WO2005061500A1 - Spiropiperidine derivatives for controlling pests - Google Patents

Spiropiperidine derivatives for controlling pests Download PDF

Info

Publication number
WO2005061500A1
WO2005061500A1 PCT/IB2004/004083 IB2004004083W WO2005061500A1 WO 2005061500 A1 WO2005061500 A1 WO 2005061500A1 IB 2004004083 W IB2004004083 W IB 2004004083W WO 2005061500 A1 WO2005061500 A1 WO 2005061500A1
Authority
WO
WIPO (PCT)
Prior art keywords
optionally substituted
alkyl
formula
compounds
alkoxy
Prior art date
Application number
PCT/IB2004/004083
Other languages
French (fr)
Inventor
Louis-Pierre Molleyres
Jerome Cassayre
Fredrik Cederbaum
Peter Maienfisch
Original Assignee
Syngenta Participations Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US10/581,176 priority Critical patent/US7960401B2/en
Priority to AP2006003672A priority patent/AP2294A/en
Application filed by Syngenta Participations Ag filed Critical Syngenta Participations Ag
Priority to NZ546995A priority patent/NZ546995A/en
Priority to EP04806330A priority patent/EP1694677B1/en
Priority to AU2004303618A priority patent/AU2004303618B2/en
Priority to EA200601110A priority patent/EA014114B1/en
Priority to BRPI0417544-1B1A priority patent/BRPI0417544B1/en
Priority to AT04806330T priority patent/ATE450538T1/en
Priority to CA2547814A priority patent/CA2547814C/en
Priority to DE602004024443T priority patent/DE602004024443D1/en
Priority to JP2006543658A priority patent/JP5015602B2/en
Priority to CN2004800370075A priority patent/CN1894249B/en
Publication of WO2005061500A1 publication Critical patent/WO2005061500A1/en
Priority to IL175744A priority patent/IL175744A/en
Priority to KR1020067011568A priority patent/KR101175119B1/en
Priority to HK07101863.5A priority patent/HK1097829A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/20—Spiro-condensed systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • 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
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/20—Spiro-condensed systems

Definitions

  • the present invention relates to hetero-spiroindoline derivatives, to processes for preparing them, to insecticidal, acaricidal, molluscicidal and nematicidal compositions comprising them and to methods of using them to combat and control insect, acarine, mollusc and nematode pests.
  • Aza-spiroindolines with pharmaceutical properties are disclosed in for example WO02/94825 and WO00/27845. Synthetic routes to selected compounds are described for instance in Bioorganic & Medicinal Chemistry Letters (1995), 5, 1875 and Tetrahedron Letters (2001) 42, 999. It has now surprisingly been found that certain hetero-spiroindolines have insecticidal properties.
  • the present invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I):
  • R 1 is hydrogen, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocyclyloxy, cyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl/formyl, optionally substituted heterocyclyl, optionally substituted alkylthio, NO or NR 13 R 14 where R 13 and R 14 are independently hydrogen, COR 15 , optionally substituted alkyl, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally
  • each R 4 is independently halogen, nitro, cyano, optionally substituted C ⁇ -8 alkyl, optionally substituted C . 6 alkenyl, optionally substituted C 2 .
  • each Ra is independently hydrogen, halogen, hydroxy, cyano, optionally substituted Ci -8 alkyl, optionally substituted C 2 - 6 alkenyl, optionally substituted C 2 .
  • R 23 and R 24 are, independently, hydrogen, C ⁇ _ 8 alkyl, C 3-7 cycloalkyl, C 3-6 alkenyl, C 3-6 alkynyl, C .
  • the alkyl groups are suitably Ci to C12 alkyl groups, but are preferably Ci-Cio, more preferably C ⁇ -C 8 , even more preferably preferably C ⁇ -C 6 and most preferably C ⁇ -C 4 alkyl groups.
  • the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, NCS-, C 3 .
  • alkenyloxycarbonyl C -6 alkynyloxycarbonyl, aryloxycarbonyl (where the aryl group is optionally substituted) and arylcarbonyl (where the aryl group is optionally substituted).
  • Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (EJ- or (Z)-configuration. Examples are vinyl, allyl and propargyl. When present, the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety.
  • acyl is optionally substituted C ⁇ -6 alkylcarbonyl (for example acetyl), optionally substituted C 2 . 6 alkenylcarbonyl, optionally substituted C 2-6 alkynylcarbonyl, optionally substituted arylcarbonyl (for example benzoyl) or optionally substituted heteroarylcarbonyl.
  • Halogen is fluorine, chlorine, bromine or iodine.
  • Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF 3 , CF 2 C1, CF 3 CH 2 or CHF 2 CH 2 .
  • aryl and aromatic ring system refer to ring systems which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
  • heteroaryl , “heteroaromatic ring” or “heteroaromatic ring system” refer to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings.
  • heteroaromatic radicals include pyridyl, pyrimidyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl, 2,1 ,3-benzoxadiazole and thiazolyl.
  • heterocycle and heterocyclyl refer to a non-aromatic ring containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N. Examples of such rings include 1 ,3-dioxolane, tetrahydrofuran and morpholine.
  • the optional substituents on heterocyclyl include C ⁇ -6 alkyl and C ⁇ -6 haloalkyl as well as those optional substituents given above for an alkyl moiety.
  • Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.
  • Cycloalkenyl includes cyclopentenyl and cyclohexenyl.
  • the optional substituents on cycloalkyl or cycloalkenyl include C ⁇ -3 alkyl as well as those optional substituents given above for an alkyl moiety.
  • Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups.
  • the optional substituents on aryl or heteroaryl are selected independently, from halogen, nitro, cyano, NCS-, C ⁇ -6 alkyl, C ⁇ -6 haloalkyl, C ⁇ _ 6 alkoxy- (C ⁇ _ 6 )alkyl, C 2 -6 alkenyl, C 2 . 6 haloalkenyl, C 2 - 6 alkynyl, C 3 .
  • arylcarbonyl (where the aryl group is itself optionally substituted with halogen or C ⁇ _ alkyl) or two adjacent positions on an aryl or heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen or C ⁇ -6 alkyl.
  • substituents for aryl or heteroaryl include aryl carbonyl amino (where the aryl group is substituted by C ⁇ -6 alkyl or halogen), (Ci. 6 )alkyloxycarbonylamino
  • 6 alkyl or halogen arylamino (where the aryl group is substituted by C ⁇ - 6 alkyl or halogen), heteroaryl amino (where the heteroaryl group is substituted by C ⁇ -6 alkyl or halogen), heterocyclylamino (where the heterocyclyl group is substituted by C ⁇ -6 alkyl or halogen), aminocarbonylamino, C ⁇ -6 alkylaminocarbonyl amino, di(C].
  • substituents are independently selected from halogen, Ci- 6 alkyl, C ⁇ - 6 haloalkyl, C ⁇ -6 alkoxy(C ⁇ .
  • Further preferred substituents are aryl and heteroaryl groups.
  • Haloalkenyl groups are alkenyl groups which are substituted with one or more of the same or different halogen atoms. It is to be understood that dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (C] -6 )alkyl groups.
  • heterocyclic rings are formed by joining two groups on an N atom
  • the resulting rings are suitably pyrrolidine, piperidine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (C ⁇ _ 6 ) alkyl groups.
  • the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, HO 2 C, C M O alkoxy (itself optionally substituted by C M O alkoxy), aryl(C ⁇ -4 )alkoxy, C O alkylthio, C M O alkylcarbonyl, C O alkoxycarbonyl, C 1-6 alkylaminocarbonyl, di(C ⁇ -6 alkylaminocarbonyl, (C ⁇ .
  • alkenyl or alkynyl include one or more of halogen, aryl and C -7 cycloalkyl.
  • a preferred optional substituent for heterocyclyl is C ⁇ -6 alkyl.
  • the optional substituents for cycloalkyl include halogen, cyano and C ⁇ -3 alkyl.
  • the optional substituents for cycloalkenyl include C ⁇ -3 alkyl, halogen and cyano.
  • R 1 is hydrogen, C ⁇ . 6 alkyl, C 1-6 cyanoalkyl, C ⁇ -6 haloalkyl, C 3 .
  • 6 alkylthio, C ⁇ -6 alkoxycarbonyl, C ⁇ -6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), aryl(C ⁇ -6 )alkyl (wherein the aryl group may be optionally substituted by halo, nitro, cyano, C ⁇ - 6 alkyl, C ⁇ -6 haloalkyl, C ⁇ -6 alkoxy, C ] -6 haloalkoxy, C ⁇ .
  • 6 alkylsulfonyl, C ⁇ -6 alkylsulfinyl, C ⁇ -6 alkylthio, C ⁇ -6 alkoxycarbonyl, C ⁇ . 6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the aryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), C ⁇ -6 alkylcarbonylamino(C ⁇ -6 )alkyl, aryl (which may be optionally substituted by halo, nitro, cyano, C ⁇ .
  • 6 alkyl, C ⁇ -6 haloalkyl, - 6 alkoxy, C ⁇ _ 6 haloalkoxy, C ⁇ -6 alkylsulfonyl, C ⁇ -6 alkylsulfinyl, C ⁇ _6 alkylthio, C ⁇ - 6 alkoxycarbonyl, C ⁇ -6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the aryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), heteroaryl (which may be optionally substituted by halo, nitro, cyano, C ⁇ _ 6 alkyl, C ⁇ -6 haloalkyl, C ⁇ -6 alkoxy, C 1-6 haloalkoxy, C ⁇ -6 alkylsulfonyl, C ⁇ .
  • R 1 is C ⁇ -6 alkyl, C 1 -6 haloalkyl, C 1 -6 alkoxy(C ⁇ _ 6 )alkyl, heteroaryl(C ⁇ . 3 )alkyl (wherein the heteroaryl group may be optionally substituted by halo, nitro, cyano, C ⁇ - 6 alkyl, C ⁇ _ 6 haloalkyl, C ⁇ -6 alkoxy, C ⁇ -6 haloalkoxy, C ⁇ -6 alkylsulfonyl, C ⁇ _ 6 alkoxycarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), phenyl(C ⁇ -3 )alkyl (wherein the phenyl group may be optionally substituted by halogen, C M alkyl, C alkoxy, C M haloalkyl, C 1-4 haloalkoxy
  • R 13 and R 14 are independently hydrogen, C ⁇ -6 alkyl or C ⁇ -6 haloalkyl, C ⁇ -6 alkoxy(C ⁇ -6 )alkyl, C 2-6 alkylcarbonyl, phenylcarbonyl, (where the phenyl is optionally substituted by halogen, C M alkyl, C M alkoxy, C haloalkyl, C ] -4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), phenyl(C ⁇ -3 )alkyl (wherein the phenyl group may be optionally substituted by halogen, C M alkyl, C M alkoxy, C M haloalkyl, C M haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), phenyl(C ⁇ -3 )alkyl (wherein the phenyl group may be optionally substituted by halogen, C
  • 6 alkoxycarbonyl, or two adjacent positions on the phenyl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen) or heteroaryl(C ⁇ .
  • heteroaryl group may be optionally substituted by halo, nitro, cyano, C ⁇ -6 alkyl, C ⁇ -6 haloalkyl, C ⁇ -6 alkoxy, C ⁇ _ 6 haloalkoxy, C ⁇ -6 alkylsulfonyl, C ⁇ - 6 alkylsulfinyl, C ⁇ _ 6 alkylthio, C ⁇ -6 alkoxycarbonyl, C ⁇ _ 6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen).
  • R 1 is C ⁇ - 6 alkyl, C ⁇ -6 haloalkyl, heteroaryl(C ⁇ -3 )alkyl (wherein the heteroaryl group may be optionally substituted by halo, cyano, C ⁇ _ 6 alkyl, C ⁇ _ 6 haloalkyl and where the heteroaryl group is a thiazole, pyridine, pyrimidine, pyrazine or pyridazine ring), heteroaryl (optionally substituted by halo, cyano, C ⁇ _ 6 alkyl, C ⁇ -6 haloalkyl and where the heteroaryl group is a pyridine, pyrimidine, 2,1 ,3-benzoxadiazole, pyrazine or pyridazine ring), C ⁇ -6 alkoxy, C ⁇ _ 6 alkoxy(C ⁇ _ 6 )alkyl, C ⁇ _ 6 alkylamino, C ⁇ _ 6 alkoxy(C ⁇ _ 6 )alkyl, C
  • R 1 is pyridyl (optionally substituted by halo, C ⁇ -3 alkyl or C ⁇ -3 haloalkyl) especially halo-substituted pyridyl.
  • R 2 and R 3 are independently hydrogen, C ⁇ -6 alkyl, C ⁇ -6 haloalkyl, C ⁇ -6 alkoxy or cyano. More preferably R 2 and R 3 are independently hydrogen, halogen, C ⁇ - 2 alkyl, C ⁇ _ 2 haloalkyl, C 1 - 2 alkoxy, cyano.
  • R arid R are independently hydrogen or CM alkyl. Yet more preferably R and R are independently hydrogen or methyl.
  • R 2 and R 3 are both hydrogen.
  • each R 4 is independently halogen, cyano, C ⁇ -8 alkyl, C ⁇ -8 haloalkyl, C ⁇ -6 cyanoalkyl, d- alkoxy(C ⁇ . 6 )alkyl, C 3 .
  • heterocyclyl group is optionally substituted by halo, nitro, cyano, C ⁇ -6 alkyl, C ⁇ -6 haloalkyl, C ⁇ - 6 alkoxy or C 1 -6 haloalkoxy), C 2 - 6 alkenyl, aminocarbonyl(C 2-6 )alkenyl, C ⁇ - 6 alkylaminocarbonyl(C 2 . 6 )alkenyl, di(C ⁇ .
  • C ]-8 cyanoalkyl C ⁇ -6 alkoxy(C ] -6 )alkyl, C 2 . 6 alkynyl, trimethylsilyl(C 2 . 6 )alkynyl, d. 6 alkoxycarbonyl, C -7 cycloalkyl, C ⁇ -3 alkyl (C 3 .
  • cycloalkyl phenyl (optionally substituted by halogen, C alkyl, C 1-4 alkoxy, C ] -4 haloalkyl, C haloalkoxy, CN, NO , aryl, heteroaryl, amino or dialkylamino), heterocyclyl (optionally substituted by halo, nitro, cyano, C ⁇ -6 alkyl, Ci.6 haloalkyl, C ⁇ -6 alkoxy or C ⁇ -6 haloalkoxy), C].
  • each R 4 is independently halogen, cyano, C ⁇ -8 alkyl, C ] -8 haloalkyl, C ⁇ _ 8 cyanoalkyl, C ⁇ -6 alkoxy(C] -6 )alkyl, C 2 - 6 alkynyl, heterocyclyl (optionally substituted by C ]-6 alkyl), C ⁇ _ 8 alkoxy, C 1 -6 haloalkoxy, phenoxy (optionally substituted by halo, cyano, C 1-3 alkyl or C ⁇ - haloalkyl), heteroaryloxy (optionally substituted by halo, cyano, C 1 .
  • each R 4 is independently fluoro, chloro, bromo, cyano, C alkyl, C haloalkyl, C M cyanoalkyl or C].
  • 3 alkoxy(C ⁇ -3 )alkyl; n is 0, 1 or 2.
  • each R 4 is independently fluoro, chloro, bromo, C M alkyl or C 1-4 haloalkyl; n is 1 or 2.
  • R is C M O alkyl, C MO haloalkyl, aryl(C ⁇ .
  • aryl group is optionally substituted by halogen, C alkyl, C alkoxy, C M haloalkyl, C M haloalkoxy, CN, NO 2 , aryl, heteroaryl, amino or dialkylamino), heteroaryl(C ⁇ _ 6 )alkyl (wherein the heteroaryl group is optionally substituted by halogen, C ]- alkyl, C M alkoxy, C 1- haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), arylcarbonyl-(C ⁇ -6 )alkyl (wherein the aryl group may be optionally substituted by halogen, C M alkyl, C M alkoxy, Ci.
  • R is phenyl(C ⁇ - )alkyl (wherein the phenyl group is optionally substituted by halogen, C M alkyl, C alkoxy, C ⁇ -4 haloalkyl, d-4 haloalkoxy, CN, NO 2 , aryl, heteroaryl, amino or dialkylamino), heteroaryl(C ⁇ - 6 )alkyl (wherein the heteroaryl group is optionally substituted halogen, C ⁇ -4 alkyl, d -4 alkoxy, d- haloalkyl, C M haloalkoxy, CN, NO 2 , aryl, heteroaryl, amino or dialkylamino), phenyl(C 2 - 6 )alkenyl (wherein the phenyl group is optionally substituted by halogen, C M alkyl, d-4 alkoxy, C M haloalkyl, C M haloalkoxy, CN, NO 2 , aryl,
  • R 51 and R 52 are preferably hydrogen.
  • R 53 and R 54 are preferably hydrogen or halogen, especially hydrogen.
  • R 55 is preferably phenyl substituted with one to three substituents selected from halogen, C M alkyl, d- 4 alkoxy, CM haloalkyl, d_ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino. It is preferred that the ring
  • ring members are each independently CH, S, N, NR 4 , O, or CR 4 provided that at least one ring member is other than CH or CR4 and that there are no more than one O or S atoms present in the ring. More preferably the ring members are each independently CH, S, N, NR 4 , O, or CR 4 provided that at least one ring member is other than CH or CR4 and that there are no more than one O or S atoms present in the ring. More preferably the ring
  • each Ra is independently hydrogen, halo, cyano, C ⁇ -3 alkyl, hydroxy or two Ra groups together with the carbon atom to which they are attached form a carbonyl group More preferably each Ra is independently hydrogen, fluoro, methyl, hydroxy or two
  • each Ra is hydrogen.
  • p is 1 , 2 or 3 and q is 1, 2 or 3 and p+q is 3, 4 or 5. More preferably p is 1 or 2 and q is 2. Most preferably p and q are both 2.
  • One group of preferred compounds of formula (I) are those where Yis C(O) and R 1 is NR 13 R 14 where R 13 and R 14 are as defined above. Certain compounds of formula I are novel.
  • One group of novel compounds is that of formula F R 8
  • R is hydrogen, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocyclyloxy, cyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, formyl, optionally substituted heterocyclyl, optionally substituted alkylthio, NO or NR 13 R 14 where R 13 and R 14 are independently hydrogen, COR 15 , optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycl
  • R 23 and R 24 are, independently, hydrogen, C ⁇ -8 alkyl, C 3 . 7 cycloalkyl, C 3-6 alkenyl, C3.6 alkynyl, C 3- cycloalkyl(d_ )alkyl, d-6 haloalkyl, C ⁇ -6 alkoxy(C ⁇ .
  • Ci-6 alkoxycarbonyl or R 23 and R 24 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by two Ra groups attached to adjacent carbon atoms form a bond, or two Ra groups together with the carbon atom to which they are attached form a three- to seven-membered ring, that may be saturated or unsaturated, and that may contain one or two hetero atoms selected from the group consisting of N, O and S, and which may be optionally substituted by one or two Ci -6 alkyl groups; or two Ra groups together form a group -CH 2 -, -CH CH- or -CH 2 CH 2 ; p is 0, 1 , 2, 3, 4, 5 or 6; q is 0, 1, 2, 3, 4, 5 or 6 provided that p+q is 1, 2, 3, 4, 5 or 6; R is optionally substituted alkyl, optionally
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 are given in Table 1.
  • Table VI provides 575 compounds of formula If
  • Table VII provides 575 compounds of formula Ig
  • Table IX provides 575 compounds of formula Ii
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table X provides 575 compounds of formula Ij
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R b and R 4c are given in Table 1.
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table XII provides 575 compounds of formula II
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR c and the values of R 8 , R 4a , R 4b and R c are given in Table 1.
  • T2 is CR a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 are given in Table 1.
  • Table XIV provides 575 compounds of formula In
  • T2 is CR a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R a , R 4b and R 4 are given in Table 1.
  • Table XV provides 575 compounds of formula Io
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table XVI provides 575 compounds of formula Ip
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR c and the values of R 8 , R a , R b and R 4c are given in Table 1.
  • T2 is CR 4a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table XX provides 575 compounds of formula It
  • T2 is CR > 4a
  • T3 is CR .4 4 b 0
  • T4 is CR 4C and the values of R R ,4a , R n' 4 lb D and J r R> 4c are given in Table 1.
  • Table XXI provides 575 compounds of formula lu
  • Table XXIII provides 575 compounds of formula Iw
  • Table XXIV provides 575 compounds of formula Ix
  • Table XXV provides 575 compounds of formula ly
  • Table XXVI provides 575 compounds of formula Iz
  • Table XXVII provides 575 compounds of fonmila Iaa
  • Table XXVIII provides 575 compounds of formula lab
  • Table XXIX provides 575 compounds of formula lac
  • Table XXX provides 575 compounds of formula lad
  • Table XXXI provides 575 compounds of formula Iae
  • Table XXXIJ provides 575 compounds of formula Iaf
  • Table XXXIV provides 575 compounds of formula lah wherein TI is N, T2 is CR 4a , T3 is CR 4b , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table XXXIV provides 575 compounds of formula lah wherein TI is N, T2 is CR 4a , T3 is CR 4b , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table XXXV provides 575 compounds of formula lai
  • Table XXXVII provides 575 compounds of formula lak
  • Table XXXVIII provides 575 compounds of formula Ial
  • Table XLX provides 575 compounds of formula Ian
  • Table XLI provides 575 compounds of formula Iao
  • Table XLV provides 575 compounds of formula las
  • Table XLV provides 575 compounds of formula Iat
  • T2 is CR ,4"a a
  • T3 is CR ,4"b°
  • T4 is CR 4 '
  • the values of R 8 , R 4a , R 4 and R 4 ' are given in Table 1.
  • Table XLVII provides 575 compounds of formula Iau
  • Table XLVIH provides 575 compounds of formula lav
  • Table IL provides 575 compounds of formula law
  • Table LI provides 575 compounds of formula lay
  • T2 is CR , 4"a a
  • T3 is CR ,4"b
  • T4 is CR , 4 4 c' and the values of R 8 , R 4a , R 4 and R 4c are given in Table 1.
  • Table LII provides 575 compounds of formula Iaz
  • Table LIU provides 575 compounds of formula Iba
  • Table LV provides 575 compounds of formula Ibc
  • Table LVIII provides 575 compounds of formula Ibf
  • Table LIX provides 575 compounds of formula Ibg
  • Table LX1N provides 575 compounds of formula Ibi
  • T2 is CR a
  • T3 is CR 4b
  • T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CI provides 575 compounds of formula la wherein TI is CR 4b , T2 is N, T3 is CR a , T4 is CR 4c and the values of R 8 , R 4a , R and R 4c are given in Table 1.
  • Table C1N provides 575 compounds of formula Id wherein TI is CR 4b , T2 is ⁇ , T3 is CR 4a , T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CV provides 575 compounds of formula le wherein TI is CR 4 , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R b and R c are given in Table 1.
  • Table CVI provides 575 compounds of formula If wherein TI is CR b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CVII provides 575 compounds of formula Ig wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CVIII provides 575 compounds of formula Ih wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CIX provides 575 compounds of formula Ii wherein TI is CR 4 , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CX provides 575 compounds of formula Ij wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXI provides 575 compounds of formula B wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXII provides 575 compounds of formula II wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXIJI provides 575 compounds of formula Im wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table CXTV provides 575 compounds of formula In wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CXV provides 575 compounds of formula Io wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXVI provides 575 compounds of formula Ip wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CXVII provides 575 compounds of formula Iq wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXVi ⁇ provides 575 compounds of formula Ir wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CXIX provides 575 compounds of formula Is wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXX provides 575 compounds of formula It wherein TI is CR 4b , T2 is N, T3 is CR a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R c are given in Table 1.
  • Table CXXI provides 575 compounds of formula lu wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table CXXII provides 575 compounds of formula Iv wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXIU provides 575 compounds of formula Iw wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CXXVI provides 575 compounds of formula Iz wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXVII provides 575 compounds of formula Iaa wherein TI is CR b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CXXVIII provides 575 compounds of formula lab wherein TI is CR b , T2 is N, T3 is CR a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXIX provides 575 compounds of formula lac wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CXXX provides 575 compounds of formula lad wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXXI provides 575 compounds of formula Iae wherein TI is CR b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXXII provides 575 compounds of formula Iaf wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CXXXffl provides 575 compounds of formula lag wherein TI is CR 4b , T2 is N, T3 is CR a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXXIV provides 575 compounds of formula lah wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CXXXV provides 575 compounds of formula lai wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXXVI provides 575 compounds of formula laj wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CXXXVII provides 575 compounds of formula lak wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXXXVIll provides 575 compounds of formula Ial wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CXXXIX provides 575 compounds of formula lam wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CXL provides 575 compounds of formula Ian wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXLI provides 575 compounds of formula Iao wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXLII provides 575 compounds of formula lap wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXLIII provides 575 compounds of formula laq wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXLIV provides 575 compounds of formula lar wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CXLV provides 575 compounds of formula las wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CXLVI provides 575 compounds of formula Iat wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are giv.en in Table 1.
  • Table CXLVII provides 575 compounds of formula Iau wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4 and R 4 ' are given in Table 1.
  • Table CXLVIII provides 575 compounds of formula lav wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CIL provides 575 compounds of formula law wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CL provides 575 compounds of formula lax wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CLI provides 575 compounds of formula wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CLII provides 575 compounds of formula Iaz wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CLIII provides 575 compounds of formula Iba wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CLIV provides 575 compounds of formula Ibb wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CLV provides 575 compounds of formula Ibc wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CLVI provides 575 compounds of formula Ibd wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CLVII provides 575 compounds of formula Ibe wherein TI is CR , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CLVIII provides 575 compounds of formula Ibf wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CLIX provides 575 compounds of formula Ibg wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CLX provides 575 compounds of formula Ibh wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CLXI provides 575 compounds of formula Ibi wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CLXII provides 575 compounds of formula Ibj wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CLXIII provides 575 compounds of formula Ibk wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CLXIV provides 575 compounds of formula Ibi wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CLXV provides 575 compounds of formula Ibm wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CLXVI provides 575 compounds of formula Ibn wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CLXVII provides 575 compounds of formula Ibo wherein TI is CR 4b , T2 is N, T3 is CR 4a , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCl provides 575 compounds of formula la wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCII provides 575 compounds of formula lb wherein TI is CR 4b , T2 is CR 4a , T3 is N,
  • T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCffl provides 575 compounds of formula Ic wherein TI is CR 4b , T2 is CR 4a , T3 is N,
  • T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCV provides 575 compounds of formula le wherein TI is CR 4b , T2 is CR 4a , T3 is N,
  • T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCVI provides 575 compounds of formula If wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4c are given in Table 1.
  • Table CCVII provides 575 compounds of formula Ig wherein TI is CR 4b , T T2 i •s T3 is N, T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCV1II provides 575 compounds of formula D wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCIX provides 575 compounds of formula Ii wherein TI is CR 4b , T2 is CR 4a , T3 is N,
  • T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXI provides 575 compounds of formula Ik wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4c are given in Table 1.
  • Table CCXII provides 575 compounds of formula II wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CCXffl provides 575 compounds of formula Im wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXTV provides 575 compounds of formula In wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXV provides 575 compounds of formula Io wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXVI provides 575 compounds of formula Ip wherein TI is CR b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table CCXVII provides 575 compounds of formula Iq wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CCXVIII provides 575 compounds of formula Ir wherein TI is CR , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXLX provides 575 compounds of formula Is wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXX provides 575 compounds of formula It wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXXI provides 575 compounds of formula lu wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXII provides 575 compounds of formula Iv wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXXIII provides 575 compounds of formula Iw wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXXIV provides 575 compounds of formula Ix wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4 and R 4c are given in Table 1.
  • Table CCXXV provides 575 compounds of formula ly wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXVI provides 575 compounds of formula Iz wherein TI is CR 4b , T2 is CR 4 ⁇ T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXVII provides 575 compounds of formula Iaa wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXVIH provides 575 compounds of formula lab wherein TI is CR 4b , T2 is CR a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXIX provides 575 compounds of formula lac wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXX provides 575 compounds of formula lad wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXXXI provides 575 compounds of formula Iae wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CCXXXffl provides 575 compounds of formula lag wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R c are given in Table 1.
  • Table CCXXXIN provides 575 compounds of formula lah wherein TI is CR 4 , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table CCXXXV provides 575 compounds of formula lai wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXXVI provides 575 compounds of formula laj wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXXXV ⁇ provides 575 compounds of formula lak wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CCXXXVIII provides 575 compounds of formula Ial wherein TI is CR 4 , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXXXIX provides 575 compounds of formula lam wherein TI is CR 4 , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R b and R c are given in Table 1.
  • Table CCXL provides 575 compounds of formula Ian wherein TI is CR 4 , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4 and R 4 ' are given in Table 1.
  • Table CCXLI provides 575 compounds of formula Iao wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXLII provides 575 compounds of formula lap wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCXLUI provides 575 compounds of formula laq wherein TI is CR b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CCXLIV provides 575 compounds of formula lar wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXLV provides 575 compounds of formula las wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCXLVI provides 575 compounds of formula Iat wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR c and the values of R 8 , R 4a , R and R 4 ' are given in Table 1.
  • Table CCXLVII provides 575 compounds of formula Iau wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R and R 4c are given in Table 1.
  • Table CCXLVI1I provides 575 compounds of formula lav wherein TI is CR 4b , T2 is CR a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCIL provides 575 compounds of formula law wherein TI is CR 4b , T2 is CR 4a , T3 is ⁇ , T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCL provides 575 compounds of formula lax wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table CCLIII provides 575 compounds of formula Iba wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCLIV provides 575 compounds of formula Ibb wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCLVII provides 575 compounds of formula Ibe wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCLVIII provides 575 compounds of formula Ibf wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCLIX provides 575 compounds of formula Ibg wherein TI is CR 4b , T2 is CR a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCLX provides 575 compounds of formula Ibh wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CCLXI provides 575 compounds of formula Ibi wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CCLXII provides 575 compounds of formula Ibj wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table CCLXffl provides 575 compounds of formula Ibk wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCLXTV provides 575 compounds of formula Ibi wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCLXV provides 575 compounds of formula Ibm wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCLXVI provides 575 compounds of formula Ibn wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4c and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCLXVII provides 575 compounds of formula Ibo wherein TI is CR 4b , T2 is CR 4a , T3 is N, T4 is CR 4 ' and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CCCI provides 575 compounds of formula la wherein TI is CR 4 ', T2 is CR4 a , T3 is
  • Table CCCII provides 575 compounds of formula lb wherein TI is CR 4 ', T2 is CR 4a , T3 is
  • Table CCCIII provides 575 compounds of formula Ic wherein TI is CR 4 ', T2 is CR 4a , T3 is CR b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCVII provides 575 compounds of formula Ig wherein TI is CR 4 CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCVIII provides 575 compounds of formula Ih wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R b and R 4c are given in Table 1.
  • Table CCCXI provides 575 compounds of formula Ik wherein TI is CR 4 ', T2 is CR 4a , T3 is CR b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXII provides 575 compounds of formula II wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCXIII provides 575 compounds of formula Im wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCX1N provides 575 compounds of formula In wherein TI is CR c , T2 is CR 4a , T3 is CR b , T4 is ⁇ and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXV provides 575 compounds of formula Io wherein TI is CR c , T2 is CR ⁇ T3 is CR 4 , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXVl provides 575 compounds of formula Ip wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4 , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXVII provides 575 compounds of formula Iq wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 'are given in Table 1.
  • Table CCCXVIII provides 575 compounds of formula Ir wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCXIX provides 575 compounds of formula Is wherein TI is CR 4 ', T2 is CR a , T3 is CR 4b , T4 is N and the values of R 8 , R 4 ⁇ R 4b and R c are given in Table 1.
  • Table CCCXX provides 575 compounds of formula It wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4 ⁇ R 4b and R 4 ' are given in Table 1.
  • Table CCCXXI provides 575 compounds of formula lu wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXIl provides 575 compounds of formula Iv wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R a , R 4 and R 4c are given in Table 1.
  • Table CCCXXIII provides 575 compounds of formula Iw wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCXXIV provides 575 compounds of formula Ix wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCXXV provides 575 compounds of formula ly wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4 , T4 is N and the values of R 8 , R a , R 4b and R 4c are given in Table 1.
  • Table CCCXXVI provides 575 compounds of formula Iz wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4 and R 4 ' are given in Table 1.
  • Table CCCXXVII provides 575 compounds of formula Iaa wherein TI is CR 4 ', T2 is CR a , T3 is CR 4b , T4 is N and the values of R 8 , R a , R and R 4c are given in Table 1.
  • Table CCCXXVIII provides 575 compounds of formula lab wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCXXIX provides 575 compounds of formula lac wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCXXX provides 575 compounds of formula lad wherein TI is CR c , T2 is CR 4a , T3 is CR b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXI provides 575 compounds of formula Iae wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXII provides 575 compounds of formula Iaf wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXIII provides 575 compounds of formula lag wherein TI is CR 4 ', T2 is CR a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXTV provides 575 compounds of formula lah wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXV provides 575 compounds of formula lai wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXVI provides 575 compounds of formula laj wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXVII provides 575 compounds of formula lak wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXVIII provides 575 compounds of formula Ial wherein TI is CR 4c , T2 is CR a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXXXIX provides 575 compounds of formula lam wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CCCXL provides 575 compounds of formula Ian wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCXLI provides 575 compounds of formula Iao wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXLII provides 575 compounds of formula lap wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXLffl provides 575 compounds of formula laq wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXLTV provides 575 compounds of formula lar wherein TI is CR 4c , T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXLV provides 575 compounds of formula las wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R b and R c are given in Table 1.
  • Table CCCXLVI provides 575 compounds of formula Iat wherein Tl is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXLVU provides 575 compounds of formula Iau wherein TI is CR 4 ', T2 is CR 4a ,
  • T3 is CR 4b
  • T4 is N
  • the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCXLVffl provides 575 compounds of formula lav wherein TI is CR 4 ', T2 is CR 4a ,
  • T3 is CR 4b
  • T4 is N and the values of R 8 , R a , R 4b and.R 4 ' are given in Table 1.
  • Table CCCIL provides 575 compounds of formula law wherein TI is CR 4 ', T2 is CR 4b , T4 is N and the values of R 8 , R 4a , R b and R 4 ' are given in Table 1.
  • Table CCCL provides 575 compounds of formula lax wherein TI is CR 4c , T2 is CR 4a , T3 is
  • CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLI provides 575 compounds of formula wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCLII provides 575 compounds of formula Iaz wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLIII provides 575 compounds of formula Iba wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLIV provides 575 compounds of formula Ibb wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • Table CCCLV provides 575 compounds of formula Ibc wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLVI provides 575 compounds of formula Ibd wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4 ', R 4b and R 4c are given in Table 1.
  • Table CCCLVII provides 575 compounds of formula Ibe wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLVIII provides 575 compounds of formula Ibf wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLIX provides 575 compounds of formula Ibg wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLX provides 575 compounds of formula Ibh wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLXI provides 575 compounds of formula Ibi wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4c are given in Table 1.
  • T3 is CR 4b
  • T4 is N
  • the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLXIV provides 575 compounds of formula Ibi wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLXV provides 575 compounds of formula Ibm wherein TI is CR 4 ', T2 is CR 4a ,
  • T3 is CR b
  • T4 is N
  • the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLXVI provides 575 compounds of formula Ibn wherein TI is CR 4 ', T2 is CR 4a ,
  • T3 is CR 4b
  • T4 is N
  • the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CCCLXV ⁇ provides 575 compounds of formula Ibo wherein TI is CR 4 ', T2 is CR 4a , T3 is CR 4b , T4 is N and the values of R 8 , R 4a , R 4b and R 4 ' are given in Table 1.
  • Table CDI provides 345 compounds of formula la wherein TI is N, T2 is CR4°, T3 is N, T4 is CR 4f and the values of R 8 , R 4e and R 4f are given in Table 2.
  • Table 2
  • Table CDII provides 345 compounds of formula lb wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R e and R 4f are given in Table 2.
  • Table CDffl provides 345 compounds of formula Ic wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R f are given in Table 2.
  • Table CDTV provides 345 compounds of formula Id wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDV provides 345 compounds of formula le wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDVI provides 345 compounds of formula If wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDVIII provides 345 compounds of formula Di wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4 ' and R 4f are given in Table 2.
  • Table CD1X provides 345 compounds of formula Ii wherein TI is N, T2 is CR 4 ', T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDX provides 345 compounds of formula Ij wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R are given in Table 2.
  • Table CDXI provides 345 compounds of formula Ik wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4 ' and R 4f are given in Table 2.
  • Table CDXII provides 345 compounds of formula II wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXIII provides 345 compounds of formula Im wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R f are given in Table 2.
  • Table CDXIV provides 345 compounds of formula In wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R f are given in Table 2.
  • Table CDXVII provides 345 compounds of formula Iq wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXVIII provides 345 compounds of formula Ir wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXI provides 345 compounds of formula lu wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXIII provides 345 compounds of formula Iw wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXTV provides 345 compounds of formula Ix wherein TI is N, T2 is CR 4 ', T3 is
  • T4 is CR 4f and the values of R8, R e and R 4f are given in Table 2.
  • Table CDXXVI provides 345 compounds of formula Iz wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXVII provides 345 compounds of formula Iaa wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXLX provides 345 compounds of formula lac wherein TI is N, T2 is CR 4e , T3 is
  • Table CDXXX provides 345 compounds of formula lad wherein TI is N, T2 is CR 4e , T3 is
  • Table CDXXXII provides 345 compounds of formula Iaf wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXXIII provides 345 compounds of formula lag wherein TI is N, T2 is CR e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXXIV provides 345 compounds of formula lah wherein TI is N, T2 is CR 4 ', T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXXV provides 345 compounds of formula lai wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXXVI provides 345 compounds of formula laj wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R c and R 4f are given in Table 2.
  • Table CDXXXV ⁇ provides 345 compounds of formula lak wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXXVffl provides 345 compounds of formula Ial wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXXXIX provides 345 compounds of formula lam wherein TI is N, T2 is CR e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXL provides 345 compounds of formula Ian wherein TI is N, T2 is CR 4 ', T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXLI provides 345 compounds of formula Iao wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXLIl provides 345 compounds of formula lap wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXLIII provides 345 compounds of formula laq wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXLIV provides 345 compounds of formula lar wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR f and the values of R8, R 4 ' and R 4f are given in Table 2.
  • Table CDXLV provides 345 compounds of formula las wherein TI is N, T2 is CR 4c , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXLVI provides 345 compounds of formula Iat wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R f are given in Table 2.
  • Table CDXLVII provides 345 compounds of formula Iau wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDXLVIII provides 345 compounds of formula lav wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDIL provides 345 compounds of formula law wherein TI is N, T2 is CR 4 ', T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDL provides 345 compounds of formula lax wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R e and R f are given in Table 2.
  • Table CDLI provides 345 compounds of formula wherein TI is N, T2 is CR 4e , T3 is N, T4 is
  • Table CDLII provides 345 compounds of formula Iaz wherein TI is N, T2 is CR e , T3 is N,
  • T4 is CR 4f and the values of R8, R e and R f are given in Table 2.
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDLV provides 345 compounds of formula Ibc wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R e and R 4f are given in Table 2.
  • Table CDLVI provides 345 compounds of formula Ibd wherein TI is N, T2 is CR 4 ', T3 is N,
  • T4 is CR 4f and the values of R8, R 4c and R 4f are given in Table 2.
  • Table CDLVII provides 345 compounds of formula Ibe wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4e and R f are given in Table 2.
  • Table CDLVIII provides 345 compounds of formula Ibf wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R e and R 4f are given in Table 2.
  • Table CDLIX provides 345 compounds of formula Ibg wherein TI is N, T2 is CR 4 ', T3 is N,
  • T4 is CR 4f and the values of R8, R e and R 4f are given in Table 2.
  • Table CDLX provides 345 compounds of formula Ibh wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDLXI provides 345 compounds of formula Ibi wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR 4f and the values of R8, R 4 ' and R 4f are given in Table 2.
  • Table CDLXII provides 345 compounds of formula Ibj wherein TI is N, T2 is CR 4e , T3 is N,
  • T4 is CR f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDLXIII provides 345 compounds of formula Ibk wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDLXIV provides 345 compounds of formula Ibi wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDLXV provides 345 compounds of formula Ibm wherein TI is N, T2 is CR 4e , T3 is N, T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDLXVI provides 345 compounds of formula Ibn wherein TI is N, T2 is CR 4e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table CDLXVII provides 345 compounds of formula Ibo wherein TI is N, T2 is CR e , T3 is
  • T4 is CR 4f and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DI provides 345 compounds of formula la wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R 8 , R 4e and R 4f are given in Table 2.
  • Table DII provides 345 compounds of formula lb wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table Dili provides 345 compounds of formula Ic wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DIV provides 345 compounds of formula Id wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4c and R 4f are given in Table 2.
  • Table DVI provides 345 compounds of formula If wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DVII provides 345 compounds of formula Ig wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R e and R 4f are given in Table 2.
  • Table DVffl provides 345 compounds of formula Ih wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DIX provides 345 compounds of formula Ii wherein TI is CR 4 ', T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DX provides 345 compounds of formula Ij wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXI provides 345 compounds of formula Ik wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXII provides 345 compounds of formula II wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXIII provides 345 compounds of fo ⁇ nula Im wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXTV provides 345 compounds of formula In wherein TI is CR 4e , T2 is N, T3 is CR f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXV provides 345 compounds of formula Io wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXVI provides 345 compounds of formula Ip wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXVII provides 345 compounds of formula Iq wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXVIII provides 345 compounds of formula Ir wherein TI is CR 4e , T2 is N, T3 is
  • Table DXLX provides 345 compounds of formula Is wherein TI is CR 4 , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXI provides 345 compounds of formula lu wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXII provides 345 compounds of formula Iv wherein TI is CR 4e , T2 is N, T3 is
  • Table DXXIII provides 345 compounds of formula Iw wherein TI is CR e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4 ' and R 4f are given in Table 2.
  • Table DXXIV provides 345 compounds of formula Ix wherein TI is CR 4 ', T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXV provides 345 compounds of formula ly wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4 ' and R 4f are given in Table 2.
  • Table DXXVI provides 345 compounds of formula Iz wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R e and R 4f are given in Table 2.
  • Table DXXVII provides 345 compounds of formula Iaa wherein TI is CR 4e , T2 is N, T3 is
  • CR f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXVffl provides 345 compounds of formula lab wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R c and R f are given in Table 2.
  • Table DXXIX provides 345 compounds of formula lac wherein TI is CR 4 ', T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R e and R f are given in Table 2.
  • Table DXXX provides 345 compounds of formula lad wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R e and R 4f are given in Table 2.
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXXII provides 345 compounds of formula Iaf wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXXffl provides 345 compounds of formula lag wherein TI is CR 4e , T2 is N, T3 is
  • Table DXXXIV provides 345 compounds of formula lah wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R f are given in Table 2.
  • Table DXXXV provides 345 compounds of formula lai wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXXVII provides 345 compounds of formula lak wherein TI is CR e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXXXVIU provides 345 compounds of formula Ial wherein TI is CR 4e , T2 is N, T3 is
  • Table DXXXIX provides 345 compounds of formula lam wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXLI provides 345 compounds of formula Iao wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4c and R 4f are given in Table 2.
  • CR 4f , T4 is N and the values of R8, R 4c and R 4f are given in Table 2.
  • Table DXLIII provides 345 compounds of formula laq wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXLIV provides 345 compounds of formula lar wherein TI is CR e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXLV provides 345 compounds of formula las wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R f are given in Table 2.
  • Table DXLVI provides 345 compounds of formula Iat wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DXLVII provides 345 compounds of formula Iau wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R f are given in Table 2.
  • Table DXLVHI provides 345 compounds of formula lav wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DIL provides 345 compounds of formula law wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R f are given in Table 2.
  • Table DL provides 345 compounds of formula lax wherein TI is CR e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DLI provides 345 compounds of formula wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DLII provides 345 compounds of formula Iaz wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R f are given in Table 2.
  • Table DLIII provides 345 compounds of formula Iba wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R f are given in Table 2.
  • Table DLIV provides 345 compounds of formula Ibb wherein TI is CR 4e , T2 is N, T3 is
  • Table DLV provides 345 compounds of formula Ibc wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4 are given in Table 2.
  • Table DLVI provides 345 compounds of formula Ibd wherein TI is CR 4 ', T2 is N, T3 is
  • Table DLVII provides 345 compounds of formula Ibe wherein TI is CR 4e , T2 is N, T3 is CR 4f , T4 is N and the values of R8, R 4 ' and R f are given in Table 2.
  • Table DLVII1 provides 345 compounds of formula Ibf wherein TI is CR 4 ', T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DLIX provides 345 compounds of formula Ibg wherein TI is CR 4 ', T2 is N, T3 is
  • Table DLX provides 345 compounds of formula Ibh wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4 are given in Table 2.
  • Table DLXI provides 345 compounds of formula Ibi wherein TI is CR 4e , T2 is N, T3 is CR 4f ,
  • T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DLXII provides 345 compounds of formula Ibj wherein TI is CR 4 ', T2 is N, T3 is CR 4f , T4 is N and the values of R8, R e and R 4f are given in Table 2.
  • Table DLXIII provides 345 compounds of formula Ibk wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R 4e and R 4f are given in Table 2.
  • Table DLXIV provides 345 compounds of formula Ibi wherein TI is CR 4e , T2 is N, T3 is
  • Table DLXV provides 345 compounds of formula Ibm wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R e and R f are given in Table 2.
  • Table DLXVI provides 345 compounds of formula Ibn wherein TI is CR 4e , T2 is N, T3 is
  • CR 4f , T4 is N and the values of R8, R e and R f are given in Table 2.
  • Table DLXVII provides 345 compounds of formula Ibo wherein TI is CR 4 ', T2 is N, T3 is CR 4f , T4 is N and the values of R8, R e and R 4f are given in Table 2.
  • Table DCIII provides 345 compounds of formula Ice
  • Table DCV provides 345 compounds of formula Ice
  • TI is S
  • T2 is CR 4e
  • T3 is CR 4f
  • R 8 , R 4e and R 4f are given in Table
  • Table DCLVII provides 345 compounds of formula leg
  • Table DCXI provides 345 compounds of formula Ick
  • Table DCXTV provides 345 compounds of formula Icn
  • Table DCXV provides 345 compounds of formula Ico
  • Table DCXVI provides 345 compounds of formula Icp
  • Table DCXX ⁇ provides 345 compounds of formula lev
  • Table DCXXV provides 345 compounds of formula Icy
  • TI is S
  • T2 is CR 4 '
  • T3 is CR 4f
  • R 8 , R 4e and R 4f are given in Table
  • TI is S
  • T2 is CR >4 4 e e
  • T3 is CR ,4 4 f 1
  • R 8 , R 4e and R 4f are given in Table
  • Table DCXLV provides 345 compounds of formula Idt
  • Table DCXLVII provides 345 compounds of formula Idu
  • Table DCXLVffl provides 345 compounds of formula Idv
  • Table DCL provides 345 compounds of formula Idx
  • TI is S
  • T2 is CR 4e
  • T3 is CR » 4 4 f 1
  • R 8 , R 4e e and R ,4 4 f' are given in Table
  • Table DCLVII provides 345 compounds of formula lee wherein TI is S, T2 is CR 4e , T3 is CR 4f and the values of R 8 , R 4e and R 4f are given in Table 2.
  • Table DCLVITI provides 345 compounds of formula Ief
  • Table DCLLX provides 345 compounds of formula leg
  • Table DCLX provides 345 compounds of formula Ieh 1 1 :
  • Table DCCI provides 207 compounds of formula lea wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table 3
  • Table DCCII provides 207 compounds of formula Icb wherein TI is S, T2 is CR e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCIII provides 207 compounds of formula Ice wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCIV provides 207 compounds of formula led wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R e are given in Table 3.
  • Table DCCV provides 207 compounds of formula Ice wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCVI provides 207 compounds of formula Icf wherein TI is S, T2 is CR 4c , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCVII provides 207 compounds of formula leg wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCVIII provides 207 compounds of formula Ich wherein TI is S, T2 is CR 4 ', T3 is N and the values of R 8 and R 4c are given in Table 3.
  • Table DCCLX provides 207 compounds of formula Ici wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCX provides 207 compounds of formula Icj wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXI provides 207 compounds of formula Ick wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R e are given in Table 3.
  • Table DCCXII provides 207 compounds of formula Icl wherein TI is S, T2 is CR 4 ', T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXIII provides 207 compounds of formula Icm wherein TI is S, T2 is CR 4e , T3 is
  • Table DCCXIV provides 207 compounds of formula Icn wherein TI is S, T2 is CR 4e , T3 is
  • Table DCCXV provides 207 compounds of formula Ico wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXVI provides 207 compounds of formula Icp wherein TI is S, T2 is CR 4e , T3 is
  • Table DCCXVII provides 207 compounds of formula Icq wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R e are given in Table 3.
  • Table DCCXVIII provides 207 compounds of formula Ir wherein TI is S, T2 is CR 4e , T3 is
  • Table DCCXIX provides 207 compounds of formula Ics wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXX provides 207 compounds of formula let wherein TI is S, T2 is CR 4e , T3 is N and the values of R 8 and R e are given in Table 3.
  • Table DCCXXI provides 207 compounds of formula Icu wherein TI is S, T2 is CR 4 ', T3 is
  • Table DCCXXH provides 207 compounds of formula lev wherein Tl is S, T2 is CR 4 ', T3 is N and the values of R 8 and R e are given in Table 3.
  • Table DCCXXffl provides 207 compounds of formula lew wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCXXV provides 207 compounds of formula Icy wherein Tl is S, T2 is CR e , T3 is
  • Table DCCXXVI provides 207 compounds of formula Icz wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCXXVI! provides 207 compounds of formula Ida wherein Tl is S, T2 is CR 4 ', T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXXVIII provides 207 compounds of formula Idb wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXXX provides 207 compounds of formula Idd wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCXXXI provides 207 compounds of formula Ide wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCXXXII provides 207 compounds of formula Idf wherein Tl is S, T2 is CR e , T3 is
  • Table DCCXXXffl provides 207 compounds of formula Idg wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXXX1V provides 207 compounds of formula Idh wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXXXV provides 207 compounds of formula Idi wherein Tl is S, T2 is CR 4 ', T3 is N and the values of R and R 4e are given in Table 3.
  • Table DCCXXXVI provides 207 compounds of formula Idj wherein Tl is S, T2 is CR 4 ', T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXXXVII provides 207 compounds of formula Idk wherein Tl is S, T2 is CR 4e , T3 is N and the values of R and R 4e are given in Table 3.
  • Table DCCXXXVffl provides 207 compounds of formula Idl wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXXXLX provides 207 compounds of formula Idm wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXL provides 207 compounds of formula Idn wherein Tl is S, T2 is CR 4 ', T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXLI provides 207 compounds of formula Ido wherein Tl is S, T2 is CR 4c , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXLII provides 207 compounds of formula Idp wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCXLffl provides 207 compounds of formula Idq wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCXLTV provides 207 compounds of formula Idr wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXLVI provides 207 compounds of formula Idt wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCXLVII provides 207 compounds of formula Idu wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCXLVIII provides 207 compounds of formula Idv wherein Tl is S, T2 is CR 4 ', T3 is N and the values of R 8 and R 4 ' are given in Table 3.
  • Table DCCIL provides 207 compounds of formula Idw wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCL provides 207 compounds of formula Idx wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCLffl provides 207 compounds of formula lea wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4e are given in Table 3.
  • Table DCCLV provides 207 compounds of formula Iec wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R e are given in Table 3.
  • Table DCCLVI provides 207 compounds of formula led wherein Tl is S, T2 is CR 4e , T3 is N and the values of R 8 and R 4 ' are given in Table 3.
  • Table DCCLVII provides 207 compounds of formula lee wherein Tl is S, T2 is CR 4e , T3 is
  • Table DCCLXIV provides 207 compounds of formula Iel wherein Tl is S, T2 is CR 4c , T3 is
  • Table DCCLXVI provides 207 compounds of formula Ien wherein Tl is S, T2 is CR e , T3 is
  • Table DCCLXVfl provides 207 compounds of formula Ieo wherein Tl is S, T2 is CR 4e , T3 is
  • a compound of formula 1 may be synthesised from compounds of formula 2 by reaction with an alkylating agent of the formula R8-L, where L is chloride, bromide, iodide or a sulfonate (e.g.
  • a compound of formula 2 may be reacted with an aldehyde of the formula RCHO at a temperature between ambient temperature and 100°C in an organic solvent such as tetrahydrofuran or ethanol or mixtures of solvents in the presence of a reducing agent such as borane-pyridine complex, sodium borohydride, sodium (triacetoxy)borohydride, sodium cyanoborohydride or such like, to produce a compound of formula 1 where R8 is CH 2 -R.
  • a compound of formula 2 may be reacted with paraformaldehyde and a boronic acid of the formula R-B(OH) 2 at a temperature between ambient temperature and
  • a compound of formula 2 may be obtained from a compound of formula 3 by reaction with an acid such as trifluoroacetic acid at ambient temperature in an organic solvent such as dichloromethane, chloroform or 1 ,2-dichloroethane followed by neutralisation of the reaction mixture with an aqueous solution of an inorganic base such as sodium carbonate, sodium bicarbonate or similar compound.
  • Compounds of formula 3 may be obtained from compounds of formula 4 by reaction with a suitable electrophilic species.
  • Compounds of formula 3 where Y is a group of formula S(O) q may be formed from compounds of formula 4 by treatment with compounds of formula of Rl-S(O) q -Cl under similar conditions.
  • mesylate or tosylate or similar leaving group at a temperature of between ambient temperature and 100°C, typically 65°C, in an organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally catalysed by halide salts such as sodium iodide, potassium iodide or tetrabutylammonium iodide.
  • organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane
  • a tertiary amine base such as triethylamine or diisopropylethylamine
  • halide salts such as sodium iodide, potassium iodide or tetrabutylammonium iodide.
  • a compound of formula 7 may be reacted with an aldehyde of the formula RCHO at a temperature between ambient temperature and 100°C in an organic solvent such as tetrahydrofuran or ethanol or mixtures of solvents in the presence of a reducing agent such as borane-pyridine complex, sodium borohydride, sodium (triacetoxy)borohydride, sodium cyanoborohydride or such like, to produce a compound of formula 1 A where R8 is CH 2 -R.
  • an organic solvent such as tetrahydrofuran or ethanol or mixtures of solvents
  • a reducing agent such as borane-pyridine complex, sodium borohydride, sodium (triacetoxy)borohydride, sodium cyanoborohydride or such like
  • Compounds of formula 8 may be obtained from compounds of formula 9 by reaction with a suitable electrophilic species.
  • Compounds of formula 8 where Y is a carbonyl group may be formed by the reaction of compounds of formula 9 with a carboxylic acid derivative of formula Rl-C(O)-Z where Z is chloride, hydroxy, alkoxy or acyloxy at a temperature between 0°C and 150°C optionally in an organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane, optionally in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally in the presence of a coupling agent such as dicyclohexylcarbodiimide.
  • Compounds of formula 8 where Y is a group of formula S(O) q may be formed from compounds of formula 9 by treatment with compounds of formula of Rl-S(O) q -Cl under similar conditions.
  • compounds of formula 8 where Y is a thiocarbonyl group and RI is a carbon substituent may be formed by treatment of compounds of formula 8 where Y is a carbonyl group and RI is a carbon substituent with a suitable thionating agent such as Lawesson's reagent.
  • a suitable thionating agent such as Lawesson's reagent.
  • a compound of formula IC may be synthesised from compounds of formula 22 by reaction with an alkylating agent of the formula R8-L, where L is chloride, bromide, iodide or a sulfonate (e.g.
  • mesylate or tosylate or similar leaving group at a temperature of between ambient temperature and 100°C, typically ambient temperature, in an organic solvent such as acetonitrile, dimethylformamide, dichloromethane, chloroform or 1 ,2-dichloroethane in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally catalysed by halide salts such as sodium iodide, potassium iodide or tetrabutylammonium iodide.
  • organic solvent such as acetonitrile, dimethylformamide, dichloromethane, chloroform or 1 ,2-dichloroethane
  • a tertiary amine base such as triethylamine or diisopropylethylamine
  • halide salts such as sodium iodide, potassium iodide or tetrabutylammonium iod
  • a compound of formula 22 may be obtained from a compound of formula 23 by reaction with an acid such as trifluoroacetic acid and a reducing agent such as triethylsilane at ambient temperature in an organic solvent such as dichloromethane, chloroform or 1,2- dichloroethane followed by neutralisation of the reaction mixture with an aqueous solution of an inorganic base such as sodium carbonate, sodium bicarbonate or similar compound.
  • an acid such as trifluoroacetic acid and a reducing agent such as triethylsilane at ambient temperature in an organic solvent such as dichloromethane, chloroform or 1,2- dichloroethane
  • an organic solvent such as dichloromethane, chloroform or 1,2- dichloroethane
  • an inorganic base such as sodium carbonate, sodium bicarbonate or similar compound.
  • a compound of formula 23 may be obtained by cyclising a compound of formula 24 under Heck conditions in the presence of a catalyst such as palladium acetate, optionally a ligand such as triphenylphosphine or/and an additive such as tetrabutylammonium bromide and a base such as triethylamine in an organic solvent such as tetrahydrofuran, acetonitrile or dimethylformamide at a temperature of between 50°C to 140°C.
  • a catalyst such as palladium acetate
  • a ligand such as triphenylphosphine or/and an additive such as tetrabutylammonium bromide and a base such as triethylamine
  • a base such as triethylamine
  • Compounds of formula 24 may be obtained from compounds of formula 25 by reaction with a suitable electrophilic species.
  • Compounds of formula 24 where Y is a carbonyl group may be fo ⁇ ned by the reaction of compounds of formula 25 with a carboxylic acid derivative of formula Rl-C(O)-Z where Z is chloride, hydroxy, alkoxy or acyloxy at a temperature between 0°C and 150°C optionally in an organic solvent such as dichloromethane, chloroform or 1 ,2-dichloroethane, optionally in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally in the presence of a coupling agent such as dicyclohexylcarbodiimide.
  • a carboxylic acid derivative of formula Rl-C(O)-Z where Z is chloride, hydroxy, alkoxy or acyloxy at a temperature between 0°C and 150°C optionally in an organic solvent such as dichloromethane, chloroform or 1 ,2-dichloroethane, optionally
  • Compounds of formula IC where Y is a group of formula S(O) q may be formed from compounds of formula 22 by treatment with compounds of formula of Rl-S(O) q -Cl under similar conditions.
  • compounds of formula 24 where Y is a thiocarbonyl group and RI is a carbon substituent may be formed by treatment of compounds of formula 24 where Y is a carbonyl group and-Rl is a carbon substituent with a suitable thionating agent such as Lawesson's reagent.
  • Compounds of formula 25 may be synthesised by alkylating a compound of formula 27 (in which the amino group may if necessary be protected e.g.
  • a compound of formula 26a or 36a which are compounds of formula 26 or 36 respectively wherein the carbon atom adjacent to the leaving group X carries groups R and R may be converted to compounds of formula I using the methods described for converting compounds of 26 or 36 respectively into compounds of formula I.
  • Compounds where the ring T is a heteroaromatic ring may be prepared according to the synthetic routes described for instance in Organic Reactions (New York) (2002), 60, 157, either by route shown in scheme V or scheme VI (both based on intramolecular Heck reactions): Scheme V
  • a compound of formula ID may be synthesised by alkylating a compound of formula 42 with a reagent of formula R8-L by methods known per se.
  • a compound of formula 42 may be obtained by reacting a compound of formula 43 with a reducing agent such as triethylsilane, sodium borohydride, sodium cyanoborohydride or borane in the presence of an acid such as trifluoroacetic acid in an organic solvent such as dichloromethane at a temperature of between -10°C to 80 °C.
  • a compound of formula 43 may be synthesised from a compound of formula 44 by reacting with a suitable electrophilic species by methods known per se.
  • a compound of formula 44 may be prepared from a compound of formula 45 by treatment with a suitable base such as potassium carbonate at a temperature of between 0°C to 80°C in an organic solvent such as methanol or ethanol in combination with water.
  • a compound of formula 45 may be synthesised by cyclising a compound of formula 46 under Heck conditions, typically in the presence of a catalyst such as palladium(IT) acetate, optionally a ligand such as triphenylphosphine or/and an additive such as tetrabutylammonium bromide and a base such as triethylamine in an organic solvent such as tetrahydrofuran, acetonitrile, dimethylformamide, N-methyl-pyrrolidinone or dimethylacetamide at a temperature of between 20°C to 140°C.
  • a catalyst such as palladium(IT) acetate
  • a ligand such as triphenylphosphine or/and an additive such as tetrabutylammonium bromide
  • a base such as triethylamine
  • organic solvent such as tetrahydrofuran, acetonitrile, dimethylformamide, N-methyl-pyrrolidinone or di
  • the skilled person will readily recognize that other compounds of formula 1 may be prepared using the methods described in Scheme VII.
  • the compounds of formula (I) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are. hereinafter collectively referred to as pests.
  • the pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
  • pest species which may be controlled by the compounds of formula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp.
  • Capsids Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp. (stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp.
  • the invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a pest, a locus of pest, or to a plant susceptible to attack by a pest,
  • the compounds of formula (I) are preferably used against insects, acarines or nematodes.
  • plant as used herein includes seedlings, bushes and trees.
  • a compound of formula (I) is usually formulated into a composition which includes, in addition to the compound of formula (I), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA).
  • SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting).
  • compositions both solid and liquid formulations
  • the composition is generally used for the control of pests such that a compound of formula (I) is applied at a rate of from 0.1 g to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
  • a compound of formula (I) is used at a rate of O.OOOlg to l Og (for example 0.00 lg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
  • the present invention provides an insecticidal, acaricidal, nematicidal or molluscicidal composition
  • an insecticidal, acaricidal, nematicidal or molluscicidal composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I) and a suitable carrier or diluent therefor.
  • the composition is preferably an insecticidal, acaricidal, nematicidal or molluscicidal composition.
  • the invention provides a method of combating and controlling pests at a locus which comprises treating the pests or the locus of the pests with an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a composition comprising a compound of formula (I).
  • the compounds of formula (I) are preferably used against insects, acarines or nematodes.
  • WP Wettable powders
  • WG Water dispersible granules
  • Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C 8 -C ⁇ o fatty acid dimethylamide) and chlorinated hydrocarbons.
  • aromatic hydrocarbons such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark
  • ketones such as
  • a compound of formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as «-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
  • a suitable medium for example water or a water miscible liquid, such as «-propanol
  • a compound of formula (I) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
  • Capsule suspensions may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I) and, optionally, a carrier or diluent therefor.
  • the polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure.
  • the compositions may provide for controlled release of the compound of formula (I) and they may be used for seed treatment.
  • a compound of formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
  • a compound of formula (I) may also be fo ⁇ nulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS).
  • DS powder for dry seed treatment
  • SS water soluble powder
  • WS water dispersible powder for slurry treatment
  • CS capsule suspension
  • the preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above.
  • Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).
  • Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di- isopropyl- and tri-tJOpropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally
  • compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
  • the compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate.
  • An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components.
  • the particular additional active ingredient will depend upon the intended utility of the composition.
  • Suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate; b) Organophosphates, such as, profenofos, sulprofos, acephat
  • insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron).
  • acaricidal ovo-larvicides such as clofentezine, flubenzimine, hexythiazox or tetradifon
  • acaricidal motilicides such as dicofol or propargite
  • acaricides such as bromopropylate or chlorobenzilate
  • growth regulators such
  • fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide (SSF- 129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole- 1-sulphonamide, ⁇ -[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]- ⁇ -butyrolactone, 4-chloro- 2-cyano-N,N-dimethyl-5- -tolylimidazole-l-sulfonamide (IKF-916, cyamidazosulfamid), 3-5-dichloro-N-(3-chloro- 1 -ethyl- l-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281, zoxamide), N-allyl-N
  • the compounds of formula (I) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
  • suitable synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.
  • Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
  • An example of a rice selective herbicide which may be included is propanil.
  • An example of a plant growth regulator for use in cotton is PIXTM.
  • Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared.
  • Step E A solution of 4-chlorocinnamyl chloride (68 mg) in acetonitrile (4 ml) was added slowly to a stirred mixture of 7- Aza-l-(2-chloropyridin-4-yl-)carbonyl-spiro[indoline-3, 4 '-piperidine];
  • Step A Potassium hexamethyldisilazane (1.2 ml, 0.5 M solution in toluene) was slowly added to a solution of 4-chloro-3-fluoro-pyridin (0.5 g) and N-Boc-4-Cyano-Piperidine (0.312 g) in
  • Step D Trifluoroacetic acid (1 ml) was added to a sti ⁇ ed solution 6-aza- l-(2-chloropyridin-4-yl-
  • Step E A solution of 4-chlorocinnamyl chloride (40 mg) in acetonitrile (3 ml) was added slowly to a stirred mixture of 4-aza-l -(2-chloropyridin-4-yl-)carbonyl-spiro[indoline-3,4'-piperidine] (100 mg) and N,N-diisopropyl-ethylamine (0.66 ml) in acetonitrile (13 ml) under an atmosphere of nitrogen at room. The reaction was stirred at room temperature for 2 hrs, heated to reflux for 2 hrs and then stirred overnight at room temperature.
  • Trifluoroacetic acid (1.47 ml) was added to a stirred solution 6-chloro-4-aza-l-(2- chloropyridin-4-yl-)carbonyl-l '-carboxylic acid tert-butylester spiro[indoline-3,4'-piperidine]
  • Step E A solution of 4-chlorocinnamyl chloride (165 mg) in acetonitrile (20 ml) was added slowly to a sti ⁇ ed mixture of 6-chloro-4-aza-l-(2-chloropyridin-4-yl-)carbonyl-spiro[indoline-3,4'- piperidine] (300 mg) and N,N-diisopropyl-ethylamine (0.66 ml) in acetonitrile (40 ml) under an atmosphere of nitrogen at room. The reaction was stirred at room temperature for 4 hrs and heated to reflux overnight.
  • Step A Triphenylphosphine (2.29 g) was dissolved in tetrahydrofuran (50 ml) and the solution was cooled to -10°C under argon. Diisopropylazodicarboxylate (1.70 ml) was added dropwise over 10 min and the resulting mixture was stirred at -10°C for 20 min (formation of a white precipitate).
  • Step B In a dried, argon purged flask, - ⁇ [(2-Iodo-thiophen-3-yl)-(2,2,2-trifluoro- acetyl)-amino]-methyl ⁇ -3,6-dihydro-2H-pyridine-l-carboxylic acid tert-butyl ester obtained in Step A (1.57 g) was dissolved in dimethylacetamide (25 ml); triethylamine (1.05 ml), tetrabutylammonium bromide (1.08 g) and palladium(II) acetate (103 mg) were successively added and the solution was heated at 80°C for 4 hours.
  • Step C 4-tri fluoroacetyl-spiro[5,6-dihydro-4H-thieno[3,2- ⁇ ]pyrrole-6,4'-(l ',2',3',4'- tetrahydropyridine)]-l ' carboxylic acid tert-butyl ester obtained in Step B (0.9 g) was dissolved in methanol (30 ml) and water (5 ml), placed under argon and potassium carbonate (28 g) was added. The reaction mixture was sti ⁇ ed for 10 min at room temperature, the mixture was filtered and the filtrate concentrated in vacuo.
  • Step D 4-(2-chloropyridin-4-yl)carbonyl-spiro[5,6-dihydro-4H-thieno[3,2- ⁇ ]pyrrole-
  • Step B Lithium bis(trimethylsilyl)amide (IM solution in THF, 5.1 ml) was added dropwise to a sti ⁇ ed solution of 3-bromo-2-chloro-4-aminopyridine (1.04 g) in tetrahydrofuran (15 ml) at -78°C under N 2 . The resulting solution was then stirred at room temperature for 30 min., warmed to 0°C then cooled again at -78°C.
  • IM solution in THF 5.1 ml
  • Step C Lithium bis(trimethylsilyl)amide (IM solution in THF, 3 ml) was added dropwise to a sti ⁇ ed solution of 4-[(3-Bromo-2-chloro-pyridin-4-ylamino)-methyl]-3,6- dihydro-2H-pyridine-l -carboxylic acid tert-butyl ester (0.53 g) in tetrahydrofuran (20ml) at -78°C under N 2 . The yellow solution was warmed to 0°C and then 2-chloroisonicotinoyl chloride (50% solution in toluene, 0.95 g) was added.
  • 2-chloroisonicotinoyl chloride 50% solution in toluene, 0.95 g
  • Step D In a dried, argon purged flask, 4- ⁇ [(3-bromo-2-chloro-pyridin-4-yl)-(2- chloro-pyridine-4-carbonyl)-amino]-methyl ⁇ -3,6-dihydro-2H-pyridine-l-carboxylic acid tert- butyl ester obtained in Step C (0.63 g) was dissolved in dimethylacetamide (10 ml); triethylamine (0.41 ml), tetrabutylammonium bromide (0.40 g) and palladium(II) acetate (40 mg) were successively added and the solution was heated at 90°C for 18 hours.
  • Step E l-(2-chloro-pyridine-4-carbonyl)-spiro[[(4-chloro-2,3-dihydro-lH- py ⁇ olo[3,2-c]pyridine)-3,4'-(r,2',3',4'-tetrahydropyridine)]- carboxylic acid tert-butyl ester obtained in Step D (0.19 g) was dissolved in dichloromethane (13 ml) and treated successively with triethylsilane (0.33 ml) and trifluoroacetic acid (0.63 ml); the solution was stirred under argon for 8 hours, diluted with dichloromethane, neutralised with aqueous sodium bicarbonate, dried (sodium sulphate) and concentrated in vacuo.
  • EXAMPLE 6 This Example illustrates the pesticidal/insecticidal properties of compounds of formula (I). Test against were performed as follows: Spodoptera littoralis (Egyptian cotton leafworm)
  • Cotton leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with 5 Li larvae. The samples were checked for mortality, repellent effect, feeding behaviour, and growth regulation 3 days after treatment (DAT). The following compounds gave at least 80% control of Spodoptera littoralis:
  • MTP microtiter plate
  • Sunflower leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with an aphid population of mixed ages. After an incubation period of 6 DAT, samples were checked for mortality. The following compounds gave at least 80% control of Myzus persicae: III-3, III-7, V-213, VHI-29, CCCm-3, CCCV-3 and DCffl-3.
  • Aedes aegypti Yellow fever mosquito
  • Aedes larvae (L2) together with a nutrition mixture are placed in 96-well microtiter plates. Test solutions at an application rate of 2ppm are pipetted into the wells. 2 days later, insects were checked for mortality and growth inhibition. The following compounds gave at least 80% control of Aedes aegypt.
  • Diabrotica balteata (Corn root worm ):
  • a 24-well microtiter plate (MTP) with artificial diet was treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After drying, the
  • MTP's were infested with larvae (L2) (6-10 per well). After an incubation period of 5 days, samples were checked for larval mortality, and growth regulation.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Environmental Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Plant Pathology (AREA)
  • Pest Control & Pesticides (AREA)
  • Health & Medical Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Indole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The use of a compound of Formula (I), Y is a single bond, C=O, C=S or S(O)m where m is 0, 1 or 2; the ring represented by T is a 5 or 6 membered heteroaromatic and R1, R2, R3, R8 and Ra are specified organic groups and p is 0, 1, 2, 3, 4, 5 or 6; p+q is 1, 2, 3, 4, 5 or 6; or salts or N-oxides thereof or compositions containing them in controlling insects, acarines, nematodes or molluscs; novel compounds are also provided.

Description

SPIROPIPERIDINE DERIVATIVES FOR CONTROLLING PESTS
The present invention relates to hetero-spiroindoline derivatives, to processes for preparing them, to insecticidal, acaricidal, molluscicidal and nematicidal compositions comprising them and to methods of using them to combat and control insect, acarine, mollusc and nematode pests. Aza-spiroindolines with pharmaceutical properties are disclosed in for example WO02/94825 and WO00/27845. Synthetic routes to selected compounds are described for instance in Bioorganic & Medicinal Chemistry Letters (1995), 5, 1875 and Tetrahedron Letters (2001) 42, 999. It has now surprisingly been found that certain hetero-spiroindolines have insecticidal properties. The present invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I):
Rc
Figure imgf000002_0001
(I) wherein Y is a single bond, C=O, C=S or S(O)m where m is 0, 1 or 2; R1 is hydrogen, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocyclyloxy, cyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl/formyl, optionally substituted heterocyclyl, optionally substituted alkylthio, NO or NR13R14 where R13 and R14 are independently hydrogen, COR15, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl or R13 and R14 together with the N atom to which they are attached form a group -N=C(R16)-NR17R18; R15 is H, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted aryloxy optionally substituted heteroaryl, optionally substituted heteroaryloxy or NR19R20; R16 , R17 and R18 are each independently H or lower alkyl; R19 and R20 are independently optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; R2 and R3 are independently hydrogen, halogen, cyano, optionally substituted alkyl, optionally substituted alkoxy or optionally substituted aryl; the ring
Figure imgf000003_0001
is a 5 or 6 membered heteroaromatic ring; each R4 is independently halogen, nitro, cyano, optionally substituted Cι-8 alkyl, optionally substituted C .6 alkenyl, optionally substituted C2.6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C3- cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio or R21R22N where R21 and R22 are, independently, hydrogen, Cι-8 alkyl, C3- cycloalkyl, C3.6 alkenyl, C -6 alkynyl, C3- cycloalkyl(Cι-4)alkyl, C2-6 haloalkyl, Cι-6 alkoxy(Cι-6)alkyl, Cι-6 alkoxycarbonyl or R21 and R22 together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι.6 alkyl groups, or 2 6,or 7 membered carbocyclic or heterocyclic ring which may be optionally substituted by halogen; n is 0, 1 , 2 or 3; each Ra is independently hydrogen, halogen, hydroxy, cyano, optionally substituted Ci-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2.6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C - cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio, optionally substituted arylthio or R23R24N where R23 and R24 are, independently, hydrogen, Cι_8 alkyl, C3-7 cycloalkyl, C3-6 alkenyl, C3-6 alkynyl, C .7 cycloalkyl(Cι-4)alkyl, C2- haloalkyl, Cι-6 alkoxy(Cι_6)alkyl, Cι_6 alkoxycarbonyl or R23 and R24 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι-6 alkyl groups, or two Ra groups attached to the same carbon atom are =O or two Ra groups attached to adjacent carbon atoms form a bond, or two Ra groups together with the carbon atom to which they are attached form a three- to seven-membered ring, that may be saturated or unsaturated, and that may contain one or two hetero atoms selected from the group consisting of N, O and S, and which may be optionally substituted by one or two Cι-6 alkyl groups; or two Ra groups together form a group -CH2-, -CH=CH- or -CH2CH2; p is 0, 1, 2, 3, 4, 5 or 6; q is 0, 1, 2, 3, 4, 5 or 6 provided that p+q is 1, 2, 3, 4, 5 or 6; R8 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl or optionally substituted alkenylcarbonyl; or salts or N- oxides thereof. The compounds of formula (I) may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. Each alkyl moiety either alone or as part of a larger group (such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso- propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl. The alkyl groups are suitably Ci to C12 alkyl groups, but are preferably Ci-Cio, more preferably Cι-C8, even more preferably preferably Cι-C6 and most preferably Cι-C4 alkyl groups. When present, the optional substituents on an alkyl moiety (alone or as part of a larger group such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) include one or more of halogen, nitro, cyano, NCS-, C3.7 cycloalkyl (itself optionally substituted with Cι_6 alkyl or halogen), C5- cycloalkenyl (itself optionally substituted with Cι-6 alkyl or halogen), hydroxy, CM O alkoxy, CM O alkoxy(Cι-ιo)alkoxy, tri(Ci_4)alkylsilyl(Ci-6)alkoxy, Cι-6 alkoxycarbonyl(Cι-ιo)alkoxy, CM O haloalkoxy, aryl(Cι-4)- alkoxy (where the aryl group is optionally substituted), C - cycloalkyloxy (where the cycloalkyl group is optionally substituted with Cι-6 alkyl or halogen), C2-ιo alkenyloxy, C2-10 alkynyloxy, SH, CM O alkylthio, CM O haloalkylthio, aryl(Cι-4)alkylthio (where the aryl group is optionally substituted), C3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with Cι-6 alkyl or halogen), tri(Cι-4)alkylsilyl(Cι ^alkylthio, arylthio (where the aryl group is optionally substituted), Cι-6 alkylsulfonyl, Cι.6 haloalkylsulfonyl, Cι-6 alkylsulfinyl, Cι_6 haloalkylsulfinyl, arylsulfonyl (where the aryl group may be optionally substituted), tri(Cι_ )alkylsilyl, aryldi(Cι- )alkylsilyl, (Cι-4)alkyldiarylsilyl, triarylsilyl, CM O alkylcarbonyl, HO2C, CM O alkoxycarbonyl, aminocarbonyl, Cι-6 alkylaminocarbonyl, di(Cι-6 alkylaminocarbonyl, N-(Cι-3 alkyl)-N-(Cι-3 alkoxy)aminocarbonyl, Cι-6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di(Cι-6)alkylaminocarbonyloxy, oximes such as =NOalkyl, =NOhaloalkyl and =NOaryl (itself optionally substituted), aryl (itself optionally substituted), heteroaryl (itself optionally substituted), heterocyclyl (itself optionally substituted with Cι-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted), heteroaryloxy, (where the heteroaryl group is optionally substituted), heterocyclyloxy (where the heterocyclyl group is optionally substituted with
Figure imgf000005_0001
alkyl or halogen), amino, Cι-6 alkylamino, di(Cι-6)alkylamino, Cι-6 alkylcarbonylamino, N-(Cι-6)alkylcarbonyl-N-(Cι-6)alkylamino, C2-6 alkenylcarbonyl, C2-6 alkynylcarbonyl, C3.6 alkenyloxycarbonyl, C -6 alkynyloxycarbonyl, aryloxycarbonyl (where the aryl group is optionally substituted) and arylcarbonyl (where the aryl group is optionally substituted). Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (EJ- or (Z)-configuration. Examples are vinyl, allyl and propargyl. When present, the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety. In the context of this specification acyl is optionally substituted Cι-6 alkylcarbonyl (for example acetyl), optionally substituted C2.6 alkenylcarbonyl, optionally substituted C2-6 alkynylcarbonyl, optionally substituted arylcarbonyl (for example benzoyl) or optionally substituted heteroarylcarbonyl. Halogen is fluorine, chlorine, bromine or iodine. Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF3, CF2C1, CF3CH2 or CHF2CH2. In the context of the present specification the terms "aryl" and "aromatic ring system" refer to ring systems which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl. In addition, the terms "heteroaryl" , "heteroaromatic ring" or "heteroaromatic ring system" refer to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulphur. Examples of such groups include furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1 ,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1 ,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, benzofuryl, benzisofuryl, benzothienyl, benzisothienyl, indolyl, isoindolyl, indazolyl, benzothiazolyl, benzisothiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, 2,1,3- benzoxadiazole quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, benzotriazinyl, purinyl, pteridinyl and indolizinyl. Preferred examples of heteroaromatic radicals include pyridyl, pyrimidyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl, 2,1 ,3-benzoxadiazole and thiazolyl. The terms heterocycle and heterocyclyl refer to a non-aromatic ring containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N. Examples of such rings include 1 ,3-dioxolane, tetrahydrofuran and morpholine. When present, the optional substituents on heterocyclyl include Cι-6 alkyl and Cι-6 haloalkyl as well as those optional substituents given above for an alkyl moiety. Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl. Cycloalkenyl includes cyclopentenyl and cyclohexenyl. When present, the optional substituents on cycloalkyl or cycloalkenyl include Cι-3 alkyl as well as those optional substituents given above for an alkyl moiety. Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups. When present, the optional substituents on aryl or heteroaryl are selected independently, from halogen, nitro, cyano, NCS-, Cι-6 alkyl, Cι-6 haloalkyl, Cι_6 alkoxy- (Cι_6)alkyl, C2-6 alkenyl, C2.6 haloalkenyl, C2-6 alkynyl, C3.7 cycloalkyl (itself optionally substituted with Cι_6 alkyl or halogen), C5-7 cycloalkenyl (itself optionally substituted with Cι-6 alkyl or halogen), hydroxy, CMO alkoxy, CM O alkoxy(Cι-ιo)alkoxy, tri(C1 -4)alkyl- silyl(Cι_6)alkoxy, Cι-6 alkoxycarbonyl(Cι-ιo)alkoxy, CMO haloalkoxy, aryl(Cι- )alkoxy (where the aryl group is optionally substituted with halogen or Cι-6 alkyl), C3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with Cι-6 alkyl or halogen), C2-10 alkenyloxy, C2-10 alkynyloxy,.SH, CMO alkylthio, CM O haloalkylthio, aryl(d.4)alkylthio C .7 cycloalkylthio (where the cycloalkyl group is optionally substituted with Cι-6 alkyl or halogen), tri(Cι-4)-alkylsilyl(Cι.6)alkylthio, arylthio, Cι-6 alkylsulfonyl, Cι_6 haloalkylsulfonyl, Cι_6 alkylsulfinyl, Cι-6 haloalkylsulfinyl, arylsulfonyl, tri(Cι-4)alkylsilyl, aryldi(Cι- )-alkylsilyl, (Ci^alkyldiarylsilyl, triarylsilyl, CMO alkylcarbonyl, HO2C, CMO alkoxycarbonyl, aminocarbonyl, Cι-6 alkylaminocarbonyl, di(Cι-6 alkyl)-aminocarbonyl, N- (Cι-3 alkyl)-N-(Cι_ alkoxy)aminocarbonyl, Cι-6 alkylcarbonyloxy, arylcarbonyloxy, di(Cι-6)alkylamino-carbonyloxy, aryl (itself optionally substituted with Cι-6 alkyl or halogen), heteroaryl (itself optionally substituted with Cι-6 alkyl or halogen), heterocyclyl (itself optionally substituted with Cι-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted with Ct-6 alkyl or halogen), heteroaryloxy (where the heteroaryl group is optionally substituted with Cι-6 alkyl or halogen), heterocyclyloxy (where the heterocyclyl group is optionally substituted with Cι-6 alkyl or halogen), amino, Cι-6 alkylamino, di(Cι. 6)alkylamino, C]-6 alkylcarbonylamino, N-(Cι-6)alkylcarbonyl-N-(C]-6)alkylamino, arylcarbonyl, (where the aryl group is itself optionally substituted with halogen or Cι_ alkyl) or two adjacent positions on an aryl or heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen or Cι-6 alkyl. Further substituents for aryl or heteroaryl include aryl carbonyl amino (where the aryl group is substituted by Cι-6 alkyl or halogen), (Ci.6)alkyloxycarbonylamino
(Cι-6)alkyloxycarbonyl-N-(Cι-6)alkylamino, aryloxycarbonylamino (where the aryl group is substituted by Cι-6 alkyl or halogen), aryloxycarbonyl-N-(Ci-6)alkylamino, (where the aryl group is substituted by Cι_6 alkyl or halogen), arylsulphonylamino (where the aryl group is substituted by Cι-6 alkyl or halogen), arylsulphonyl-N-(Cι-6)alkylamino (where the aryl group is substituted by Cι-6 alkyl or halogen), aryl-N-(Cι-6)alkylamino (where the aryl group is substituted by C].6 alkyl or halogen), arylamino (where the aryl group is substituted by Cι-6 alkyl or halogen), heteroaryl amino (where the heteroaryl group is substituted by Cι-6 alkyl or halogen), heterocyclylamino (where the heterocyclyl group is substituted by Cι-6 alkyl or halogen), aminocarbonylamino, Cι-6 alkylaminocarbonyl amino, di(C].6)alkylaminocarbonyl amino, arylaminocarbonyl amino where the aryl group is substituted by Cι-6 alkyl or halogen), aryl-N-(C).6)alkylaminocarbonylamino where the aryl group is substituted by Cι_6 alkyl or halogen), Cι_6 alkylaminocarbonyl -N-(Cι-6)alkyl amino,- di(Cι_6)alkylaminocarbonyl- N-(Cι-6)alkyl amino, aryl aminocarbonyl -N-(Cι-6)alkyl amino where the aryl group is substituted by Cι-6 alkyl or halogen) and aryl-N-(Ci-6)alkylaminocarbonyl-N-(Ci_6)alkyl amino where the aryl group is substituted by Cι-6 alkyl or halogen). For substituted phenyl moieties, heterocyclyl and heteroaryl groups it is preferred that one or more substituents are independently selected from halogen, Ci-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy(Cι.6)alkyl, Cι-6 alkoxy, C1-6 haloalkoxy, Cι-6 alkylthio, Cι-6 haloalkylthio, Cι_6 alkylsulfinyl, Cι-6 haloalkylsulfinyl, Cι-6 alkylsulfonyl, Cι-6 haloalkylsulfonyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C .7 cycloalkyl, nitro, cyano, CO2H, Cι-6 alkylcarbonyl, Cι.6 alkoxycarbonyl, R25R26N or R27R28NC(O); wherein R25, R26, R27 and R28 are, independently, hydrogen or Cι-6 alkyl. Further preferred substituents are aryl and heteroaryl groups. Haloalkenyl groups are alkenyl groups which are substituted with one or more of the same or different halogen atoms. It is to be understood that dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (C]-6)alkyl groups. When heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, piperidine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (Cι_6) alkyl groups. Preferably the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, HO2C, CM O alkoxy (itself optionally substituted by CM O alkoxy), aryl(Cι-4)alkoxy, C O alkylthio, CM O alkylcarbonyl, C O alkoxycarbonyl, C1-6 alkylaminocarbonyl, di(Cι-6 alkylaminocarbonyl, (Cι.6)alkylcarbonyloxy, optionally substituted phenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy, heterocyclyl, heterocyclyloxy, C3- cycloalkyl (itself optionally substituted with (Cι-6)alkyl or halogen), C3- 7 cycloalkyloxy, C5- cycloalkenyl, Cι-6 alkylsulfonyl, Cι_6 alkylsulfϊnyl, tri(C1_4)alkylsilyl, tri(Cι.4)alkylsilyl(Cι-6)alkoxy, aryldi(C 1 -4)alkylsilyl, (Cι-4)alkyldiaryjsilyl and triarylsilyl. Preferably the optional substituents on alkenyl or alkynyl include one or more of halogen, aryl and C -7 cycloalkyl. A preferred optional substituent for heterocyclyl is Cι-6 alkyl. Preferably the optional substituents for cycloalkyl include halogen, cyano and Cι-3 alkyl. Preferably the optional substituents for cycloalkenyl include Cι-3 alkyl, halogen and cyano. Preferably Y is a single bond, C=O or S(O)m where m is 0, 1 or 2. More preferably Y is a single bond, C=O or SO2. Yet more preferably Y is a single bond or C=O. Most preferably Y is C=O. Preferably R1 is hydrogen, Cι.6 alkyl, C1-6 cyanoalkyl, Cι-6 haloalkyl, C3.7 cycloalkyl(Cι-4)alkyl, Ci-6 alkoxy(Cι- )alkyl, heteroaryl(Cι-6)alkyl (wherein the heteroaryl group maybe optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy, C].6 haloalkoxy, Cι-6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι.6 alkylthio, Cι-6 alkoxycarbonyl, Cι-6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), aryl(Cι-6)alkyl (wherein the aryl group may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy, C] -6 haloalkoxy, Cι.6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι-6 alkylthio, Cι-6 alkoxycarbonyl, Cι.6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the aryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), Cι-6 alkylcarbonylamino(Cι-6)alkyl, aryl (which may be optionally substituted by halo, nitro, cyano, Cι.6 alkyl, Cι-6 haloalkyl, -6 alkoxy, Cι_6 haloalkoxy, Cι-6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι_6 alkylthio, Cι-6 alkoxycarbonyl, Cι-6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the aryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), heteroaryl (which may be optionally substituted by halo, nitro, cyano, Cι_6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy, C1-6 haloalkoxy, Cι-6 alkylsulfonyl, Cι.6 alkylsulfinyl, Cι_6 alkylthio, Ci-6 alkoxycarbonyl, Cι-6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), Cι-6 alkoxy, Cι_6 haloalkoxy, phenoxy (wherein the phenyl group is optionally substituted by halogen, C]- alkyl, C]-4 alkoxy, C haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryloxy (optionally substituted by halo, nitro, cyano, Cι_6 alkyl, C].6 haloalkyl, Cι_6 alkoxy or Cι-6 haloalkoxy), heterocyclyloxy (optionally substituted by halo, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy), cyano, C2-6 alkenyl, C2-6 alkynyl, C3_6 cycloalkyl, C5- cycloalkenyl, heterocyclyl (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy or Cι-6 haloalkoxy), Cι_6 alkylthio, Cι-6 haloalkylthio or NRI3R14 where R13 and R14 are independently hydrogen, Cι-6 alkyl, Cι-6 haloalkyl, Cι_6 alkoxy(Cι.
6)alkyl, phenyl (which may be optionally substituted by halogen, C1 -4 alkyl, Cι- alkoxy, Cι-4 haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino or CM alkoxycarbonyl), phenyl (Cι- )alkyl (wherein the phenyl group may be optionally substituted by halogen, CM alkyl, Cι-4 alkoxy, CM haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino, Ci-6 alkylsulfonyl, Cι-6 alkoxycarbonyl, or two adjacent positions on the phenyl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), heteroaryl (Cι-6)alkyl (wherein the heteroaryl group may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy, Cι-6 haloalkoxy, Cι-6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι-6 alkylthio, Ci-6 alkoxycarbonyl, Cι-6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen) or heteroaryl (which may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy, Cι_ 4 alkoxycarbonyl Cι-6 alkylcarbonylamino, phenyloxycarbonylamino (wherein the phenyl group is optionally substituted by halogen, C1 -4 alkyl, CM alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), amino, Cι-6 alkylamino or phenylamino (wherein the phenyl group is optionally substituted halogen, CM alkyl, C1-4 alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino)). More preferably R1 is Cι-6 alkyl, C1 -6 haloalkyl, C1 -6 alkoxy(Cι_6)alkyl, heteroaryl(Cι. 3)alkyl (wherein the heteroaryl group may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι_6 haloalkyl, Cι-6 alkoxy, Cι-6 haloalkoxy, Cι-6 alkylsulfonyl, Cι_6 alkoxycarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), phenyl(Cι-3)alkyl (wherein the phenyl group may be optionally substituted by halogen, CM alkyl, C alkoxy, CM haloalkyl, C1-4 haloalkoxy, CN, NO , aryl, heteroaryl, amino, dialkylamino, Cι-6 alkylsulfonyl, C).6 alkoxycarbonyl, or two adjacent positions on the phenyl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), phenyl (which may be optionally substituted by halogen, C1 -4 alkyl, C1-4 alkoxy, C haloalkyl, C1-4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino, Cι-6 alkylsulfonyl, C1 -6 alkoxycarbonyl, or two adjacent positions on the phenyl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), heteroaryl (which may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy, Cι-6 haloalkoxy, C|_6 alkylsulfonyl, Cι-6 alkoxycarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), C1-6 alkoxy, Cι_6 haloalkoxy, C2-6 alkenyl, heterocyclyl (optionally substituted by halo, cyano, C1-6 alkyl, Cι-6 haloalkyl, Cι.6 alkoxy or Cι.6 haloalkoxy), Cι-6 alkylthio, Cι-6 haloalkylthio or NR1 R14 where R13 and R14 are independently hydrogen, Cι-6 alkyl or Cι-6 haloalkyl, Cι-6 alkoxy(Cι-6)alkyl, C2-6 alkylcarbonyl, phenylcarbonyl, (where the phenyl is optionally substituted by halogen, CM alkyl, CM alkoxy, C haloalkyl, C] -4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), phenyl(Cι-3)alkyl (wherein the phenyl group may be optionally substituted by halogen, CM alkyl, CM alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino, Cι-6 alkylsulfonyl, Cι.6 alkoxycarbonyl, or two adjacent positions on the phenyl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen) or heteroaryl(Cι.3)alkyl (wherein the heteroaryl group may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy, Cι_6 haloalkoxy, Cι-6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι_6 alkylthio, Cι-6 alkoxycarbonyl, Cι_6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen). Even more preferably R1 is Cι-6 alkyl, Cι-6 haloalkyl, heteroaryl(Cι-3)alkyl (wherein the heteroaryl group may be optionally substituted by halo, cyano, Cι_6 alkyl, Cι_6 haloalkyl and where the heteroaryl group is a thiazole, pyridine, pyrimidine, pyrazine or pyridazine ring), heteroaryl (optionally substituted by halo, cyano, Cι_6 alkyl, Cι-6 haloalkyl and where the heteroaryl group is a pyridine, pyrimidine, 2,1 ,3-benzoxadiazole, pyrazine or pyridazine ring), Cι-6 alkoxy, Cι_6 alkoxy(Cι_6)alkyl, Cι_6 alkylamino, Cι_6 alkoxy(Cι_6)alkylamino or heteroaryl(Ci-3)alkylamino (wherein the heteroaryl group may be optionally substituted by halo, cyano, Cι-6 alkyl, Cι-6 haloalkyl and where the heteroaryl group is a thiazole, pyridine, pyrimidine, pyrazine or pyridazine ring). Most preferably R1 is pyridyl (optionally substituted by halo, Cι-3 alkyl or Cι-3 haloalkyl) especially halo-substituted pyridyl. It is preferred that R2 and R3 are independently hydrogen, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or cyano. More preferably R2 and R3 are independently hydrogen, halogen, Cι-2 alkyl, Cι_2 haloalkyl, C1-2 alkoxy, cyano. Even more preferably R arid R are independently hydrogen or CM alkyl. Yet more preferably R and R are independently hydrogen or methyl. Most preferably R2 and R3 are both hydrogen. Preferably each R4 is independently halogen, cyano, Cι-8 alkyl, Cι-8 haloalkyl, Cι-6 cyanoalkyl, d- alkoxy(Cι.6)alkyl, C3. cycloalkyl(Cι-6)alkyl, C5-6 cycloalkenyl(Cι-6)alkyl, C -6 alkenyloxy(Cι.6)alkyl, C3.6 alkynyloxy(Cι_6)alkyl, aryloxy(Cι-6)alkyl, Cι_6 carboxyalkyl, Cι-6 alkylcarbonyl(Cι.6)alkyl, C2-6 alkenylcarbonyl(Cι-6)alkyl, C2-6 alkynylcarbonyl(Cι-6)- alkyl, Cι-6 alkoxycarbonyl(Cι-6)alkyl, C3. alkenyloxycarbonyl(Cι-6)alkyl, C3-6 alkynyloxycarbonyl(Cι-6)alkyl, aryloxycarbonyl(Cι-6)alkyl, Cι_6 alkylthio(Ct.6)alkyl, Cι-6 alkylsulfmyl(Cι-6)alkyl, C].6 alkylsulfonyl(Cι.6)alkyl, aminocarbonyl(Cι.6)alkyl, Ct.6 alkylaminocarbonyl(Cι .6)alkyl, di(C i .6)alkylaminocarbonyl(Cι .6)alkyl, phenyl(Cι - )alkyl (wherein the phenyl group is optionally substituted by halogen, CM alkyl, CM alkoxy, C1 - haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl(Cι-4)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, C1 -6 alkyl, C].6 haloalkyl, Cι-6 alkoxy or Cι_6 haloalkoxy), heterocyclyl(Cι-4)alkyl
(wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or C1 -6 haloalkoxy), C2-6 alkenyl, aminocarbonyl(C2-6)alkenyl, Cι-6 alkylaminocarbonyl(C2.6)alkenyl, di(Cι.6)alkylaminocarbonyl(C2-6)alkenyl, phenyl(C2-4)- alkenyl, (wherein the phenyl group is optionally substituted by halogen, C alkyl, CM alkoxy, C1-4 haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), C2-6 alkynyl, trimethylsilyl(C2.6)alkynyl, aminocarbonyl(C2-6)alkynyl, Cι.6 alkylaminocarbonyl(C2-6)alkynyl, di(Cι-6)alkylaminocarbonyl(C2-6)alkynyl, C1 -6 alkoxycarbonyl, C -7 cycloalkyl, C3-7 halocycloalkyl, C3-7 cyanocycloalkyl, C1-3 alkyl(C3.7)- cycloalkyl, Cι-3 alkyl(C3-7)halocycloalkyl,phenyl (optionally substituted by halogen, C1- alkyl, C1- alkoxy, C1- haloalkyl, C1- haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl (optionally substituted by halo, nitro, cyano, C1-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι_6 haloalkoxy), heterocyclyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Cι-6 alkyl, C1 -6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy), or 2 adjacent groups R4 together with the carbon atoms to which they are attached form a 4, 5, 6 or 7 membered carbocylic or heterocyclic ring which may be optionally substituted by halogen, C!-8 alkoxy, Cι-6 haloalkoxy, phenoxy (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, C1-6 alkoxy or Cι-6 haloalkoxy), heteroaryloxy (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy), Cι-8 alkylthio or R19R20N where R19 and R20 are, independently, hydrogen, Cι-8 alkyl, C3-7 cycloalkyl, C3-6 alkenyl, C3-6 alkynyl, C2-6 haloalkyl, Cι-6 alkoxycarbonyl or R19 and R20 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι-6 alkyl groups; n is 0, 1, 2 or 3. More preferably each R4 is independently halogen, cyano, Cι-8 alkyl, C1-8 haloalkyl,
C]-8 cyanoalkyl, Cι-6 alkoxy(C] -6)alkyl, C2.6 alkynyl, trimethylsilyl(C2.6)alkynyl, d.6 alkoxycarbonyl, C -7 cycloalkyl, Cι-3 alkyl (C3.7) cycloalkyl, phenyl (optionally substituted by halogen, C alkyl, C1-4 alkoxy, C] -4 haloalkyl, C haloalkoxy, CN, NO , aryl, heteroaryl, amino or dialkylamino), heterocyclyl (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Ci.6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy), C].8 alkoxy, Cι-6 haloalkoxy, phenoxy (optionally substituted by halogen, CM alkyl, Cι- alkoxy, Cι- haloalkyl, C)- haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryloxy (optionally substituted by halo, nitro, cyano, Cι-3 alkyl, Cι-3 haloalkyl, Cι- alkoxy or Cι- haloalkoxy), di(Cj_ 8)alkylamino, or 2 adjacent groups R4 together with the carbon atoms to which they are attached form a 4, 5, 6 or 7 membered carbocylic or heterocyclic ring which may be optionally substituted by halogen; n is 0, 1, 2 or 3. Even more preferably each R4 is independently halogen, cyano, Cι-8 alkyl, C] -8 haloalkyl, Cι_8 cyanoalkyl, Cι-6 alkoxy(C]-6)alkyl, C2-6 alkynyl, heterocyclyl (optionally substituted by C]-6 alkyl), Cι_8 alkoxy, C1 -6 haloalkoxy, phenoxy (optionally substituted by halo, cyano, C1-3 alkyl or Cι- haloalkyl), heteroaryloxy (optionally substituted by halo, cyano, C1.3 alkyl or Cι-3 haloalkyl), di(Cι-8)alkylamino or 2 adjacent groups R4 together with the carbon atoms to which they are attached form a 4, 5, 6 or 7 membered carbocylic or heterocyclic ring which may be optionally substituted by halogen; n is 0, 1, 2 or 3. Yet more preferably each R4 is independently fluoro, chloro, bromo, cyano, C alkyl, C haloalkyl, CM cyanoalkyl or C].3 alkoxy(Cι-3)alkyl; n is 0, 1 or 2. Most preferably each R4 is independently fluoro, chloro, bromo, CM alkyl or C1-4 haloalkyl; n is 1 or 2. Preferably R is CM O alkyl, CMO haloalkyl, aryl(Cι.6)alkyl (wherein the aryl group is optionally substituted by halogen, C alkyl, C alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl(Cι_6)alkyl (wherein the heteroaryl group is optionally substituted by halogen, C]- alkyl, CM alkoxy, C1- haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), arylcarbonyl-(Cι-6)alkyl (wherein the aryl group may be optionally substituted by halogen, CM alkyl, CM alkoxy, Ci. 4 haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino and the alkyl group may be optionally substituted by aryl), C2-8 alkenyl, C2.8 haloalkenyl, aryl(C2.6)-alkenyl (wherein the aryl group is optionally substituted halogen, C alkyl, CM alkoxy, C)- haloalkyl, CM haloalkoxy, CN, NO , aryl, heteroaryl, amino or dialkylamino, Cι-6 alkoxycarbonyl, or two adjacent substituents can cyclise to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring), heteroaryl(C2-6)-alkenyl (wherein the heteroaryl group is optionally substituted halogen, CM alkyl, CM alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino, Cι-6 alkoxycarbonyl, or two adjacent substituents can cyclise to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring), C2-6 alkynyl, phenyl(C2-6)alkynyl (wherein the phenyl group is optionally substituted by halogen, CM alkyl, CM alkoxy, C haloalkyl, C]- haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), C3.7 cycloalkyl, Cι-6 alkoxycarbonyl, Cι-6 alkylcarbonyl, Cι_6 haloalkylcarbonyl or aryl(C2-6)alkenylcarbonyl (wherein the aryl group may be optionally substituted halogen, CM alkyl, Cι-4 alkoxy, CM haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), or -C(R51)(R52)-[CR53=CR 54]z-R55 where z is 1 or 2, R51 and R52 are each independently H, halo or Cι-2 alkyl, R53 and R54 are each independently H, halogen, CM alkyl or CM haloalkyl and R55 is optionally substituted aryl or optionally substituted heteroaryl. More preferably R is phenyl(Cι- )alkyl (wherein the phenyl group is optionally substituted by halogen, CM alkyl, C alkoxy, Cι-4 haloalkyl, d-4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl(Cι-6)alkyl (wherein the heteroaryl group is optionally substituted halogen, Cι-4 alkyl, d-4 alkoxy, d- haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), phenyl(C2-6)alkenyl (wherein the phenyl group is optionally substituted by halogen, CM alkyl, d-4 alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl(C2-6)alkenyl (wherein the heteroaryl group is optionally substituted by halogen, CM alkyl, d-4 alkoxy, C haloalkyl, Cι-4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino) or phenyl(C2-6)alkynyl (wherein the phenyl group is optionally substituted by halogen, d-4 alkyl, CM alkoxy, d-4 haloalkyl, d-4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino, or - C(R51)(R52)-[CR53=CR54]z-R55 where z is 1 or 2, R51 and R52 are each independently H, halo or C ι-2 alkyl, R53 and R54 are each independently H, halogen, CM alkyl or C haloalkyl and R55 is optionally substituted aryl or optionally substituted heteroaryl. Most preferably R8 is -C(R51)(R52)-[CR53=CR5 ]z-R55 where z is 1 or 2, preferably 1, R51 and R52 are each independently H, halo or C 1-2 alkyl, R53 and R54 are each independently H, halogen, CM alkyl or C haloalkyl and R55 is phenyl substituted by halogen, CM alkyl, C1 - alkoxy, CM haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino or heteroaryl substituted by halogen, d-4 alkyl, CM alkoxy, C1- haloalkyl, Ci- 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino. R51 and R52 are preferably hydrogen. R53 and R54 are preferably hydrogen or halogen, especially hydrogen. R55 is preferably phenyl substituted with one to three substituents selected from halogen, CM alkyl, d-4 alkoxy, CM haloalkyl, d_4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino. It is preferred that the ring
Figure imgf000016_0001
a 5 or 6 membered heteroaromatic ring wherein the ring members are each independently CH, S, N, NR4, O, or CR4 provided that at least one ring member is other than CH or CR4 and that there are no more than one O or S atoms present in the ring. More preferably the ring
Figure imgf000016_0002
is a pyridine, pyrimidine, pyrazine, pyridazine, triazine, furan, thiophene, pyrrole, imidazole, pyrazole, oxazole, thiazole, isoxazole, isothiazole, [l,2,3]triazole, [l ,2,3]oxadiazole or [l ,2,3]thiadiazole. Preferably each Ra is independently hydrogen, halo, cyano, Cι-3 alkyl, hydroxy or two Ra groups together with the carbon atom to which they are attached form a carbonyl group More preferably each Ra is independently hydrogen, fluoro, methyl, hydroxy or two
Ra groups together with the carbon atom to which they are attached form a carbonyl group Most preferably each Ra is hydrogen. Preferably p is 1 , 2 or 3 and q is 1, 2 or 3 and p+q is 3, 4 or 5. More preferably p is 1 or 2 and q is 2. Most preferably p and q are both 2. One group of preferred compounds of formula (I) are those where Yis C(O) and R1 is NR13R14 where R13 and R14 are as defined above. Certain compounds of formula I are novel. One group of novel compounds is that of formula F R8
Figure imgf000017_0001
(i') wherein Y is C=O, C=S; R is hydrogen, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocyclyloxy, cyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, formyl, optionally substituted heterocyclyl, optionally substituted alkylthio, NO or NR13R14 where R13 and R14 are independently hydrogen, COR15, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl or R13 and R14 together with the N atom to which they are attached form a group -N=C(R16)-NR17R18; R15 is H, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted aryloxy optionally substituted heteroaryl, optionally substituted heteroaryloxy or NR19R20; R16 , R17 and R18 are each independently H or lower alkyl; R19 and R20 are independently optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; R and R are independently hydrogen, halogen, cyano, optionally substituted alkyl, optionally substituted alkoxy or optionally substituted aryl;
Figure imgf000018_0001
is a 5 or 6 membered heteroaromatic ring; each R is independently halogen, nitro, cyano, optionally substituted C1 -8 alkyl, optionally substituted C2.6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C3.7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio or R21R22N where R21 and R22 are, independently, hydrogen, Cι_8 alkyl, C3- cycloalkyl, C3-6 alkenyl, C3-6 alkynyl, C3.7 cycloalkyl(d- )alkyl, d-6 haloalkyl, Cι_6 alkoxy(C],6)alkyl, Cι-6 alkoxycarbonyl or R21 and R together with the N atom to which they are attached form' a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι_6 alkyl groups, or 2 adjacent groups R4 together with the carbon atoms to which they are attached form a 4, 5, 6,or 7 membered carbocyclic or heterocyclic ring which may be optionally substituted by halogen; n is 0, 1, 2 or 3; each Ra is independently hydrogen, halogen, hydroxy, cyano, optionally substituted Cι-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C3.7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio, optionally substituted arylthio or R23R24N where R23 and R24 are, independently, hydrogen, Cι-8 alkyl, C3.7 cycloalkyl, C3-6 alkenyl, C3.6 alkynyl, C3- cycloalkyl(d_ )alkyl, d-6 haloalkyl, Cι-6 alkoxy(Cι.6)alkyl, Ci-6 alkoxycarbonyl or R23 and R24 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by two Ra groups attached to adjacent carbon atoms form a bond, or two Ra groups together with the carbon atom to which they are attached form a three- to seven-membered ring, that may be saturated or unsaturated, and that may contain one or two hetero atoms selected from the group consisting of N, O and S, and which may be optionally substituted by one or two Ci-6 alkyl groups; or two Ra groups together form a group -CH2-, -CH=CH- or -CH2CH2; p is 0, 1 , 2, 3, 4, 5 or 6; q is 0, 1, 2, 3, 4, 5 or 6 provided that p+q is 1, 2, 3, 4, 5 or 6; R is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl or optionally substituted alkenylcarbonyl; or salts or N-oxides thereof. The compounds in Tables I- DCCLXVϋ below illustrate the compounds of the invention. Table I provides 575 compounds of formula la
Figure imgf000019_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R c are given in Table 1. Table 1
Figure imgf000019_0002
Figure imgf000020_0001
Figure imgf000021_0001
21
Figure imgf000022_0001
Figure imgf000023_0001
500 23-
Figure imgf000024_0001
61500 -24
Figure imgf000025_0001
00 25-
Figure imgf000026_0001
1500 -26
Figure imgf000027_0001
1500 -27
Figure imgf000028_0001
150 -28
Figure imgf000029_0001
29
Figure imgf000030_0001
1500 30
Figure imgf000031_0001
1 31
Figure imgf000032_0001
/061500 32
Figure imgf000033_0001
-33
Figure imgf000034_0001
50 34-
Figure imgf000035_0001
35 -
Figure imgf000036_0001
Table II provides 575 compounds of formula lb
Figure imgf000037_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4 are given in Table 1.
Table III provides 575 compounds of formula Ic
Figure imgf000037_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR c and the values of R8, R4a, R4b and R4c are given in Table 1. Table IV provides 575 compounds of formula Id
Figure imgf000037_0003
wherein TI is N, T2 is CR a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4 are given in Table 1. Table V provides 575 compounds of formula le
Figure imgf000038_0001
wherein TI is'N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4 are given in Table 1.
Table VI provides 575 compounds of formula If
Figure imgf000038_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1.
Table VII provides 575 compounds of formula Ig
Figure imgf000039_0001
wherein TI is N, T2 is CR4a, T3 is CR >44bD, T4 is CR ,44cC and the values of R , 8δ, π R4a, R n 44bD a „_nd. R -,4"c are given in Table 1.
Table VIII provides 575 compounds of formula D
Figure imgf000039_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1. Table IX provides 575 compounds of formula Ii
Figure imgf000039_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1.
Table X provides 575 compounds of formula Ij
Figure imgf000040_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R b and R4c are given in Table 1.
Table XI provides 575 compounds of formula Ik
Figure imgf000040_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1.
Table XII provides 575 compounds of formula II
Figure imgf000040_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR c and the values of R8, R4a, R4b and R c are given in Table 1.
Table XIII provides 575 compounds of formula Im
Figure imgf000041_0001
wherein TI is N, T2 is CR a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4 are given in Table 1.
Table XIV provides 575 compounds of formula In
Figure imgf000041_0002
wherein TI is N, T2 is CR a, T3 is CR4b, T4 is CR4c and the values of R8, R a, R4b and R4 are given in Table 1.
Table XV provides 575 compounds of formula Io
Figure imgf000041_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1.
Table XVI provides 575 compounds of formula Ip
Figure imgf000042_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1.
Table XVII provides 575 compounds of formula Iq
Figure imgf000042_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR c and the values of R8, R a, R b and R4c are given in Table 1.
Table XNHI provides 575 compounds of formula Ir R8
Figure imgf000043_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R a, R4b and R4c are given in Table 1.
Table XIX provides 575 compounds of formula Is
Figure imgf000043_0002
wherein TI is N, T2 is CR a, T3 is CR4b, T4 is CR c and the values of R8, R4a, R4b and R4 are given in Table 1. Table XX provides 575 compounds of formula It
Figure imgf000044_0001
wherein TI is N, T2 is CR >4a , T3 is CR .44b0, T4 is CR4C and the values of R R ,4a , R n'4lbD and J r R> 4c are given in Table 1.
Table XXI provides 575 compounds of formula lu
Figure imgf000044_0002
wherein TI is N, T2 is CR ,4"aa, T3 is CR , 4"bD, T4 is CR ,44cC a. nd the values of R8, R4a, R4b and R4c are given in Table 1. Table XXII provides 575 compounds of formula Iv
Figure imgf000044_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R b and R4c are given in Table 1. Table XXIII provides 575 compounds of formula Iw
Figure imgf000045_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1. Table XXIV provides 575 compounds of formula Ix
Figure imgf000045_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R c are given in Table 1. Table XXV provides 575 compounds of formula ly
Figure imgf000045_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4 are given in Table 1. Table XXVI provides 575 compounds of formula Iz
Figure imgf000046_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1. Table XXVII provides 575 compounds of fonmila Iaa
Figure imgf000046_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R c are given in Table 1. Table XXVIII provides 575 compounds of formula lab
Figure imgf000046_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XXIX provides 575 compounds of formula lac
Figure imgf000047_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1. Table XXX provides 575 compounds of formula lad
Figure imgf000047_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table XXXI provides 575 compounds of formula Iae
Figure imgf000047_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table XXXIJ provides 575 compounds of formula Iaf
Figure imgf000048_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4 are given in Table 1. Table XXXIII provides 575 compounds of formula lag
Figure imgf000048_0002
wherein TI is N, T2 is CR4a, T3 is CR b, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table XXXIV provides 575 compounds of formula lah
Figure imgf000049_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XXXV provides 575 compounds of formula lai
Figure imgf000049_0002
wherein TI is N, T2 is CR ,44aa, T3 is CR , 4"bD, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1. Table XXXVI provides 575 compounds of formula laj
Figure imgf000049_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table XXXVII provides 575 compounds of formula lak
Figure imgf000050_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XXXVIII provides 575 compounds of formula Ial
Figure imgf000050_0002
wherein TI is N, T2 is CR ,4"aa, T3 is CR ,4"bD, T4 is CR , 4"c' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XXXIX provides 575 compounds of formula lam
Figure imgf000051_0001
wherein TI is N, T2 is CR a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XLX provides 575 compounds of formula Ian
Figure imgf000051_0002
wherein TI is N, T2 is CR >4"aa, T3 is CR ,4"b", T4 is CR ,4"c' and the values of R8, R4a, R4b and R4c are given in Table 1. Table XLI provides 575 compounds of formula Iao
Figure imgf000051_0003
wherein TI is N, T2 is CR ,4"aa, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1. Table XLII provides 575 compounds of formula lap
Figure imgf000052_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XLIII provides 575 compounds of formula laq
Figure imgf000052_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XLIV provides 575 compounds of formula Iar
Figure imgf000052_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table XLV provides 575 compounds of formula las
Figure imgf000053_0001
wherein TI is N, T2 is CR ,4"aa, T3 is CR >4"bD, T4 is CR , 4"c' and the values of R8, R4a, R4b and R4' are given in Table 1. Table XLV provides 575 compounds of formula Iat
Figure imgf000053_0002
wherein TI is N, T2 is CR ,4"aa, T3 is CR ,4"b°, T4 is CR4' and the values of R8, R4a, R4 and R4' are given in Table 1. Table XLVII provides 575 compounds of formula Iau
Figure imgf000053_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R a, R4b and R4 are given in Table 1. Table XLVIH provides 575 compounds of formula lav
Figure imgf000054_0001
wherein TI is N, T2 is CR , T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4 are given in Table 1. Table IL provides 575 compounds of formula law
Figure imgf000054_0002
wherein TI is N, T2 is CR , T3 is CR , T4 is CR4' and the values of R8, R4a, R4b and R4 are given in Table 1. Table L provides 575 compounds of formula lax
Figure imgf000054_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1. Table LI provides 575 compounds of formula lay
Figure imgf000055_0001
wherein TI is N, T2 is CR , 4"aa, T3 is CR ,4"b", T4 is CR , 44c' and the values of R8, R4a, R4 and R4c are given in Table 1. Table LII provides 575 compounds of formula Iaz
Figure imgf000055_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LIU provides 575 compounds of formula Iba
Figure imgf000055_0003
wherein TI is N, T2 is CR , 44aa, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LIV provides 575 compounds of formula Ibb
Figure imgf000056_0001
wherein TI is N, T2 is CR ,44aa, T3 is CR >™4b, T4 is CR ,4"cC and the values of R8, R , R4b and R4 are given in Table 1. Table LV provides 575 compounds of formula Ibc
Figure imgf000056_0002
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LVI provides 575 compounds of formula Ibd
Figure imgf000056_0003
wherein TI is N, T2 is CR ,4a , T3 is CR , T4 is CR4' and the values of Rs, R4a, R4b and R ,4c are given in Table 1. Table LVII provides 575 compounds of formula Ibe
Figure imgf000057_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LVIII provides 575 compounds of formula Ibf
Figure imgf000057_0002
wherein TI is N, T2 is CR , 44aa, T3 is CR ,44b0, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LIX provides 575 compounds of formula Ibg
Figure imgf000057_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table LX provides 575 compounds of formula Ibh
Figure imgf000058_0001
wherein TI is N, T2 is CR ,44aa, T3 is CR ,44bD, T4 is CR ,44c' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LXI provides 575 compounds of formula Ibi
Figure imgf000058_0002
wherein TI is N, T2 is CR >44aa, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LXII provides 575 compounds of formula Ibj
Figure imgf000058_0003
wherein TI is N, T2 is CR , 44aa, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table LXHI provides 575 compounds of formula Ibk
Figure imgf000059_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LX1N provides 575 compounds of formula Ibi
Figure imgf000059_0002
wherein TI is Ν, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LXV provides 575 compounds of formula Ibm
Figure imgf000059_0003
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR c and the values of R8, R4a, R4b and R4' are given in Table 1. Table LXVI provides 575 compounds of formula Ibn
Figure imgf000060_0001
wherein TI is N, T2 is CR4a, T3 is CR4b, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table LXVII provides 575 compounds of formula Ibo
Figure imgf000060_0002
wherein TI is N, T2 is CR a, T3 is CR4b, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CI provides 575 compounds of formula la wherein TI is CR4b, T2 is N, T3 is CR a, T4 is CR4c and the values of R8, R4a, R and R4c are given in Table 1.
Table CII provides 575 compounds of formula lb wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR c and the values of R8, R4a, R4b and R4c are given in Table 1. Table CIII provides 575 compounds of formula Ic wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4c and the values of R8; R4a, R4b and R4c are given in Table 1. Table C1N provides 575 compounds of formula Id wherein TI is CR4b, T2 is Ν, T3 is CR4a, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1. Table CV provides 575 compounds of formula le wherein TI is CR4 , T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R b and R c are given in Table 1. Table CVI provides 575 compounds of formula If wherein TI is CR b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CVII provides 575 compounds of formula Ig wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CVIII provides 575 compounds of formula Ih wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CIX provides 575 compounds of formula Ii wherein TI is CR4 , T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CX provides 575 compounds of formula Ij wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXI provides 575 compounds of formula B wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXII provides 575 compounds of formula II wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXIJI provides 575 compounds of formula Im wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1. Table CXTV provides 575 compounds of formula In wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CXV provides 575 compounds of formula Io wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXVI provides 575 compounds of formula Ip wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CXVII provides 575 compounds of formula Iq wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXViπ provides 575 compounds of formula Ir wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1. Table CXIX provides 575 compounds of formula Is wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CXX provides 575 compounds of formula It wherein TI is CR4b, T2 is N, T3 is CR a, T4 is CR4' and the values of R8, R a, R4b and R c are given in Table 1. Table CXXI provides 575 compounds of formula lu wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1. Table CXXII provides 575 compounds of formula Iv wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXXIU provides 575 compounds of formula Iw wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CXXIV provides 575 compounds of formula Ix wherein TI is CR4 , T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CXXV provides 575 compounds of formula Iy wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CXXVI provides 575 compounds of formula Iz wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXXVII provides 575 compounds of formula Iaa wherein TI is CR b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CXXVIII provides 575 compounds of formula lab wherein TI is CR b, T2 is N, T3 is CR a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXXIX provides 575 compounds of formula lac wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CXXX provides 575 compounds of formula lad wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CXXXI provides 575 compounds of formula Iae wherein TI is CR b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXXXII provides 575 compounds of formula Iaf wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CXXXffl provides 575 compounds of formula lag wherein TI is CR4b, T2 is N, T3 is CR a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXXXIV provides 575 compounds of formula lah wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CXXXV provides 575 compounds of formula lai wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CXXXVI provides 575 compounds of formula laj wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CXXXVII provides 575 compounds of formula lak wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXXXVIll provides 575 compounds of formula Ial wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CXXXIX provides 575 compounds of formula lam wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CXL provides 575 compounds of formula Ian wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXLI provides 575 compounds of formula Iao wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CXLII provides 575 compounds of formula lap wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXLIII provides 575 compounds of formula laq wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXLIV provides 575 compounds of formula lar wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1. Table CXLV provides 575 compounds of formula las wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1. Table CXLVI provides 575 compounds of formula Iat wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are giv.en in Table 1.
Table CXLVII provides 575 compounds of formula Iau wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4 and R4' are given in Table 1. Table CXLVIII provides 575 compounds of formula lav wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CIL provides 575 compounds of formula law wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CL provides 575 compounds of formula lax wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CLI provides 575 compounds of formula wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1.
Table CLII provides 575 compounds of formula Iaz wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CLIII provides 575 compounds of formula Iba wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CLIV provides 575 compounds of formula Ibb wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CLV provides 575 compounds of formula Ibc wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CLVI provides 575 compounds of formula Ibd wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CLVII provides 575 compounds of formula Ibe wherein TI is CR , T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CLVIII provides 575 compounds of formula Ibf wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CLIX provides 575 compounds of formula Ibg wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CLX provides 575 compounds of formula Ibh wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CLXI provides 575 compounds of formula Ibi wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CLXII provides 575 compounds of formula Ibj wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1.
Table CLXIII provides 575 compounds of formula Ibk wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CLXIV provides 575 compounds of formula Ibi wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CLXV provides 575 compounds of formula Ibm wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CLXVI provides 575 compounds of formula Ibn wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CLXVII provides 575 compounds of formula Ibo wherein TI is CR4b, T2 is N, T3 is CR4a, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCl provides 575 compounds of formula la wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCII provides 575 compounds of formula lb wherein TI is CR4b, T2 is CR4a, T3 is N,
T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCffl provides 575 compounds of formula Ic wherein TI is CR4b, T2 is CR4a, T3 is N,
T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCIV provides 575 compounds of formula Id wherein TI is CR4b, T2 is CR4a, T3 is N,
T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCV provides 575 compounds of formula le wherein TI is CR4b, T2 is CR4a, T3 is N,
T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCVI provides 575 compounds of formula If wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R b and R4c are given in Table 1.
Table CCVII provides 575 compounds of formula Ig wherein TI is CR 4b , T T2 i •s
Figure imgf000065_0001
T3 is N, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCV1II provides 575 compounds of formula D wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCIX provides 575 compounds of formula Ii wherein TI is CR4b, T2 is CR4a, T3 is N,
T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCX provides 575 compounds of formula Ij wherein TI is CR 4b , τ T-2o i •s CnR4a, T3 is N,
T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCXI provides 575 compounds of formula Ik wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R b and R4c are given in Table 1.
Table CCXII provides 575 compounds of formula II wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1. Table CCXffl provides 575 compounds of formula Im wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCXTV provides 575 compounds of formula In wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXV provides 575 compounds of formula Io wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCXVI provides 575 compounds of formula Ip wherein TI is CR b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1.
Table CCXVII provides 575 compounds of formula Iq wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CCXVIII provides 575 compounds of formula Ir wherein TI is CR , T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXLX provides 575 compounds of formula Is wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXX provides 575 compounds of formula It wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCXXI provides 575 compounds of formula lu wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXXII provides 575 compounds of formula Iv wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4c and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCXXIII provides 575 compounds of formula Iw wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCXXIV provides 575 compounds of formula Ix wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4 and R4c are given in Table 1. Table CCXXV provides 575 compounds of formula ly wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXXVI provides 575 compounds of formula Iz wherein TI is CR4b, T2 is CR4\ T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXXVII provides 575 compounds of formula Iaa wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCXXVIH provides 575 compounds of formula lab wherein TI is CR4b, T2 is CR a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXXIX provides 575 compounds of formula lac wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CCXXX provides 575 compounds of formula lad wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCXXXI provides 575 compounds of formula Iae wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1. Table CCXXXI1 provides 575 compounds of formula laf wherein TI is CR b, T2 is CR4a, T3 is N, T4 is CR4c and the values of R8, R4a, R b and R c are given in Table 1.
Table CCXXXffl provides 575 compounds of formula lag wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R c are given in Table 1. Table CCXXXIN provides 575 compounds of formula lah wherein TI is CR4 , T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1. Table CCXXXV provides 575 compounds of formula lai wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXXXVI provides 575 compounds of formula laj wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXXXVπ provides 575 compounds of formula lak wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1. Table CCXXXVIII provides 575 compounds of formula Ial wherein TI is CR4 , T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCXXXIX provides 575 compounds of formula lam wherein TI is CR4 , T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R b and R c are given in Table 1. Table CCXL provides 575 compounds of formula Ian wherein TI is CR4 , T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4 and R4' are given in Table 1. Table CCXLI provides 575 compounds of formula Iao wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXLII provides 575 compounds of formula lap wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCXLUI provides 575 compounds of formula laq wherein TI is CR b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R b and R4' are given in Table 1.
Table CCXLIV provides 575 compounds of formula lar wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCXLV provides 575 compounds of formula las wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCXLVI provides 575 compounds of formula Iat wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR c and the values of R8, R4a, R and R4' are given in Table 1. Table CCXLVII provides 575 compounds of formula Iau wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R and R4c are given in Table 1. Table CCXLVI1I provides 575 compounds of formula lav wherein TI is CR4b, T2 is CR a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCIL provides 575 compounds of formula law wherein TI is CR4b, T2 is CR4a, T3 is Ν, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCL provides 575 compounds of formula lax wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1. Table CCLI provides 575 compounds of formula wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCLII provides 575 compounds of formula Iaz wherein TI is CR b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CCLIII provides 575 compounds of formula Iba wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCLIV provides 575 compounds of formula Ibb wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCLV provides 575 compounds of formula Ibc wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCLVI provides 575 compounds of formula Ibd wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCLVII provides 575 compounds of formula Ibe wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCLVIII provides 575 compounds of formula Ibf wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCLIX provides 575 compounds of formula Ibg wherein TI is CR4b, T2 is CR a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCLX provides 575 compounds of formula Ibh wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CCLXI provides 575 compounds of formula Ibi wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1. Table CCLXII provides 575 compounds of formula Ibj wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4c are given in Table 1. Table CCLXffl provides 575 compounds of formula Ibk wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCLXTV provides 575 compounds of formula Ibi wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCLXV provides 575 compounds of formula Ibm wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCLXVI provides 575 compounds of formula Ibn wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4c and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCLXVII provides 575 compounds of formula Ibo wherein TI is CR4b, T2 is CR4a, T3 is N, T4 is CR4' and the values of R8, R a, R4b and R4' are given in Table 1.
Table CCCI provides 575 compounds of formula la wherein TI is CR4', T2 is CR4a, T3 is
CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCII provides 575 compounds of formula lb wherein TI is CR4', T2 is CR4a, T3 is
CR , T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCIII provides 575 compounds of formula Ic wherein TI is CR4', T2 is CR4a, T3 is CR b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCTV provides 575 compounds of formula Id wherein TI is CR4', T2 is CR a, T3 is CR b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCV provides 575 compounds of formula le wherein TI is CR4c, T2 is CR4a, T3 is CR b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCVI provides 575 compounds of formula If wherein TI is CR4', T2 is CR4a, T3 is
CR , T4 is N and the values of R8, R ,4a, R r»44bD and R4' are given in Table 1. Table CCCVII provides 575 compounds of formula Ig wherein TI is CR4 CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCVIII provides 575 compounds of formula Ih wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R b and R4c are given in Table 1.
Table CCCIX provides 575 compounds of formula li wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R c are given in Table 1. Table CCCX provides 575 compounds of formula Ij wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R c are given in Table 1. Table CCCXI provides 575 compounds of formula Ik wherein TI is CR4', T2 is CR4a, T3 is CR b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXII provides 575 compounds of formula II wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCCXIII provides 575 compounds of formula Im wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCX1N provides 575 compounds of formula In wherein TI is CR c, T2 is CR4a, T3 is CR b, T4 is Ν and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXV provides 575 compounds of formula Io wherein TI is CR c, T2 is CR \ T3 is CR4 , T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXVl provides 575 compounds of formula Ip wherein TI is CR4', T2 is CR4a, T3 is CR4 , T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXVII provides 575 compounds of formula Iq wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4'are given in Table 1. Table CCCXVIII provides 575 compounds of formula Ir wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCCXIX provides 575 compounds of formula Is wherein TI is CR4', T2 is CR a, T3 is CR4b, T4 is N and the values of R8, R4\ R4b and R c are given in Table 1.
Table CCCXX provides 575 compounds of formula It wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4\ R4b and R4' are given in Table 1. Table CCCXXI provides 575 compounds of formula lu wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXIl provides 575 compounds of formula Iv wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R a, R4 and R4c are given in Table 1. Table CCCXXIII provides 575 compounds of formula Iw wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCCXXIV provides 575 compounds of formula Ix wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCCXXV provides 575 compounds of formula ly wherein TI is CR4', T2 is CR4a, T3 is CR4 , T4 is N and the values of R8, R a, R4b and R4c are given in Table 1. Table CCCXXVI provides 575 compounds of formula Iz wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4 and R4' are given in Table 1. Table CCCXXVII provides 575 compounds of formula Iaa wherein TI is CR4', T2 is CR a, T3 is CR4b, T4 is N and the values of R8, R a, R and R4c are given in Table 1. Table CCCXXVIII provides 575 compounds of formula lab wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCCXXIX provides 575 compounds of formula lac wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCCXXX provides 575 compounds of formula lad wherein TI is CR c, T2 is CR4a, T3 is CR b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXXI provides 575 compounds of formula Iae wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R a, R4b and R4' are given in Table 1. Table CCCXXXII provides 575 compounds of formula Iaf wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXXIII provides 575 compounds of formula lag wherein TI is CR4', T2 is CR a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXXTV provides 575 compounds of formula lah wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXXV provides 575 compounds of formula lai wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCXXXVI provides 575 compounds of formula laj wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXXVII provides 575 compounds of formula lak wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXXVIII provides 575 compounds of formula Ial wherein TI is CR4c, T2 is CR a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXXXIX provides 575 compounds of formula lam wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R b and R4' are given in Table 1. Table CCCXL provides 575 compounds of formula Ian wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCCXLI provides 575 compounds of formula Iao wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXLII provides 575 compounds of formula lap wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXLffl provides 575 compounds of formula laq wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R a, R4b and R4' are given in Table 1. Table CCCXLTV provides 575 compounds of formula lar wherein TI is CR4c, T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXLV provides 575 compounds of formula las wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R b and R c are given in Table 1.
Table CCCXLVI provides 575 compounds of formula Iat wherein Tl is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCXLVU provides 575 compounds of formula Iau wherein TI is CR4', T2 is CR4a,
T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCXLVffl provides 575 compounds of formula lav wherein TI is CR4', T2 is CR4a,
T3 is CR4b, T4 is N and the values of R8, R a, R4b and.R4' are given in Table 1. Table CCCIL provides 575 compounds of formula law wherein TI is CR4', T2 is CR4b, T4 is N and the values of R8, R4a, R b and R4' are given in Table 1.
Table CCCL provides 575 compounds of formula lax wherein TI is CR4c, T2 is CR4a, T3 is
CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCLI provides 575 compounds of formula wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCCLII provides 575 compounds of formula Iaz wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLIII provides 575 compounds of formula Iba wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLIV provides 575 compounds of formula Ibb wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1. Table CCCLV provides 575 compounds of formula Ibc wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLVI provides 575 compounds of formula Ibd wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4', R4b and R4c are given in Table 1.
Table CCCLVII provides 575 compounds of formula Ibe wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLVIII provides 575 compounds of formula Ibf wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLIX provides 575 compounds of formula Ibg wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLX provides 575 compounds of formula Ibh wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLXI provides 575 compounds of formula Ibi wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4c are given in Table 1.
Table CCCLXII provides 575 compounds of formula Ibj wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLXIII provides 575 compounds of formula Ibk wherein TI is CR4', T2 is CR4a,
T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCLXIV provides 575 compounds of formula Ibi wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1. Table CCCLXV provides 575 compounds of formula Ibm wherein TI is CR4', T2 is CR4a,
T3 is CR b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCLXVI provides 575 compounds of formula Ibn wherein TI is CR4', T2 is CR4a,
T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CCCLXVπ provides 575 compounds of formula Ibo wherein TI is CR4', T2 is CR4a, T3 is CR4b, T4 is N and the values of R8, R4a, R4b and R4' are given in Table 1.
Table CDI provides 345 compounds of formula la wherein TI is N, T2 is CR4°, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table 2
Figure imgf000073_0001
Figure imgf000074_0001
0 74-
Figure imgf000075_0001
75
Figure imgf000076_0001
-76
Figure imgf000077_0001
00 77
Figure imgf000078_0001
500 78
Figure imgf000079_0001
500 79-
Figure imgf000080_0001
0 -80-
Figure imgf000081_0001
00 81
Figure imgf000082_0001
00 -82-
Figure imgf000083_0001
Figure imgf000084_0001
Table CDII provides 345 compounds of formula lb wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R e and R4f are given in Table 2.
Table CDffl provides 345 compounds of formula Ic wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R f are given in Table 2.
Table CDTV provides 345 compounds of formula Id wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDV provides 345 compounds of formula le wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDVI provides 345 compounds of formula If wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CD VII provides 345 compounds of formula Ig wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDVIII provides 345 compounds of formula Di wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4' and R4f are given in Table 2.
Table CD1X provides 345 compounds of formula Ii wherein TI is N, T2 is CR4', T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDX provides 345 compounds of formula Ij wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R are given in Table 2.
Table CDXI provides 345 compounds of formula Ik wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4' and R4f are given in Table 2.
Table CDXII provides 345 compounds of formula II wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXIII provides 345 compounds of formula Im wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R f are given in Table 2.
Table CDXIV provides 345 compounds of formula In wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R f are given in Table 2. Table CDXV provides 345 compounds of formula Io wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXVI provides 345 compounds of formula Ip wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R f are given in Table 2.
Table CDXVII provides 345 compounds of formula Iq wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXVIII provides 345 compounds of formula Ir wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXIX provides 345 compounds of formula Is wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDXX provides 345 compounds of formula It wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXI provides 345 compounds of formula lu wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXII provides 345 compounds of formula Iv wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXIII provides 345 compounds of formula Iw wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDXXTV provides 345 compounds of formula Ix wherein TI is N, T2 is CR4', T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXV provides 345 compounds of formula ly wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R e and R4f are given in Table 2. Table CDXXVI provides 345 compounds of formula Iz wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXVII provides 345 compounds of formula Iaa wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXVIII provides 345 compounds of formula lab wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXLX provides 345 compounds of formula lac wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXX provides 345 compounds of formula lad wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDXXXI provides 345 compounds of formula lae wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R e and R4f are given in Table 2.
Table CDXXXII provides 345 compounds of formula Iaf wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXXIII provides 345 compounds of formula lag wherein TI is N, T2 is CR e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXXIV provides 345 compounds of formula lah wherein TI is N, T2 is CR4', T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXXV provides 345 compounds of formula lai wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDXXXVI provides 345 compounds of formula laj wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R c and R4f are given in Table 2.
Table CDXXXVϋ provides 345 compounds of formula lak wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXXVffl provides 345 compounds of formula Ial wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXXXIX provides 345 compounds of formula lam wherein TI is N, T2 is CR e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDXL provides 345 compounds of formula Ian wherein TI is N, T2 is CR4', T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXLI provides 345 compounds of formula Iao wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDXLIl provides 345 compounds of formula lap wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXLIII provides 345 compounds of formula laq wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXLIV provides 345 compounds of formula lar wherein TI is N, T2 is CR4e, T3 is N, T4 is CR f and the values of R8, R4' and R4f are given in Table 2.
Table CDXLV provides 345 compounds of formula las wherein TI is N, T2 is CR4c, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXLVI provides 345 compounds of formula Iat wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R f are given in Table 2. Table CDXLVII provides 345 compounds of formula Iau wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDXLVIII provides 345 compounds of formula lav wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDIL provides 345 compounds of formula law wherein TI is N, T2 is CR4', T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDL provides 345 compounds of formula lax wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R e and R f are given in Table 2.
Table CDLI provides 345 compounds of formula wherein TI is N, T2 is CR4e, T3 is N, T4 is
CR4f and the values of R8, R4e and R4f are given in Table 2. Table CDLII provides 345 compounds of formula Iaz wherein TI is N, T2 is CR e, T3 is N,
T4 is CR4f and the values of R8, R e and R f are given in Table 2.
Table CDLffl provides 345 compounds of formula Iba wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDLIV provides 345 compounds of formula Ibb wherein TI is N, T2 is CR4', T3 is N, T4 is CR4f and the values of R8, R4' and R4f are given in Table 2.
Table CDLV provides 345 compounds of formula Ibc wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R e and R4f are given in Table 2. Table CDLVI provides 345 compounds of formula Ibd wherein TI is N, T2 is CR4', T3 is N,
T4 is CR4f and the values of R8, R4c and R4f are given in Table 2.
Table CDLVII provides 345 compounds of formula Ibe wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4e and R f are given in Table 2. Table CDLVIII provides 345 compounds of formula Ibf wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R e and R4f are given in Table 2.
Table CDLIX provides 345 compounds of formula Ibg wherein TI is N, T2 is CR4', T3 is N,
T4 is CR4f and the values of R8, R e and R4f are given in Table 2.
Table CDLX provides 345 compounds of formula Ibh wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDLXI provides 345 compounds of formula Ibi wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR4f and the values of R8, R4' and R4f are given in Table 2.
Table CDLXII provides 345 compounds of formula Ibj wherein TI is N, T2 is CR4e, T3 is N,
T4 is CR f and the values of R8, R4e and R4f are given in Table 2. Table CDLXIII provides 345 compounds of formula Ibk wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDLXIV provides 345 compounds of formula Ibi wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDLXV provides 345 compounds of formula Ibm wherein TI is N, T2 is CR4e, T3 is N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDLXVI provides 345 compounds of formula Ibn wherein TI is N, T2 is CR4e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2.
Table CDLXVII provides 345 compounds of formula Ibo wherein TI is N, T2 is CR e, T3 is
N, T4 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DI provides 345 compounds of formula la wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4fare given in Table 2.
Table DII provides 345 compounds of formula lb wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table Dili provides 345 compounds of formula Ic wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DIV provides 345 compounds of formula Id wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R e and R4f are given in Table 2. Table DV provides 345 compounds of formula le wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4c and R4f are given in Table 2.
Table DVI provides 345 compounds of formula If wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DVII provides 345 compounds of formula Ig wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R e and R4f are given in Table 2.
Table DVffl provides 345 compounds of formula Ih wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DIX provides 345 compounds of formula Ii wherein TI is CR4', T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DX provides 345 compounds of formula Ij wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXI provides 345 compounds of formula Ik wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DXII provides 345 compounds of formula II wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXIII provides 345 compounds of foπnula Im wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXTV provides 345 compounds of formula In wherein TI is CR4e, T2 is N, T3 is CR f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXV provides 345 compounds of formula Io wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXVI provides 345 compounds of formula Ip wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DXVII provides 345 compounds of formula Iq wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXVIII provides 345 compounds of formula Ir wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXLX provides 345 compounds of formula Is wherein TI is CR4 , T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXX provides 345 compounds of formula It wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DXXI provides 345 compounds of formula lu wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXXII provides 345 compounds of formula Iv wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R c and R4f are given in Table 2. Table DXXIII provides 345 compounds of formula Iw wherein TI is CR e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4' and R4f are given in Table 2.
Table DXXIV provides 345 compounds of formula Ix wherein TI is CR4', T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXXV provides 345 compounds of formula ly wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4' and R4f are given in Table 2.
Table DXXVI provides 345 compounds of formula Iz wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R e and R4f are given in Table 2.
Table DXXVII provides 345 compounds of formula Iaa wherein TI is CR4e, T2 is N, T3 is
CR f, T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DXXVffl provides 345 compounds of formula lab wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R c and R f are given in Table 2.
Table DXXIX provides 345 compounds of formula lac wherein TI is CR4', T2 is N, T3 is
CR4f, T4 is N and the values of R8, R e and R f are given in Table 2.
Table DXXX provides 345 compounds of formula lad wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R e and R4f are given in Table 2.
Table DXXXI provides 345 compounds of formula lae wherein TI is CR e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXXXII provides 345 compounds of formula Iaf wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DXXXffl provides 345 compounds of formula lag wherein TI is CR4e, T2 is N, T3 is
CR f, T4 is N and the values of R8, R4e and R f are given in Table 2.
Table DXXXIV provides 345 compounds of formula lah wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R f are given in Table 2.
Table DXXXV provides 345 compounds of formula lai wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXXXVI provides 345 compounds of formula laj wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DXXXVII provides 345 compounds of formula lak wherein TI is CR e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXXXVIU provides 345 compounds of formula Ial wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4c and R4f are given in Table 2. Table DXXXIX provides 345 compounds of formula lam wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXL provides 345 compounds of formula Ian wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXLI provides 345 compounds of formula Iao wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4c and R4f are given in Table 2.
Table DXL1I provides 345 compounds of formula lap wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4c and R4f are given in Table 2.
Table DXLIII provides 345 compounds of formula laq wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DXLIV provides 345 compounds of formula lar wherein TI is CR e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXLV provides 345 compounds of formula las wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R f are given in Table 2.
Table DXLVI provides 345 compounds of formula Iat wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DXLVII provides 345 compounds of formula Iau wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R f are given in Table 2.
Table DXLVHI provides 345 compounds of formula lav wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DIL provides 345 compounds of formula law wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R f are given in Table 2.
Table DL provides 345 compounds of formula lax wherein TI is CR e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DLI provides 345 compounds of formula wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DLII provides 345 compounds of formula Iaz wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R f are given in Table 2. Table DLIII provides 345 compounds of formula Iba wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R f are given in Table 2.
Table DLIV provides 345 compounds of formula Ibb wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4c and R4f are given in Table 2. Table DLV provides 345 compounds of formula Ibc wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4 are given in Table 2.
Table DLVI provides 345 compounds of formula Ibd wherein TI is CR4', T2 is N, T3 is
CR f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DLVII provides 345 compounds of formula Ibe wherein TI is CR4e, T2 is N, T3 is CR4f, T4 is N and the values of R8, R4' and R f are given in Table 2.
Table DLVII1 provides 345 compounds of formula Ibf wherein TI is CR4', T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DLIX provides 345 compounds of formula Ibg wherein TI is CR4', T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DLX provides 345 compounds of formula Ibh wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4 are given in Table 2.
Table DLXI provides 345 compounds of formula Ibi wherein TI is CR4e, T2 is N, T3 is CR4f,
T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DLXII provides 345 compounds of formula Ibj wherein TI is CR4', T2 is N, T3 is CR4f, T4 is N and the values of R8, R e and R4f are given in Table 2.
Table DLXIII provides 345 compounds of formula Ibk wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2.
Table DLXIV provides 345 compounds of formula Ibi wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R4e and R4f are given in Table 2. Table DLXV provides 345 compounds of formula Ibm wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R e and R f are given in Table 2.
Table DLXVI provides 345 compounds of formula Ibn wherein TI is CR4e, T2 is N, T3 is
CR4f, T4 is N and the values of R8, R e and R f are given in Table 2.
Table DLXVII provides 345 compounds of formula Ibo wherein TI is CR4', T2 is N, T3 is CR4f, T4 is N and the values of R8, R e and R4f are given in Table 2.
Table DCI provides 345 compounds of formula lea
Figure imgf000093_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCII provides 345 compounds of formula Icb
Figure imgf000093_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values ooffRR88,, R c and R4f are given in Table 2. Table DCIII provides 345 compounds of formula Ice
Figure imgf000093_0003
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DC1N provides 345 compounds of formula led
Figure imgf000093_0004
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCV provides 345 compounds of formula Ice
Figure imgf000094_0001
wherein TI is S, T2 is CR4e , T3 is CR4f and the values of R8, R4e and R4f are given in Table
Table DCVI provides 345 compounds of formula Icf
Figure imgf000094_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCLVII provides 345 compounds of formula leg
Figure imgf000094_0003
wherein TI is S, T2 is CR e, T3 is CR4f and the values of R8, R4e and R fare given in Table 2. Table DCVIII provides 345 compounds of formula Ich
Figure imgf000095_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCIX provides 345 compounds of formula Ici
Figure imgf000095_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLX provides 345 compounds of formula Icj
Figure imgf000095_0003
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4c and R4fare given in Table 2. Table DCXI provides 345 compounds of formula Ick
Figure imgf000095_0004
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCXII provides 345 compounds of formula Icl
Figure imgf000096_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXIII provides 345 compounds of formula Icm
Figure imgf000096_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXTV provides 345 compounds of formula Icn
Figure imgf000096_0003
wherein TI is S, T2 is CR4e , T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXV provides 345 compounds of formula Ico
Figure imgf000096_0004
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCXVI provides 345 compounds of formula Icp
Figure imgf000097_0001
wherein TI is S, T2 is CR4', T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCXVII provides 345 compounds of formula Icq
Figure imgf000097_0002
wherein TI is S, T2 is CR4', T3 is CR4f and the values of fRR88,, R R4e and R4f are given in Table 2. Table DCXVIϋ provides 345 compounds of formula Icr
Figure imgf000097_0003
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCXLX provides 345 compounds of formula Ics
Figure imgf000098_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXX provides 345 compounds of formula let
Figure imgf000098_0002
wherein TI is S, T2 is CR4', T3 is CR4f and the values of R8, R4e and R4fare given in Table 2. Table DCXXI provides 345 compounds of formula Icu
Figure imgf000098_0003
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXπ provides 345 compounds of formula lev
Figure imgf000099_0001
wherein TI is S, T2 is CR , 44e', T3 is CR41 and the values of Rβ, R4e and R41 are given in Table 2. Table DCXXIII provides 345 compounds of formula lew
Figure imgf000099_0002
wherein TI is S, T2 is CR4', T3 is CR4 and the values of R8, R4e and R4f are given in Table 2. Table DCXXIV provides 345 compounds of formula lex
Figure imgf000099_0003
wherein TI is S, T2 is CR e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXV provides 345 compounds of formula Icy
Figure imgf000100_0001
wherein TI is S, T2 is CR4e, T3 is CR f and the values of R8, R4e and R4f are given in Table 2. Table DCXXVI provides 345 compounds of formula Icz
Figure imgf000100_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXVII provides 345 compounds of formula Ida
Figure imgf000100_0003
wherein TI is S, T2 is CR >4e , T3 is CR ,4f a . nd the values of R , R ,4e and R >4f a . re given in Table 2. Table DCXXVIII provides 345 compounds of formula Idb
Figure imgf000101_0001
wherein TI is S, T2 is CR ,44cC, T3 is CR >44f1 and the values of Rδ, R ,44e' and R ,441'" are given in Table 2. Table DCXX1X provides 345 compounds of formula Idc
Figure imgf000101_0002
wherein TI is S, T2 is CR4', T3 is CR4f and the values of R8, R4e and R4f are given in Table
Table DCXXX provides 345 compounds of formula Idd
Figure imgf000101_0003
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXXI provides 345 compounds of formula Ide
Figure imgf000102_0001
wherein TI is S, T2 is CR >44ee, T3 is CR ,44f1 and the values of R8, R4e and R4f are given in Table
2. Table DCXXXII provides 345 compounds of formula Idf
Figure imgf000102_0002
(Idf) wherein TI is S, T2 is CR , 44c', T3 is CR >44f1 and the values of R8, R >44ee and R >44f1 a . re given in Table 2. Table DCXXXIII provides 345 compounds of formula Idg
Figure imgf000102_0003
wherein TI is S, T2 is CR >44ee, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXXIV provides 345 compounds of formula Idh
Figure imgf000103_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXXV provides 345 compounds of formula Idi
Figure imgf000103_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXXVI provides 345 compounds of formula Idj
Figure imgf000103_0003
wherein TI is S, T2 is CR >4"e', T3 is CR > 44f1 a . nd the values of Rβ, R ,4"ee and R > 44f' are given in Table 2. Table DCXXXVII provides 345 compounds of formula Idk
Figure imgf000104_0001
wherein TI is S, T2 is CR ,44ee, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXXXVIII provides 345 compounds of formula Idl
Figure imgf000104_0002
wherein TI is S, T2 is CR ,4e, T3 is CR , 4"f a . nd the values of R8, R , 44ee and R >4"f a . re given in Table 2. Table DCXXXLX provides 345 compounds of formula Idm
Figure imgf000105_0001
wherein TI is S, T2 is CR4', T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXLX provides 345 compounds of formula Idn
Figure imgf000105_0002
wherein TI is S, T2 is CR >4e , T3 is CR ,4f a . nd the values of R , R , 4e' and R >4f a . re given in Table 2. Table DCXLI provides 345 compounds of formula Ido
Figure imgf000105_0003
wherein TI is S, T2 is CR >44e', T3 is CR ,44f1 and the values of Rβ, R ,44ee and R ,44f1 a . re given in Table 2. Table DCXL1I provides 345 compounds of formula Idp
Figure imgf000106_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4' and R4f are given in Table 2. Table DCXLffl provides 345 compounds of formula Idq
Figure imgf000106_0002
wherein TI is S, T2 is CR , 44ee, T3 is CR > 44f1 a . nd the values of R8, R , 44c' and R ,44f' are given in Table 2. Table DCXLIV provides 345 compounds of formula Idr
Figure imgf000106_0003
wherein TI is S, T2 is CR ,44c', T3 is CR4' and the values of Rs, R4e and R4' are given in Table 2. Table DCXLV provides 345 compounds of formula Ids
Figure imgf000107_0001
wherein TI is S, T2 is CR4', T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXLV provides 345 compounds of formula Idt
Figure imgf000107_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXLVII provides 345 compounds of formula Idu
Figure imgf000107_0003
wherein TI is S, T2 is CR ,44cC, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCXLVffl provides 345 compounds of formula Idv
Figure imgf000108_0001
wherein TI is S, T2 is CR , 44c', T3 is CR »44f' and the values of R8, R , 44ee and R >44f1 are given in Table 2. Table DCIL provides 345 compounds of formula Idw
Figure imgf000108_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCL provides 345 compounds of formula Idx
Figure imgf000108_0003
wherein TI is S, T2 is CR4e, T3 is CR >44f1 a . nd the values of R8, R ,44ee and R , 44f1 are given in Table 2. Table DCLI provides 345 compounds of formula Idy
Figure imgf000109_0001
wherein TI is S, T2 is CR4e, T3 is CR » 44f1 and the values of R8, R 4ee and R ,44f' are given in Table
2. Table DCLII provides 345 compounds of formula Idz
Figure imgf000109_0002
wherein TI is S, T2 is CR ,44e', T3 is CR ,4f and the values of R8, R , 44ee and R ,4f ' a . re given in Table 2. Table DCLIII provides 345 compounds of formula lea
Figure imgf000109_0003
wherein TI is S, T2 is CR , 4e , T3 is CR ,44f1 and the values of R8, R ,44ee and j R T144f1 a . re given in Table 2. Table DCLIV provides 345 compounds of formula Ieb
Figure imgf000110_0001
wherein TI is S, T2 is CR > 4e , T3 is CR > 44f1 and the values of R8, R >44ee and R > 44f1 are given in Table 2. Table DCLV provides 345 compounds of formula Iec
Figure imgf000110_0002
wherein TI is S, T2 is CR ,44e', T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLVI provides 345 compounds of formula led
Figure imgf000110_0003
wherein TI is S, T2 is CR ,44e', T3 is CR , 44f1 a . nd the values of R8, R >44ee and R , 44f1 are given in Table 2. Table DCLVII provides 345 compounds of formula lee
Figure imgf000111_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLVITI provides 345 compounds of formula Ief
Figure imgf000111_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLLX provides 345 compounds of formula leg
Figure imgf000111_0003
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLX provides 345 compounds of formula Ieh 1 1 :
Figure imgf000112_0001
wherein TI is S, T2 is CR4e, T3 is CR > 44f1 and the values of R8, R , 44cC and R ,44f1 are given in Table 2. Table DCLXI provides 345 compounds of formula lei
Figure imgf000112_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLXII provides 345 compounds of formula Iej
Figure imgf000112_0003
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4' and R4f are given in Table 2. Table DCLXffl provides 345 compounds of formula lek
Figure imgf000113_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLXIV provides 345 compounds of formula Iel
Figure imgf000113_0002
wherein TI is S, T2 is CR ,44e', T3 is CR > 44f1 and the values of R8, R , 44e' and R ,44f1 are given in Table 2. Table DCLXV provides 345 compounds of formula lem
Figure imgf000113_0003
wherein TI is S, T2 is CR4c, T3 is CR4f and the values of R8, R4e and R4f are given in Table 2. Table DCLXVI provides 345 compounds of formula Ien
Figure imgf000114_0001
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4' and R4f are given in Table 2. Table DCLXVII provides 345 compounds of formula Ieo
Figure imgf000114_0002
wherein TI is S, T2 is CR4e, T3 is CR4f and the values of R8, R4' and R4f are given in Table 2.
Table DCCI provides 207 compounds of formula lea wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3. Table 3
Figure imgf000114_0003
14
Figure imgf000115_0001
Figure imgf000116_0001
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Table DCCII provides 207 compounds of formula Icb wherein TI is S, T2 is CR e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCIII provides 207 compounds of formula Ice wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCIV provides 207 compounds of formula led wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R e are given in Table 3. Table DCCV provides 207 compounds of formula Ice wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCVI provides 207 compounds of formula Icf wherein TI is S, T2 is CR4c, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCVII provides 207 compounds of formula leg wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3. Table DCCVIII provides 207 compounds of formula Ich wherein TI is S, T2 is CR4', T3 is N and the values of R8 and R4c are given in Table 3.
Table DCCLX provides 207 compounds of formula Ici wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3. Table DCCX provides 207 compounds of formula Icj wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXI provides 207 compounds of formula Ick wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R e are given in Table 3.
Table DCCXII provides 207 compounds of formula Icl wherein TI is S, T2 is CR4', T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXIII provides 207 compounds of formula Icm wherein TI is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXIV provides 207 compounds of formula Icn wherein TI is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3. Table DCCXV provides 207 compounds of formula Ico wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXVI provides 207 compounds of formula Icp wherein TI is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXVII provides 207 compounds of formula Icq wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R e are given in Table 3.
Table DCCXVIII provides 207 compounds of formula Ir wherein TI is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXIX provides 207 compounds of formula Ics wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3. Table DCCXX provides 207 compounds of formula let wherein TI is S, T2 is CR4e, T3 is N and the values of R8 and R e are given in Table 3.
Table DCCXXI provides 207 compounds of formula Icu wherein TI is S, T2 is CR4', T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXXH provides 207 compounds of formula lev wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R e are given in Table 3.
Table DCCXXffl provides 207 compounds of formula lew wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3. Table DCCXXIV provides 207 compounds of formula lex wherein Tl is S, T2 is CR4e, T3 is
N and the values of R and R are given in Table 3.
Table DCCXXV provides 207 compounds of formula Icy wherein Tl is S, T2 is CR e, T3 is
N and the values of R8 and R4e are given in Table 3. Table DCCXXVI provides 207 compounds of formula Icz wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R e are given in Table 3.
Table DCCXXVI! provides 207 compounds of formula Ida wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXXVIII provides 207 compounds of formula Idb wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXXIX provides 207 compounds of formula Idc wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXXX provides 207 compounds of formula Idd wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R e are given in Table 3. Table DCCXXXI provides 207 compounds of formula Ide wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4c are given in Table 3.
Table DCCXXXII provides 207 compounds of formula Idf wherein Tl is S, T2 is CR e, T3 is
N and the values of R8 and R4c are given in Table 3.
Table DCCXXXffl provides 207 compounds of formula Idg wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXXX1V provides 207 compounds of formula Idh wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXXXV provides 207 compounds of formula Idi wherein Tl is S, T2 is CR4', T3 is N and the values of R and R4e are given in Table 3. Table DCCXXXVI provides 207 compounds of formula Idj wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXXXVII provides 207 compounds of formula Idk wherein Tl is S, T2 is CR4e, T3 is N and the values of R and R4e are given in Table 3.
Table DCCXXXVffl provides 207 compounds of formula Idl wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXXXLX provides 207 compounds of formula Idm wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3. Table DCCXL provides 207 compounds of formula Idn wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXLI provides 207 compounds of formula Ido wherein Tl is S, T2 is CR4c, T3 is N and the values of R8 and R4e are given in Table 3. Table DCCXLII provides 207 compounds of formula Idp wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXLffl provides 207 compounds of formula Idq wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXLTV provides 207 compounds of formula Idr wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXLV provides 207 compounds of formula Ids wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCXLVI provides 207 compounds of formula Idt wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3. Table DCCXLVII provides 207 compounds of formula Idu wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCXLVIII provides 207 compounds of formula Idv wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R4' are given in Table 3.
Table DCCIL provides 207 compounds of formula Idw wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCL provides 207 compounds of formula Idx wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCLI provides 207 compounds of formula wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R4e are given in Table 3. Table DCCLII provides 207 compounds of formula Idz wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4' are given in Table 3.
Table DCCLffl provides 207 compounds of formula lea wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCLIV provides 207 compounds of formula Ieb wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCLV provides 207 compounds of formula Iec wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R e are given in Table 3. Table DCCLVI provides 207 compounds of formula led wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4' are given in Table 3.
Table DCCLVII provides 207 compounds of formula lee wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3. Table DCCLVIII provides 207 compounds of formula Ief wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCLLX provides 207 compounds of formula leg wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCLX provides 207 compounds of formula Ieh wherein Tl is S, T2 is CR4', T3 is N and the values of R8 and R e are given in Table 3.
Table DCCLXI provides 207 compounds of formula lei wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCLXII provides 207 compounds of formula Iej wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3. Table DCCLXffl provides 207 compounds of formula lek wherein Tl is S; T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCLXIV provides 207 compounds of formula Iel wherein Tl is S, T2 is CR4c, T3 is
N and the values of R8 and R4e are given in Table 3.
Table DCCLXV provides 207 compounds of formula lem wherein Tl is S, T2 is CR4e, T3 is N and the values of R8 and R4e are given in Table 3.
Table DCCLXVI provides 207 compounds of formula Ien wherein Tl is S, T2 is CR e, T3 is
N and the values of R8 and R e are given in Table 3.
Table DCCLXVfl provides 207 compounds of formula Ieo wherein Tl is S, T2 is CR4e, T3 is
N and the values of R8 and R4e are given in Table 3. Mass spectra data were obtained for selected compounds of Tables I to DCCLXVII using LCMS: LC5 (or LCMS:LC3; retention times with * in the table 4): 254nm - gradient
10% A to 100% B A=H2O+0.01%HCOOH B=CH3CN/CH3OH+0.01 %HCOOH positive electrospray 150-1000 m/z. The data are shown in Table 4. Table 4
Figure imgf000126_0001
Figure imgf000127_0001
Figure imgf000128_0002
The compounds of the invention may be made in a variety of ways. For example as shown in Scheme I.
SCHEME I
Figure imgf000128_0001
(1)
Thus a compound of formula 1 may be synthesised from compounds of formula 2 by reaction with an alkylating agent of the formula R8-L, where L is chloride, bromide, iodide or a sulfonate (e.g. mesylate or tosylate) or similar leaving group at a temperature of between ambient temperature and 100°C, typically 65°C, in an organic solvent such as dichloromethane, chloroform or 1 ,2-dichloroethane in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally catalysed by halide salts such as sodium iodide, potassium iodide or tetrabutylammonium iodide. Alternatively, a compound of formula 2 may be reacted with an aldehyde of the formula RCHO at a temperature between ambient temperature and 100°C in an organic solvent such as tetrahydrofuran or ethanol or mixtures of solvents in the presence of a reducing agent such as borane-pyridine complex, sodium borohydride, sodium (triacetoxy)borohydride, sodium cyanoborohydride or such like, to produce a compound of formula 1 where R8 is CH2-R. Alternatively, a compound of formula 2 may be reacted with paraformaldehyde and a boronic acid of the formula R-B(OH)2 at a temperature between ambient temperature and
100°C in an organic solvent such as ethanol, 1,4-dioxane or water to produce a compound of formula 1 where R8 is CH2-R. A compound of formula 2 may be obtained from a compound of formula 3 by reaction with an acid such as trifluoroacetic acid at ambient temperature in an organic solvent such as dichloromethane, chloroform or 1 ,2-dichloroethane followed by neutralisation of the reaction mixture with an aqueous solution of an inorganic base such as sodium carbonate, sodium bicarbonate or similar compound. Compounds of formula 3 may be obtained from compounds of formula 4 by reaction with a suitable electrophilic species. Compounds of formula 3 where Y is a carbonyl group may be formed by the reaction of compounds of formula 4 with a carboxylic acid derivative of formula Rl-C(O)-Z where Z is chloride, hydroxy, alkoxy or acyloxy at a temperature between 0°C and 150°C optionally in an organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane, optionally in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally in the presence of a coupling agent such as dicyclohexylcarbodiimide. Compounds of formula 3 where Y is a carbonyl group and RI is an amino substituent of formula R'-NH- may be formed by the reaction of compounds of formula 4 with an isocyanate of formula R'-N=C=O under similar conditions. Compounds of formula 3 where Y is a group of formula S(O)q may be formed from compounds of formula 4 by treatment with compounds of formula of Rl-S(O)q-Cl under similar conditions. Compounds of formula 3 where Y is a thiocarbonyl group and RI is an amino substituent of formula R'-NH- may be formed by the reaction of compounds of formula 3 with an isothiocyanate of formula R'- =C=S under similar conditions. Alternatively compounds of formula 3 where Y is a thiocarbonyl group and RI is a carbon substituent may be formed by treatment of compounds of formula 3 where Y is a carbonyl group and RI is a carbon substituent with a suitable thionating agent such as Lawesson's reagent. In the above procedures, acid derivatives of the formula Rl-C(O)-Z, isocyanates of formula R'-N=C=O, isothiocyanates of formula R'-N=C=S and sulfur electrophiles of formula RI -S(O)q-Cl are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Compounds of formula 4 may be obtained from compounds of formula 5 by reaction with a suitable reducing agent such as lithium-tri-tert-butoxyaluminohydride or similar hydrides or alkoxyhydrides in an organic solvent such as in dioxane or at temperature of between 100°C and 125°C, following the procedure described in WO-0027845. Compounds of formula 5 may be obtained from compounds of formula 6, following the procedure described in WO00/27845. Compounds of formula 6 may be obtained following the procedure described by Bremner et al. in Synthesis 1991, 528. Compounds of formula 5 and 6 are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Certain compounds of formula 2, 3 and 4 are novel compounds and as such form a further aspect of the invention. Alternatively compounds of formula 1 may be made by the reactions summarised in
Scheme II SCHEME II
Electrophil
Figure imgf000131_0001
Thus a compound of formula 1A may be synthesised from compounds of formula 7 by reaction with an alkylating agent of the formula R8-L, where L is chloride, bromide, iodide or a sulfonate (e.g. mesylate or tosylate) or similar leaving group at a temperature of between ambient temperature and 100°C, typically 65°C, in an organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally catalysed by halide salts such as sodium iodide, potassium iodide or tetrabutylammonium iodide. Alternatively, a compound of formula 7 may be reacted with an aldehyde of the formula RCHO at a temperature between ambient temperature and 100°C in an organic solvent such as tetrahydrofuran or ethanol or mixtures of solvents in the presence of a reducing agent such as borane-pyridine complex, sodium borohydride, sodium (triacetoxy)borohydride, sodium cyanoborohydride or such like, to produce a compound of formula 1 A where R8 is CH2-R. Alternatively, a compound of formula 7 may be reacted with paraformaldehyde and a boronic acid of the formula R-B(OH)2 at a temperature between ambient temperature and 100°C in an organic solvent such as ethanol, 1,4-dioxane or water to produce a compound of formula 1A where R8 is CH2-R. A compound of formula 7 may be obtained from a compound of formula 8 by reaction with an acid such as trifluoroacetic acid at ambient temperature in an organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane followed by neutralisation of the reaction mixture with an aqueous solution of an inorganic base such as sodium carbonate, sodium bicarbonate or similar compound. Compounds of formula 8 may be obtained from compounds of formula 9 by reaction with a suitable electrophilic species. Compounds of formula 8 where Y is a carbonyl group may be formed by the reaction of compounds of formula 9 with a carboxylic acid derivative of formula Rl-C(O)-Z where Z is chloride, hydroxy, alkoxy or acyloxy at a temperature between 0°C and 150°C optionally in an organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane, optionally in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally in the presence of a coupling agent such as dicyclohexylcarbodiimide. Compounds of formula 8 where Y is a carbonyl group and RI is an amino substituent of formula R'-NH- may be formed by the reaction of compounds of formula 9 with an isocyanate of formula R'-N=C=O under similar conditions. Compounds of formula 8 where Y is a group of formula S(O)q may be formed from compounds of formula 9 by treatment with compounds of formula of Rl-S(O)q-Cl under similar conditions. Compounds of formula 8 where Y is a thiocarbonyl group and RI is an amino substituent of formula R'-NH- may be fonned by the reaction of compounds of formula 8 with an isόthiocyanate of formula R'-N=C=S under similar conditions. Alternatively compounds of formula 8 where Y is a thiocarbonyl group and RI is a carbon substituent may be formed by treatment of compounds of formula 8 where Y is a carbonyl group and RI is a carbon substituent with a suitable thionating agent such as Lawesson's reagent. In the above procedures, acid derivatives of the formula Rl-C(O)-Z, isocyanates of formula R'-N=C=O, isothiocyanates of formula R'-N=C=S and sulfur electrophiles of formula Rl-S(O)q-Cl are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Compounds of formula 9 may be obtained from compounds of formula 10 by reaction with a suitable reducing agent such as lithium-tri-tert-butoxyaluminohydride or similar hydrides or alkoxyhydrides in an organic solvent such as in dioxane or at temperature of between 100°C and 125°C, following the procedure described in WO00/27845. Compounds of formula 10 may be obtained from compounds of formula 1 1 and 12, following known procedures. Compounds of foπnula 10, 1 1 and 12 are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Certain compounds of formula 7, 8 and 9 are novel compounds and as such form a further aspect of the invention. Compounds of formula 1 may also be made by the routes described in scheme III:
SCHEME III
Figure imgf000134_0001
Acid, then neutralise
Figure imgf000134_0002
Compounds of formula 16 and 17 are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Certain compounds of formula 13, 14 and 15 are novel compounds and as such form
a further aspect of the invention.
Further compounds of formula I may be made by the route of Scheme IN.
Figure imgf000135_0001
A compound of formula IC may be synthesised from compounds of formula 22 by reaction with an alkylating agent of the formula R8-L, where L is chloride, bromide, iodide or a sulfonate (e.g. mesylate or tosylate) or similar leaving group at a temperature of between ambient temperature and 100°C, typically ambient temperature, in an organic solvent such as acetonitrile, dimethylformamide, dichloromethane, chloroform or 1 ,2-dichloroethane in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally catalysed by halide salts such as sodium iodide, potassium iodide or tetrabutylammonium iodide. A compound of formula 22 may be obtained from a compound of formula 23 by reaction with an acid such as trifluoroacetic acid and a reducing agent such as triethylsilane at ambient temperature in an organic solvent such as dichloromethane, chloroform or 1,2- dichloroethane followed by neutralisation of the reaction mixture with an aqueous solution of an inorganic base such as sodium carbonate, sodium bicarbonate or similar compound. A compound of formula 23 may be obtained by cyclising a compound of formula 24 under Heck conditions in the presence of a catalyst such as palladium acetate, optionally a ligand such as triphenylphosphine or/and an additive such as tetrabutylammonium bromide and a base such as triethylamine in an organic solvent such as tetrahydrofuran, acetonitrile or dimethylformamide at a temperature of between 50°C to 140°C. Compounds of formula 24 may be obtained from compounds of formula 25 by reaction with a suitable electrophilic species. Compounds of formula 24 where Y is a carbonyl group may be foπned by the reaction of compounds of formula 25 with a carboxylic acid derivative of formula Rl-C(O)-Z where Z is chloride, hydroxy, alkoxy or acyloxy at a temperature between 0°C and 150°C optionally in an organic solvent such as dichloromethane, chloroform or 1 ,2-dichloroethane, optionally in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine and optionally in the presence of a coupling agent such as dicyclohexylcarbodiimide. Compounds of formula 24 where Y is a carbonyl group and RI is an amino substituent of formula R'-NH- may be formed by the reaction of compounds of formula 25 with an isocyanate of formula R'-N=C=O under similar conditions. Compounds of formula IC where Y is a group of formula S(O)q may be formed from compounds of formula 22 by treatment with compounds of formula of Rl-S(O)q-Cl under similar conditions. Compounds of formula 24 where Y is a thiocarbonyl group and RI is an amino substituent of formula R'-NH- may be formed by the reaction of compounds of formula 25 with an isothiocyanate of formula R'-N=C=S under similar conditions. Alternatively compounds of formula 24 where Y is a thiocarbonyl group and RI is a carbon substituent may be formed by treatment of compounds of formula 24 where Y is a carbonyl group and-Rl is a carbon substituent with a suitable thionating agent such as Lawesson's reagent.
In the above procedures, acid derivatives of the formula Rl-C(O)-Z, isocyanates of formula R'-N=C=O, isothiocyanates of formula R'-N=C=S and sulfur electrophiles of formula Rl- S(O)q-Cl are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Compounds of formula 25 may be synthesised by alkylating a compound of formula 27 (in which the amino group may if necessary be protected e.g. by an acyl group which can be removed after the reaction) with a compound of formula 26 in the presence of a base such as sodium hydride, lithium aluminium hydride or potassium tertbutoxide at a temperature of between -78°C to 100°C in an organic solvent such as tetrahydrofuran or dimethyformamide. Compounds of formula 25, 26 and 27 are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Certain compounds of formula 22, 23 and 24 are novel compounds and as such form a further aspect of the invention. Compounds of formula I where R2 and R3 are other than hydrogen may be made by routes described in WO03/106457. Thus for example a compound of formula 26a or 36a which are compounds of formula 26 or 36 respectively wherein the carbon atom adjacent to the leaving group X carries groups R and R may be converted to compounds of formula I using the methods described for converting compounds of 26 or 36 respectively into compounds of formula I. Compounds where the ring T is a heteroaromatic ring (such as pyrimidine or thiophene) may be prepared according to the synthetic routes described for instance in Organic Reactions (New York) (2002), 60, 157, either by route shown in scheme V or scheme VI (both based on intramolecular Heck reactions): Scheme V
Figure imgf000137_0001
(32)
Scheme VI
Figure imgf000138_0001
The above methods, particularly scheme V may be varied according to the knowledge of the skilled person. Thus for example compounds of formula 1 where the ring T is a thiophene ring may be synthesised by the method outlined in Scheme VII. Thus, a compound of formula ID may be synthesised by alkylating a compound of formula 42 with a reagent of formula R8-L by methods known per se. A compound of formula 42 may be obtained by reacting a compound of formula 43 with a reducing agent such as triethylsilane, sodium borohydride, sodium cyanoborohydride or borane in the presence of an acid such as trifluoroacetic acid in an organic solvent such as dichloromethane at a temperature of between -10°C to 80 °C. A compound of formula 43 may be synthesised from a compound of formula 44 by reacting with a suitable electrophilic species by methods known per se. A compound of formula 44 may be prepared from a compound of formula 45 by treatment with a suitable base such as potassium carbonate at a temperature of between 0°C to 80°C in an organic solvent such as methanol or ethanol in combination with water. A compound of formula 45 may be synthesised by cyclising a compound of formula 46 under Heck conditions, typically in the presence of a catalyst such as palladium(IT) acetate, optionally a ligand such as triphenylphosphine or/and an additive such as tetrabutylammonium bromide and a base such as triethylamine in an organic solvent such as tetrahydrofuran, acetonitrile, dimethylformamide, N-methyl-pyrrolidinone or dimethylacetamide at a temperature of between 20°C to 140°C. Compounds of formula 46 may be synthesised by coupling compounds of formula 47 with the known alcohol 8 (J. Org. Chem. 2001, 66, 5545-5551) under Mitsunobu conditions, typically using a phosphine such as triphenylphosphine and an azo compound such as di ethyl azodicarboxylate or diisopropylazodicarboxylate in an organic solvent such as tetrahydrofuran or toluene at a temperature of between 0°C to 80°C. Compounds of formula 46 and 47 are either known compounds or may be formed from known compounds by known methods by a person skilled in the art. Certain compounds of formula 42, 43 and 44 are novel compounds and as such form a further aspect of the invention.
SCHEME VII
Figure imgf000140_0001
The skilled person will readily recognize that other compounds of formula 1 may be prepared using the methods described in Scheme VII. The compounds of formula (I) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are. hereinafter collectively referred to as pests. The pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies). Examples of pest species which may be controlled by the compounds of formula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp.
(capsids), Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp. (stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (white flies), Bemisia tabaci (white fly), Ostrinia nubilalis (European corn borer), Spodoptera littoralis (cotton leafworm), Heliothis virescens (tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pieris brassicae (white butterfly), Plutella xylostella (diamond back moth), Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta_ migratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp. (rootworms), Panonychus ulmi (European red mite), Panonychus citri (citrus red mite), Tetranychus urticae (two-spotted spider mite), Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpus spp. (flat mites), Boophilus microplus (cattle tick), Dermacentor variabilis (American dog tick), Ctenocephalides felis (cat flea), Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti (mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes), Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplaneta ameήcana (cockroach), Blatta orientalis (cockroach), termites of the Mastotermitidae (for example Mastotermes spp.), the Kalotermitidae (for example Neotermes spp.), the Rhinotermitidae (for example Coptotermes formosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R. hesperus, and R. santonensis) and the Termitidae (for example Globitermes sulphureus), Solenopsis geminata (fire ant), Monomorium pharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (biting and sucking lice), Meloidogyne spp. (root knot nematodes), Globodera spp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesion nematodes), Rhodopholus spp. (banana buπowing nematodes), Tylenchulus spp. (citrus nematodes), Haemonchus contortus (barber pole worm), Caenorhabditis eelworm), Trichostrongylus spp. (gastro intestinal nematodes) and Deroceras reticulatum (slug). The invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a pest, a locus of pest, or to a plant susceptible to attack by a pest, The compounds of formula (I) are preferably used against insects, acarines or nematodes. The term "plant" as used herein includes seedlings, bushes and trees. In order to apply a compound of formula (I) as an insecticide, acaricide, nematicide or molluscicide to a pest, a locus of pest, or to a plant susceptible to attack by a pest, a compound of formula (I) is usually formulated into a composition which includes, in addition to the compound of formula (I), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%), of a compound of formula (I). The composition is generally used for the control of pests such that a compound of formula (I) is applied at a rate of from 0.1 g to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare. When used in a seed dressing, a compound of formula (I) is used at a rate of O.OOOlg to l Og (for example 0.00 lg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed. In another aspect the present invention provides an insecticidal, acaricidal, nematicidal or molluscicidal composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I) and a suitable carrier or diluent therefor. The composition is preferably an insecticidal, acaricidal, nematicidal or molluscicidal composition. In a still further aspect the invention provides a method of combating and controlling pests at a locus which comprises treating the pests or the locus of the pests with an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a composition comprising a compound of formula (I). The compounds of formula (I) are preferably used against insects, acarines or nematodes. The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (I). Dustable powders (DP) may be prepared by mixing a compound of formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder. Soluble powders (SP) may be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG). Wettable powders (WP) may be prepared by mixing a compound of formula (I) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG). Granules (GR) may be formed either by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or, by adsorbing a compound of formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent). Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank). Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C8-Cιo fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water. Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (I) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion. Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I). SCs may be prepared by ball or bead milling the solid compound of formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of formula (I) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product. Aerosol formulations comprise a compound of formula (I) and a suitable propellant
(for example w-butane). A compound of formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as «-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps. A compound of formula (I) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound. Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula (I) and they may be used for seed treatment. A compound of formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound. A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (I)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (I)). A compound of formula (I) may also be foπnulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier). Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type. Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts. Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di- isopropyl- and tri-tJOpropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates. Suitable SFAs of the amphoteric type include betaines, propionates and glycinates. Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins. Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite). A compound of formula (I) may be applied by any of the known means of applying pesticidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil suπounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment. A compound of formula (I) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems. Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (I) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used. A compound of formula (I) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types include granules of fertiliser. The mixtures suitably contain up to 25% by weight of the compound of formula (I). The invention therefore also provides a fertiliser composition comprising a fertiliser and a compound of formula (I). The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity. The compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition. Examples of suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate; b) Organophosphates, such as, profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon; c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl; d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or chlorfluazuron; e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin; f) Pyrazoles, such as tebufenpyrad and fenpyroximate; g) Macrolides, such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad or azadirachtin; h) Hormones or pheromones; i) Organochlorine compounds such as endosulfan, benzene hexachloride, DDT, chlordane or dieldrin; j) Amidines, such as chlordimeform or amitraz; k) Fumigant agents, such as chloropicrin, dichloropropane, methyl bromide or metam; 1) Chloronicotinyl compounds such as imidacloprid, thiacloprid, acetamiprid, nitenpyram or thiamethoxam; m) Diacylhydrazines, such as tebufenozide, chromafenozide or methoxyfenozide; n) Diphenyl ethers, such as diofenolan or pyriproxifen; o) Indoxacarb; p) Chlorfenapyr; or q) Pymetrozine. In addition to the major chemical classes of pesticide listed above, other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition. For instance, selective insecticides for particular crops, for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed. Alternatively insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron). Examples of fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide (SSF- 129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole- 1-sulphonamide, α-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-γ-butyrolactone, 4-chloro- 2-cyano-N,N-dimethyl-5- -tolylimidazole-l-sulfonamide (IKF-916, cyamidazosulfamid), 3-5-dichloro-N-(3-chloro- 1 -ethyl- l-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281, zoxamide), N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide (MOΝ65500), N- (l-cyano-l,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide (AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, acibenzolar (CGA245704), alanycarb, aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, biloxazol, bitertanol, blasticidin S, bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate and Bordeaux mixture, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide l,l'-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb, difenoconazole, difenzoquat, diflumetorim, O,O-di-wo-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol, ethyl(Z)-N-benzyl-N([methyl(methyl-thioethylideneaminooxycarbonyl)amino]thio)-β -alaninate, etridiazole, famoxadone, fenamidone (RPA407213), fenarimol, fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil, metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothal-tsopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, propionic acid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyπolnitrin, quaternary ammonium compounds, quinomethionate, quinoxyfen, quintozene, sipconazole (F-155), sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemoφh, trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, zineb and ziram. The compounds of formula (I) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases. Examples of suitable synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole. Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required. An example of a rice selective herbicide which may be included is propanil. An example of a plant growth regulator for use in cotton is PIX™. Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.
The invention is illustrated by the following Examples: EXAMPLE 1 This example illustrate the preparation of compound CCCIII-3, 7-aza-l-(2- chloropyridin-4-yl-)carbonyl- -[trans-3-(4-chlorophenylallyl]spiro[indoline-3,4'-piperidine] Step A:
NaH (4.25 g) was slowly added to a solution of 3-chloro-2-pyridylacetonitrile (10 g) in DMSO (140 ml) under nitrogen. The mixture was stirred at room temperature for lh. A solution of bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (15.87 g) in DMSO (140 ml) was added and the resulting mixture was stirred at 70°C for 2 hrs. After cooling, the reaction mixture was partitioned between ethyl acetate and water, the combined organic layers were washed with saturated sodium bicarbonate and brine, dried (sodium sulfate), filtered and concentrated in vacuo. The crude product was purified by chromatography [SiO2; ethyl acetate-hexane (3:7)] to give 12.96 g (61%) of 2-chloro-4'-cyano-3',4',5',6'-tetrahydro-2'H- [3,4']bipyridinyl-l '-carboxylic acid tert-butyl ester as a white solide; MS (ES+) 322/324 (M+H+). Step B:
A mixture of 2-chloro-4'-cyano-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridinyl-l '-carboxylic acid tert-butyl ester (6 g) and lithium tri-tert-butoxyaluminohydride (72.34 ml), IM solution in THF) in 1-4-dioxane (90 ml) was refluxed overnight. After cooling, 1 N NaOH (100 ml) and H2O (100 ml) were added slowly at 0°C. Dichloromethane was added to the mixture. The aqueous phase was extracted twice with dichloromethane and the combined organic layers were washed with saturated sodium bicarbonate, dried (magnesium sulfate), filtered and concentrated in vacuo. The crude product was purified by chromatography [SiO2; dichloromethane-methanol (95:5)] to give 5.5 g (46%) of 7-Aza- spiro[indoline-3,4'- piperidine]- l '-carboxylic acid tert-butylester; MS (ES+) 290 (M+H+). Step C:
A mixture of 2-chloro-isonicotinic acid (441 mg), thionyl chloride (0.6 ml), DMF (trace) in toluene (9 ml) was heated to reflux for 2 hrs. After concentration in vacuo, the residue was dissolved in 12 ml dichloromethane and added dropwise at 0°C under nitrogen to a mixture of 7-aza- spiro[indpline-3,4'-piperidine]-l '-carboxylic acid tert-butylester, (405 mg), triethylamine (0.86 ml) and dichloromethane ((12 ml). The mixture was stirred at room temperature for 2 hrs. The mixture was diluted in a saturated sodium carbonate solution. The organic layer was separated and the aqueous phase was extracted twice with dichloromethane and the combined organic layers were washed with saturated sodium bicarbonate, dried (magnesium sulfate), filtered and concentrated in vacuo 630 mg of 7-Aza-l -(2-chloropyridin- 4-yl-)carbonyl-l '-carboxylic acid tert-butylester spiro[indoline-3,4'-piperidine; MS (ES+) 429 (M+H+). Step D:
Trifluoroacetic acid (1.92 ml) was added to a stirred solution of 7-Aza-l -(2-chloropyridin-4- yl-)carbonyl-l '-carboxylic acid tert-butylester spiro[indoline-3,4'-piperidine] (0.62 g) in anhydrous dichloromethane (20 ml) under an atmosphere of nitrogen. The reaction was left as such for 2 h. The reaction was washed with saturated bicarbonate solution and dried over sodium sulphate and concentrated in vacuo to yield 427 mg (90%) of 7-aza-l-(2- chloropyridin-4-yl-)carbonyl-spiro[indoline-3,4'-piperidine]; MS (ES+) 329 (M+H+).
Step E: A solution of 4-chlorocinnamyl chloride (68 mg) in acetonitrile (4 ml) was added slowly to a stirred mixture of 7- Aza-l-(2-chloropyridin-4-yl-)carbonyl-spiro[indoline-3, 4 '-piperidine];
(100 mg) and potassium carbonate (0.42 g) in acetonitrile (16 ml) under an atmosphere of nitrogen at room. The reaction was heated to 70 C for 2 hrs. The reaction was diluted in diethylether, washed with H2O and dried over sodium sulphate and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate-triethylamine
(2:8:0.1)] to give 84 mg (58%) of 7-aza-l-(2-chloropyridin-4-yl-)carbonyl-l '-[trans-3-(4- chlorophenylallyl]spiro[indoline-3,4'-piperidine]; MS (ES+) 479 (M+H+).
Compound Nos CCCI-3, CCCV-3 and CCCVI-3 were prepared by analogous methods to those of Example 1. EXAMPLE 2 This Example illustrates the preparation of compound CCIII-3, 6-Aza-l-(2- chloropyridin-4-yl-)carbonyl- -[trans-3-(4-chlorophenylallyl]spiro[indoline-3,4'- piperidine].
Step A: Potassium hexamethyldisilazane (1.2 ml, 0.5 M solution in toluene) was slowly added to a solution of 4-chloro-3-fluoro-pyridin (0.5 g) and N-Boc-4-Cyano-Piperidine (0.312 g) in
1.5ml toluene at room temperature, under nitrogen. The mixture was stirred at 80°C for 2 hrs. After cooling, the reaction mixture was quenched in IN HCl. The aqueous phase was extracted twice with toluene and the combined organic were dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product was purified by chromatography [SiO2; ethyl acetate-hexane (1 :1)] to give 104 mg (90%) of 4-cyano-3'- fluoro-3,4,5,6-tetrahydro-2H-[4,4']bipyridinyl-l -carboxylic acid tert-butyl ester; MS (ES+) 306 (M+H+). Step B:
A mixture of 4-cyano-3'-fluoro-3, 4,5, 6-tetrahydro-2H-[4,4']bipyridinyl-l -carboxylic acid tert-butyl ester (1 g) and lithium tri-tert-butoxyaluminohydride (12.7 ml), IM solution in THF) in 1-4-dioxane (15 ml) was stirred at 130°C (sealed tube) for 1 hr. After cooling, 1 N NaOH (100 ml) and H2O (100 ml) were added slowly at 0°C. Ethyl acetate was added to the mixture. The aqueous phase was extracted twice with ethyl acetate and the combined organic layers were washed with saturated sodium bicarbonate, dried (magnesium sulfate), filtered and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate (7:3)] to give 230 mg g (24%) of 6-aza- spiro[indoline-3,4'-piperidine]- 1 '-carboxylic acid tert-butylester; MS (ES+) 290 (M+H+). Step C:
A mixture of 2-chloro-isonicotinic acid (239 mg), thionyl chloride (0.33 ml), DMF (trace) in toluene (5 ml) was heated to reflux for 2 hrs. After concentration in vacuo, the residue was dissolved in 2 ml dichloromethane and added dropwise at 0°C under nitrogen to a mixture of 6-aza- spiro[indoline-3,4'-piperidine]-l '-carboxylic acid tert-butylester, (220 mg), triethylamine (0.47 ml) and dichloromethane ((13 ml). The mixture was stirred at room temperature for 1 hr. The mixture was diluted in a saturated sodium carbonate solution. The organic layer was separated and the aqueous phase was extracted twice with dichloromethane and the combined organic layers were washed with saturated sodium bicarbonate, dried
(magnesium sulfate), filtered and concentrated in vacuo 340 mg of 6-aza- 1 -(2-chloropyridin-
4-yl-)carbonyl-l '-carboxylic acid tert-butylester spiro[indoline-3,4'-piperidine]; MS (ES+)
429 (M+H+).
Step D: Trifluoroacetic acid (1 ml) was added to a stiπed solution 6-aza- l-(2-chloropyridin-4-yl-
)carbonyl-l '-carboxylic acid tert-butylester spiro[indoline-3,4'-piperidine] (0.33 g) in anhydrous dichloromethane (10 ml) under an atmosphere of nitrogen. The reaction was left as such for 2 h. The reaction was washed with saturated bicarbonate solution and dried over sodium sulphate and concentrated in vacuo to yield 210 mg (83%) of 4-aza-l-(2- chloropyridin-4-yl-)carbonyl-spiro[indoline-3,4'-piperidine]; MS (ES+) 329 (M+H+). Step E: A solution of 4-chlorocinnamyl chloride (40 mg) in acetonitrile (3 ml) was added slowly to a stirred mixture of 4-aza-l -(2-chloropyridin-4-yl-)carbonyl-spiro[indoline-3,4'-piperidine] (100 mg) and N,N-diisopropyl-ethylamine (0.66 ml) in acetonitrile (13 ml) under an atmosphere of nitrogen at room. The reaction was stirred at room temperature for 2 hrs, heated to reflux for 2 hrs and then stirred overnight at room temperature. The reaction was diluted in diethylether, washed with H2O, then with brine and dried over sodium sulphate and concentrated in vacuo. The crude product was purified by chromatography [SiO2; ethyl acetate-methanol-triethylamine (9:10:0.1)] to give 72 mg (76%> over 3 steps) of 6-aza- 1 -(2- chloropyridin-4-yl-)carbonyl-r-[trans-3-(4-chlorophenylallyl]spiro[indoline-3,4'-piperidine]; MS (ES+) 479 (M+H+). Compound Nos CCIIT6 and CCIII-7 were prepared by analogous methods to those of Example 2. EXAMPLE 3 This Example illustrates the preparation of compound III-210, 6-chloro-4-aza-l-(2- chloropyridin-4-yl-)carbonyl-l '-[trans-3-(4-chlorophenylallyl]spiro [indoline-3,4'- piperidine]
Step A:
Potassium hexamethyldisilazane (1.34 ml, 0.5 M solution in toluene) was slowly added to a solution of 5-Chloro-2,3-difluoro-pyridine (0.1 g) and N-Boc-4-Cyano-Piperidine (0.14 g) in
3 ml toluene at 0°C, under nitrogen. The mixture was stirred at 0°C for lhr. After cooling, the reaction mixture was quenched in IN HCl. The aqueous phase was extracted twice with ethyl acetate and the combined organic were washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate-hexane (4:1)] to give 1 11 mg (49%>) of 5- chloro-4'-cyano-3-fluoro-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-T-carboxylic acid tert- butyl ester; MS (ES+) 240 (M-Boc+ H+).
Step B:
A mixture of 5-chloro-4'-cyano-3-fluoro-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-l'- carboxylic acid tert-butyl ester (0.05 g) and lithium tri-tert-butoxyaluminohydride (0.57 ml), IM solution in THF) in 1-4-dioxane (0.75 ml) was refluxed under nitrogen for 4 hrs. After cooling, 1 N NaOH and H2O and ethyl acetate were added slowly to the mixture at 0°C. The aqueous phase was extracted twice with ethyl acetate and the combined organic layers were washed with saturated sodium bicarbonate, dried (sodium sulfate), filtered and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate- triethylamine (75:25:1)] to give 18 mg g (38%) of 6-chloro-4-aza-spiro[indoline-3,4'- piperidine]-l'-carboxylic acid tert-butylester; MS (ES+) 324 (M+H+).
Step C:
A mixture of 2-chloro-isonicotinic acid (324 mg), thionyl chloride (0.43 ml), DMF (trace) in toluene (6.4 ml) was heated to reflux for 2 hrs. After concentration in vacuo, the residue was dissolved in 2 ml dichloromethane and added dropwise at 0°C under nitrogen to a mixture of 6-chloro-4-aza-spiro[indoline-3,4'-piperidine]-l '-carboxylic acid tert-butylester, (220 mg), triethylamine (0.6 ml) and dichloromethane ((20 ml). The mixture was stiπed at room temperature for 1 hr. The mixture was diluted in a saturated sodium carbonate solution. The organic layer was separated and the aqueous phase was extracted twice with dichloromethane and the combined organic layers were washed with saturated sodium bicarbonate, dried (magnesium sulfate), filtered and concentrated in vacuo 473 mg (102%) of 6-chloro-4-aza-l- (2-chloropyridin-4-yl-)carbonyl-l '-carboxylic acid tert-butylester spiro[indoline-3,4'- piperidine]; MS (ES+) 407 (M - Me2C=CH2+H+).
Step D:
Trifluoroacetic acid (1.47 ml) was added to a stirred solution 6-chloro-4-aza-l-(2- chloropyridin-4-yl-)carbonyl-l '-carboxylic acid tert-butylester spiro[indoline-3,4'-piperidine]
(0.47 g) in anhydrous dichloromethane (15 ml) under an atmosphere of nitrogen. The reaction was left as such for 1 hr. The reaction was washed with saturated bicarbonate solution and dried over sodium sulphate and concentrated in vacuo to yield 363 mg (98%) of 6-chloro-4-aza-l-(2-chloropyridin-4-yl-)carbonyl-spiro[indoline-3,4'-piperidine]; MS (ES+) 363 (M+H+). Step E: A solution of 4-chlorocinnamyl chloride (165 mg) in acetonitrile (20 ml) was added slowly to a stiπed mixture of 6-chloro-4-aza-l-(2-chloropyridin-4-yl-)carbonyl-spiro[indoline-3,4'- piperidine] (300 mg) and N,N-diisopropyl-ethylamine (0.66 ml) in acetonitrile (40 ml) under an atmosphere of nitrogen at room. The reaction was stirred at room temperature for 4 hrs and heated to reflux overnight. The reaction was diluted in diethylether, washed with H2O, then with brine and dried over sodium sulphate and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate-triethylamine (8:2:0.1)] to give 310 mg (73%) of 6-chloro-4-aza-l -(2-chloropyridin-4-yl-)carbonyl-l '-[trans-3-(4- chlorophenylallyl]spiro[indoline-3,4'-piperidine]; MS (ES+) 513 (M+H+).
Compound Nos 1-26, 1-29, 1-30, 1-210, 1-213, 1-214, 1-233, 1-237, 11-26, 11-29, 11-30, 11-210, π-213, 11-214, III-3, III-6, III-7, 111-26, 111-29, 111-30, IH -210, III -210 N-oxide, III -213, III -214, 111-233, πi-236, 111-237, III-302, III -325, HI -328, III -329, V-26, V-29, V-30, V-209, V-210, V-213, V-214, V-233, V-236, V-237, V-509, VIII-26, VIII-29, VIII-30, VIII-210, VIII-213, VIII-214, XX-26, XX-29, XX-30, XX-210, XX-213, XX-214, XX-233, XX-236, XX-237, CI1I-49, CIII-52, Cffl-53, COI-210, CIII-214, CIII-555, CCCI-3, CCCIII-26, CCCIII-29, CCCIII-30, CCCV-26, CCCV-29 and CCCV-30 were prepared by analogous methods to those of Example 3. EXAMPLE 4 This Example illustrates the preparation of compound DCIII-3, 4-(2-chloropyridin-4- yl)carbonyl- -[tr-7«^-3-(4-chlorophenyl)allyl]spiro[5,6-dihydro-4H-thieno[3,2-ό]pyrrole-
6,4'-piperidine)] Step A: Triphenylphosphine (2.29 g) was dissolved in tetrahydrofuran (50 ml) and the solution was cooled to -10°C under argon. Diisopropylazodicarboxylate (1.70 ml) was added dropwise over 10 min and the resulting mixture was stirred at -10°C for 20 min (formation of a white precipitate). 2,2,2-Trifluoro-N-(2-iodo-thiophen-3-yl)-acetamide (2.25 g) dissolved in a minimum volume of tetrahydrofuran was added, followed by 4-Hydroxymethyl-3,6- dihydro-2H-pyridine-l -carboxylic acid tert-butyl ester (J. Org. Chem. 2001, 66, 5545-5551, 1.49 g) dissolved in a minimum volume of tetrahydrofuran. The reaction mixture was allowed to warm to room temperature and stirred for 12 hours. The solution was then concentrated in vacuo and the residue subjected to silica gel chromatography (cyclohexane:ethyl acetate 93:7) to afford 4-{[(2-Iodo-thiophen-3-yl)-(2,2,2-trifluoro-acetyl)- amino]-methyl}-3,6-dihydro-2H-pyridine-l -carboxylic acid tert-butyl ester as a colourless oil (2.27 g). Η NMR (400 MHz, CDC13) 1.5 (s, 9H), 2.15 (m, 2H), 3.43 (m, IH), 3.52 (m, IH), 3.75 (d, J = 19 Hz, IH), 3.77 (m, 2H), 4.76 (d, J = 17 Hz, IH), 5.41 (s, IH), 6.68 (br d, j = 5.5 Hz, IH), 7.42 (d, J = 5.5 Hz, IH); MS (ES+) 417 (M+H+-CO2-isobutene), 458 (M+H+- isobutene). Step B: In a dried, argon purged flask, -{[(2-Iodo-thiophen-3-yl)-(2,2,2-trifluoro- acetyl)-amino]-methyl}-3,6-dihydro-2H-pyridine-l-carboxylic acid tert-butyl ester obtained in Step A (1.57 g) was dissolved in dimethylacetamide (25 ml); triethylamine (1.05 ml), tetrabutylammonium bromide (1.08 g) and palladium(II) acetate (103 mg) were successively added and the solution was heated at 80°C for 4 hours. Palladium(II) acetate (20 mg) was added again and the mixture stiπed at 80°C for 3 more hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over sodium sulphate and concentrated in vacuo. Silica gel chromatography of the residue (cyclohexane:ethyl acetate 8:2) afforded 4-trifluoroacetyl-spiro[5,6-dihydro-4H-thieno[3,2- b]pyιτole-6,4'-(r,2',3',4'-tetrahydropyridine)]-l ' carboxylic acid tert-butyl ester (0.9 g). Η NMR (40 MHz, CDC13) 2 rotamers, 1.54 (s, 9H), 2.05 (m, 2H), 3.65-3.80 (m, 2H), 4.20-4.30 (m, 2H), 4.70 and 4.80 (m, IH), 6.82 and 6.96 (m, IH), 7.23 (d, J = 5.5 Hz, IH), 7.42 (d, J = 5.5 Hz, IH); MS (ES+) 288 (M+H+-isobutene).
Step C: 4-tri fluoroacetyl-spiro[5,6-dihydro-4H-thieno[3,2-ό]pyrrole-6,4'-(l ',2',3',4'- tetrahydropyridine)]-l ' carboxylic acid tert-butyl ester obtained in Step B (0.9 g) was dissolved in methanol (30 ml) and water (5 ml), placed under argon and potassium carbonate (28 g) was added. The reaction mixture was stiπed for 10 min at room temperature, the mixture was filtered and the filtrate concentrated in vacuo. The residue was diluted with ethyl acetate, washed with brine, dried (sodium sulphate) and concentrated in vacuo. The residue was immediately dissolved in dichloromethane (40 ml) and acylated with 2- chloroisonicotinoyl chloride (800 mg) in the presence of triethylamine (1 ml) at 0°C for 1 hour. Standard aqueous work-up and silica gel chromatography (cyclohexane:ethyl acetate 8:2) afforded 4-(2-chloropyridin-4-yl)carbonyl-spiro[5,6-dihydro-4H-thieno[3, 2-ό]pyrrole- 6,4'-(l ',2',3',4'-tetrahydropyridine)]-r carboxylic acid tert-butyl ester (0.83 g). M.p. 63- 65°C; MS (ES+) 332/334 (M+H+-CO2-isobutene), 376/378 (M+H+-isobutene), 432/434 (M+H+). Step D: 4-(2-chloropyridin-4-yl)carbonyl-spiro[5,6-dihydro-4H-thieno[3,2-ό]pyrrole-
6,4'-(r,2',3',4'-tetrahydropyridine)]-l ' carboxylic acid tert-butyl ester obtained in Step C (216 mg) was dissolved in dichloromethane (15 ml) and treated successively with triethylsilane (0.4 ml) and trifluoroacetic acid (0.75 ml); the solution was stiπed under argon for 6 hours, diluted with dichloromethane, neutralised with aqueous sodium bicarbonate, dried (sodium sulphate) and concentrated in vacuo. The residue was dissolved in acetonitrile (15 ml) and treated with diisopropylethylamine (0.14 ml) and 4-chlorocinnamyl chloride (96 mg) for 24 hours at room temperature. Standard aqueous work-up afforded a residue which was purified by flash chromatography (silica gel, cyclohexane:ethyl acetate 8:2+ 0.5 % triethylamine) to give the title product (170 mg) as a colourless solid. M.p. 81-82°C; 1H NMR (600 MHz, CDC13) 2 rotamers: 1.81-1.94 (m, 4H), 2.60-2.71 (m, 4H), 3.21 and 3.23 (d, J = 7 Hz, 2H), 4.03 and 4.35 (s, 2H), 5.63 and 7.55 (d, J = 5.9 Hz, IH), 6.26 and 6.29 (dt, J = 12.9 Hz, 7 Hz, IH), 6.51 and 6.53 (d, J = 12.9 Hz, IH), 6.96 and 7.23 (d, J = 5.9 Hz, IH), 7.26-7.49 (m, 6H), 8.53 and 8.54 (d, J = 5.9 Hz, IH); 13C NMR (125 MHz, CDC12CDC12, 80°C) selected data 37.3, 51.0, 61.1 , 67.1 and 77.2, 114.4 and 117.5, 120.3, 122.3, 127.1, 127.5, 127.9, 128.8, 132.0, 150.6; MS (ES+) 484/486/487/489 (M+H+). Compound Nos DCIII-3, DCIII-6, DCIII-7, DCIII-52, DCIII-53 and DCV-53. were prepared by analogous methods to those of Example 4.
EXAMPLE 5
This Example illustrates the preparation of compound Cffl-210, 4-chloro-5-aza-l-(2- chloropyridin-4-yl)carbonyl- -[tra«5-3-(4-chlorophenyl)allyl]spiro[indoline-3,4'-piperidine] Step A: 2-Chloro-4-amino-pyridine was brominated according to the method described in Synthesis 2001, 14, 2175-2179: a solution of 4-chloro-4-amino-pyridine (12.3 g) in acetonitrile (500 ml) was treated with N-bromosuccinimide (17.8 g) and the resulting solution was stiπed at room temperature for 24 hours. The solution was then concentrated in vacuo and the residue subjected to silica gel chromatography (cyclohexane: ethyl acetate 8:2) to afford 3-bromo-2-chloro-4-aminopyridine (12.2 g, m.p. 146°C (hexane/ether)) and 5- bromo-2-chloro-4-aminopyridine (2.9 g, m. p. 1 17-119°C). Step B: Lithium bis(trimethylsilyl)amide (IM solution in THF, 5.1 ml) was added dropwise to a stiπed solution of 3-bromo-2-chloro-4-aminopyridine (1.04 g) in tetrahydrofuran (15 ml) at -78°C under N2. The resulting solution was then stirred at room temperature for 30 min., warmed to 0°C then cooled again at -78°C. 4-Chloromethyl-3,6- - dihydro-2H-pyridine-l -carboxylic acid tert-butyl ester (1.16 g, prepared according to WO 98/25605) dissolved in a minimum volume of THF was added dropwise then the solution was refluxed for 14 hours. The reaction mixture was cooled to room temperature, poured into diluted aqueous ammonium chloride, extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (CH2CI2 then CH2Cl2/EtOAc 8:2 cyclohexane:ethyl acetate 8:2) to afford 4-[(3-bromo-2-chloro-pyridin-4-ylamino)-methyl]-3,6-dihydro-2H- pyridine-1 -carboxylic acid tert-butyl ester (1.42 g), which was identified by its mass and IH NMR spectra. MS (ES+) 346/348/350 (MH+-isoprene), 402/404/406 (MH+). Step C: Lithium bis(trimethylsilyl)amide (IM solution in THF, 3 ml) was added dropwise to a stiπed solution of 4-[(3-Bromo-2-chloro-pyridin-4-ylamino)-methyl]-3,6- dihydro-2H-pyridine-l -carboxylic acid tert-butyl ester (0.53 g) in tetrahydrofuran (20ml) at -78°C under N2. The yellow solution was warmed to 0°C and then 2-chloroisonicotinoyl chloride (50% solution in toluene, 0.95 g) was added. The solution was stiπed at 0°C for 10 min., quenched by addition of aqueous ammonium chloride, extracted with EtOAc, dried (Na2SO ) and concentrated in vacuo. The residue was purified by silica gel chromatography (CH2C12 then CH2Cl2/EtOAc 8:2 cyclohexane:ethyl acetate 8:2) to afford 4-{[(3-bromo-2- chloro-pyridin-4-yl)-(2-chloro-pyridine-4-carbonyl)-amino] -methyl} -3, 6-dihydro-2H- pyridine-1 -carboxylic acid tert-butyl ester (0.63 g), which was identified by its mass and IH NMR spectra. MS (ES+) 443/445 (MH+-BOC), 484/486 (MH+-isoprene). Step D: In a dried, argon purged flask, 4-{[(3-bromo-2-chloro-pyridin-4-yl)-(2- chloro-pyridine-4-carbonyl)-amino]-methyl}-3,6-dihydro-2H-pyridine-l-carboxylic acid tert- butyl ester obtained in Step C (0.63 g) was dissolved in dimethylacetamide (10 ml); triethylamine (0.41 ml), tetrabutylammonium bromide (0.40 g) and palladium(II) acetate (40 mg) were successively added and the solution was heated at 90°C for 18 hours. After cooling to room temperature, the reaction mixture was diluted with diethyl ether, washed with brine, dried over sodium sulphate and concentrated in vacuo. Silica gel chromatography of the residue (cyclohexane:ethyl acetate 8:2) afforded l-(2-chloro-pyridine-4-carbonyl)-spiro[[(4- chloro-2,3-dihydro-lH-pyπOlo[3,2-c]pyridine)-3,4'-(l ',2',3',4'-tetrahydropyridine)]-r carboxylic acid tert-butyl ester (0.21 g), which was identified by its mass and IH NMR spectra. MS (ES+) 461/463 (MH+). Step E: l-(2-chloro-pyridine-4-carbonyl)-spiro[[(4-chloro-2,3-dihydro-lH- pyπolo[3,2-c]pyridine)-3,4'-(r,2',3',4'-tetrahydropyridine)]- carboxylic acid tert-butyl ester obtained in Step D (0.19 g) was dissolved in dichloromethane (13 ml) and treated successively with triethylsilane (0.33 ml) and trifluoroacetic acid (0.63 ml); the solution was stirred under argon for 8 hours, diluted with dichloromethane, neutralised with aqueous sodium bicarbonate, dried (sodium sulphate) and concentrated in vacuo. The residue was dissolved in acetonitrile (13 ml) and treated with diisopropylethylamine (0.12 ml) and 4- chlorocinnamyl chloride (84 mg) for 48 hours at room temperature. Standard aqueous work- up afforded a residue which was purified by flash chromatography (silica gel, cyclohexane: ethyl acetate 8:2+ 0.5 % triethylamine) to give the title product (43 mg) as a colourless solid. M.p. 95-96°C; MS (ES+) 513/515 (M+H+).
Compound Nos CDIII-49, CDIII-52, CDIII-53, CDV-49, CDV-52, DIII-3, DIII-210, DV-3, D V-213 and D V-214 were prepared by analogous methods to those of Example 5.
EXAMPLE 6 This Example illustrates the pesticidal/insecticidal properties of compounds of formula (I). Test against were performed as follows: Spodoptera littoralis (Egyptian cotton leafworm)
Cotton leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with 5 Li larvae. The samples were checked for mortality, repellent effect, feeding behaviour, and growth regulation 3 days after treatment (DAT). The following compounds gave at least 80% control of Spodoptera littoralis:
1-26, 1-30, 1-237, 11-26, 11-29, IΪ-30, 11-210, 11-213, 11-214, III-3, III-6, III-7, πi-26, 111-29, III- 30, III -210, lu -210 N-oxide, III-233, III-236, ffl-237, 111-302, ITI -325, III -328, m-329, V-26, V-29, V-30, V-209, V-210, V-213, V-214, V-233, V-236, V-237, V-509, VIII-26, Vm-29, VIII-30, VIII-210, VHI-213, XX-26, XX-29, XX-30, XX-210, XX-214, XX-233, XX-236, XX-237, Cffl-210, CIII-214, CCCDI-3, CCCIII-26, CCCV-3, CCCV-26, CCCVI-3, CDiπ-49, CDIII-52, CDHI-53, CDV-49, CDV-52 and DV-3.
Heliothis virescens ( Tobacco budworm):
Eggs (0-24 h old) were placed in 24-well microtiter plate on artificial diet and treated with test solutions at an application rate of 200 ppm by pipetting. After an incubation period of 4 days, samples were checked for egg mortality, larval mortality, and growth regulation. The following compounds gave at least 80% control of Heliothis virescens:
1-26, 1-29, 1-30, 1-210, 1-213, 1-214, 1-233, 1-237, 11-26, 11-29, 11-30, 11-210, 11-213, 11-214, III- 3, m-6, III-7, m-26, m-29, m-30, III -2IO, m -2IO N-oxide, in -213, III -214, ffl-233, III-236, III-237, IIΪ-302, πi -325, III -328, m -329, V-26, V-29, V-30, V-209, V-210, V-213, V-214, V-233, V-236, V-237, V-509, VI1I-26, Viπ-29, VIII-30, VIII-210, Vπi-213, VIII-214, XX-26, XX-29, XX-30, XX-210, XX-213, XX-214, XX-233, XX-236, XX-237, CIII-49, CIII-52, CII1-53, CIII-210, CIII-214, CIII-555, CCIII-3, CCIII-6, CCIII-7, CCCI-3, CCCm-3, CCCIII-26, CCCIII-29, CCCIII-30, CCCV-3, CCCV-26, CCCV-29, CCCV-30, CCCVI-3, CDIII-49, CDπi-52, CDIII-53, CDV-49, CDV-52, DI1I-3, DIII-210, DV-3, DCπi-3, DCIII-7, DCIII-52 and DCV-53.
Plutella xylostella (Diamond back moth):
24-well microtiter plate (MTP) with artificial diet was treated with test solutions at an application rate of 18.2 ppm by pipetting. After drying, the MTP's were infested with larvae
(L2)(10-15 per well). After an incubation period of 5 days, samples were checked for larval mortality, antifeedant and growth regulation. The following compounds gave at least 80% control of Plutella xylostella:
11-26, 11-29, 11-30, 11-210, 11-214, III-3, ITI-6, Iϋ-7, 111-26, 111-29, 111-30, III -210, III -210 N- oxide, m -213, III -214, 111-233, III-236, III-237, ffl-302, III -325, in -328, ffl -329, V-26, V-29, V-30, V-209, V-210, V-213, V-214, V-233, V-236, V-237, V-509, VIII-26, VIU-29, VIII-30, VIII-210, VIII-213, VIII-214, XX-26, XX-29, XX-30, XX-210, XX-213, XX-214, XX-233, XX-236, XX-237, CIII-49, CUI-52, CIII-53, CUI-210, CIII-214, Cπi-555, CCin-3, CCCIII-3, CCCIII-26, CCCni-29, CCCV-3, CCCV-26, CCCV-29, CCCV-30, CCCVI-3, CDIII-49, CDUI-52, CDUI-53, CDV-52, DV-3, DV-213, DV-214, DCIU-53 and DCV-53.
Myzus persicae (Green peach aphid):
Sunflower leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with an aphid population of mixed ages. After an incubation period of 6 DAT, samples were checked for mortality. The following compounds gave at least 80% control of Myzus persicae: III-3, III-7, V-213, VHI-29, CCCm-3, CCCV-3 and DCffl-3.
Aedes aegypti (Yellow fever mosquito):
10-15 Aedes larvae (L2) together with a nutrition mixture are placed in 96-well microtiter plates. Test solutions at an application rate of 2ppm are pipetted into the wells. 2 days later, insects were checked for mortality and growth inhibition. The following compounds gave at least 80% control of Aedes aegypt. i 1-26, 1-210, 1-213, 1-214, 1-233, 1-236, 1-237, H-26, π-29, U-30, π-210, 11-213, 11-214, III-3, ffl-6, III-7, ni-26, 111-29, 111-30, πi -210, III -2IO N-oxide, HI -213, m -214, iπ-233, πi-236, πi-237, III-302, in -325, III -328, m -329, V-26, V-29, V-30, V-210, V-213, V-214, V-236, V-237, V-509, Vπi-26, VIII-29, VUI-30, VUI-210, VHI-213, VIII-214, XX-26, XX-29, XX-30, XX-210, XX-213, XX-214, XX-233, XX-236, XX-237, CUI-52,' Cin-53, CIII-210, CIII-214, CCUI-3, CCIII-6, CCIII-7, CCCI-3, CCCIII-3, CCCIII-26, CCCV-3, CCCni-26, CCCVI-3, CDIII-49, CDIII-52, CDffl-53, CDV-49, CDV-52, DCIII-3, DCIII-6, DCIU-52, DCIII-53 and DCV-53.
Diabrotica balteata (Corn root worm ):
A 24-well microtiter plate (MTP) with artificial diet was treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After drying, the
MTP's were infested with larvae (L2) (6-10 per well). After an incubation period of 5 days, samples were checked for larval mortality, and growth regulation.
The following compounds gave at least 80% control of Diabrotica balteata :
11-29, U-30, 111-29, 111-30, III-213, πi-236, III-237, V-26, V-29, V-30, V-210, V-213, V-214, V-236, V-237, VI1I-29, VIII-30, XX-30, XX-237, CIII-52, CIII-210, CIII-214, CCCIII-29, CCCIII-30, CCCV-3, CCCV-26, CCCV-29, CCCV-30, CDni-49, CDIII-52, CDIII-53, CDV-49, CDV-52, DV-3, DV-210, DV-213, DCIII-6, DCffl-7 and DCV-53.

Claims

CLAΠVIS
1. A method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula I.
Figure imgf000164_0001
(I)
wherein Y is a single bond, C=O, C=S or S(O)m where m is 0, 1 or 2;
R1 is hydrogen, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocyclyloxy, cyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, formyl, optionally substituted heterocyclyl, optionally substituted alkylthio, NO or NR13R14 where R13 and R14 are independently hydrogen, COR15, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl or R13 and R14 together with the N atom to which they are attached form a group -N=C(RI 6)-NR17R18; R15 is H, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted aryloxy optionally substituted heteroaryl, optionally substituted heteroaryloxy or NR19R20; R16 , R17 and R18 are each independently H or lower alkyl; R19 and R20 are independently optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl;
R and R are independently hydrogen, halogen, cyano, optionally substituted alkyl, optionally substituted alkoxy or optionally substituted aryl; the ring
Figure imgf000165_0001
is a 5 or 6 membered heteroaromatic ring; each R4 is independently halogen, nitro, cyano, optionally substituted Cι-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C3-7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio or R21R22N where R21 and R22 are, independently, hydrogen, Cι-8 alkyl, C . cycloalkyl, C3-6 alkenyl, C3.6 alkynyl, C -7 cycloalkyl(Cι_ 4)alkyl, C2-6 haloalkyl, Cι-6 alkoxy(C]-6)alkyl, Cι-6 alkoxycarbonyl or R21 and R22 together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι-6 alkyl groups, or 2 adjacent groups R4 together with the carbon atoms to which they are attached form a 4, 5, 6,or 7 membered carbocyclic or heterocyclic ring which may be optionally substituted by halogen; n is 0, 1, 2 or 3; each Ra is independently hydrogen, halogen, hydroxy, cyano, optionally substituted Cι-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C - cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio, optionally substituted arylthio or R23R24N where R23 and R24 are, independently, hydrogen, Cι-8 alkyl, C3. cycloalkyl, C3.6 alkenyl, C3-6 alkynyl, C .7 cycloalkyl(Cι-4)alkyl, C2-6 haloalkyl, Cι- alkoxy(Cι-6)alkyl, Cι- alkoxycarbonyl or R23 and R24 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι_6 alkyl groups, or two Ra groups attached to the same carbon atom are =O or two Ra groups attached to adjacent carbon atoms form a bond, or two Ra groups together with the carbon atom to which they are attached form a three- to seven-membered ring, that may be saturated or unsaturated, and that may contain one or two hetero atoms selected from the group consisting of N, O and S, and which may be optionally substituted by one or two Cι-6 alkyl groups; or two Ra groups together form a group -CH2-, -CH=CH- or -CH2CH2; p is 0, 1 , 2, 3, 4, 5 or 6; q is 0, 1 , 2, 3, 4, 5 or 6 provided that p+q is 1 , 2, 3, 4, 5 or 6; R8 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl or optionally substituted alkenylcarbonyl; or salts or N-oxides thereof.
2. A method according to claim 1 wherein the ring
Figure imgf000166_0001
is a 5 or 6 membered heteroaromatic ring wherein the ring members are each independently CH, S, N, NR4, O, or CR4 provided that at least one ring member is other than CH or CR4 and that there are no more than one O or S atoms present in the ring.
3. A method according to claim 1 or claim 2 wherein Y is a single bond or C=O.
4. A method according to any preceeding claim wherein R and R are each independently hydrogen, Cι-6 alkyl, Cι_6 haloalkyl, Cι-6 alkoxy or cyano.
5. A method according to any preceeding claim wherein R1 is hydrogen, Cι-6 alkyl, Cι-6 cyanoalkyl, Cι-6 haloalkyl, C3- cycloalkyl(Cι_4)alkyl, Cι-6 alkoxy(Cι.6)alkyl, heteroaryl(Cι-6)alkyl (wherein the heteroaryl group may be optionally substituted by halo, nitro, cyano, Cι- alkyl, Cι-6 haloalkyl, Ci-6 alkoxy, C1-6 haloalkoxy, .6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι_6 alkylthio, Cι_6 alkoxycarbonyl, Cι_6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), aryl(Ci-6)alkyl (wherein the aryl group may be optionally substituted by halo, nitro, cyano, Cι_6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy, Cι_ 6 haloalkoxy, Cι-6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι-6 alkylthio, Cι-6 alkoxycarbonyl, Cι- alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the aryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), Cι_ alkylcarbonylamino(Cι-6)alkyl, aryl (which may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι- haloalkyl, C]-6 alkoxy, Cι-6 haloalkoxy, Cι-6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι-6 alkylthio, Cι_6 alkoxycarbonyl, Cι-6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the aryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), heteroaryl (which may be optionally substituted by halo, nitro, cyano, Cι_6 alkyl, Cι_6 haloalkyl, Cι-6 alkoxy, Cι-6 haloalkoxy, Cι-6 alkylsulfonyl, Cι-6 alkylsulfinyl, Cι-6 alkylthio, Cι-6 alkoxycarbonyl, Cι-6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), Cι-6 alkoxy, Cι-6 haloalkoxy, phenoxy (wherein the phenyl group is optionally substituted by halogen, Cι-4 alkyl, C]-4 alkoxy, Cι-4 haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryloxy (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι- alkoxy or Cι-6 haloalkoxy), heterocyclyloxy (optionally substituted by halo, C1 -6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or C].6 haloalkoxy), cyano, C2.6 alkenyl, C .6 alkynyl, C .6 cycloalkyl, C .7 cycloalkenyl, heterocyclyl (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι_6 haloalkoxy), Cι_6 alkylthio, Cι-6 haloalkylthio or NR13R14 where R13 and R14 are independently hydrogen, Cι-6 alkyl, C]-6 haloalkyl, Cι-6 alkoxy(Cι-6)alkyl, phenyl (which may be optionally substituted by halogen, C1 -4 alkyl, Cι-4 alkoxy, Cι-4 haloalkyl, Cι-4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino or C1- alkoxycarbonyl), phenyl (C].6)alkyl (wherein the phenyl group may be optionally substituted by halogen, C1 -4 alkyl, C alkoxy, C haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino, Cι_6 alkylsulfonyl, Cι-6 alkoxycarbonyl, or two adjacent positions on the phenyl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen), heteroaryl (Ci.6)alkyl (wherein the heteroaryl group may be optionally substituted by halo, nitro, cyano, Cι-6 alkyl, C1-6 haloalkyl, Cι-6 alkoxy, Cι_6 haloalkoxy, Cι -6 alkylsulfonyl, Cι_6 alkylsulfinyl, Cι_6 alkylthio, Cι.6 alkoxycarbonyl, Ci-6 alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen) or heteroaryl (which may be optionally substituted by halo, nitro, cyano, Cι_6 alkyl, Cι_6 haloalkyl, Cι-6 alkoxy or C1 -6 haloalkoxy, CM alkoxycarbonyl C1-6 alkylcarbonylamino, phenyloxycarbonylamino (wherein the phenyl group is optionally substituted by halogen, C] -4 alkyl, CM alkoxy, Cι-4 haloalkyl, C1- haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), amino, C].6 alkylamino or phenylamino (wherein the phenyl group is optionally substituted halogen, CM alkyl, C alkoxy, Cι-4 haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino)).
6. A method according to any preceeding claim wherein each R4 is independently halogen, cyano, Cι-8 alkyl, Ct.8 haloalkyl, Cι-6 cyanoalkyl, Cι-6 alkoxy(Cι-6)alkyl, C3.7 cycloalkyl(Cι-6)alkyl, C5.6 cycloalkenyl(Cι-6)alkyl, C3-6 alkenyloxy(Cι-6)alkyl, C3.6 alkynyloxy(C]-6)alkyl, aryloxy(Cι-6)alkyl, Cι-6 carboxyalkyl, Cι-6 alkylcarbonyl(Cι. 6)alkyl, C2-6 alkenylcarbonyl(Cι-6)alkyl, C -6 alkynylcarbonyl(Cι-6)-alkyl, Cι-6 alkoxycarbonyl(Cι-6)alkyl, C3.6 alkenyloxycarbonyl(Cι.6)alkyl, C -6 alkynyloxycarbonyl(Cι-ό)alkyl, aryloxycarbonyl(Cι- )alkyl, Ci-6 alkylthio(Cι_6)alkyl, C]. alkylsulfinyl(Ci_6)alkyl, Cι-6 alkylsulfonyl(Cι-6)alkyl, aminocarbonyl(Cι_6)alkyl, C i .(, alkylaminocarbonyl(C i .6)alkyl, di(C i _6)alkylaminocarbonyl(C ι .6)alkyl, phenyl(C].4)alkyl (wherein the phenyl group is optionally substituted by halogen, C alkyl, C alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl(Cι_4)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι.6 haloalkoxy), heterocyclyl(Cι-4)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy), C2-6 alkenyl, aminocarbonyl(C2-ό)alkenyl, Cι_6 alkylaminocarbonyl(C2- 6)alkenyl, di(Cι_6)alkylaminocarbonyl(C2-6)alkenyl, phenyl(C2-4)-alkenyl, (wherein the phenyl group is optionally substituted by halogen, C] -4 alkyl, CM alkoxy, .4 haloalkyl, C haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), C2-6 alkynyl, trimethylsilyl(C2-6)alkynyl, aminocarbonyl(C2-6)alkynyl, Cι-6 alkylaminocarbonyl(C2-6)alkynyl, di(C 1 -6)alkylaminocarbonyl(C2-6)alkynyl, C 1 _6 alkoxycarbonyl, C3. cycloalkyl, C3-7 halocycloalkyl, C3-7 cyanocycloalkyl, Cι-3 alkyl(C3-7)-cycloalkyl, Cι-3 alkyl(C .7)halocycloalkyl,phenyl (optionally substituted by halogen, C alkyl, C1-4 alkoxy, C1-4 haloalkyl, C] - haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl (optionally substituted by halo, nitro, cyano, C1-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy), heterocyclyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, C1-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι_6 haloalkoxy), or 2 adjacent groups R4 together with the carbon atoms to which they are attached form a 4, 5, 6 or 7 membered carbocylic or heterocyclic ring which may be optionally substituted by halogen, Cι. alkoxy, Cι.6 haloalkoxy, phenoxy (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι.6 haloalkoxy), heteroaryloxy (optionally substituted by halo, nitro, cyano, Cι-6 alkyl, Cι-6 haloalkyl, Cι-6 alkoxy or Cι-6 haloalkoxy), Cι-8 alkylthio or R19R20N where R19 and R20 are, independently, hydrogen, Cι-8 alkyl, C3. cycloalkyl, C3-6 alkenyl, C .6 alkynyl, C -6 haloalkyl, Cι-6 alkoxycarbonyl or R19 and R20 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι_6 alkyl groups; and n is 0, 1 , 2 or 3.
7. A method according to any preceeding claim wherein R is CMO alkyl, C O haloalkyl, aryl(Cι-6)alkyl (wherein the aryl group is optionally substituted by halogen, C alkyl, Cι-4 alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO , aryl, heteroaryl, amino or dialkylamino), heteroaryl(Cι_6)alkyl (wherein the heteroaryl group is optionally substituted by halogen, CM alkyl, C1-4 alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), arylcarbonyl-(Cι. 6)alkyl (wherein the aryl group may be optionally substituted by halogen, CM alkyl, CM alkoxy, C1-4 haloalkyl, Cι-4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino and the alkyl group may be optionally substituted by aryl), C2.8 alkenyl, C2-S haloalkenyl, aryl(C2-6)-alkenyl (wherein the aryl group is optionally substituted halogen, CM alkyl, Cι-4 alkoxy, CM haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino, Cι-6 alkoxycarbonyl, or two adjacent substituents can cyclise to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring), heteroaryl(C2-6)-alkenyl (wherein the heteroaryl group is optionally substituted halogen, CM alkyl, C1 -4 alkoxy, Cι- haloalkyl, C1-4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino, C1 -6 alkoxycarbonyl, or two adjacent substituents can cyclise to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring), C2-6 alkynyl, phenyl(C2-6)alkynyl (wherein the phenyl group is optionally substituted by halogen, C alkyl, C1 -4 alkoxy, C1 - haloalkyl, C1- haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), C .7 cycloalkyl, Cι-6 alkoxycarbonyl, Cι-6 alkylcarbonyl, Cι-6 haloalkylcarbonyl or aryl(C2- )alkenylcarbonyl (wherein the aryl group may be optionally substituted halogen, C1- alkyl, C alkoxy, C haloalkyl, CM haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), or -C(R51)(R52)- [CR53=CR 54]z-R55 where z is 1 or 2, R51 and R52 are each independently H, halo or C1-2 alkyl, R53 and R54 are each independently H, halogen, CM alkyl or Cι-4 haloalky and R55 is optionally substituted aryl or optionally substituted heteroaryl.
8. A method according to any preceeding claim wherein each Ra is hydrogen.
9. A method according to any preceeding claim wherein p is 1 or 2 and q is 2 or 3.
10. A compound of formula F
Figure imgf000171_0001
(i') wherein Y is C=O, C=S; R1 is hydrogen, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocyclyloxy, cyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, formyl, optionally substituted heterocyclyl, optionally 'substituted alkylthio, NO or NR13R14 where R13 and R14 are independently hydrogen, COR15, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl or R13 and R14 together with the N atom to which they are attached form a group -N=C(R16)-NR17R18; R15 is H, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted aryloxy optionally substituted heteroaryl, optionally substituted heteroaryloxy or NR19R20; R16 , R17 and R18 are each independently H or lower alkyl; R19 and R20 are independently optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; R2 and R3 are independently hydrogen, halogen, cyano, optionally substituted alkyl, optionally substituted alkoxy or optionally substituted aryl; the ring
Figure imgf000172_0001
is a 5 or 6 membered heteroaromatic ring; each R4 is independently halogen, nitro, cyano, optionally substituted Cι-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C .7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, 91 79 91 99 optionally substituted alkylthio or R R N where R and R are, independently, hydrogen, Cι-8 alkyl, C - cycloalkyl, C3-6 alkenyl, C -6 alkynyl, C -7 cycloalkyl(Cι- 4)alkyl, C2-6 haloalkyl, Cι-6 alkoxy(Cι-6)alkyl, Cι-6 alkoxycarbonyl or R21 and R22 together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι-6 alkyl groups, or 2 adjacent groups R4 together with the carbon atoms to which they are attached form a 4, 5, 6,or 7 membered carbocyclic or heterocyclic ring which may be optionally substituted by halogen; n is 0, 1, 2 or 3; each Ra is independently hydrogen, halogen, hydroxy, cyano, optionally substituted
C1-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted C3- cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio, optionally substituted arylthio or R23R24N where R23 and R are, independently, hydrogen, Cι-8 alkyl, C3- cycloalkyl, C3.6 alkenyl, C3.6 alkynyl, C -7 cycloalkyl(Cι.4)alkyl, C2-6 haloalkyl, Cι-6 alkoxy(Cι-6)alkyl, Cι-6 alkoxycarbonyl or R23 and R24 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Cι_6 alkyl groups, or two Ra groups attached to the same carbon atom are =O or two Ra groups attached to adjacent carbon atoms form a bond, or two Ra groups together with the carbon atom to which they are attached form a three- to seven-membered ring, that may be saturated or unsaturated, and that may contain one or two hetero atoms selected from the group consisting of N, O and S, and which may be optionally substituted by one or two C1 -6 alkyl groups; or two Ra groups together form a group -CH2-, -CH=CH- or -CH2CH2; p is 0, 1 , 2, 3, 4, 5 or 6; q is 0, 1 , 2, 3, 4, 5 or 6 provided that p+q is 1 , 2, 3, 4, 5 or 6; R is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl or optionally substituted alkenylcarbonyl; or salts or N-oxides thereof.
1 1. A compound of formula II
Figure imgf000173_0001
wherein R8 is H or tert-butoxycarbonyl and n, p, q, R1 , R2 , R3, R4 and Ra are as defined in claim 10.
12. An insecticidal acaricidal and nematicidal composition comprising an insecticidally, acaricidally or nematicidally effective amount of a compound of formula I as defined in claim 1.
PCT/IB2004/004083 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests WO2005061500A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
CA2547814A CA2547814C (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
AT04806330T ATE450538T1 (en) 2003-12-12 2004-12-09 SPIROPIPERIDINE DERIVATIVES FOR PEST CONTROL
NZ546995A NZ546995A (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
AP2006003672A AP2294A (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests.
AU2004303618A AU2004303618B2 (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
EA200601110A EA014114B1 (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
DE602004024443T DE602004024443D1 (en) 2003-12-12 2004-12-09 SPIROPIPERIDINE DERIVATIVES FOR COMBATING PESTS
US10/581,176 US7960401B2 (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
EP04806330A EP1694677B1 (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
BRPI0417544-1B1A BRPI0417544B1 (en) 2003-12-12 2004-12-09 Hetero-spiroindoline derivatives, composition and method for the control and control of insects, mites, nematodes or molluscs
JP2006543658A JP5015602B2 (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
CN2004800370075A CN1894249B (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests
IL175744A IL175744A (en) 2003-12-12 2006-05-18 Method for controlling pests using derivatives of piperidine, spirocondensed with pyrrolidine which is orthocondensed with heteroaromatic rings
KR1020067011568A KR101175119B1 (en) 2003-12-12 2006-06-12 Spiropiperidine Derivatives for Controlling Pests
HK07101863.5A HK1097829A1 (en) 2003-12-12 2007-02-15 Spiropiperidine derivatives for controlling pests

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0328905.5A GB0328905D0 (en) 2003-12-12 2003-12-12 Chemical compounds
GB0328905.5 2003-12-12

Publications (1)

Publication Number Publication Date
WO2005061500A1 true WO2005061500A1 (en) 2005-07-07

Family

ID=30130163

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2004/004083 WO2005061500A1 (en) 2003-12-12 2004-12-09 Spiropiperidine derivatives for controlling pests

Country Status (23)

Country Link
US (1) US7960401B2 (en)
EP (1) EP1694677B1 (en)
JP (1) JP5015602B2 (en)
KR (1) KR101175119B1 (en)
CN (3) CN1894249B (en)
AP (1) AP2294A (en)
AR (1) AR046880A1 (en)
AT (1) ATE450538T1 (en)
AU (1) AU2004303618B2 (en)
BR (1) BRPI0417544B1 (en)
CA (1) CA2547814C (en)
DE (1) DE602004024443D1 (en)
EA (1) EA014114B1 (en)
ES (1) ES2337693T3 (en)
GB (1) GB0328905D0 (en)
HK (1) HK1097829A1 (en)
IL (1) IL175744A (en)
MA (1) MA28285A1 (en)
NZ (1) NZ546995A (en)
TW (1) TWI343241B (en)
UA (1) UA87480C2 (en)
WO (1) WO2005061500A1 (en)
ZA (1) ZA200604644B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1716148A2 (en) 2003-12-23 2006-11-02 Arena Pharmaceuticals, Inc. Novel spiroindoline or spiroisoquinoline compounds, methods of use and compositions thereof
WO2015100232A3 (en) * 2013-12-24 2015-09-03 Zoetis Services Llc Spiroindoline antiparasitic derivatives
WO2016209635A1 (en) 2015-06-23 2016-12-29 Zoetis Services Llc Carboline antiparasitics

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8309603B2 (en) 2004-06-07 2012-11-13 University Of Tennessee Research Foundation SARMs and method of use thereof
GB0601402D0 (en) * 2006-01-24 2006-03-08 Syngenta Participations Ag Chemical Compounds
US9730908B2 (en) 2006-08-24 2017-08-15 University Of Tennessee Research Foundation SARMs and method of use thereof
US10010521B2 (en) 2006-08-24 2018-07-03 University Of Tennessee Research Foundation SARMs and method of use thereof
US9844528B2 (en) 2006-08-24 2017-12-19 University Of Tennessee Research Foundation SARMs and method of use thereof
EP3027616B1 (en) 2013-07-30 2018-01-10 Boehringer Ingelheim International GmbH Azaindole compounds as modulators of rorc
CN111269237B (en) * 2018-12-04 2022-05-24 南开大学 Gem-difluorinated spiro-gamma-lactam indoline compound, preparation method thereof and application thereof in preventing and treating plant diseases and insect pests

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995001358A1 (en) * 1993-07-02 1995-01-12 Bayer Aktiengesellschaft Substituted spiroheterocyclic 1h-3-arylpyrrolidine-2,4-dione derivatives, methods of preparing them and their use as pest-control agents
WO2000027845A1 (en) * 1998-11-10 2000-05-18 Merck & Co., Inc. Spiro-indolines as y5 receptor antagonists
WO2002094825A1 (en) * 2001-05-22 2002-11-28 Banyu Pharmaceutical Co., Ltd. Novel spiropiperidine derivative
WO2003106457A1 (en) * 2002-06-14 2003-12-24 Syngenta Limited Spiroindolinepiperidine derivatives

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0328907D0 (en) * 2003-12-12 2004-01-14 Syngenta Participations Ag Chemical compounds
GB0328908D0 (en) * 2003-12-12 2004-01-14 Syngenta Participations Ag Chemical compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995001358A1 (en) * 1993-07-02 1995-01-12 Bayer Aktiengesellschaft Substituted spiroheterocyclic 1h-3-arylpyrrolidine-2,4-dione derivatives, methods of preparing them and their use as pest-control agents
WO2000027845A1 (en) * 1998-11-10 2000-05-18 Merck & Co., Inc. Spiro-indolines as y5 receptor antagonists
WO2002094825A1 (en) * 2001-05-22 2002-11-28 Banyu Pharmaceutical Co., Ltd. Novel spiropiperidine derivative
WO2003106457A1 (en) * 2002-06-14 2003-12-24 Syngenta Limited Spiroindolinepiperidine derivatives

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CIGANEK: "Tertiary Carbinamines by Addition of Organocerium Reagents to Nitriles", J. ORG. CHEM., vol. 57, 1992, pages 4521 - 4527, XP002325113 *
GENIN ET AL.: "Design and synthesis of a conformationally constrained analog of the bis(heteroaryl)piperazine (BHAP) HIV-1 reverse transcriptase inhibitor atevirdine", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 5, no. 16, 1995, pages 1875 - 1880, XP002325114 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1716148A2 (en) 2003-12-23 2006-11-02 Arena Pharmaceuticals, Inc. Novel spiroindoline or spiroisoquinoline compounds, methods of use and compositions thereof
WO2015100232A3 (en) * 2013-12-24 2015-09-03 Zoetis Services Llc Spiroindoline antiparasitic derivatives
CN105829311A (en) * 2013-12-24 2016-08-03 硕腾服务有限责任公司 Spiroindoline antiparasitic derivatives
AU2014370025B2 (en) * 2013-12-24 2017-08-17 Zoetis Services Llc Spiroindoline antiparasitic derivatives
WO2016209635A1 (en) 2015-06-23 2016-12-29 Zoetis Services Llc Carboline antiparasitics
US10570129B2 (en) 2015-06-23 2020-02-25 Zoetis Services Llc Carboline antiparasitics
AU2016283538B2 (en) * 2015-06-23 2020-02-27 Zoetis Services Llc Carboline antiparasitics

Also Published As

Publication number Publication date
CN1894249B (en) 2011-06-15
US20070135408A1 (en) 2007-06-14
CN101544640A (en) 2009-09-30
EA014114B1 (en) 2010-10-29
CN1894249A (en) 2007-01-10
AP2006003672A0 (en) 2006-08-31
EA200601110A1 (en) 2006-12-29
JP5015602B2 (en) 2012-08-29
IL175744A0 (en) 2006-09-05
ES2337693T3 (en) 2010-04-28
IL175744A (en) 2012-06-28
ATE450538T1 (en) 2009-12-15
UA87480C2 (en) 2009-07-27
US7960401B2 (en) 2011-06-14
CN101940214A (en) 2011-01-12
AP2294A (en) 2011-10-31
EP1694677A1 (en) 2006-08-30
TW200528452A (en) 2005-09-01
MA28285A1 (en) 2006-11-01
DE602004024443D1 (en) 2010-01-14
BRPI0417544A (en) 2007-03-27
GB0328905D0 (en) 2004-01-14
CN101940214B (en) 2013-01-23
JP2007516972A (en) 2007-06-28
EP1694677B1 (en) 2009-12-02
BRPI0417544B1 (en) 2015-01-20
HK1097829A1 (en) 2007-07-06
ZA200604644B (en) 2007-11-28
CA2547814A1 (en) 2005-07-07
KR20060123308A (en) 2006-12-01
NZ546995A (en) 2010-07-30
KR101175119B1 (en) 2012-08-22
TWI343241B (en) 2011-06-11
CA2547814C (en) 2013-06-25
AU2004303618B2 (en) 2010-08-05
AU2004303618A1 (en) 2005-07-07
AR046880A1 (en) 2005-12-28

Similar Documents

Publication Publication Date Title
EP1515969B2 (en) Spiroindolinepiperidine derivatives
WO2005115146A1 (en) Piperazin derivatives and their use in controlling pests
EP1763302A2 (en) Chemical compounds
IL175744A (en) Method for controlling pests using derivatives of piperidine, spirocondensed with pyrrolidine which is orthocondensed with heteroaromatic rings
EP1694676A1 (en) Spiroindoline derivatives having insecticidal properties
EP2117310A2 (en) Chemical compounds
EP1979354A1 (en) Diaza-spiro-[4, 5]-decanes useful as pesticides
EP1732385A1 (en) Use of (3-(1-(3-phenyl-propenyl)-piperidin-4-yl)-2,3-dihydro-indol-1-yl)-(pyridin-4-yl)-methanone derivatives and related compounds as insecticides
EP1958508A1 (en) Phenoxymethyl imidazoline derivatives and their use as pesticides
WO2005061512A1 (en) Spiro-condensed indoline derivates as pesticides
WO2008098674A2 (en) Phenoxymethyl imidazoline derivatives and their use as pesticides
EP2207421B1 (en) Haloalkylsubstituted aryloxyalkylimidazolines for use as pesticides
WO2008009881A1 (en) Chemical compounds
WO2005058836A1 (en) Insecticidal spiroindane derivatives
WO2007072143A2 (en) Chemical compounds
WO2016012333A1 (en) Pesticidal compounds
WO2009036908A1 (en) Halosubstituted aryloxyalkylimidazolines for use as pesticides
MXPA06006212A (en) Spiropiperidine derivatives for controlling pests
EP2190823A1 (en) Halosubstituted aryloxyalkylimidazolines for use as pesticides
WO2007060541A2 (en) Piperazine derivatives and their use as insecticides, acaricides, molluscicides, and nematicides

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200480037007.5

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2004806330

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 12006500899

Country of ref document: PH

WWE Wipo information: entry into national phase

Ref document number: 546995

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 175744

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 2004303618

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2547814

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: PA/a/2006/006212

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2006/04644

Country of ref document: ZA

Ref document number: 200604644

Country of ref document: ZA

WWE Wipo information: entry into national phase

Ref document number: 2006543658

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 1020067011568

Country of ref document: KR

Ref document number: 2073/CHENP/2006

Country of ref document: IN

ENP Entry into the national phase

Ref document number: 2004303618

Country of ref document: AU

Date of ref document: 20041209

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 2004303618

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: AP/P/2006/003672

Country of ref document: AP

Ref document number: 200601110

Country of ref document: EA

WWE Wipo information: entry into national phase

Ref document number: 06066822

Country of ref document: CO

WWP Wipo information: published in national office

Ref document number: 2004806330

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1020067011568

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2007135408

Country of ref document: US

Ref document number: 10581176

Country of ref document: US

ENP Entry into the national phase

Ref document number: PI0417544

Country of ref document: BR

WWP Wipo information: published in national office

Ref document number: 10581176

Country of ref document: US