Aryl means a monovalent moncyclic or bicyclic aromatic hydrocarbon radical of six to ten ring carbons atoms. Suitable aryl groups include phenyl and naphthyl, in particular, phenyl.
  • Heteroaryl means a monovalent monocyclic or bicyclic aromatic hydrocarbon radical of five to ten ring atoms, preferably five or six ring atoms, containing one, two, three or four ring heteroatoms selected, independently, from N, O or S, the remaining ring atoms being carbon.
  • heteroaryl groups include, but are not limited to pyridyl, pyrimidinyl, pyrazolyl, thiazolyl, thiophenyl, isoazolyl, and tetrazolyl groups.
  • Heterocyclic ring or “ heterocycle” means a saturated or fully unsaturated or partially unsaturated monovalent cyclic radical of three to eight ring atoms, preferably 3-6 or 4-6 ring atoms, containing one, two or three ring heteroatoms independently selected from N, O and S(O) n (where n is an integer from 0 to 2).
  • a heterocyclic ring may be a heteroaryl group or a heterocycloalkyl group as defined above.
  • Alkoxy means a monovalent radical -OR, where R is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, or optionally substituted heteroaryl.
  • R may be an optionally substituted Ci_6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted 3-6 membered heterocycloalkyl, optionally substituted C 4 - 6 cycloalkenyl, optionally substituted phenyl, or optionally substituted heterophenyl.
  • R may be an optionally substituted aralkyl or optionally substituted heteroaralkyl group.
  • an alkoxy group is selected from methoxy, ethoxy, 1-methylethoxy, propoxy, 1-methylpropoxy and 2-methylpropoxy. More preferably alkoxy means methoxy or ethoxy.
  • Alkoxyalkyl means a monovalent linear radical -R a OR b , wherein R a is an optionally substituted alkyl group, e.g. optionally substituted Ci_6 alkyl, and R b is an optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl group, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl or optionally substituted heteroaryl group.
  • R b may be an optionally substituted Ci_6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C 3-6 cycloalkyl, optionally substituted 3-6 membered heterocycloalkyl, optionally substituted C4-6 cycloalkenyl, optionally substituted phenyl, or optionally substituted heterophenyl.
  • R b may be an optionally substituted aralkyl or optionally substituted heteroaralkyl group, as defined herein.
  • Halo or halogen means fluoro, chloro, bromo or iodo, preferably chloro or fluoro.
  • Haloalkyl means alkyl as defined above substituted with one or more of the same or different halo atoms.
  • a substituted alkyl group may be a haloalkyl group.
  • haloalkyl groups include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-trifluoroethyl, 2-chloro-ethyl, 2-iodoethyl, 3-fluoropropyl, 3-chloropropyl, 2-trifluoro-l-chloroethyl and l-difluoro-2-difluoro-3-trifluoropropyl.
  • Haloalkenyl means alkenyl as defined above substituted with one or more of the same or different halo atoms.
  • a substituted alkenyl group may be a haloalkenyl group.
  • haloalkenyl groups include, but are not limited to 2-dibromoethenyl, 2-fluoro-2- bromoethenyl, 5-bromopent-3-enyl and 3-dichloroprop-2-enyl.
  • Alkyl means a monovalent radical -R a R b , wherein R a is an alkylene or alkenylene group and R b is an aryl group, each as defined above.
  • Hetero aralkyl means a monovalent radical -R a R b where R a is an alkylene or alkenylene group and R b is a heteroaryl group, each as defined above.
  • Acyl means a monovalent radical -C(O)R, wherein R is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl or optionally substituted heteroaryl.
  • R may be an optionally substituted Ci_6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C 3-6 cycloalkyl, optionally substituted 3-6 membered heterocycloalkyl, optionally substituted C 4-6 cycloalkenyl, optionally substituted phenyl, or optionally substituted heterophenyl.
  • Acyloxy means a monovalent radical -OC(O)R, wherein R is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl or optionally substituted heteroaryl.
  • R may be an optionally substituted Ci_6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C 3-6 cycloalkyl, optionally substituted 3-6 membered heterocycloalkyl, optionally substituted C 4-6 cycloalkenyl, optionally substituted phenyl, or optionally substituted heterophenyl.
  • alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl groups may be unsubstitued, or may be substituted by one or more substituents independently selected from halogen, hydroxyl, cyano, alkyl (optionally substituted by cyano), e.g. d- 4 alkyl, haloalkyl, e.g. d- 4 haloalkyl, alkenyl, e.g. C2-4 alkenyl, haloalkenyl, e.g.
  • R and R' are, independently, hydrogen or alkyl (in particular, methyl or ethyl).
  • Preferred optional substituents are alkoxy (in particular, methoxy or ethoxy), hydroxyl, cyano, halogen (in particular, fluoro, chloro or bromo), heterocycloalkyl (in particular, oxirane or tetrahydrofuran), heteroaryl (in particular, pyridyl), -C(O)OR (wherein R is hydrogen or alkyl (in particular, methyl or ethyl)) and trialkylsilyl (in particular, trimethylsilyl).
  • alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl groups may be independently selected from halogen, hydroxyl, Ci_ 4 alkyl, Ci_ 4 haloalkyl, -NH 2 , and cyano; in particular halogen.
  • the compounds of formula (I) may exist in different geometric or optical isomeric forms or in different tautomeric forms.
  • One or more centres of chirality may be present, in which case compounds of the formula (I) may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of diastereomers.
  • Centres of tautomerisation may be present. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.
  • Suitable salts of the compounds of formula (I) include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulfuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid.
  • organic carboxylic acids include haloacids such as trifluoroacetic acid. This invention covers all such salts of compounds of formula (I).
  • N-oxides are oxidised forms of tertiary amines or oxidised forms of nitrogen containing heteroaromatic compounds. They are described in many books for example in "Heterocyclic N-oxides" by Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Florida, 1991. This invention covers all such N-oxide forms of compounds of formula (I).
  • the preferred groups for X 1 and X 2 and R 1 to R 25 are as set out below.
  • G 1 is CR 8
  • G 2 is CR 1
  • G 3 is N.
  • X 1 is CH.
  • X 2 is CR 5 . More preferably, X 2 is CH.
  • R 1 is:
  • R 1 is hydrogen, halogen, cyano, optionally substituted Ci_6 alkyl, optionally substituted C 2 -6 alkenyl, optionally substituted C 2 -6 alkynyl, optionally substituted aryl, e.g. optionally substituted phenyl, or -C(O)R 10 .
  • R 1 is hydrogen, chloro, bromo, cyano, methyl or 2-trimethylsilyl-ethynyl.
  • R 1 is hydrogen, chloro or methyl.
  • R 2 is: (i) hydrogen, or
  • R 2 is hydrogen or Ci_6 alkyl.
  • R 3 is: (i) hydrogen or hydroxyl, (ii) optionally substituted Ci_6 alkyl, optionally substituted C 2 -6 alkenyl or optionally substituted C 2 -6 alkynyl,
  • optionally substituted cycloalkyl e.g. optionally substituted C 3-6 cycloalkyl, or (iv) -C(O)R 12 , -OR 12 , -C(O)OR 12 , -OC(O)R 12 or -S(O) 2 R 12 ; wherein the optional substitutents in all cases are as defined above and, more preferably, are selected from cyano, halogen, hydroxyl, Ci_ 4 alkyl, C 2 - 4 alkenyl, alkoxy, e.g. -O-Ci_ 4 alkyl (optionally substituted by alkoxy, e.g.
  • acyl e.g. -(O)C-C 1-3 alkyl
  • cycloalkyl e.g. C3-6 cycloalkyl
  • cycloalkenyl e.g. C3-6 cycloalkenyl
  • heterocycloalkyl e.g. 3-6-membered heterocycloalkyl
  • aryl e.g. phenyl, heteroaryl, e.g. heterophenyl, -NH 2 , trialkylsilyl, -C(O)R and -C(O)OR
  • R is hydrogen, methyl or ethyl
  • R 3 is hydrogen, hydroxyl, -C(O)R 12 , -OR 12 , -C(O)OR 12 , -OC(O)R 12 ,
  • Ci_6 alkyl optionally substituted C 2 -6 alkenyl, optionally substituted C 2 -6 alkynyl, optionally substituted cycloalkyl, e.g. optionally substituted C 3 _6 cycloalkyl.
  • R 3 may be optionally substituted Ci_6 alkyl, optionally substituted C 2 -6 alkenyl or optionally susbtituted C 2 -6 alkynyl, wherein the optional substituents of the alkyl, alkenyl and alkynyl are selected from cyano, methoxy, and halogen.
  • R is C 3 _ 4 alkenyl or C 3 _ 4 alkynyl.
  • R 4 is: (i) hydrogen or halogen, (ii) optionally substituted C 2 -6 alkynyl, or (iii) optionally substituted aryl, e.g. optionally substituted phenyl, or optionally substituted heteroaryl, e.g. optionally substituted heterophenyl; wherein the optional substituents in all cases are as defined above and, more preferably, are selected from hydroxyl, halogen (in particular, fluoro or chloro), haloalkyl, e.g. Ci_ 4 haloalkyl, acyl, e.g. -(O)C-C 1-3 alkyl, and Ci_ 4 alkyl (in particular, methyl).
  • the Ci_ 4 alkyl may be Ci_ 4 haloalkyl.
  • R 4 is hydrogen, halogen, optionally substituted C 2 -6 alkynyl or optionally substituted aryl, e.g. optionally substituted phenyl, or optionally substituted heteroaryl, e.g. optionally substituted heterophenyl. Even more preferably, R 4 is phenyl, 3- methylphenyl, 3-trifluoromethylphenyl, 2-fluorophenyl, 3 -fluorophenyl, 4-fluorophenyl, 2,5- difluorophenyl, 3-methyl-4-fluorophenyl, 2,4-difluorophenyl, 2,6-diflurophenyl, or 2,4,6- diflurophenyl.
  • R 4 may be phenyl optionally substituted by 1 to 3 groups independently selected from Ci_ 4 alkyl, Ci_ 4 haloalkyl and halogen, e.g. R4 is phenyl optionally substituted by 1-3 halogen atoms.
  • R 5 is: (i) hydrogen, or halogen
  • Ci_6 alkyl optionally substituted C 2 -6 alkenyl or optionally substituted C 2 -6 alkynyl, or
  • optionally substituted aryl e.g. optionally substituted phenyl, optionally substituted heteroaryl, e.g. optionally substituted heterophenyl, optionally substituted cycloalkyl, e.g. optionally substituted C 3-6 cycloalkyl, optionally substituted cycloalkenyl, e.g. optionally substituted C 4 -6 cycloalkenyl, or an optionally substituted heterocycylic ring formed with R 6 , e.g. a 5 or 6 membered heterocycle; wherein the optional substituents in all cases are as defined above and, more preferably, are selected from halogen, cyano, hydroxyl, Ci_ 4 haloalkyl and Ci_ 4 alkyl.
  • R 5 is hydrogen or halogen.
  • R 6 is:
  • optionally substituted aryl e.g. optionally substituted phenyl, optionally substituted heteroaryl, e.g. optionally substituted heterophenyl, optionally substituted cycloalkyl, e.g. optionally substituted C3-6 cycloalkyl, optionally substituted cycloalkenyl, e.g. optionally substituted C4-6 cycloalkenyl, or an optionally substituted heterocyclic ring formed with R 5 as defined above, e.g. a 5 or 6 membered heterocycle; or (iii) -C(O)OR 18 , -NR 18 R 19 (e.g.
  • R 6 is hydrogen or -NR 18 R 19 , e.g. -NHR 19 .
  • R 6 is -
  • R 23 is preferably Ci_4 alkyl, e.g. ethyl, isopropyl, or cyclopropyl or cyclobutyl.
  • R 6 may be hydrogen or -NHR 19 in which R 19 is hydrogen, Ci_ 4 alkyl optionally substituted with hydroxy or Ci_4 alkoxy which in turn may be substituted by hydroxy, or R 19 is -C(O)R 23 , and R 23 is Ci_ 4 alkyl, C 2 - 4 alkenyl, C 2 - 4 alkynyl, or C 3 - 4 cycloalkyl.
  • R 7 and R 8 are, independently: (i) hydrogen, hydroxyl, or cyano, optionally substituted Ci_6 alkyl, wherein the optional subsituents are as defined above and, more preferably, are selected from halogen, cyano, hydroxyl and haloalkyl e.g. Ci_ 4 haloalkyl, or (ii) -NR 21 R 22 ;
  • R 7 and R 8 are, independently, hydrogen, hydroxyl, cyano -NR 21 R 22 , or optionally substituted Ci_6 alkyl. Most preferably, R 7 and R 8 are, independently, hydrogen, hydroxyl or NR 21 R 22 .
  • R 10 , R 11 , R 14 , R 15 , R 16 and R 17 are, independently: (i) hydrogen, or (ii) optionally substituted Ci_6 alkyl, optionally substituted C 2 _6 alkenyl or optionally substituted C 2 _6 alkynyl, wherein the optional substituents are as defined above and, more preferably, are selected from hydroxyl, halogen, cyano and alkoxy, e.g. -O-Ci_4 alkyl.
  • R 10 , R 11 , R 14 , R 15 , R 16 and R 17 are, independently, hydrogen or optionally substituted Ci_ 3 alkyl. Most preferably, R 10 , R 11 , R 14 , R 15 , R 16 and R 17 are, independently, hydrogen, methyl or ethyl.
  • R 12 and R 13 are, independently: (i) optionally substituted Ci_6 alkyl, optionally substituted C 2 -6 alkenyl, optionally substituted C2-6 alkynyl, or (ii) optionally substituted C3-6 cycloalkyl or optionally substituted C 4 -6 cycloalkenyl; wherein optional substituents in all cases are as defined above and, more preferably are selected from hydroxyl, halogen, cyano, alkoxy, e.g. -O-Ci_ 4 alkyl, cycloalkyl (optionally substituted with hydroxyl or methyl), e.g.
  • R 12 and R 13 are, independently, optionally substituted Ci_ 4 alkyl, including Ci_ 4 alkyl-0-Ci_ 4 alkyl, optionally substituted C 2 - 4 alkenyl or optionally substituted C 2 - 4 alkynyl. Most preferably, R 12 and R 13 are, independently, cyanomethyl, (1-methyl)- cyanomethyl, prop-2-enyl, prop-2-ynyl or methoxymethyl.
  • R 18 is:
  • an optionally substituted heterocyclic ring formed with R 19 e.g. a 5 or 6 membered heterocyclic ring, or
  • R 18 is hydrogen, Ci_ 4 alkyl, C 2 - 4 alkenyl, or C 2 - 4 alkynyl. More preferably Ri 8 is hydrogen, ethyl, ⁇ o-propyl, prop-2-enyl, prop-2ynyl or but-2-ynyl.
  • R 19 is: (i) hydrogen
  • Ci_6 alkyl optionally substituted C 2 -6 alkenyl or optionally substituted C 2 -6 alkynyl
  • optionally substituted aryl e.g. optionally substituted phenyl, optionally substituted heteroaryl, e.g. optionally substituted heterophenyl, optionally substituted cycloalkyl, e.g. optionally substituted C3-6 cycloalkyl, optionally substituted cycloalkenyl, e.g. optionally substituted C 4 -6 cycloalkenyl, or optionally substituted heterocycloalkyl, e.g. a 3-6 member optionally substituted heterocycloalkyl, or an optionally substituted heterocyclic ring formed with R 18 , e.g. a 5 or 6 membered heterocyclic ring, or
  • R 19 is hydrogen, -C(S)R 23 , -C(O)R 23 or -C(O)OR 23 or optionally substituted d_ 4 alkyl. Most preferably, R 19 is hydrogen, ⁇ o-butyl, -C(O)R 23 or -C(O)OR 23 .
  • R 20 is -NR 21 R 22 ;
  • R 21 and R 22 are, independently: (i) hydrogen,
  • Ci_6 alkyl e.g. Ci_ 4 alkyl
  • optional substituents are as defined above and, more preferably, are selected from hydroxyl, cyano, halogen, alkoxy, e.g. -O-Ci_ 4 alkyl, acyl, e.g. -(O)C-C 1-3 acyl, cycloalkyl, e.g. C3-6 cycloalkyl, cycloalkenyl, e.g. C 4 -6 cycloalkenyl, heterocycloalkyl, e.g. a 3-6-membered heterocycloalkyl, or
  • R 21 and R 22 are, independently, hydrogen or optionally substituted
  • R 21 and R 22 are, independently, hydrogen, methyl or ethyl.
  • R 23 and R 24 are, independently:
  • optionally substituted cycloalkyl e.g. optionally substituted C 3 _6 cycloalkyl, optionally substituted cycloalkenyl, e.g. optionally substituted C 4 _ 6 cycloalkenyl or optionally substituted aryl, e.g. optionally substituted phenyl; wherein the optional substituents in all cases are as defined above and, more preferably, are selected from hydroxyl, halogen, cyano, Ci_ 4 alkyl, alkoxy, e.g. -O-Ci_ 4 alkyl, cycloalkyl, e.g. C3-6 cycloalkenyl, cycloalkenyl e.g.
  • R is cycloalkyl, e.g. C3-6 cycloalkyl, or cycloalkenyl, e.g. C4-6 cycloalkenyl).
  • R 23 and R 24 are, independently, hydrogen, hydroxyl, optionally substituted Ci_6 alkyl, e.g. Ci-6 alkyl-O-Ci_6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted cycloalkyl, e.g. optionally substituted C 3-6 cycloalkyl, or optionally substituted cycloalkenyl, e.g. optionally substituted C 4-6 cycloalkenyl.
  • Ci_6 alkyl e.g. Ci-6 alkyl-O-Ci_6 alkyl
  • C2-6 alkenyl optionally substituted cycloalkyl, e.g. optionally substituted C 3-6 cycloalkyl
  • optionally substituted cycloalkenyl e.g. optionally substituted C 4-6 cycloalkenyl.
  • R 23 and R 24 are, independently, methyl, ethyl, ⁇ o-propyl, methoxymethyl, cyclopropyl or cyclo butyl, in which the cyclopropyl or cyclo butyl group may be substituted with one or more substituents being selected from cyano, halogen (preferably fluoro), Ci_4 alkyl (preferably methyl or ethyl) or haloalkenyl.
  • R 25 is Ci_4 alkyl. More preferably, R 25 is methyl, ethyl, propyl or 2- dimethylethyl.
  • R 3 when R 3 is hydrogen, R 6 is other than hydrogen. More preferably, R 3 is hydrogen and R 6 is -NR 18 R 19 . More preferably, R 3 is hydrogen and R 6 is -NHR 19 . More preferably, R 3 is hydrogen and R 6 is -NHC(O)R 23 .
  • R 6 is hydrogen and R 3 is other than hydrogen. More preferably, R 6 is hydrogen and R 3 is -OR 12 or optionally substituted Ci_6 alkyl, C2-4 alkenyl, e.g. C3_4 allenyl, or C2-4 alkynyl. Most preferably, R 6 is hydrogen and R 3 is cyanomethyl, aminoethyl, aminopropyl, prop-2-enyl, prop-2-ynyl, prop-l,2-dienyl, methoxymethyl, 2-fluoromethyl, -OCH 2 C ⁇ CH, -OCH 2 OCH 3 , -OCH 2 CN, -OCH(CH 3 )CN.
  • the method of the invention may utilise a compound of the formula (Ia):
  • X 1 , X 2 , R 1 , R 2 , R 3 , R 4 , R 6 , and R 7 are as defined above for the compound of formula (I), in any combination thereof.
  • the method of the invention may utilise a compound of the formula (Ib):
  • the method of the invention may utilise a compound of the formula (Ic):
  • the method of the invention utilises a compound of formula (Id):
  • any one of G 1 , G 2 and G 3 is N and the other two of G 1 , G 2 and G 3 are CR 8 , CR 1 or CR 2 , such that when G 1 is not N, G 1 is CR 8 ; when G 2 is not N, G 2 is CR 1 ; when G 3 is not N, G 3 is CR 2 ; R 1 , R 2 , R 3 , R 4 , R 6 and R 8 are as defined for formula (I) above, in any combination thereof; and, preferably, in any combination:
  • R 1 is hydrogen, halogen, cyano, optionally substituted Ci_ 6 alkyl (in particular, optionally substituted Ci_ 4 alkyl and, most particularly, optionally substituted methyl or ethyl, wherein the optional substitutent is as defined above and more preferably is hydroxyl, e.g. 1-hydroxylethyl) or -C(O)R 10 in which R 10 is hydrogen or Ci_ 4 alkyl;
  • R 2 is hydrogen, halogen or Ci_ 4 alkyl
  • R 3 is hydrogen, hydroxyl, cyano, optionally substituted Ci_6 alkyl, optionally substituted C2-6 alkenyl, including optionally substituted C 3-6 allenyl, optionally substituted C2-6 alkynyl, -NR 12 R 13 , -OR 12 or -C(O)R 12 , wherein:
  • the optional substituents on the alkyl, alkenyl and alkynyl groups are as defined above and, more preferably, are independently selected from halo, cyano, hydroxyl, alkoxy (optionally substituted by alkoxy or acyl), e.g. -O-Ci_ 4 alkyl, Ci_ 4 alkyl, C 2 - 4 alkenyl, cycloalkyl, e.g. C3-6 cycloalkyl, cycloalkenyl, e.g. C 4 -6 cycloalkenyl, heterocycloalkyl, e.g. 3-6 membered heterocycloalkyl, aryl, e.g. phenyl, heteroaryl, e.g. heterophenyl,
  • R is hydrogen, Ci_ 4 alkyl, C 2 - 4 alkenyl or C 2 - 4 alkynyl, and
  • R 12 and R 13 are, independently, optionally substituted alkyl, e.g. optionally substituted Ci_6 alkyl, optionally substituted alkenyl, e.g. optionally substituted C 2 -6 alkenyl, optionally substituted alkynyl, e.g. optionally substituted C 2 -6 alkenyl, optionally substituted cycloalkyl, e.g. optionally substituted C3-6 cycloalkyl, or optionally substituted cycloalkenyl, e.g. optionally substituted C 4 _6 cycloalkenyl; the optional substituents being as defined above and, more preferably, halo, cyano, hydroxyl, alkoxy, e.g.
  • cycloalkyl e.g. C 3-6 cycloalkyl
  • cycloalkenyl e.g. C 4 _6 cycloalkenyl
  • heterocycloalkyl e.g. 3-6 membered heterocycloalkyl, -C(O)R, -C(O)OR or -OS(O)NRR', wherein R and R' are, independently, hydrogen or alkyl, e.g.
  • Ci_ 4 alkyl is optionally substituted aryl (in particular, optionally substituted phenyl or optionally substituted naphthyl), the optional substituents being as defined above and, more preferably halogen or Ci_4 alkyl;
  • R 6 is hydrogen, halogen or -NR 18 R 19 , wherein:
  • R 18 is hydrogen, -C(O)R 23 , -C(O)OR 23 or optionally substituted Ci_ 4 alkyl, optionally substituted C2-4 alkenyl or optionally substituted C2-4 alkynyl, in which R 23 is optionally substituted Ci_4 alkyl, the optional substituents being as defined above, and
  • R 19 is hydrogen, optionally substituted Ci_4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C 2 - 4 alkynyl, -C(S)R 23 -C(O)R 23 or -C(O)OR 23 , in which R 23 is hydrogen, optionally substituted Ci_4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C2-4 alkynyl, optionally substituted C 3-6 cycloalkyl or optionally substituted C 3-6 cycloalkenyl, the optional substituents being as defined above;
  • R 8 is hydrogen, halogen or Ci_4 alkyl.
  • R 1 is hydrogen, halo or optionally substituted Ci_4 alkyl, wherein the optional substituent is preferably hydro xyl;
  • R 2 and R 8 are, independently: hydrogen, methyl, ethyl or chloro;
  • R 3 is hydrogen, -OR 12 , optionally substituted Ci_4 alkyl, optionally substituted C2-4 alkenyl, or optionally substituted C2-4 alkynyl;
  • R 4 is phenyl, which is optionally substituted by at least one substituent selected from halogen and Ci_ 4 alkyl (in particular, methyl);
  • R 6 is halogen or -NR 18 R 19 , wherein R 18 is hydrogen, prop-2-enyl or prop-2-ynyl, and R 19 is -C(O)R 23 , in which R 23 is hydrogen, methyl, ethyl, ⁇ o-propyl, 1-methylethyl, 1-methylpropyl, 2-dimethylethyl, propyl, 1-
  • R 1 is hydrogen, chloro or methyl
  • R 2 and R 8 are, independently, hydrogen, methyl, ethyl or chloro
  • R 3 is hydrogen, cyanomethyl, prop- 2-enyl or prop-2-ynyl
  • R 4 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 4- chlorophenyl, 3-methylphenyl or 3-methyl-4-fluorophenyl
  • R 6 is -NR 18 R 19 in which R 18 is hydrogen and R 19 is -C(O)R 23 , in which R 23 is methyl, ethyl, ⁇ o-propyl, cyclopropyl, eye Io butyl or 1-methylcyclopropyl.
  • the method of the invention may utilise a compound of formula (Ie):
  • R 1 , R 2 , R 3 , R 4 and R 6 are as defined above for compound (Id), in any combination thereof.
  • the method of the invention may utilise a compound of formula (If):
  • R 2 , R 3 , R 4 , R 6 and R 8 are as defined above for compound (Id), in any combination thereof.
  • the method of the invention may utilise a compound of formula (Ig):
  • R 1 , R 3 , R 4 , R 6 and R 8 are as defined above for compound (Id), in any combination thereof.
  • the method of the invention utilises a compound of formula (Ih):
  • any one of G 1 , G 2 and G 3 is N and the other two of G 1 , G 2 and G 3 are CR 8 , CR 1 or CR 2 , such that when G 1 is not N, G 1 is CR 8 ; when G 2 is not N, G 2 is CR 1 ; when G 3 is not N, G 3 is CR 2 ;
  • R 1 , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 are as defined for formula (I) above, in any combination thereof; and preferably:
  • R 1 is hydrogen, halogen, optionally substituted Ci_ 6 alkyl or -C(O)R 10 , in which R 10 is hydrogen or Ci_4 alkyl, the optional substituents being as defined above;
  • R is hydrogen or Ci_ 4 alkyl
  • R 3 is hydrogen, hydroxyl, optionally substituted Ci_6 alkyl, optionally substituted C2-6 alkenyl or optionally substituted C2-6 alkynyl, -C(O)R 12 or -OR 12 , in which R 12 is optionally substituted Ci .4 alkyl, optionally substituted C3-6 cycloalkyl, or optionally substituted C4-6 cycloalkenyl, the optional substituents in all cases being as defined above and, more preferably, selected from halogen, cyano, hydroxyl, alkoxy, e.g. -O-Ci_4 alkyl, cycloalkyl, e.g.
  • C3_6 cycloalkyl cycloalkenyl, e.g. C4_6 cycloalkenyl, heterocycloalkyl, e.g. 3-6- membered cycloalkyl, aryl, e.g. phenyl, heteroaryl, e.g. heterophenyl, -NH 2 , trialkylsilyl and C(O)OR, wherein R is hydrogen, Ci_4 alkyl, C2-4 alkenyl or C2-4 alkynyl;
  • R 4 is optionally substituted aryl, the optional substituents being as defined above and, more preferably halogen or Ci_4 alkyl;
  • R 6 is hydrogen, halogen, hydroxyl, -O-Ci_6 alkyl, or -NR 18 R 19 , wherein:
  • R 18 is hydrogen, -C(O)R 23 , -C(O)OR 23 , optionally substituted Ci_ 4 alkyl, optionally substituted C2-4 alkenyl or optionally substituted C2-4 alkynyl, in which R 23 is optionally substituted Ci_4 alkyl, the optional substituents being as defined above, and
  • R 19 is hydrogen, optionally substituted Ci_4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C 2 - 4 alkynyl, -C(S)R 23 -C(O)R 23 or -C(O)OR 23 , in which R 23 is hydrogen, optionally substituted Ci_4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C2-4 alkynyl, optionally substituted C 3-6 cycloalkyl or optionally substituted C4-6 cycloalkenyl, the optional substituents being as defined above;
  • R is hydrogen, halogen or Ci_ 4 alkyl
  • R is hydrogen, halogen, Ci _4 alkyl or NR R , in which R and R are, independently, hydrogen or Ci_4 alkyl.
  • R 1 is hydrogen, halo or optionally substituted Ci_4 alkyl, the optional substituents being as defined above;
  • R 2 is hydrogen or methyl;
  • R 3 is hydrogen, optionally substituted Ci_ 4 alkyl, optionally substituted C 2 - 4 alkenyl, optionally substituted C2-4 alkynyl, or -OR 12 , in which R 12 is optionally substituted Ci_4 alkyl, optionally substituted C 3-6 cycloalkyl or optionally substituted C4_6 cycloalkenyl, the optional substituents in all cases being as defined above;
  • R 4 is phenyl, which is optionally substituted by at least one substituent selected from halogen and Ci_ 4 alkyl;
  • R 6 is halogen or -NR 18 R 19 , in which R 18 is hydrogen, prop-2-enyl or prop-2-ynyl, and R 19 is -C(O)R 23 , in which R 23 is hydrogen, methyl, ethyl,
  • R 1 is hydrogen, chloro or methyl
  • R 2 is hydrogen or methyl
  • R 3 is hydrogen, cyanomethyl, prop-2-enyl, prop-2-ynyl or benzyl
  • R 4 is 2-fluorophenyl, 3 -fluorophenyl, 4-fluorophenyl, 4-chlorophenyl, 3-methylphenyl or 3- methyl-4-fluorophenyl
  • R 6 is -NR 18 R 19 , in which R 18 is hydrogen, and R 19 is -C(O)R 23 , in which R 23 is methyl, ethyl, ⁇ o-propyl, cyclopropyl, eye Io butyl or 1-methylcyclopropyl
  • R 7 is hydrogen, chloro, fluoro or methyl
  • R 8 is hydrogen, chloro or methyl.
  • the method of the invention may utilise a compound of formula l(h) in which: R 1 is hydrogen, halogen, -NH-C M alkyl, -NH-C M haloalkyl, wherein the Ci_ 4 alkyl and Ci_ 4 haloalkyl are optionally substituted by Ci_4 alkoxy or Ci_4 haloalkoxy; R 2 is hydrogen, halogen, hydroxy, -NH-Ci_ 4 alkyl, -NH-Ci_ 4 haloalkyl, -N(Ci -4 alkyl)-Ci_ 4 alkyl, -N(Ci -4 haloalkyl)-Ci_ 4 alkyl, -N(Ci -4 alkyl)-C M haloalkyl, -N(Ci -4 haloalkyl)-C M haloalkyl, -NH-C3_6 cycloalkyl, -NH-C3_6 halocyclo
  • R 6 is hydrogen, halogen, hydroxy, Ci_4 alkoxy, Ci_4 haloalkoxy, -NH 2 , -NH-C M alkyl, -NH- Ci_ 4 haloalkyl, wherein the alkyl and haloalkyl are optionally substituted by hydroxy or Ci_ 4 alkoxy, which in turn may be substituted by hydroxy, or R 6 is -NH-C(O)-C 1-4 alkyl, -NH- C(O)-CL 4 haloalkyl, -NH-C(O)-C 3-6 cycoalkyl, -NH-C(O)-C 3-6 halocycloalkyl, -NH-C(O)- C2-4 alkenyl, NH-C(O)-C 2 - 4 haloalkenyl, -NH-C(O)-C 2-4 alkynyl, or -NH-C(O)-C 2-4 haloalkynyl
  • R 7 is hydrogen or halogen
  • R 8 is hydrogen or halogen
  • the method of the invention may utilise a compound of formula l(h) in which: R 1 is hydrogen, -NH-C M alkyl, wherein the C M alkyl is optionally substituted by methoxy; R 2 is hydrogen or halogen;
  • R 3 is hydrogen, C M alkyl, C 3 _ 4 alkenyl, C 3 _ 4 alkynyl, wherein the C M alkyl is optionally substited by cyano or methoxy;
  • R 4 is phenyl optionally substituted with 1-3 halogen atoms;
  • R 6 is hydrogen,-NH-Ci_4 alkyl, wherein the alkyl is optionally substituted by hydroxy or C M alkoxy, which in turn may be substituted by hydroxy, or R 6 is -NH-C(O)-C 1-4 alkyl, NH- C(O)-C 3-4 cycoalkyl, -NH-C(O)-C 3-4 alkenyl, or -NH-C(O)-C 2-4 alkynyl; R 7 is hydrogen or halogen; R 8 is hydrogen or halogen.
  • the method of the invention may utilise a compound of formula (Ii):
  • R 1 , R 2 , R 3 , R 4 , R 6 , and R 7 are as defined for formula (Ih) above, in any combination thereof.
  • the method of the invention may utilise a compound of formula (Ij):
  • R 2 , R 3 , R 4 , R 6 , R 7 , and R 8 are as defined for formula (Ih) above, in any combination thereof.
  • the method of the invention may utilise a compound of formula (Ik):
  • R 1 , R 3 , R 4 , R 6 , R 7 , and R 8 are as defined for formula (Ih) above, in any combination thereof.
  • the method of the invention utilises a compound of formula (II)
  • any one of G 1 , G 2 and G 3 is N and the other two of G 1 , G 2 and G 3 are CR 8 , CR 1 or CR 2 , such that when G 1 is not N, G 1 is CR 8 ; when G 2 is not N, G 2 is CR 1 ; when G 3 is not N, G 3 is CR 2 ; and preferably, in any combination:
  • R 1 is hydrogen, halogen or Ci_4 alkyl
  • R 2 is hydrogen, halogen or Ci_4 alkyl
  • R , 3 is hydrogen, optionally substituted Ci_6 alkyl, optionally substituted C2-6 alkenyl or optionally substituted C2-6 alkynyl, the optional substituents being as defined above and, more preferably, halogen or alkoxy, e.g. -O-Ci_4 alkyl;
  • R 4 is optionally substituted aryl, e.g. optionally substituted phenyl, the optional subsituents being as defined above and, more preferably, halogen;
  • R 6 is hydrogen, -SR 18 or -NR 18 R 19 , wherein R 18 is hydrogen or Ci_ 4 alkyl, and R 19 is optionally substituted C 1-4 alkyl, -C(S)R 23 or -C(O)R 23 , and R 23 is hydrogen or Ci_ 4 alkyl, the optional substituents being as defined above;
  • R 7 is hydrogen, halogen or Ci_4 alkyl
  • R 8 is hydrogen, halogen or Ci_4 alkyl. More preferably, in any combination thereof: R 1 is hydrogen, methyl, ethyl or chloro; R 2 is hydrogen, methyl, ethyl or chloro; R 3 is hydrogen, halo-Ci_4 alkyl, Ci_4 alkyl-O-Ci_4 alkyl, Ci_ 4 alkyl, C 2 - 4 alkenyl or C 2 - 4 alkynyl, in particular hydrogen, 2-fluoroethyl, methoxymethyl, prop-l,2-diene or prop-2-ynyl; R 4 is optionally substituted phenyl, the optional substituent being halogen, e.g.
  • R 6 is hydrogen or -NR 18 R 19 , wherein R 18 is hydrogen, and R 19 is 2-methoxy-l-methylethyl, -C(S)R 23 or -C(O)R 23 , and R 23 is Ci_ 4 alkyl, in particular 1- methylethyl, 1-dimethylethyl or 3-methylpropyl;
  • R 7 is hydrogen, methyl, ethyl or chloro; and
  • R 8 is hydrogen, methyl, ethyl or chloro.
  • the method of the invention may utilise a compound of formula (Im):
  • R 1 , R 2 , R 3 , R 4 , R 6 and R 7 are as defined for formula (II) above, in any combination thereof.
  • the method of the invention may utilise a compound of formula (In):
  • R 2 , R 3 , R 4 , R 6 , R 7 and R 8 are as defined for formula (II) above, in any combination thereof.
  • the method of the invention may utilise a compound of formula (Io):
  • R 1 , R 3 , R 4 , R 6 , R 7 and R 8 are as defined for formula (II) above, in any combination thereof.
  • the present invention provides a compound of formula (I) as defined above with the provisos that:
  • the compound of formula (I) is not: 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[3,2-c]pyridazine; 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[3,2-d]pyrimidine; 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine;
  • the also invention provides a compound of formula (Ia) as defined above, with the proviso that the compound of formula (Ia) is not: 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[3,2-c]pyridazine.
  • the invention also provides a compound of formula (Ib) as defined above, with the proviso that the compound of formula (Ib) is not: 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[3,2-d]pyrimidine; or 7-(4-fluorophenyl)-6-(pyridine-4-yl)-5H-pyrrolo[3,2-d]pyrimidine.
  • the invention also provides a compound of formula (Ic) as defined above, with the provisos that:
  • the compound of formula (Ic) is not: 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine.
  • the invention also provides a compound of formula (Id), (Ih) or (II) as defined above, with the provisos that:
  • the invention also provides a compound of formula (Ie), (Ii) or (Im) as defined above, with the proviso that the compound of formula (Ie), (Ii) or (Im) is not:
  • the invention also provides a compound of formula (If), (Ij) or (In) as defined above, with the proviso that the compound of formula (If), (ij) or (In) is not:
  • the invention also provides a compound of formula (Ig), (Ik) or (Io) as defined above, with the provisos that:
  • R 4 is not 4-fluorophenyl; and (ii) the compound of formula (Ig), (Ik) or (Io) is not: 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine;
  • the present invention provides a compound of any one of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), and (Io) with the proviso that the compound is not one that is disclosed in WO 99/20624.
  • the compounds listed above are named according to the scheme outlined on pages 17 and 18 of WO 99/20624.
  • WO 99/20624 is incorporated herein by reference.
  • the invention also provides a compound of any one of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), and (Io), wherein, when present: G 1 , G 2 , G 3 , X 1 , X 2 , R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 20 , R 21 , R 22 , R 23 , R 24 , and R 25 are as defined above for formula (I), in any combination thereof, and, in any combination:
  • R 6 is:
  • aryl e.g. optionally substituted phenyl, optionally substituted heteroaryl, e.g. optionally substituted heterophenyl, optionally substituted cycloalkyl, e.g. optionally
  • R 6 is -NR 18 R 19 , e.g. -NHR 19 .
  • R 6 is -NHC(O)R 23 , in which R 23 is preferably Ci_ 4 alkyl, e.g. ethyl, isopropyl, or cyclopropyl or cyclobutyl.
  • R 18 is: (i) hydrogen
  • Ci_6 alkyl optionally substituted C 2 -6 alkenyl or optionally substituted C 2 -6 alkynyl
  • an optionally substituted heterocyclic ring formed with R 19 e.g. a 5 or 6 membered heterocycle, or
  • R 18 is hydrogen, Ci_ 4 alkyl, C 2 - 4 alkenyl, or C 2 - 4 alkynyl. More preferably Ri 8 is hydrogen, ethyl, ⁇ o-propyl, prop-2-enyl, prop-2ynyl or but-2-ynyl.
  • R 19 is:
  • Ci_6 alkyl optionally substituted C 2 -6 alkenyl or optionally substituted C 2 -6 alkynyl
  • optionally substituted aryl e.g. optionally substituted phenyl, optionally substituted heteroaryl, e.g. optionally substituted heterophenyl
  • optionally substituted cycloalkyl e.g. optionally substituted C3-6 cycloalkyl
  • optionally substituted cycloalkenyl e.g. optionally substituted C 4 -6 cycloalkenyl, or optionally substituted heterocycloalkyl, e.g.
  • R 19 is hydrogen, -C(S)R 23 , -C(O)R 23 or -C(O)OR 23 or Ci -4 alkyl.
  • R 19 is hydrogen, wo-butyl, -C(O)R 23 or -C(O)OR 23 .
  • the invention also provides a compound of any one of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), and (Io), wherein, when present: G 1 , G 2 , G 3 , X 1 , X 2 , R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , and R 25 are as defined above for formula (I), in any combination thereof, and:
  • R 3 is: (v) hydroxyl
  • Ci_6 alkyl optionally substituted C 2 -6 alkenyl or optionally substituted C 2 -6 alkynyl
  • optionally substituted cycloalkyl e.g. optionally substituted C 3-6 cycloalkyl, or (viii) -C(O)R 12 , -OR 12 , -C(O)OR 12 , -OC(O)R 12 or -S(O) 2 R 12 ; wherein the optional substitutents in all cases are as defined above and, more preferably, are selected from cyano, halogen, hydroxyl, Ci_ 4 alkyl, C 2 - 4 alkenyl, alkoxy, e.g. -O-Ci_ 4 alkyl (optionally substituted by alkoxy, e.g.
  • acyl e.g. -(O)C-C 1-3 alkyl
  • cycloalkyl e.g. C 3-6 cycloalkyl
  • cycloalkenyl e.g. C 3 _ 6
  • heterocycloalkyl e.g. 3-6-membered heterocycloalkyl
  • aryl e.g. phenyl, heteroaryl, e.g. heterophenyl, -NH 2 , trialkylsilyl, -C(O)R and -C(O)OR (wherein R is hydrogen, methyl or ethyl).
  • R 3 is hydroxyl, -C(O)R 12 , -OR 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O) 2 R 12 , optionally substituted Ci_6 alkyl, optionally substituted C 2 -6 alkenyl, optionally substituted C 2 -6 alkynyl, optionally substituted cycloalkyl, e.g. optionally substituted C 3 _6 cycloalkyl.
  • the invention relates to a process for the preparation of a compound the of the invention, e.g. compounds of formula (I), as defined according to any of the aspects above, comprising: a) cyclising a compound of formula (F)
  • G 1 , G 2 , G 3 , R 1 , R 2 , R 4 and R 8 are as defined for formula (I), X is a halogen, and R is a group of formula:
  • R 3 is as defined for formula (I); preferably said derivatisation is by reaction with R -LG, wherein LG is a leaving group and R 3 is an alkyl group, or by reaction with R 12 CO-LG, wherein R 12 is as defined for formula (I) and LG is a leaving group; or b) reacting an azaindole of formula (K)
  • G 1 , G 2 , G 3 , R 1 , R 2 and R 8 are as defined for formula (I), R is as defined above, and LG is a leaving group,
  • R 3 is as defined for formula (I); preferably said derivatisation is by reaction with R 3 -LG, wherein LG is a leaving group and R 3 is an alkyl group, or by reaction with R 12 CO-LG, wherein R 12 is as defined for formula (I) and LG is a leaving group; or
  • G 1 , G 2 , G 3 , R 1 , R 2 , R 4 , and R 8 are defined for formula (I), and R is as defined above,
  • Suitable leaving groups are well known in the art and may be, for example, halogen, triflate or mesylate.
  • a method of the present invention may include converting a compound of formula (I) to a salt of N-oxide thereof.
  • R is:
  • X 1 and X 2 , R 1 to R 8 are as defined above and X is halogen.
  • Compounds of formula C can be obtained by reaction between an ester of formula A and an acetonitrile derivative of formula B in the presence of a base such as sodium methoxide or potassium t-butoxide in suitable alcoholic solvent, (see J. Med. Chem. 2003, 46, 4702-4713).
  • a base such as sodium methoxide or potassium t-butoxide in suitable alcoholic solvent
  • compound F may exist as its enamine-imine equilibrium; both compounds might be separated under state of the art purification condition such as chromatography.
  • Heterocycle of formula E such as 3-chloro-pyridazin-4-ylamine or 3-Bromo- pyrazin-2-ylamine, may be commercially available or may be prepared by known methodologies. For example, by reduction of the corresponding nitro derivative (see J. Chem. Soc, 1952, 2042). As further example, pyridazine derivatives can be prepared according to the procedures reported in Journal of Heterocyclic Chemistry 1964, 1(5), 247-50 .
  • the di-azaindole (5H-Pyrrolo[3,2-c]pyridazine; 5H-Pyrrolo[3,2-d]pyrimidine or 5H- Pyrrolo[2,3-b]pyrazine) of formula G is obtained by cyclisation of the enamine F in the presence of a tertiary amine base such as DABCO and a palladium catalyst such as palladium acetate (II) or dichlorobis(triphenylphosphine) palladium (II) in an inert solvent such as dimethylformamide or dimethylacetamide (see J. Org. Chem. 1997, 62, 2676-2677).
  • a tertiary amine base such as DABCO
  • a palladium catalyst such as palladium acetate (II) or dichlorobis(triphenylphosphine) palladium (II) in an inert solvent such as dimethylformamide or dimethylacetamide
  • Compounds of formula H, where R 3 is not hydrogen may be obtained by alkylation or acylation of compounds of formula G.
  • This alkylation can be realized with an alkylating agent of formula R -Y (where Y is a leaving group such as halogen, triflate, mesylate and the like) in the presence of a base such as sodium hydride or lithium hexamethyldisilazane in an aprotic solvent such as dimethylformamide or tetrahydrofuran.
  • Compounds of formula J may be obtained in a single step condensation-cyclisation of a compound of formula E and compound of formula I.
  • the reaction is carried out in the presence of a base, such as potassium phosphate or potassium carbonate, a dehydrating agent, such as magnesium or sodium sulphate, and a palladium catalyst, preferably (di-t- butylphoshino) palladium, in an inert solvent, such as dimethylformamide or dimethylacetamide, under an inert atmosphere in a closed vessel, (see: Angew. Chem. Int. Ed. Eng. 2004, 4526-4528).
  • Compounds of formula J can be regioselectively brominated in the presence of bromine or N-bromosuccinimide in a solvent, such as carbon tetrachloride or DMF, to give a compound of formula K (see: Synthesis, 1982, 1096).
  • Compounds of formula G can be obtained by further treatment of a compound of formula K in the presence of a boronic acid of formula R 4 B(OH) 2 (where R 4 is as previously defined) under Suzuki cross coupling conditions (see: Chem. Comm. 1979, 866) under thermal or microwave conditions.
  • Compounds of formula L may be obtained by sequential protection of the corresponding heterocycle E (see “Protective groups in organic chemistry” Greene and Wuts 4 th edition, Wiley Interscience).
  • Compounds of formula L can be coupled with compounds of formula M under Sonogashira coupling conditions (see: Synthesis 1980, (8) 627-630) and subsequently treated with iodine in an inert solvent, such as dichloromethane, to undergo direct iodo cyclisation and formation of N (see: Org. Letters 2004, 6(6) 1037-1040).
  • Compounds of formula M can be prepared from the parent halogenated compound by reaction under Sonogashira conditions (see: Synthesis, 1980, (8) 627-630) with trimethylsilyl acetylene, followed by deprotection under basic conditions of the trimethyl silyl group.
  • Compounds of formula M may also be prepared from the parent aldehyde under Corey- Fuchs reaction conditions (see: Tet. Lett. 1972, (36) 3769).
  • Compounds of formula O may be obtained by treatment of N under the same conditions as the ones described above for K in scheme 2 in the presence of a boronic acid.
  • acetate as protective group can be deprotected under acidic conditions such as HCl or basic conditions such as LiOH. It is to be noted that weak protecting groups may be deprotected during the course of reactions to generate compounds of formula N or O. It is also to be noticed that PG and R 3 may be the same from the beginning of the preparation thus the deprotection step may not be required.
  • Compounds of formula J may also be obtained by direct treament of the amino heterocycle E in two steps by reacting with a compound of formula M under Sonogashira conditions followed by a cyclisation under basic conditions (NEt 3 , KOH) as described in Tet. Lett., 2007, 48, 6951-6953. The remaining sequence to reach G and H may be as previously described.
  • Scheme 4 describes an alternative method for the preparation of compound of formula (I) where R 3 is OR 12 as described previously:
  • Compounds of formula Q can be selectively reduced at the nitro position under alternative conditions to generate the 1 -hydroxy fused pyrrole of formula S.
  • compounds of formula Q can be treated under Bechamp conditions in the presence of iron in an acidic aqueous media to give compounds of formula S. Under these conditions, the complete reduced form of the azaindole may also be formed.
  • Compounds of formula Q can also be treated under catalytic hydrogenation conditions, in the presence of hydrogen, with or without pressure, with a catalyst such as palladium on charcoal in an alcoholic solvent such as ethanol.
  • Compounds of formula S can then be treated under the same conditions as those discribed for G in scheme 1 in order to generate compound of formula T, where R 12 is as previously described.
  • Scheme 5 describes an alternative method for the preparation of compound of formula (I) where R is not hydrogen.
  • a pyridine of formula U where R is as previously described can be transformed into its acetal V by treating the corresponding aldehyde in methanol or in suitable trialkyl ortho formate, such as trimethylortho formate (for the preparation of the dimethylacetal), in the presence of a catalytic amount of an acid such as sulfuric acid.
  • Compounds of formula U may be commercially available, for example 4-pyridine carboxaldehyde, 3-nitro isonicotinaldehyde and 3-chloro-4-pyridine carboxaldehyde, but may also be prepared by state of the art methodology, for example by starting from the hydroxymethyl derivative and using an oxidation procedure (see: Aus. J.
  • the compound of formula U may also be prepared from the halogen or unsubstituted analogue by halogen-metal or hydrogen-metal exchange followed by treatment with a suitable electrophile such as dimethylformamide (see: Synthesis 1999, 306-311).
  • Compounds of formula Z can be obtained by treating compounds of formula V with a suitable base, such a n-butyl lithium, sodium hydride or lithium hexamethyldisilazane, in an aprotic solvent, such a tetrahydrofuran or diethyl ether, preferably at low temperature followed by the treatment of the anion by a compound of formula W where X is a leaving group such as halogen (chlorine, bromine or iodide) or a mesylate and R 4 is as previously described.
  • a suitable base such as a n-butyl lithium, sodium hydride or lithium hexamethyldisilazane
  • an aprotic solvent such as a tetrahydrofuran or diethyl ether
  • Compounds of formula Z can be oxidized to generate compounds of formula AA, for example in the presence of hydrogen peroxide in a solvent, such as dichloromethane, in the presence of a catalyst, such as methyl trioxorhenium (see Tet. Lett., 1996, 37(6), 805-808), or in the presence of hydrogen peroxide-urea complex in a solvent such as dichloromethane (see Chem. Ber. 1992, 125(8), 1965-1966).
  • a solvent such as dichloromethane
  • a catalyst such as methyl trioxorhenium
  • Compounds of formula AA can be treated by the previously described amino heterocycle of formula E under the conditions described for the preparation of F in scheme 1 to generate compound of formula AB.
  • compounds of formula AB can be obtained by reacting compounds of formula AA and E together in the absence of solvent at a temperature allowing the distillation of the alcohol formed (see: Synthesis 1993, 12, 1227- 1229).
  • compounds of formula AB can exist as two isomers, imine and enamine, that may also be separated for example by chromatography.
  • Compounds of formula AD where X is halogen such as chlorine or bromine can be prepared by treating compounds of formula AC with POCI3 or POBr 3 under conditions used in state of the art methodology such as chlorination of substituted pyridines in Chem. and Pharm. Bull. 1994, 42(9), 1841-1849.
  • Compounds of formula AE can be prepared from compounds of formula AD by Buchwald amination or amidation reaction in the presence of a primary amide or amine, a palladium (II) catalyst such as palladium diacetate, a ligand such as Xantphos®, a base such as potassium or cesium carbonate, in an aprotic solvent such as dioxane or tetrahydrofuran, under thermal or microwave conditions (see Org. Let. 2001, 3(21) 3417-3419).
  • a palladium (II) catalyst such as palladium diacetate
  • a ligand such as Xantphos®
  • a base such as potassium or cesium carbonate
  • Compounds of formula AE may also be prepared from AD by direct treatment with an amine such as benzyl amine under thermal or microwave conditions, followed by treatment with a strong acid such as concentrated sulphuric acid to generate the compound where R 6 is NH 2 .
  • Such an intermediate can be further treated by an appropriate non nucleophilic base, such as pyridine, in a solvent, such as dimethylformamide or tetrahydrofuran, and an acylating agent, such as R 20 COX, where X is chlorine or fluorine and R 20 is as previously described. It can also be treated with an alkylating agent, such as R 18 -X where X is a leaving group such as halogen or a mesylate, under the same conditions.
  • R 6 is neither an amine nor an amide
  • compounds of formula AC may be treated with an activator such as benzoyl chloride in the presence of a cyanide source such as trimethylsilyl-cyanide in an aprotic solvent such as dimethylformamide or tetrahydrofuran (See J. Org. Chem. 1983, 48, 1375-1377).
  • an activator such as benzoyl chloride
  • a cyanide source such as trimethylsilyl-cyanide in an aprotic solvent such as dimethylformamide or tetrahydrofuran
  • Compounds of formula AE where R 6 is cyanide can be further modified by state of the art methods to generate all the possible derivatives of the cyanide group: for example, reduction to the acid or ester, reduction to the amide or reduction to the amine, addition on cyanide by an alkyl or aryl Grignard to generate the ketone.
  • Compounds of formula AI can be prepared from compounds of formula AD following the methodology described in scheme 1 for the preparation of compounds of formula H from compounds of formula G.
  • Compounds of formula AG can be prepared from compounds of formula AE following the methodology used for the preparation of compounds of formula AI.
  • Compounds of formula AG can also be prepared from compounds of formula AI following the methodologies used for the preparation of compounds of formula AE from compounds of formula AD.
  • Compounds of formula AF can be prepared from compounds of formula AE by the following treatment: oxidation of the pyridine following the preparation described for compounds of formula AA from compounds of formula Z direct reaction to introduce R 7 as described for the introduction of R 6 in the preparation of compounds of formula AE from compounds of formula AD - R 7 may also be introduced by the methodologies described for the introduction of
  • Scheme 6 describes an alternative method for the preparation of compounds of formula (I) where X 1 is CH and X 2 is N (compounds of formula (Ic), for example, where G 1 , G 2 , G 3 , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , and R 8 are defined for formula (I).
  • Compounds of formula AL can be prepared by treatment of a pyrimidine of formula AJ, where X is a halogen such as bromine, chlorine or iodide and R 7 is as previously described, in the presence of a suitable base to realize the metal halogen exchange, n-butyl lithium or s-butyl lithium may be used in an aprotic solvent, such as tetrahydrofuran, preferably at low temperature.
  • the acyl chloride of formula AK can then react with the previously formed anion of the pyrimidine to give compounds of formula AL.
  • Compounds of formula AJ may be commercially available such as the 4-iodo-2- methylthio- pyrimidine or obtained by state of the art methods (see for examples Tet. Lett. 2001, 42(2), 311-313).
  • Compounds of formula AK are usually commercially available, for example phenylacetyl chloride, m-tolylacetyl chloride or 4-fluoro benzeneacetyl chloride, but may also be prepared from the corresponding acid.
  • Compounds of formula AM can be prepared from the condensation between compounds of formula E and AL under the conditions described for the formation of compound F in scheme 1, followed by the cyclisation of the imine or enamine obtained under the conditions described in scheme 1 for the formation of compound G.
  • an oxidant such as m-chloroperbenzoique acid
  • a solvent such as dichloromethane
  • Compounds of formula AN may be obtained by treatment of compounds of formula AM following the same procedure as the one previously described for the formation of compounds of formula H from compound of formula G.
  • Compounds of formula AO can be prepared from compounds of formula AN using methodology as previously described for the preparation of compounds of formula AP from compounds of formula AM .
  • Compounds of formula AO may also be prepared by the direct introduction of R 3 at the indole ring of the compounds of formula AP following the procedure previously described for the formation of compounds of formula H from compounds of formula G in scheme 1.
  • the compounds of formula I are useful in controlling plant pathogenic fungi when they are applied to a plant or plant propagation material in a fungicidally effective amount.
  • Plant propagation material is meant generative parts of a plant including seeds of all kinds (fruit, tubers, bulbs, grains etc), roots, rhizomes, cuttings, cut shoots and the like. Plant propagation material may also include plants and young plants which are to be transplanted after germination or after emergence from the soil.
  • a compound that "controls fungal infection" in plants and/or plant propagation material is, for example, a compound that inhibits, e.g. selectively inhibits, an existing fungal infection in a plant or plant propagation material.
  • the compound may slow the rate of fungal growth and/or reduce fungal growth in a plant or plant propagation material, e.g. compared to the absence of the compound.
  • a compound that "prevents fungal infection” in plants or plant propagation material is, for example, a compound that inhibits e.g. selectively inhibits, the emergence of a fungal infection in a plant or plant propagation material.
  • the compound may slow the appearance of a fungal infection and/or reduce the rate of fungal emergence in a plant or plant propagation material, e.g. compared to the absence of the compound.
  • a compound that controls and/or prevents a fungal infection in a plant or plant propagation material may reduce the ability of a fungus to grow in and/or on a plant or plnat propagation material and/or reduce the rate at which the fungal infection spreads to any neighbouring plants.
  • the compound may be biologically active, e.g. it may impede the normal internal biochemistry of the fungus.
  • the compound is toxic for the fungus, e.g. it kills the fungus on contact.
  • Applying the compound to a plant or plant propagation material means, for example, contacting the compound with a plant or plant propagation material to be treated.
  • the methods, compounds and compositions of the present invention are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria), Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia), Ascomycetes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula and Pyrenophora) and Oomycetes (e.g. Phytophthora, Pythium, Plasmopara).
  • Fungi imperfecti e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria
  • Basidiomycetes e.g. Rhizoctonia, Hemileia, Puccinia
  • Ascomycetes
  • the methods, compounds and compositions of the present invention are effective against Botrytis spp., Pyricularia spp., Fusarium spp. Septoria spp., Rhizoctonia spp., Puccinia spp., Erysiphe spp., Phytophthoria spp., Pythium spp. and Plasmopara spp.
  • the methods, compounds and compositions of the present invention are effective against Botrytis cinerea, Pyricularia oryzae, Fusarium culmorum, Septoria nodurum and Septoria tritici, Rhizoctonia solani, Puccinia recondite, Erysiphe graminis, Pyrenophora teres, Phytophthora infestans, Pythium ultimum and Plasmopara viticola.
  • the methods, compounds and compositions of the present invention are suitable for controlling such disease on a number of plants and their propagation material including, but not limited to the following target crops: cereals (wheat, barley, rye, oats, maize (including field corn, pop corn and sweet corn), rice, sorghum and related crops); beet (sugar beet and fodder beet); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, sunflowers); cucumber plants (marrows, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); vegetables (spinach, lettuce, asparagus, cabbages, carrots, eggplants, onions, pepper, tomatoes, potatoes, paprika, okra); plantation crops (bananas, fruit trees, rubber trees, tree nurseries), ornamentals (flowers, shrubs, broad-leaved trees and evergreens, such as conifers); as well as other plants such as vines, bushberries (such as blue
  • ryegrasses such as perennial ryegrass (Lolium perenne L.) and annual (Italian) ryegrass (Lolium multiflorum Lam.)) and warm-season turf grasses (for example, Bermudagrasses (Cynodon L. C. Rich), including hybrid and common Bermudagrass; Zoysiagrasses (Zoysia Willd ), St. Augustinegrass (Stenotaphrum secundatum (Walt.) Kuntze); and centipedegrass (Eremochloa ophiuroides (Munro.) hack.)).
  • Crops' are to be understood to include those crops that have been made tolerant to pests and pesticides, including herbicides or classes of herbicides, as a result of conventional methods of breeding or genetic engineering.
  • Tolerance to e.g. herbicides means a reduced susceptibility to damage caused by a particular herbicide compared to conventional crop breeds.
  • Crops can be modified or bred so as to be tolerant, for example, to HPPD inhibitors such as mesotrione or EPSPS inhibitors such as glyphosate.
  • the compounds of formula I find general use as fungicides and may therefore also be used to control pathogenic fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.
  • the present invention further provides the use of a compound of formula I for controlling fungi.
  • the compound of the invention is normally applied to plants and/or plant propagation material in a fungicidally effective amount. The amount used will of course depend on several factors such as the plant or propagation material, the type of fungus and the particular compound of the invention.
  • the compounds of formula I may be in unmodified form or, preferably, formulated together with carriers and adjuvants conventionally employed in the art of formulation.
  • the invention therefore also relates to a composition for the control of fungal infection comprising a compound of formula I as defined above and an agriculturally acceptable carrier or diluent.
  • the agrochemical composition will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.
  • the agrochemical compositions and formulations of the present invention are applied prior to disease development.
  • Rates and frequency of use of the formulations are those conventionally used in the art and will depend on the risk of infestation by the fungal pathogen, the developmental stage of the plant and on the location, timing and application method.
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 1Og to lkg a.i./ha, most preferably from 2Og to 60Og a.i./ha.
  • convenient rates of application are from 1 Omg to 1 g of active substance per kg of seeds.
  • the agrochemical compositions comprising compound of formula (I) are usually applied as a formulation containing the various adjuvants and carriers known to or used in the industry. They may thus be formulated as granules, as wettable or soluble powders, as emulsifiable concentrates, as coatable pastes, as dusts, as flowables, as solutions, as suspensions or emulsions, or as controlled release forms such as microcapsules. These formulations are described in more detail below and may contain as little as about 0.5% to as much as about 95% or more by weight of the active ingredient. The optimum amount will depend on formulation, application equipment and nature of the plant pathogenic fungi to be controlled.
  • 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 about 0.5% to about 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 about 5% to about 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent.
  • Emulsif ⁇ able 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 about 0.5% to about 95% of the concentrate.
  • Granular formulations include both extrudates and relatively coarse particles and are usually applied without dilution to the area in which control of plant pathogenic fungi 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 about 5% to about 25% 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.
  • 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 about 1 to 50 microns in diameter.
  • the enclosed liquid typically constitutes about 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.
  • Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.
  • compositions 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. Suitable examples of the different classes are found in the non- limiting list below.
  • Liquid carriers that can be employed include 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, di
  • Suitable solid carriers include 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, lignin and the like.
  • 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.
  • 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
  • salts of mono and dialkyl phosphate esters such as mono and dialkyl phosphate esters.
  • 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, sticking agents, and the like.
  • biocidally active ingredients or compositions may be used in the methods of the invention and applied simultaneously or sequentially with the compound of formula (I). When applied simultaneously, these further active ingredients may be formulated together with the compound 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.
  • formulations of the invention and for use in the methods of the invention can be applied to the areas where control is desired by conventional methods such as spraying atomising, dusting, scattering, coating or pouring.
  • Dust and liquid compositions for example, can be applied by the use of power-dusters, broom and hand sprayers and spray dusters.
  • the formulations can also be applied from airplanes as a dust or a spray or by rope wick applications.
  • Both solid and liquid formulations may also be applied to the soil in the locus of the plant to be treated allowing the active ingredient to penetrate the plant through the roots.
  • the formulations of the invention may also be used for dressing applications on plant propagation material to provide protection against fungus infections on the plant propagation material as well as against phytopathogenic fungi occurring in the soil.
  • the active ingredient may be applied to plant propagation material to be protected by impregnating the plant propagation material, in particular, seeds, either with a liquid formulation of the fungicide or coating it with a solid formulation.
  • plant propagation material in particular, seeds
  • other types of application are also possible, for example, the specific treatment of plant cuttings or twigs serving propagation.
  • the compounds of formula (I) as defined above can be used in the treatment of fungal infections of human and animal subjects.
  • the active compounds as described herein may be combined with a pharmaceutically acceptable carrier and administered or applied to such subjects or infections in an amount effective to treat the infection in accordance with known techniques.
  • the present invention also provides the use of a compound of formula (I) as defined above in the manufacture of a medicament for the treatment of a fungal infection in a human or animal.
  • the present invention also provides a compound of formula (I) for use in the treatment of a fungal infection in a human or animal.
  • reaction mixture is poured into ice-water (1.2L) and the pH is adjusted to 7 with a 25% solution of ammonium hydroxide. After extraction in ethyl acetate, the organic layers are dried over magnesium sulfate and the residue after concentration is purified by chromatography on silica gel (ethylacetate/hexane 2/1) to give 133 g of 2-(4- fluorophenyl)-l-(pyridine-4-yl)ethanone as a yellowish solid.
  • Step 2 A mixture of hydrazine monohydrate (2.95g), 2-(4-fluorophenyl)-l-(pyridine- 4-yl)ethanone (5 g, 23 mmoles) are dissolved in 500 rnL of ethanol in the presence of a catalytic amount of acetic acid. The reaction is heated to reflux for 2 hours. The reaction mixture is then concentrated to 25% of the original volume and extracted in ethyl acetate / saturated ammonium chloride solution. The organic phase is washed with water and dried over magnesium sulfate.
  • Step 3 2.73 g of [2-(4-Fluoro-phenyl)-l-pyridin-4-yl-ethylidene]-hydrazine are dissolved in 20 mL of toluene under argon. 2.95 g of 5-bromopyrimidine (18mmoles) and 1.8 g of sodium tert-butylate (18.5 mmoles) are then added to the mixture, followed by Ig of DPPF ([l-l '-bis-(diphenylphosphine)ferrocene]) and 0.48 g of PdC12(DPPF) dichloro- methane complex. The reaction mixture is heated at 100 0 C for 12 hours..
  • DPPF [l-l '-bis-(diphenylphosphine)ferrocene]
  • Step 4 1.1 g ofN-[2-(4-Fluoro-phenyl)-l-pyridin-4-yl-ethylidene]-N'-pyrimidin-5- yl-hydrazine 4 mL of diethylene glycol under nitrogen is heated at 250 0 C for 4 hours in a metal bath. The cooled reaction mixture is then poured into concentrated NaCl solution and extracted with ethyl acetate. The organic phase is washed with water and dried over magnesium sulfate. Chrommatography of the solid residue after concentration affords 250 mg of 7-(4-Fluoro-phenyl)-6-pyridin-4-yl-5H-pyrrolo[3,2-d]pyrimidine as beige crystals.
  • Step 5 Sodium hydride (52mg, 1.29 mmole 60% in oil) is added to a solution of 125 mg (0.43 mmole) of 7-(4-Fluoro-phenyl)-6-pyridin-4-yl-5H-pyrrolo[3,2-d]pyrimidine in 6 mL of dimethylformamide at room temperature. After 30 min. at room temperature, 547 mg of l-bromo-2-fluoroethane is added to the reaction mixture. After 90min. at room temperature, the reaction mixture is poured into ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed with water and dried over magnesium sulfate.
  • Step 1 To 2,3-dichloropyrazine (100 g, 0.671 mol) in dioxane (150 rnL), was added benzylamine (86.3 g, 0.805 mol), triethylamine (140 mL, 1.0 mol), and the reaction mixture was heated at 100 0 C for 6-7 h. After completion of the reaction, most of the solvent was evaporated under reduced pressure, the reaction mass was diluted with water, and extracted with dichloromethane.
  • Step 2 To 2-chloro-3-iodopyridine (100 g, 0.418 mol) in dry DMF (250 mL) under an atmosphere of nitrogen was added Pd 2 (dba)3 (19.1 g, 0.021 mol, 5 mol%), triethylamine (300 mL), and CuI (0.398 g, 0.0021 mol, 0.5 mol%). The reaction mixture was cooled to O 0 C and to this was added trimethylsilylacetylene (35.1 mL, 0.459 mol) dropwise. The reaction mixture was allowed to stir at room temperature (25 0 C) for 3-4 h. After completion of the reaction, the reaction mixture was diluted with cold water, and filtered over a celite bed.
  • Step 3 To 2-benzylamino-3-chloropyrazine (50 g, 0.228 mol) in dimethyl formamide
  • reaction mixture was heated at HO 0 C for 4-5h. After completion of the reaction, the reaction mixture was filtered through a celite bed, the filtrate diluted with cold water, and extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, concentrated under reduced pressure, and purified by chromatography on neutral alumina (ethylacetate/hexane, 1/5) to yield 32.8 g (45%) of 2-(2-chloro-4-ethynylpyridine)- 3-benzylaminopyrazine.
  • Step 4 A solution of 2-(2-chloro-4-ethynyl pyridine)-3-benzylaminopyrazine (37 g,
  • Step 5 A mixture of palladium acetate (1.23 g, 0.00547 mol, 5 mol%), X-Phos (5.21 g, 0.011 mol, 10 mol%), and potassium tertiary butoxide (18.4 g, 0.164 mol) in toluene/ethanol (2:1, 10OmL) under an atmosphere of nitrogen was heated to 7O 0 C. To this was added 2-(2-chloro pyridyl)-l-benzyl-4,7-diazaindole (35 g, 0.11 mol) as a solution in toluene/ethanol (2:1, 15OmL) dropwise. After completion of addition the reaction mixture was heated at 90-100 0 C for 1-2 h.
  • Step 6 2-(2-ethoxy pyridyl)-l-benzyl-4,7-diazaindole (35 g, 0.11 mol) in dicholoromehtane (150 mL) under an atmosphere of nitrogen was cooled to O 0 C, to this was added bromine (1.47 mL, 0.11 mol) dissolved in dichloromethane (100 mL) dropwise. After addition was complete the reaction mixture was allowed to stir at room temperature (25 0 C) for 1 h. After completio of the reaction, the reaction mass was quenched with aqueous solution of sodium thiosulfate, extracted with dichloromethane, and the combined organic layers were washed with aqueous sodium bicarbonate.
  • Step 7 A mixture of palladium acetate (0.55 g, 0.0025 mol, 5 mol%), X-Phos (2.33 g, 0.0049 mol, 10 mol%), and cesium carbonate (48 g, 0.147 mol) in toluene/ethanol (3:1, 60 mL) under an atmosphere of nitrogen was allowed to stir for 5-10 min. To this was added a solution of phenyl boronic acid (6.58 g, 0.054 mol) and 2-(2-ethoxy pyridyl)-3-bromo-l- benzyl-4,7-diazaindole (20 g, 0.049 mol) in toluene/ethanol (3:1, 60 mL), dropwise.
  • reaction mixture was heated at 6O 0 C for 5 h.
  • solvent was evaporated under reduced pressure, the reaction mass diluted with water, and extracted with ehtylacetate. The combine organic layers were dried over sodium sulfate and evaporated under reduced pressure to yield 17 g (85%) of 2-(2-ethoxy pyridyl)-3- phenyl-l-benzyl-4,7-diazaindole, which was pure enough to be used as such for the next step.
  • Step 1 2-(2-ethoxy pyridyl)-3-phenyl-l-benzyl-4,7-diazaindole (17 g, 0.042 mol) in 33% HBr in glacial acetic acid (50 mL) was heated at 100-11O 0 C for 6-7 h.
  • Step 2 2-(2-hydroxy pyridyl)-3-phenyl-l-benzyl-4,7-diazaindole (13 g, 0.035 mol) in phosphorous oxychloride (50 mL) was heated at 100-11O 0 C for 7 h. After completion of the reaction, the phosphorous oxy chloride was distilled out, the reaction mass neutralized with aqueous IN sodium hydroxide solution, and the aqueous phase extracted with dichloromethane.
  • Step 3 2-(2-chloro pyridyl)-3-phenyl-N-benzyl-4,7-diazaindole (11 g, 0.028 mol) in cone sulfuric acid (20 mL) was heated at 8O 0 C for 8 h. After completion of the reaction, the reaction mixture was cooled to room temperature (25 0 C), diluted with ice, extracted with dichloromethane by adjusting the aqueous layer to neutral and basic pH.
  • Step 4 A mixture of para methoxy benzylamine (3.6 g, 0.026 mol), palladium acetate (0.18 g, 0.00065 mol, 5 mol%), X-Phos (0.62 g, 0.0013 mol, 10 mol%), and potassium tertiary butoxide (3.67 g, 0.033 mol) in toluene (25 mL) under an atmosphere of nitrogen was heated to 7O 0 C.
  • Step 5 To 2-[2-(p-methoxy benzylamino) pyridyl]-3-phenyl-4,7-diazaindole (2 g, 0.0049 mol) in dimethyl formamide (10 mL) was added cesium carbonate (4 g, 0.012 mol) and the mixture was allowed to stir at room temperature (25 0 C) for 10 min. To this was added allyl bromide (0.65 g, 0.0054 mol) dropwise and the reaction mixture was stirred at room temperature (25 0 C) for 15 min. After completion of the reaction, the reaction mixture was diluted with water and extracted with dichloromethane.
  • Step 6 2-[2-(p-methoxy benzylamino) pyridyl]-3-phenyl-N-propargyl-4,7- diazaindole (1.8 g, 0.004 mol) in trifluoro acetic acid (5 mL) was heated at 50-60 0 C under an atmosphere of nitrogen for 2 h. After completion of the reaction, the excess trifluoroacetic acid was distilled out under reduced pressure. The reaction mass was diluted with water, adjusted to basic pH using IN sodium hydroxide, and extracted with dichloromethane.
  • Step 7 To 2-(2-amino pyridyl)-3-phenyl-l-allyl-4,7-diazaindole (0.2 g, 0.0006 mol) in pyridine (2 mL) was added propionyl chloride (0.06 g, 0.00067 mol) dropwise and the reaction mixture was stirred at room temperature (25 0 C) for 15 min. After completion of the reaction, pyridine was evaporated under reduced pressure, the reaction mass diluted with water, and extracted with dichloromethane. The combined organic layers were washed with IN hydrochloric acid, water, dried over sodium sulfate, and concentrated under reduced pressure.
  • Ethyl formate (14.17g, 0.19 mol) is added dropwise to a solution of sodium methoxide in methanol (prepared by dissolving 10.3g sodium in 100ml methanol).
  • Benzyl cyanide (2Og, 0.17 mol) in methanol is then added dropwise to the above mixture.
  • the reaction mixture is then heated to reflux till complete precipitation of white salt. After cooling down to room temperature, the reaction mixture is filtered through buchner funnel, washed with diethyl ether and dried to obtain the white solid (21 g).
  • 3-Amino-4-phenyl-lH-pyrrole-2-carboxylic acid ethyl ester (27g, 0.12 mol) is dissolved in ethanol and stirred at room temperature for 10 minutes.
  • Formamidine acetate (27g, 0.258 mol) is then added to the above mixture and stirred for 10 minutes at room temperature.
  • the reaction mixture is then heated to reflux for 8h. Cooled reaction mixture is filtered, washed with ethanol (25ml x 4) and dried to yield 7-Phenyl-5H-pyrrolo[3,2-d]pyrimidin-4-ol as white solid (2Ig).
  • Step 5 4-Chloro-7-phenyl-5H-pyrrolo[3,2-d]pyrimidine
  • Phosphorus oxy chloride 120ml, 10 vol
  • phenyl-5H-pyrrolo[3,2-d]pyrimidin-4-ol (12g, 0.056 mol)
  • the reaction mixture is then refluxed at 105 0 C for 4 hours.
  • the organic layer is washed with water, aq. NaHCO 3 solution, dried with Na 2 SO 4 and concentrated under vacuum to afford 4-Chloro-7-phenyl-5H-pyrrolo[3,2-d]pyrimidine (9.8g.)
  • Step 8 7-Phenyl-6-pyridin-4-yl-5H-pyrrolo[3,2-d]pyrimidine
  • Example 6 Biological activity of the compounds of the invention
  • the compounds of the invention were tested in a leaf disk assay, as described below to determine their preventative action against a number of fungal species.
  • the test compounds were dissolved in DMSO and diluted into water to 200 ppm.
  • the final test solution contained 2% DMSO and 0.025% Tween ® 20.
  • Botrytis cinerea grey mould: Bean leaf disks were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing the disks to dry completely (24 hours), they were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed three days after inoculation as preventive fungicidal activity.
  • Tomato leaf disks were placed on water agar in a 24-well plate and sprayed with a solution of the test compound. After allowing the disks to dry completely (24 hours), they were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
  • Plasmopara viticola downy mildew of grapevine: Grapevine leaf disks were placed on agar in a 24-well plate and sprayed a solution of the test compound. After allowing the disks to dry completely (for between 12 and 24 hours), they were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed seven days after inoculation as preventive fungicidal activity.
  • the compounds of the invention were also tested for their ability to inhibit the growth of fungal spores in nutrient broth.
  • test plates were incubated at 24 C and the inhibition of growth was determined photometrically after 72 hrs (Septoria tritici, Botrytis cinerea, Pyricularia oryzae) or 48 hrs (Rhizoctonia solani, Fusarium culmorum).
  • Type of column Water atlantis del 8; Column length: 20 mm; Internal diameter of column: 3 mm; Particle Size: 3 micron; Temperature: 40 0 C.
  • Method B (Agilentl 100 Series LC) with the following HPLC gradient conditions : Solvent A: 0.1% formic acid in water / acetonitrile (9:1) Solvent B: 0.1% formic acid in acetonitrile)
  • Type of column Water atlantis dcl8; Column length: 20 mm; Internal diameter of column: 3 mm; Particle Size: 3 micron; Temperature: 40 0 C.
  • Type of column Waters, symmetry C-18; Column length: 50mm; Internal diameter of column: 4.6mm; Particle Size: 3.5 micron;
  • Method D Thermo HPLC with the following HPLC gradient conditions: Solvent A: 0.25 % formic acid in water Solvent B: 0.025% formic acid in acetonitrile
  • Type of column Waters, symmetry C-18; Column length: 50mm; Internal diameter of column: 4.6mm; Particle Size: 3.5 micron;

Abstract

La présente invention concerne de nouveaux composés de formule (I) où l'un quelconque des groupements G1, G2 et G3 représente N et les deux autres groupements G1, G2 et G3 représentent CR8, CR1 ou CR2, de sorte que lorsque G1 ne représente pas N, G1 représente CR8 ; lorsque G2 ne représente pas N, G2 représente CR1 ; lorsque G3 ne représente pas N, G3 représente CR2 ; et X1, X2, R1, R2, R3, R4, R6, R7 et R8 sont tels que définis dans les revendications. En particulier, la présente invention concerne l'application de ces composés à des méthodes de lutte et/ou de prévention contre des infections fongiques de végétaux. La présente invention concerne également des compositions contenant ces composés ainsi que des méthodes de synthèse de ces composés.
PCT/EP2009/062673 2008-10-21 2009-09-30 Dérivés de diazaindole et leur emploi en tant que fongicides WO2010046215A2 (fr)

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EP2338890A1 (fr) * 2009-12-22 2011-06-29 Bayer CropScience AG Dérivés de 4,7-diazaindole et leur utilisation en tant que fongicides
JP2012025741A (ja) * 2010-06-23 2012-02-09 Sumitomo Chemical Co Ltd 有害節足動物防除組成物および複素環化合物
CN109071444A (zh) * 2016-03-16 2018-12-21 拜耳作物科学股份公司 作为农药和植物保护剂的n-(氰苄基)-6-(环丙基-羰基氨基)-4-(苯基)-吡啶-2-羧酰胺衍生物及相关化合物
US10239881B2 (en) 2014-10-27 2019-03-26 University Health Network RIPK2 inhibitors and method of treating cancer with same
WO2022023341A1 (fr) * 2020-07-29 2022-02-03 Bayer Aktiengesellschaft Composés de 1h-pyrrolo [3,2-b] pyridine substitués et leurs procédés d'utilisation
WO2022023340A1 (fr) * 2020-07-29 2022-02-03 Bayer Aktiengesellschaft Composés hétérocycliques substitués et leurs utilisations thérapeutiques
CN114409657A (zh) * 2022-02-11 2022-04-29 湖南科技大学 一种4-芳(甲)基咪唑啉并喹喔啉酮类化合物及其制备方法和用途

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2338890A1 (fr) * 2009-12-22 2011-06-29 Bayer CropScience AG Dérivés de 4,7-diazaindole et leur utilisation en tant que fongicides
JP2012025741A (ja) * 2010-06-23 2012-02-09 Sumitomo Chemical Co Ltd 有害節足動物防除組成物および複素環化合物
US10239881B2 (en) 2014-10-27 2019-03-26 University Health Network RIPK2 inhibitors and method of treating cancer with same
US10875863B2 (en) 2014-10-27 2020-12-29 University Health Network RIPK2 inhibitors and method of treating cancer with same
CN109071444A (zh) * 2016-03-16 2018-12-21 拜耳作物科学股份公司 作为农药和植物保护剂的n-(氰苄基)-6-(环丙基-羰基氨基)-4-(苯基)-吡啶-2-羧酰胺衍生物及相关化合物
WO2022023341A1 (fr) * 2020-07-29 2022-02-03 Bayer Aktiengesellschaft Composés de 1h-pyrrolo [3,2-b] pyridine substitués et leurs procédés d'utilisation
WO2022023340A1 (fr) * 2020-07-29 2022-02-03 Bayer Aktiengesellschaft Composés hétérocycliques substitués et leurs utilisations thérapeutiques
CN114409657A (zh) * 2022-02-11 2022-04-29 湖南科技大学 一种4-芳(甲)基咪唑啉并喹喔啉酮类化合物及其制备方法和用途
CN114409657B (zh) * 2022-02-11 2023-02-24 湖南科技大学 一种4-芳(甲)基咪唑啉并喹喔啉酮类化合物及其制备方法和用途

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