WO2013106254A1 - Pesticidal compositions and processes related thereto - Google Patents

Pesticidal compositions and processes related thereto Download PDF

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Publication number
WO2013106254A1
WO2013106254A1 PCT/US2013/020440 US2013020440W WO2013106254A1 WO 2013106254 A1 WO2013106254 A1 WO 2013106254A1 US 2013020440 W US2013020440 W US 2013020440W WO 2013106254 A1 WO2013106254 A1 WO 2013106254A1
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Prior art keywords
alkenyl
alkynyl
alkyl
phenyl
heterocyclyl
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PCT/US2013/020440
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French (fr)
Inventor
Mark A. Pobanz
William Hunter DENT
Zoltan L. Benko
W. Randal Erickson
Chaoxian Geng
Gerald B. Watson
Thomas C. Sparks
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Dow Agrosciences Llc
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Publication of WO2013106254A1 publication Critical patent/WO2013106254A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the invention disclosed in this document is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.
  • pesticides e.g., acaricides, insecticides, molluscicides, and nematicides
  • Alkenyl means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.
  • Alkenyloxy means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.
  • Alkoxy means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and ieri-butoxy.
  • Alkyl means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, (C3)alkyl which represents n-propyl and isopropyl), (C 4 )alkyl which represents n-butyl, sec-butyl, isobutyl, and ieri-butyl.
  • Alkynyl means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.
  • Alkynyloxy means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.
  • Aryl means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.
  • (C x -C y ) where the subscripts "x” and “y” are integers such as 1, 2, or 3, means the range of carbon atoms for a substituent - for example, (Ci-C 4 )alkyl means methyl, ethyl, n- propyl, isopropyl, n-butyl, sec -butyl, isobutyl, and ieri-butyl.
  • Cycloalkenyl means a monocyclic or polycyclic, unsaturated (at least one carbon- carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl,
  • Cycloalkenyloxy means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.
  • Cycloalkyl means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.
  • Cycloalkoxy means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and
  • Halo means fluoro, chloro, bromo, and iodo.
  • Haloalkoxy means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2- tetrafluoroethoxy, and pentafluoroethoxy.
  • Haloalkyl means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2- difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.
  • Heterocyclyl means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, that atom can be in other oxidation states such as a sulfoxide and sulfone.
  • aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzo thiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiadiazolyl, thiazolinyl, thiazolyl, thiazo
  • heterocyclyls examples include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, oxiranyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl.
  • partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro- oxazolyl, 4,5-dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[l,3,4]- oxadiazolyl. Additional examples include the following
  • (A2) X 2 is selected from N and CR
  • R 1 and R 2 are (each independently) selected from
  • each said phenyl and heterocyclyl in (e) and (f) of (Bl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Bl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Bl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Bl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Bl) may (each independently) be substituted with one or more substituents selected from
  • R 1 and R 2 along with N 1 can instead form a 5- or 6- membered ring, where said ring may be saturated or unsaturated, where the additional atoms in said ring (ring atoms) are selected from C, S, S(O), S(0) 2 , N, or O (provided that two oxygen atoms are not bonded to each other), and where each C or N ring atom that can have non-ring bonds is bonded to one or more of the following excluding N-F, N-Cl, N-Br and N-I
  • (B2) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e) and (f) of (B2) may (each independently) be substituted with one or more substituents selected from
  • R 3 and R 4 are (each independently) selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (h) of (CI) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e) and (f) of (CI) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Cl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Cl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (CI) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (CI) may (each independently) be substituted with one or more substituents selected from
  • R 5 and R 6 are (each independently) selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d), and (h) of (Dl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e) and (f) of (Dl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Dl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Dl) may (each independently) be substituted with one or more substituents selected from
  • (h4) (C 3 -C 8 )cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Dl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Dl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl in (a), (b), (c), and (h) of (El) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (d) and (e) of (El) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (El) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (El) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (El) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (El) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (g) of (Fl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e) and (f) of (Fl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Fl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Fl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Fl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d) and (g) of (Gl) may (each independently) be substituted with one or more substituents selected from (al) F, CI, Br, I, CN, N0 2 , OH, OSi((Ci-C 8 )alkyl) 3 ,
  • each said phenyl and heterocyclyl in (e) and (f) of (Gl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Gl) may (each independently) be substituted with one or more substituents selected from
  • each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Gl) may (each independently) be substituted with one or more substituents selected from
  • each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Gl) may (each independently) be substituted with one or more substituents selected from
  • Embodiment Al Formula One with items (A)-(G) are hereafter referred to as Embodiment Al.
  • R 3 is CF 3 ; where R 4 is (Ci-C 8 )alkyl or phenyl, where said alkyl and said phenyl may optionally be substituted with one or more of - F, CI, Br, and I; where R 4 is selected from one, or any combinations of more than one, of the following, - CF 2 CF 3 , CF 2 C1, CF 3 , CH(CH 3 ) 2 , CH 2 F, CH 3 , CHF 2 , and chlorophenyl; where R 4 is CF 3 ; where R 3 and R 4 are both CF 3 ; where R 7 is (Ci-C 8 )alkyl where said alkyl may optionally be substituted with one or more phenyls, where said phenyl may optionally be substituted with one or more of - F, CI, Br, I, and (Ci-C 8 )alkyl (which may optionally be substituted with one or more of
  • the preparation of the compounds of Formula V wherein R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos can be accomplished in two steps from the compounds of Formula II, such as 2,2,2-trifluoroacetamide, or in one step from commercially available substituted acetonitriles (compounds of Formula III).
  • step a of Scheme 1 the R 3 - substituted nitrile, a compound of Formula III, is generated in situ as in Parker, M. H. et al.
  • step c of Scheme I the butenoate (compound of Formula V) is added to a solution of lithium diisopropylamide in a polar, aprotic solvent, such as THF, at low temperature such as -78 °C.
  • a polar, aprotic solvent such as THF
  • the mixture is stirred at low temperature for about 1 hour (h) and then is treated at low temperature with the appropriate alkyl ester such as ethyl ester, a compound of Formula VI, to provide a compound of Formula Vila as prepared in Lee, L. F.
  • the acid of Formula Villa can be transformed into the amide of Formula FXa, wherein X 1 is CR 5 , X 2 is N, R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos and R 4 is as previously disclosed in embodiment Al, in two steps.
  • step e of Scheme 1 the acid chloride is formed by reaction with a chlorinating reagent such as thionyl chloride at reflux temperature, and then the acid chloride is converted to the amide of Formula IXa, wherein X 1 is CR 5 , X 2 is N and R 4 is as previously disclosed in embodiment Al, by treatment with ammonium hydroxide (NH 4 OH) in a non-reactive solvent such as dichloromethane (CH 2 CI 2 ) at approximately 25°C , as in step / of Scheme 1.
  • a chlorinating reagent such as thionyl chloride at reflux temperature
  • Conversion of the hydroxy group to the chloride in conjunction with dehydration of the amide to form the cyano group is effected using a chlorinating reagent such as phosphorus oxychloride in the absence or presence of a base, such as l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), at reflux temperature as is steps gi ox g 2 , respectively, of Scheme 1 to afford the compound of Formula Xa, wherein X 1 is CR 5 , X 2 is N, R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos and R 4 is as previously disclosed in embodiment Al.
  • a chlorinating reagent such as phosphorus oxychloride in the absence or presence of a base, such as l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), at reflux temperature as is steps gi ox g 2 , respectively, of Scheme 1
  • the acid of Formula VHIb can be transformed into the amide of Formula FXb, wherein X 1 is CR 5 , X 2 is N and R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos in two steps.
  • step e 2 of Scheme 2 the acid chloride is formed by reaction with a chlorinating reagent such as thionyl chloride at reflux temperature, and then the acid chloride is converted to the amide of Formula IXb, wherein X 1 is CR 5 , X 2 is N and R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos by treatment with NH4OH in a non-reactive solvent such as CH2CI2 at approximately 25°C, as in step f2 of Scheme 2.
  • a chlorinating reagent such as thionyl chloride at reflux temperature
  • Conversion of the hydroxy group to the chloride in conjunction with dehydration of the amide to form the cyano group is effected using a chlorinating reagent such as phosphorus oxychloride in the presence of a base, such as DBU, at reflux temperature as in step g2 of Scheme 2.
  • a chlorinating reagent such as phosphorus oxychloride
  • a base such as DBU
  • step h of Scheme 2 the methyl group in Formula Xb is removed with a demethylating reagent such as boron tribromide in a non-reactive solvent such as CH2CI2 at approximately 25°C to afford the hydroxymethyl compound of Formula Xc, wherein X 1 is CR 5 , X 2 is N and R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more of halos.
  • Fluorination of the compound of Formula Xc can be accomplished using a fluorinating reagent such as diethylaminosulfur trifluoride in a non-reactive solvent, such as CH2CI2, at lower temperature such as 0 °C to provide the compound of Formula Xd, wherein X 1 is CR 5 , X 2 is N and R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more of halos as in step i in Scheme 2.
  • a fluorinating reagent such as diethylaminosulfur trifluoride in a non-reactive solvent, such as CH2CI2, at lower temperature such as 0 °C to provide the compound of Formula Xd, wherein X 1 is CR 5 , X 2 is N and R 3 is a (Ci-Cs)alkyl substituted with at least 2 or more of halos as in step i in Scheme 2.
  • step j of Scheme 3 reaction of a compound of Formula XI, with 2-cyanoacetamide, in the presence of a base, such as diethylamine or piperidine, in a polar, protic solvent such as ethyl alcohol (EtOH), at a higher temperature such as 50 to 70 °C as in Narsaiah, B. et al. Org. Prep. Proced. Int. 1993, 25, 116-117, provides the compounds of Formula XIII.
  • a base such as diethylamine or piperidine
  • a polar, protic solvent such as ethyl alcohol (EtOH)
  • EtOH ethyl alcohol
  • the hydroxyl group in Formula XIII is converted to a chloride in one of three ways: (1) via reaction with phosphorus oxychloride as in step gi of Scheme 3; (2) by reaction with phosphorus oxychloride in the presence of a base such as N,N- diethylbenzeneamine as in step g 3 of Scheme 3; or (3) via reaction with phenylphosphonic dichloride as in step g4 of Scheme 3 to provide the compounds of Formula Xe .
  • the hydroxyl group in both Formula XV and Formula XVI can be converted to a chloride with concomitant amide dehydration to the nitrile in one of two ways: (1) by reaction with phosphorus oxychloride in the presence of a base such as N,N- diethylbenzeneamine as in step g 3 of Scheme 4; or (2) via reaction with phosphorus oxychloride in the presence of a base such as triethylamine as in step gs of Scheme 4 to provide the compounds of Formula Xe.
  • a base such as N,N- diethylbenzeneamine
  • a base such as triethylamine
  • step g of Scheme 5 the hydroxyl group in Formula XVIII is converted to a chloride via reaction with phosphorus oxychloride in a solvent such as acetonitrile at a temperature between 60 and 70 °C to provide the compounds of Formula Xf .
  • the molecules of Formula One are synthesized in one of six ways as shown in Scheme 6: (1) by reaction of the compounds of Formula Xa as disclosed in Scheme I, or Xd as disclosed in Scheme II with a hydrazine in the presence of a polar, protic solvent such as EtOH, at a higher temperature such as 80 °C, as in step m of Scheme 6; (2) by reaction of the compounds of Formula Xe, as disclosed in Schemes III and IV, with a hydrazine in the presence of a polar, protic solvent such as EtOH, and a base such as triethylamine, at a higher temperature such as 80 °C, as in step n of Scheme 6; (3) by reaction of the compounds of Formula Xe, as disclosed in Schemes III and IV, with a hydrazine in the presence of a polar, protic solvent such as n-butyl alcohol (n-BuOH) at a higher temperature such as between 80 and 90 °C, as in step o of Scheme 6; (4)
  • step s of Scheme 7 reaction of compounds of Formula One, with electrophiles, such as but not limited to, alkyl halides, anhydrides, acid chlorides, isocyanates, and isothiocyanates, in the presence of a base, such as triethylamine, diisopropylethylamine, pyridine, NW-dimethylpyridin-4-amine, potassium carbonate and potassium phosphate tribasic, in a polar, aprotic solvent such as acetonitrile, THF or CH2CI2, between approximately 25°C and 60 °C to provide compounds of Formula One, wherein R 1 and R 2 are as previously disclosed.
  • a base such as triethylamine, diisopropylethylamine, pyridine, NW-dimethylpyridin-4-amine, potassium carbonate and potassium phosphate tribasic
  • a polar, aprotic solvent such as acetonitrile, THF or CH2CI2, between approximately 25°C and 60
  • a three-neck flask was equipped with a thermometer and gas inlet tube.
  • the reaction vessel was charged with potassium ieri-butoxide (1.78 grams (g), 0.016 moles (mol)) and dry tetrahydrofuran (THF; 500 milliliters (mL).
  • Ethyl 3-oxobutanoate (69 g, 0.53 mol) was added dropwise. The mixture was allowed to stir at room temperature for 1 hour (h).
  • a second three-neck flask was fitted with a gas outlet tube connected to the first three-neck flask. The flask was charged with 2,2,2-trifluoroacetamide (90 g, 0.796 mol) and pyridine (400 mL).
  • Example 7 Using the procedure of Example 7 with 2-hydroxy-6-methyl-4- (trifluoromethyl)nicotinonitrile as the starting material, the product was isolated as a yellow oil (6.4 g, 58%): ] H NMR (300 MHz, CDC1 3 ) ⁇ 7.492 (s, 1H), 2.727 (s, 3H); 13 C NMR (75 MHz, CDCI 3 ) ⁇ 165.504, 154.358, 122.752, 119.008, 111.962, 104.325, 25.418; EIMS m/z 220.
  • the orange suspension was heated at 60 °C for 1 h and then cooled to 5 °C with an ice bath.
  • a solution of tin (II) chloride (3.16 g, 16.67 mmol) in hydrochloric acid (37%; 2.5 mL, 82 mmol) dropwise causing an exotherm and forming a thick white precipitate.
  • the precipitate was filtered over a fritted glass funnel, and the solid was transferred in portions to a mixture of ammonium hydroxide (NH 4 OH, 28% in H 2 0; 30 mL, 770 mmol) and ice (50 g).
  • the white suspension was stirred for 30 min and then diluted with Et 2 0 (300 mL).
  • Example 21 Preparation of a library of 4,6-bis(trifluoromethyl)-2H-pyrazolo[4,3-c]- and -[3,5-ft]-pyridin-3-amines
  • the hydrazines used include: (4-(trifluoromethyl)phenyl)hydrazine, (2,4- dichlorophenyl)hydrazine, (2-methoxyphenyl)hydrazine, (4-ieri-butylphenyl)hydrazine, p- tolylhydrazine, (4-(methylsulfonyl)phenyl)hydrazine, (2,6-dichlorophenyl)hydrazine, (4- chloro-2-methoxyphenyl)hydrazine, (4-chloro-2-methylphenyl)hydrazine, (2-chloro-4- methylphenyl)hydrazine, (2,6-dimethylphenyl)hydrazine, (2,6-dichloro-4- methylphenyl)hydrazine, (4-(trifluoromethoxy)phenyl)hydrazine, (2,6-dichloro-4- (methylsulfonyl)phenyl)hydr
  • the hydrazines used include: [2,6-dichloro-4-(pentafluoro- 6 - sulfanyl)phenyl]hydrazine (prepared as in Critcher, D. J. et al. WO 2005/090313), (2,3,5,6- tetrafluoro-4-(trifluoromethyl)phenyl)hydrazine, (2,6-dichloro-3,5-difluoro-4-
  • hydrochloride (2-(trifluoromethoxy)phenyl)hydrazine hydrochloride, (2,6- dimethylphenyl)hydrazine hydrochloride, (2,4,6-trichlorophenyl)hydrazine, (4-fluoro-2- (methylsulfonyl)phenyl)hydrazine, (4-(2,2,2-trifluoroethoxy)phenyl)hydrazine hydrochloride, 2-hydrazinyl-3-(trifluoromethyl)pyridine, (2,6-dichloro-4-
  • the hydrazines used include: (2-chlorophenyl)hydrazine hydrochloride, (4- (trifluoromethyl)phenyl)hydrazine, (2-chloro-4-(trifluoromethyl)phenyl)hydrazine, 3,6- dichloro-4-hydrazinylpyridazine.
  • Argonaut PS-CHO resin (1.08 mmol/g; 100- 120 mg, 0.108-0.130 mmol) was added to scavenge the remaining hydrazine. The samples were heated at 50 °C for 1 h. The liquid was removed by pipette and filtered into a plate.
  • the hydrazines used include: 3,6-dichloro-4-hydrazinylpyridazine, 2-hydrazinyl-5- phenyl-l,3,4-thiadiazole, 3,5-dichloro-2-hydrazinylpyridin-4-amine, 4-hydrazinyl- benzenesulfonamide, 2-hydrazinylpyrimidine, 3,5,6-trichloro-4-hydrazinylpicolinonitrile, 5- hydrazinyl-6-methyl-3-(methylthio)-l,2,4-triazine, 6-hydrazinyl-l,3-dimethylpyrimidine- 2,4(lH,3H)-dione, 2-chloro-4-hydrazinyl-5-methoxypyrimidine, (4-chlorophenyl)hydrazine, (2-methoxyphenyl)hydrazine, 2-hydrazinylpyridine.
  • TFA trifluoroacetic acid
  • the mixture was heated at reflux for 1 h. More TFA (3 mL) was added, and heating was continued for 90 min.
  • the mixture was concentrated in vacuo and diluted with CH 2 C1 2 (150 mL).
  • the organic layer was washed with brine (2 x 150 mL) and water (50 mL) mixed with satd aq sodium bicarbonate (NaHCC ⁇ ) solution.
  • NaHCC ⁇ sodium bicarbonate
  • the organic layer was dried (MgS0 4 ), filtered and concentrated to give a yellow solid residue.
  • the electrophiles (1-9 equiv) used include: iodoethane, 2-iodopropane,
  • Example 26 Using the procedure of Example 26 with 2-(2,6-dichloro-4-(pentafluoro- 6 - sulfanyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-J
  • reaction mixture was diluted with diethyl ether (Et 2 0; 150 mL) and washed with a mixture of satd aq NaCl (50 mL) and H 2 0 (50 mL). The combined aqueous layer was extracted with Et 2 0 (1 x 25 mL). The combined organic layer was dried with Na 2 S0 4 , filtered and concentrated in vacuo to give a viscous orange/yellow material.
  • Et 2 0 diethyl ether
  • Compound 215 in Table 1 was made in accordance with the procedures disclosed in Example 29.
  • Example 29 Using the procedure of Example 29 with 2-(2,6-dichloro-4-(pentafluoro- 6 - sulfanyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-(i]pyrimidin-3-amine as the starting material, the product was isolated as an orange solid (0.036 g, 22%): mp 176-180 °C; ] H NMR (400 MHz, DMSO- ) ⁇ 8.66 (s, 2H), 2.92 (s, 6H); ESIMS m/z 571.16 ([M+H] + ).
  • Electrophiles used in the above reaction 5-bromopentanenitrile, 5-bromopentan-l-ol, l-bromo-4-methoxybutane, 4-bromobut-l-ene, l-bromopent-2-yne.
  • Example 37 Preparation of V-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4- ⁇ /]pyrimidin-3-yl)- V-(3,3-dimethylbutanoyl)-3,3- dimethylbutanamide (Compound 237) and V-(2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-yl)- 3,3-dimethylbutanamide (Compound 238).
  • Example 38 Preparation of bis-2,2,2-trichloroethyl (2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3- yl)carbamate (Compound 239).
  • Hunig's base (96 ⁇ , 0.553 mmol) in THF (2.2 mL) was added dropwise 2,2,2-trichloroethyl carbonochloridate (38 ⁇ , 0.276 mmol), and the mixture was stirred at room temperature for 3 h. TLC analysis indicated mostly starting material. Another equivalent of Hunig's base and the chloroformate was added, and the mixture was heated at 50 °C for 3 h. The mixture was diluted with EtOAc (10 mL), and the organic layer was washed with H 2 0 and brine, dried (MgS0 4 ) and evaporated.
  • BIOASSAYS ON BEET ARMYWORM (“BAW”) AND CORN EARWORM (“CEW”) BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants.
  • CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants.
  • CEW is also known to be resistant to certain insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.
  • Bioassays on BAW were conducted using a 128-well diet tray assay, one to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 ⁇ g/cm 2 of the test compound (dissolved in 50 ⁇ of 90: 10 acetone- water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25 °C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in Table 3 in the column entitled "BAW Results" (See Table Section). BIOASSAYS ON CEW (Helicoverpa zed)
  • Bioassays on CEW were conducted using a 128-well diet tray assay.
  • One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 ⁇ g /cm 2 of the test compound (dissolved in 50 ⁇ L ⁇ of 90: 10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25 °C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in Table 3 in the column entitled "CEW Results" (See Table Section).
  • Example B Bio ASSAYS ON GREEN PEACH APHID ("GPA”) (Myzus persicae).
  • GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed resistance to many pesticides.
  • the seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application.
  • Test compounds (2 mg) were dissolved in 2 mL of acetone/methanol (1 : 1) solvent, forming stock solutions of 1000 ppm test compound.
  • the stock solutions were diluted 5X with 0.025% Tween 20 in H 2 0 to obtain the solution at 200 ppm test compound.
  • a hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff.
  • Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/methanol (1: 1) solvent. Treated plants were held in a holding room for three days at approximately 25 °C and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W.S. Abbott, "A Method of Computing the Effectiveness of an
  • Example C BIOASSAYS ON Yellow Fever Mosquito "YFM" (Aedes aegypti).
  • YFM prefers to feed on humans during the daytime and is most frequently found in or near human habitations.
  • YFM is a vector for transmitting several diseases. It is a mosquito that can spread the dengue fever and yellow fever viruses. Yellow fever is the second most dangerous mosquito-borne disease after malaria. Yellow fever is an acute viral hemorrhagic disease and up to 50% of severely affected persons without treatment will die from yellow fever. There are an estimated 200,000 cases of yellow fever, causing 30,000 deaths, worldwide each year. Dengue fever is a nasty, viral disease; it is sometimes called
  • Master plates containing 400 ⁇ g of a molecule dissolved in 100 ⁇ L of dimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used.
  • a master plate of assembled molecules contains 15 ⁇ L per well.
  • 135 ⁇ L of a 90: 10 watenacetone mixture is added to each well. This solvent addition is completed shortly before actual run time on the Sagian to minimize any molecules incompatibility or stability issues.
  • the Sagian robot is programmed to dispense 15 ⁇ L aspirations from the master plate into an empty 96- well shallow plate ("daughter" plate). There are 6 reps ("daughter" plates) created per master. The created daughter plates are then immediately infested with YFM larvae.
  • Molecules of Formula One may be formulated into pesticidally acceptable acid addition salts.
  • an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids.
  • an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesium.
  • a salt derivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a salt.
  • a free base may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate.
  • a pesticide such as 2,4-D, is made more water-soluble by converting it to its dimethylamine salt..
  • Molecules of Formula One may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as "solvates.” However, it is particularly desirable to form stable hydrates with water as the solvent.
  • Molecules of Formula One may be made into ester derivatives. These ester derivatives can then be applied in the same manner as the invention disclosed in this document is applied.
  • Molecules of Formula One may be made as various crystal polymorphs.
  • Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.
  • Molecules of Formula One may be made with different isotopes. Of particular importance are molecules having 2 H (also known as deuterium) in place of ] ⁇ . Molecules of Formula One may be made with different radionuclides. Of particular importance are molecules having 14 C.
  • Molecules of Formula One may exist as one or more stereoisomers. Thus, certain molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molecules disclosed in this document can exist as two or more isomers. The various isomers include geometric isomers, diastereomers, and enantiomers. Thus, the molecules disclosed in this document include geometric isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the present disclosure are drawn in only one geometric form for clarity, but are intended to represent all geometric forms of the molecule.
  • Molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties.
  • the molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists.
  • Examples of such compounds in the above groups that may be used with the Molecules of Formula One are - (3-ethoxypropyl)mercury bromide, 1 ,2-dichloropropane, 1,3- dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri- iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6- TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5- T-isobutyl, 2,4,5-
  • difenoconazole difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate,
  • dimethylvinphos dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, diprope
  • fenchlorphos fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop- butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop- potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin,
  • MAMA mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA- 2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA- olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-
  • methylneodecanamide metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, m
  • oxpoconazole oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide
  • Molecules of Formula One may also be used in combination (such as in a
  • biopesticide is used for microbial biological pest control agents that are applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and
  • Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents have also been controlled with microbial agents.
  • One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides.
  • Biological insecticides include products based on:
  • entomopathogenic nematodes e.g. Steinernema feltiae
  • entomopathogenic viruses e.g. Cydia pomonella granulo virus.
  • entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia.
  • Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the genetically modified organism.
  • the molecules of Formula One may be used with one or more biopesticides in the area of seed treatments and soil amendments.
  • the Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology -based control) products. Copping L.G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.
  • Molecules of Formula One may also be used in combination (such as in a
  • compositional mixture or a simultaneous or sequential application) with one or more of the following:
  • Molecules of Formula One may be used with certain active compounds to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the molecules of Formula One are the same, similar, or different.
  • modes of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs).
  • Formula One in a synergistic mixture with another compound are from about 10:1 to about 1:10, in another embodiment from about 5:1 to about 1:5, and in another embodiment from about 3:1, and in another embodiment about 1: 1.
  • pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra low volume solutions.
  • baits concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra low volume solutions.
  • Pesticides are applied most often as aqueous suspensions or emulsions prepared from concentrated formulations of such pesticides.
  • Such water-soluble, water- suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous suspensions.
  • Wettable powders which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants.
  • the concentration of the pesticide is usually from about 10% to about 90% by weight.
  • the carrier is usually selected from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates.
  • Effective surfactants comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed
  • naphthalenesulfonates naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.
  • Emulsifiable concentrates of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers.
  • Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha.
  • Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol.
  • Suitable emulsifiers for emulsifiable concentrates are selected from conventional anionic and non-ionic surfactants.
  • Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight.
  • Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.
  • Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil.
  • Granular compositions usually contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance.
  • Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm.
  • Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.
  • Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine. It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.
  • a suitable dusty agricultural carrier such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine. It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.
  • Pesticides can also be applied in the form of an aerosol composition.
  • the pesticide is dissolved or dispersed in a carrier, which is a pressure- generating propellant mixture.
  • the aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.
  • Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.
  • Fumigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces.
  • the toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest' s respiratory system or being absorbed through the pest's cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in special chambers.
  • Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.
  • Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the pesticide in solution.
  • Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide.
  • Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.
  • Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non- ionic hydrophilic surface-active agent and (3) at least one ionic surface- active agent, wherein the globules having a mean particle diameter of less than 800 nanometers.
  • such formulation can also contain other components.
  • these components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.
  • a wetting agent is a substance that when added to a liquid increases the spreading or penetration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading.
  • Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrates for soluble liquids or suspension concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable powders and to improve the penetration of water into water-dispersible granules.
  • wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.
  • a dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from
  • Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates.
  • dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.
  • An emulsifying agent is a substance which stabilizes a suspension of droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases.
  • the most commonly used emulsifier blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil- soluble calcium salt of dodecylbenzenesulfonic acid.
  • a range of hydrophile-lipophile balance (“HLB”) values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.
  • a solubilizing agent is a surfactant which will form micelles in water at
  • the micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobic part of the micelle.
  • the types of surfactants usually used for solubilization are non- ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.
  • Surfactants are sometimes used, either alone or with other additives such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target.
  • the types of surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.
  • a carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength.
  • Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and water- dispersible granules.
  • Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil- in-water emulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used.
  • the first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins.
  • the second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and CIO aromatic solvents.
  • Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power.
  • Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.
  • Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed particles or droplets.
  • Thickening, gelling, and anti-settling agents generally fall into two categories, namely water- insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and attapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic derivatives of cellulose.
  • guar gum examples include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC).
  • SCMC carboxymethyl cellulose
  • HEC hydroxyethyl cellulose
  • Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.
  • Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p- hydroxybenzoate; and l,2-benzisothiazolin-3-one (BIT).
  • anti-foam agents are often added either during the production stage or before filling into bottles.
  • silicones are usually aqueous emulsions of dimethyl polysiloxane
  • non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica.
  • the function of the anti-foam agent is to displace the surfactant from the air-water interface.
  • Green agents ⁇ e.g., adjuvants, surfactants, solvents
  • Green agents can reduce the overall environmental footprint of crop protection formulations.
  • Green agents are biodegradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources. Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides.
  • the molecules of Formula One may be used to control pests e.g. beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
  • pests e.g. beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
  • the molecules of Formula One may be used to control pests in the Phyla Nematoda and/or Arthropoda.
  • the molecules of Formula One may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.
  • the molecules of Formula One may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta. In another embodiment, the molecules of Formula One may be used to control pests of the Order Anoplura.
  • a non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp.
  • a non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.
  • the molecules of Formula One may be used to control pests in the Order Coleoptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spppp
  • a non-exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius,
  • Sitophilus granarius Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.
  • the molecules of Formula One may be used to control pests of the Order Dermaptera. In another embodiment, the molecules of Formula One may be used to control pests of the Order Blattaria.
  • a non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.
  • the molecules of Formula One may be used to control pests of the Order Diptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp.
  • a non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum,
  • the molecules of Formula One may be used to control pests of the Order Hemiptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp.,
  • a non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri,
  • the molecules of Formula One may be used to control pests of the Order Hymenoptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp.
  • a non-exhaustive list of particular species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.
  • the molecules of Formula One may be used to control pests of the Order Isoptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp.,
  • Procornitermes spp. Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp.
  • a non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus,
  • Microtermes obesi Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.
  • the molecules of Formula One may be used to control pests of the Order Lepidoptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp.,
  • a non-exhaustive list of particular species includes, but is not limited to, Achaeajanata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Co
  • Helicoverpa zea Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae,
  • Maruca testulalis Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu,
  • the molecules of Formula One may be used to control pests of the Order Mallophaga.
  • a non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp.
  • a non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.
  • the molecules of Formula One may be used to control pests of the Order Orthoptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., and Pterophylla spp.
  • a non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.
  • the molecules of Formula One may be used to control pests of the Order Siphonaptera.
  • a non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis,
  • the molecules of Formula One may be used to control pests of the Order Thysanoptera.
  • a non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp.
  • a non- exhaustive list of particular sp. includes, but is not limited to, Frankliniella fusca,
  • Frankliniella occidentalis Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips t abaci.
  • the molecules of Formula One may be used to control pests of the Order Thysanura.
  • a non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Thermobia spp.
  • the molecules of Formula One may be used to control pests of the Order Acarina.
  • a non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp.
  • a non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus Desendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus lotus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.
  • the molecules of Formula One may be used to control pest of the Order Symphyla.
  • a non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.
  • the molecules of Formula One may be used to control pests of the Phylum Nematoda.
  • a non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp.
  • Aphelenchoides spp. Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp.
  • Molecules of Formula One are generally used in amounts from about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.
  • the area to which a molecule of Formula One is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder species, vines, turf and ornamental plants, are growing; where domesticated animals are residing; the interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used in building (such as impregnated wood), and the soil around buildings.
  • Particular crop areas to use a molecule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use ammonium sulfate with a molecule of Formula One when growing various plants. Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area.
  • pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area.
  • pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent.
  • the area is not in or on a human; consequently, the locus is generally a non-human area.
  • the molecules of Formula One may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions).
  • Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1- methylcyclopropene (also known as 1-MCP).
  • 1-MCP 1- methylcyclopropene
  • such molecules may be used during times when pest activity is low, such as before the plants that are growing begin to produce valuable agricultural commodities. Such times include the early planting season when pest pressure is usually low.
  • the molecules of Formula One can be applied to the foliar and fruiting portions of plants to control pests.
  • the molecules will either come in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide.
  • the molecules of Formula One can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled.
  • the roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.
  • Baits are placed in the ground where, for example, termites can come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with, and/or be attracted to, the bait. Baits can comprise a molecule of Formula One.
  • the molecules of Formula One can be encapsulated inside, or placed on the surface of a capsule.
  • the size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).
  • Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the molecules of Formula One to a different portion of the plant.
  • control of foliar- feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.
  • Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized traits will germinate.
  • Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as "Roundup Ready” seed, or those with "stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other beneficial traits.
  • such seed treatments with the molecules of Formula One may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time.
  • about 1 gram of the molecules of Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits, amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.
  • the molecules of Formula One may be used on, in, or around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition- enhancement, or any other beneficial traits.
  • specialized traits such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition- enhancement, or any other beneficial traits.
  • the molecules of Formula One may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping.
  • the molecules of Formula One are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.
  • the molecules of Formula One may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animals.
  • Suitable formulations are administered orally to the animals with the drinking water or feed. The dosages and formulations that are suitable depend on the species.
  • the molecules of Formula One may also be used for controlling parasitic worms, especially of the intestine, in the animals listed above.
  • the molecules of Formula One may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.
  • Pests around the world have been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment.
  • the molecules of Formula One may also be used on such new invasive species to control them in such new environment.
  • the molecules of Formula One may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants.
  • the use of such molecules in such area is to benefit the plants being grown in the area.
  • Such benefits may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients), improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.
  • a molecule according to Formula One can be tested to determine its efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties.
  • the headings in this document are for convenience only and must not be used to interpret any portion hereof.

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Abstract

This document discloses pesticidal compositions comprising molecules having the following formula ("Formula One"): and processes related thereto.

Description

PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
FIELD OF THE INVENTION
The invention disclosed in this document is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.
BACKGROUND
Pests cause millions of human deaths around the world each year. Furthermore, there are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year.
Termites cause damage to all kinds of private and public structures. The world-wide termite damage losses amount to billions of U.S. dollars each year.
Stored food pests eat and adulterate stored food. The world-wide stored food losses amount to billions of U.S. dollars each year, but more importantly, deprive people of needed food.
There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The development of resistance to some of the older pesticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pesticides.
Therefore, for many reasons, including the above reasons, a need exists for new pesticides. DEFINITIONS
The examples given in the definitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical bonding rules and steric compatibility constraints in relation to the particular molecule to which it is attached.
"Alkenyl" means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl. "Alkenyloxy" means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.
"Alkoxy" means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and ieri-butoxy.
"Alkyl" means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, (C3)alkyl which represents n-propyl and isopropyl), (C4)alkyl which represents n-butyl, sec-butyl, isobutyl, and ieri-butyl.
"Alkynyl" means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.
"Alkynyloxy" means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.
"Aryl" means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.
"(Cx-Cy)" where the subscripts "x" and "y" are integers such as 1, 2, or 3, means the range of carbon atoms for a substituent - for example, (Ci-C4)alkyl means methyl, ethyl, n- propyl, isopropyl, n-butyl, sec -butyl, isobutyl, and ieri-butyl.
"Cycloalkenyl" means a monocyclic or polycyclic, unsaturated (at least one carbon- carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl,
tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.
"Cycloalkenyloxy" means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.
"Cycloalkyl" means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.
"Cycloalkoxy" means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and
bicyclo[2.2.2]octyloxy.
"Halo" means fluoro, chloro, bromo, and iodo.
"Haloalkoxy" means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2- tetrafluoroethoxy, and pentafluoroethoxy.
"Haloalkyl" means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2- difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.
"Heterocyclyl" means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, that atom can be in other oxidation states such as a sulfoxide and sulfone. Examples of aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzo thiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiadiazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, oxiranyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro- oxazolyl, 4,5-dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[l,3,4]- oxadiazolyl. Additional examples include the following
Figure imgf000004_0001
thietanyl thietanyl-dioxide.
DETAILED DESCRIPTION
This document discloses molecules having the following formula ("Formula One"):
Figure imgf000005_0001
wherein
(A) (Al) X1 is selected from N and CR
(A2) X2 is selected from N and CR
(B) (Bl) R1 and R2 are (each independently) selected from
(a) H, OH, SH,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000005_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl,
C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C3- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, S- heterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g) N(R8)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, OC(=0)N(R9)2,
SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, and
(h) C3-C8 cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d), and (h) of (Bl) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(bl)
Figure imgf000006_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a2) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000006_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b3)
Figure imgf000007_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, (h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a4) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000008_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000008_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000009_0001
C8)alkyl, S(0)(CrC8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl, (B2) optionally R1 and R2 along with N1 can instead form a 5- or 6- membered ring, where said ring may be saturated or unsaturated, where the additional atoms in said ring (ring atoms) are selected from C, S, S(O), S(0)2, N, or O (provided that two oxygen atoms are not bonded to each other), and where each C or N ring atom that can have non-ring bonds is bonded to one or more of the following excluding N-F, N-Cl, N-Br and N-I
(a) H, F, CI, Br, I, CN, N02, OH, SH, (=0),
(b) (C C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000010_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl,
C(=S)0(C3-C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl,
Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g) N(R8)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), and (d) of
(B2) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000010_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (B2) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000011_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl, (C) (CI) R3 and R4 are (each independently) selected from
(a) H, F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000012_0001
C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2- C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl,
(d) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C3-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, S(C3-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2- C8)alkynyl, OC(=0)0(C3-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C3-C8)alkenyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl,
(g) N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=S)N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (h) of (CI) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000012_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (CI) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000013_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Cl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b3)
Figure imgf000014_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Cl) may (each independently) be substituted with one or more substituents selected from
(a4) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000014_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (CI) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000015_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(d-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and (h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (CI) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000016_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl,
(D) (Dl) R5 and R6 are (each independently) selected from
(a) H, F, CI, Br, I, CN, OH, OSi((C C8)alkyl)3,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000016_0002
C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-
C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, (d) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C3- C8)alkynyl, OC(=0)(C2-C8)alkynyl, S(C3-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2- C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl,
(g) N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=S)N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d), and (h) of (Dl) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000017_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and (hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000018_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b3)
Figure imgf000018_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a4) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000019_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b5)
Figure imgf000020_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000020_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl,
(E) (El) R7 is selected from
(a) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, S(0)(C
C8)alkyl, S(0)2(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl,
(b) (C3-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, (0)(C2- C8)alkenyl, S(0)2(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl,
(c) (C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C2-C8)alkynyl,
(d) phenyl, C(=0)phenyl, C(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, S(0)phenyl, S(0)2phenyl,
(e) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(f) C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (a), (b), (c), and (h) of (El) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3, (bl)
Figure imgf000022_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (d) and (e) of (El) may (each independently) be substituted with one or more substituents selected from
(a2) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (C C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000022_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-
C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, (f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (El) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b3)
Figure imgf000023_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (El) may (each independently) be substituted with one or more substituents selected from
(a4) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3, (b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000024_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (El) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000024_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, (f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (El) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000025_0001
C8)alkyl, S(0)(CrC8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl, (F) (Fl) R8 (each independently) is selected from
(a) H, CN, OH, (b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, C(=0)NH(C
C8)alkyl, C(=S)NH(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, C(=0)NH(C2- C8)alkenyl, C(=S)NH(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(0)(C2-
C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, C(=0)NH(C2- C8)alkynyl, C(=S)NH(C2-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(0)(C3- C8)alkynyl, S(0)2(C3-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, C(=0)NHphenyl, C(=S)NHphenyl,
C(=S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)2phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, C(=0)NH- heterocyclyl, C(=S)NH-heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl,
S(0)heterocyclyl, S(0)2heterocyclyl, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (g) of (Fl) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000026_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMd-CgJalkyl
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl, (gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (C C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000027_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b3)
Figure imgf000027_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl, (c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a4) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000028_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl, (g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3),
(c4), (d3), (d4), (h3), and (h4) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000029_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl,
OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000029_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl, (c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl,
C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl;
(G) (Gl) R9 (each independently) is selected from
(a) H, CN, OH, OSi((Ci-C8)alkyl)3,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000030_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C3- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl,
C(=S)0(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C2-C8)alkynyl, 0(C3-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(0)(C3-C8)alkynyl, S(0)2(C3-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, C(=S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)2phenyl
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl,
S(0)2heterocyclyl, and
(g) (C3-C8)cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d) and (g) of (Gl) may (each independently) be substituted with one or more substituents selected from (al) F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(bl)
Figure imgf000031_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2- C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2- C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-
C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a2) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl, OC(=0)(C C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl , S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl, (e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b3)
Figure imgf000032_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2- C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2- C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2- C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Gl) may
(each independently) be substituted with one or more substituents selected from
(a4) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3, (b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000033_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2,
ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5) C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl, OC(=0)(C
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-
C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2- C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2- C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, (f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000034_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl.
Formula One with items (A)-(G) are hereafter referred to as Embodiment Al. Some other embodiments of this invention are: where R1 and R2 are independently selected from one, or any combinations of more than one, of the following, - (C C8)alkyl, (C2-C8)alkenyl, (Ci-C8)alkylS(C C8)alkyl, (C2-C8)alkynyl, (Ci-C8)alkylO(C C8)alkyl, (C C8)alkylOC(=0)(Ci-C8)alkyl, (C
C8)alkylOH, (Ci-C8)alkylOSi((Ci-C8)alkyl)3, C(=0)(C C8)alkyl, C(=0)N(R8)2, C(=0)0(C C8)alkyl, C(=0)0(C C8)substituted alkyl, (Ci-C8)alkyl(C3-C8)cycloalkyl, (C C8)alkyl(C3- C8)substituted cycloalkyl, (Ci-C8)alkyl(substituted phenyl), H, and 0(Ci-C8)substituted alkyl; where R1 and R2 are independently selected from one, or any combinations of more than one, of the following, - (CH2)2C(CH3)3, (CH2)2CH=CH2, (CH2)2SCH3, (CH2)4C≡CH, (CH2)4CH3, (CH2)4OCH3, (CH2)5OC(=0)CH3, (CH2)5OH, (CH2)5OSi(CH3)2(C(CH3)3), C(=0)(CH2)3CH3, C(=0)CH3, C(=0)N(H)(C(=0)CC13), C(=0)NH2, C(=0)OC(CH3)3, C(=0)0CH2CC13, C(=0)OCH3, CH(CH3)2, CH2C≡CCH2CH3, CH2CH3, CH2-cyclopentyl, CH2-cyclopropyl, CH2-halocyclopropyl, CH2-halomethylphenyl, CH2-halophenyl, CH3, and H; where R1 and R2 are the same; where R1 and R2 are different; where R3 is (Ci-C8)alkyl, which may optionally be substituted with one or more
F, CI, Br, and I; where R3 is CF3; where R4 is (Ci-C8)alkyl or phenyl, where said alkyl and said phenyl may optionally be substituted with one or more of - F, CI, Br, and I; where R4 is selected from one, or any combinations of more than one, of the following, - CF2CF3, CF2C1, CF3, CH(CH3)2, CH2F, CH3, CHF2, and chlorophenyl; where R4 is CF3; where R3 and R4 are both CF3; where R7 is (Ci-C8)alkyl where said alkyl may optionally be substituted with one or more phenyls, where said phenyl may optionally be substituted with one or more of - F, CI, Br, I, and (Ci-C8)alkyl (which may optionally be substituted with one or more of - F, CI, Br, and I); where R7 is a phenyl, where said phenyl may optionally be substituted with one or more of - F, CI, Br, I, N02, (C C8)alkyl, S(0)2(C C8)alkyl, 0(C C8)alkyl, halothio, S(0)2N(R8)2, and Ophenyl, where each of said alkyls may optionally be substituted with one or more of - F, CI, Br, and I; where R7 is a heterocyclyl selected from one, or any combinations of more than one, of the following, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, oxiranyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[l,3,4]-oxadiazolyl, thietanyl, and thietanyl-dioxide. where R7 is a heterocyclyl selected from one, or any combinations of more than one, of the following, - pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrazolyl, imidazolyl, thienyl, quinolinyl, and thiadiazolyl, where said heterocyclyls may optionally be substituted with one or more of - F, CI, Br, I, CN, 0=, (C C8)alkyl, 0(C C8)alkyl, N(R8)2, and phenyl, where each of said alkyls may optionally be substituted with one or more of - F, CI, Br, and I; where R7 is a phenyl that has one or more substituents, where said substituent are selected from one, or any combinations of more than one, of the following, - C(CH3)3, CF3, CH2CH3, CH3, OCH3, F, CI, Br, I, S(0)2CH3, OCF3, SCF3, SF5, N02, OCH2CF3, Ophenyl, and S(0)2CF3; where R7 is selected from one, or any combinations of more than one, of the following, - pyridyl, pyrimidinyl, pyridazinyl, triazinyl, quinolinyl, and thiadiazolyl, each of which may optionally be substituted, where said substituents are selected from one, or any combinations of more than one, of the following, - CF3, CCI3, N¾, CN, CH3, OCH3, 0=, F, CI, Br, I, SCH3, and phenyl; and where R7 is (C]-C8)alkyl, aryl, or heterocyclyl and where R7 has 1, 2, 3, 4, or 5 substituents. The molecules of Formula One will generally have a molecular mass of about 100
Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass is from about 120 Daltons to about 900 Daltons, and it is even more generally preferred if the molecular mass is from about 140 Daltons to about 600 Daltons. The preparation of the compounds of Formula V wherein R3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos can be accomplished in two steps from the compounds of Formula II, such as 2,2,2-trifluoroacetamide, or in one step from commercially available substituted acetonitriles (compounds of Formula III). In step a of Scheme 1, the R3- substituted nitrile, a compound of Formula III, is generated in situ as in Parker, M. H. et al. Synth. Commun. 2004, 34, 903-907 by treatment of the R3-substituted amide, a compound of Formula II, with a pre-mixed solution of trifluoroacetic anhydride and pyridine in a solvent such as pyridine at approximately 25°C. The R3-substituted acetonitrile (compound of Formula III) is added directly to a solution of ethyl 3-oxobutanoate (compound of Formula IV) and a base, such as potassium ieri-butoxide, in a polar, aprotic solvent such as tetrahydrofuran (THF), at approximately 25°C to provide the butenoate (compound of
Formula V) as in Lee, L. F. et al. EP 0182769 Al, May 28, 1986, and step b of Scheme 1. In step c of Scheme I, the butenoate (compound of Formula V) is added to a solution of lithium diisopropylamide in a polar, aprotic solvent, such as THF, at low temperature such as -78 °C. The mixture is stirred at low temperature for about 1 hour (h) and then is treated at low temperature with the appropriate alkyl ester such as ethyl ester, a compound of Formula VI, to provide a compound of Formula Vila as prepared in Lee, L. F. et al., EP 0182769 Al, May 28, 1986 wherein X1 is CR5, X2 is N, R3 is a (C C8)alkyl substituted with at least 2 or more halos. Saponification of the ester is accomplished with a base, such as sodium hydroxide (NaOH), in a polar, protic solvent, such as methyl alcohol (CH3OH) at a higher temperature such as 40 °C to afford the acid of Formula Villa, wherein X1 is CR5, X2 is N. R3 is a (C Cs)alkyl substituted with at least 2 or more halos and R4 is as previously disclosed in embodiment Al as in step di of Scheme 1. The acid of Formula Villa can be transformed into the amide of Formula FXa, wherein X1 is CR5, X2 is N, R3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos and R4 is as previously disclosed in embodiment Al, in two steps. In step e of Scheme 1 , the acid chloride is formed by reaction with a chlorinating reagent such as thionyl chloride at reflux temperature, and then the acid chloride is converted to the amide of Formula IXa, wherein X1 is CR5, X2 is N and R4 is as previously disclosed in embodiment Al, by treatment with ammonium hydroxide (NH4OH) in a non-reactive solvent such as dichloromethane (CH2CI2) at approximately 25°C , as in step / of Scheme 1. Conversion of the hydroxy group to the chloride in conjunction with dehydration of the amide to form the cyano group is effected using a chlorinating reagent such as phosphorus oxychloride in the absence or presence of a base, such as l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), at reflux temperature as is steps gi ox g2, respectively, of Scheme 1 to afford the compound of Formula Xa, wherein X1 is CR5, X2 is N, R3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos and R4 is as previously disclosed in embodiment Al.
Scheme 1
Figure imgf000038_0001
II III IV V
Figure imgf000038_0002
VI Vila Villa
Figure imgf000038_0003
IXa Xa In the case wherein R4 = a mono halo alkyl such as C¾F, of Formula Vila, saponification of the ester is accomplished with a base, such as NaOH, in a polar, protic solvent, such as CH3OH, at a higher temperature such as 40 °C, to afford the acid of Formula VHIb, wherein X1 is CR5, X2 is N and R3 is a (Ci-Cs)alkyl substituted with at least 2 or more of halos, as in step <¾ of Scheme 2. The acid of Formula VHIb can be transformed into the amide of Formula FXb, wherein X1 is CR5, X2 is N and R3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos in two steps. In step e2 of Scheme 2, the acid chloride is formed by reaction with a chlorinating reagent such as thionyl chloride at reflux temperature, and then the acid chloride is converted to the amide of Formula IXb, wherein X1 is CR5, X2 is N and R3 is a (Ci-Cs)alkyl substituted with at least 2 or more halos by treatment with NH4OH in a non-reactive solvent such as CH2CI2 at approximately 25°C, as in step f2 of Scheme 2.
Conversion of the hydroxy group to the chloride in conjunction with dehydration of the amide to form the cyano group is effected using a chlorinating reagent such as phosphorus oxychloride in the presence of a base, such as DBU, at reflux temperature as in step g2 of Scheme 2. In step h of Scheme 2, the methyl group in Formula Xb is removed with a demethylating reagent such as boron tribromide in a non-reactive solvent such as CH2CI2 at approximately 25°C to afford the hydroxymethyl compound of Formula Xc, wherein X1 is CR5, X2 is N and R3 is a (Ci-Cs)alkyl substituted with at least 2 or more of halos. Fluorination of the compound of Formula Xc can be accomplished using a fluorinating reagent such as diethylaminosulfur trifluoride in a non-reactive solvent, such as CH2CI2, at lower temperature such as 0 °C to provide the compound of Formula Xd, wherein X1 is CR5, X2 is N and R3 is a (Ci-Cs)alkyl substituted with at least 2 or more of halos as in step i in Scheme 2.
Scheme 2
Figure imgf000040_0001
Vila Vlllb IXb
Figure imgf000040_0002
The synthesis of the compounds of Formula Xe, wherein X1 is N, X2 is CR5, and R3 and R4 are disclosed in embodiment Al (except for moieties having different reactivity under the reaction conditions such as H, F, CI, Br, I, CN, (Ci-Cs)alkoxy, S(0)(C]-C8)alkyl,
S(0)2(C C8)alkyl, C(=0)N(R¾, S(0)2N(R¾, N(R¾, C(=0)0(C C8)alkyl), is
accomplished in two steps. In step j of Scheme 3, reaction of a compound of Formula XI, with 2-cyanoacetamide, in the presence of a base, such as diethylamine or piperidine, in a polar, protic solvent such as ethyl alcohol (EtOH), at a higher temperature such as 50 to 70 °C as in Narsaiah, B. et al. Org. Prep. Proced. Int. 1993, 25, 116-117, provides the compounds of Formula XIII. The hydroxyl group in Formula XIII is converted to a chloride in one of three ways: (1) via reaction with phosphorus oxychloride as in step gi of Scheme 3; (2) by reaction with phosphorus oxychloride in the presence of a base such as N,N- diethylbenzeneamine as in step g3 of Scheme 3; or (3) via reaction with phenylphosphonic dichloride as in step g4 of Scheme 3 to provide the compounds of Formula Xe .
Scheme 3
Figure imgf000040_0003
XI XII XIII Xe Scheme 4 is a further example of the synthesis of compounds of formula Xe, wherein X1 is N, X2 is CR5, and R3 and R4 are disclosed in embodiment Al (except for moieties having different reactivity under the reaction conditions such as H, F, CI, Br, I, CN, (Cr C8)alkoxy, S(0)(C C8)alkyl, S(0)2(C C8)alkyl, C(=0)N(R8)2, S(0)2N(R8)2, N(R8)2,
Figure imgf000041_0001
In step k of Scheme 4, reaction of a compound of Formula XI with malonamide in a polar high boiling solvent such as dimethyl sulfoxide (DMSO) or sulfolane at a higher temperature such as 80 to 160 °C (as in Umemoto and Tomisawa, JP 10168061 A, June 23, 1998) provides the regioisomeric compounds of Formula XV (major isomer) and Formula XVI (minor isomer). The hydroxyl group in both Formula XV and Formula XVI can be converted to a chloride with concomitant amide dehydration to the nitrile in one of two ways: (1) by reaction with phosphorus oxychloride in the presence of a base such as N,N- diethylbenzeneamine as in step g3 of Scheme 4; or (2) via reaction with phosphorus oxychloride in the presence of a base such as triethylamine as in step gs of Scheme 4 to provide the compounds of Formula Xe.
Scheme 4
Figure imgf000041_0002
XI XIV XV XVI
major isomer minor isomer
Figure imgf000041_0003
XV Xe
The synthesis of compounds of formula Xf, wherein X1 is N, X2 is N, and R3 = R4 and is a (Ci-Cs)alkyl substituted with at least 2 or more halos can be accomplished in two steps. In step I of Scheme 5 and as in Parker, M. H. et al. Synth. Commun. 2004, 34, 903-907, reaction of two equivalents of a compound of Formula III (prepared as in Scheme 1) with ethyl 2-cyanoacetate in a solvent such as THF and a non-nucleophilic base such as potassium ieri-butoxide at approximately 25°Cprovides the compound of Formula XVIII. In step g of Scheme 5, the hydroxyl group in Formula XVIII is converted to a chloride via reaction with phosphorus oxychloride in a solvent such as acetonitrile at a temperature between 60 and 70 °C to provide the compounds of Formula Xf .
Scheme 5
Figure imgf000042_0001
III XVII XVIII Xf
X3=R3=R4 X3=R3=R4
The molecules of Formula One are synthesized in one of six ways as shown in Scheme 6: (1) by reaction of the compounds of Formula Xa as disclosed in Scheme I, or Xd as disclosed in Scheme II with a hydrazine in the presence of a polar, protic solvent such as EtOH, at a higher temperature such as 80 °C, as in step m of Scheme 6; (2) by reaction of the compounds of Formula Xe, as disclosed in Schemes III and IV, with a hydrazine in the presence of a polar, protic solvent such as EtOH, and a base such as triethylamine, at a higher temperature such as 80 °C, as in step n of Scheme 6; (3) by reaction of the compounds of Formula Xe, as disclosed in Schemes III and IV, with a hydrazine in the presence of a polar, protic solvent such as n-butyl alcohol (n-BuOH) at a higher temperature such as between 80 and 90 °C, as in step o of Scheme 6; (4) by reaction of the compounds of Formula Xf as disclosed in Scheme 5, with a hydrazine in the presence of a polar, aprotic solvent such as 1,4-dioxane or DMF, and a base such as triethylamine at a temperature between
approximately 25°C and 90 °C, as in steps pi or p2, respectively, of Scheme 6; (5) by reaction of the compound of Formula Xf, as disclosed in Scheme 5 with a ieri-butoxycarbonyl (Boc)- protected hydrazine in the presence of a polar, aprotic solvent such as 1,4-dioxane, followed by reaction with triethylsilane and an acid such as trifluoroacetic acid in a non-reactive solvent such as (¾(¾ at a temperature between approximately 25°C and 50 °C, as in step q of Scheme 6; or (6) by reaction of the compounds of Formula Xf as disclosed in Scheme 5 with a hydrazine in the presence of a polar, protic solvent such as EtOH, with or without a base such as triethylamine, at ambient temperature, as in steps ri or r2, respectively of Scheme 6. 6
Figure imgf000043_0001
Xa, Xd
Figure imgf000043_0002
Formula One
R' =R2=H
Figure imgf000043_0003
Xf
The synthesis of compounds of Formula One, wherein R1 and R2 are H is accomplished in one step. In step s of Scheme 7, reaction of compounds of Formula One, with electrophiles, such as but not limited to, alkyl halides, anhydrides, acid chlorides, isocyanates, and isothiocyanates, in the presence of a base, such as triethylamine, diisopropylethylamine, pyridine, NW-dimethylpyridin-4-amine, potassium carbonate and potassium phosphate tribasic, in a polar, aprotic solvent such as acetonitrile, THF or CH2CI2, between approximately 25°C and 60 °C to provide compounds of Formula One, wherein R1 and R2 are as previously disclosed.
Figure imgf000043_0004
R'=R2=H
Formula One Formula One EXAMPLES
The examples are for illustration purposes and are not to be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.
Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seal™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and are uncorrected. Molecules are given their known names, named according to naming programs within ISIS Draw, ChemDraw or ACD Name Pro. If such programs are unable to name a molecule, the molecule is named using conventional naming rules. ]H NMR spectral data are in ppm (δ) and were recorded at 300, 400 or 600 MHz, and 13C NMR spectral data are in ppm (δ) and were recorded at 75, 100 or 150 MHz, unless otherwise stated. Example 1: Preparation of ethyl 2-acetyl-3-amino-4,4,4-trifluorobut-2-enoate (1-1)
Figure imgf000044_0001
A three-neck flask was equipped with a thermometer and gas inlet tube. The reaction vessel was charged with potassium ieri-butoxide (1.78 grams (g), 0.016 moles (mol)) and dry tetrahydrofuran (THF; 500 milliliters (mL). Ethyl 3-oxobutanoate (69 g, 0.53 mol) was added dropwise. The mixture was allowed to stir at room temperature for 1 hour (h). A second three-neck flask was fitted with a gas outlet tube connected to the first three-neck flask. The flask was charged with 2,2,2-trifluoroacetamide (90 g, 0.796 mol) and pyridine (400 mL). A premixed solution of trifluoroacetic anhydride (TFAA; 167 g, 0.796 mol) in pyridine (500 mL) was added dropwise, and the gas formed (2,2,2-trifluoroacetonitrile) was directly bubbled through the first three-neck flask. At the conclusion of gas addition, the first three- neck flask was left to stir at room temperature for 24 h. The solvent was concentrated in vacuo, the residue was purified by column chromatography (eluting with 10: 1 petroleum ether-ethyl acetate (EtOAc)) to give the title compound as a yellow solid (88 g, 73.9%): mp 55.2-56.8 °C; ]H NMR (300 MHz, CDC13) δ 4.29 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H); ESIMS m/z 226 ([M+l]+).
Example 2: Preparation of ethyl 4-hydroxy-6-methyl-2-(trifluoromethyl)nicotinate (1-2)
Figure imgf000045_0001
To a dried, 3-liter (L), three-necked flask equipped with nitrogen inlet, low temperature thermometer, and 500 mL addition funnel was charged diisopropylamine (27 g, 0.267 mol) and dry THF (300 mL). The resulting solution was cooled to -78 °C using an acetone-dry ice bath. To this was slowly added n-butyllithium (n-BuLi, 2.5 M in hexane; 107 mL, 0.267 mol) at such a rate that the reaction temperature was kept below -60 °C. After stirring at -78 °C for 1 h, a solution of ethyl 2-acetyl-3-amino-4,4,4-trifluoro-2-butenoate (20 g, 0.089 mol) in dry THF (200 mL) was added dropwise. After 1 h of stirring at -78 °C, the reaction mixture was treated with EtOAc (23.5 g, 0.267 mol) at such a rate that the reaction temperature was kept below -60 °C. The reaction mixture was left at -78 °C for 1 h, then was warmed to room temperature and stirred for 18 h. The resulting solution was poured into 10% hydrochloride acid (HC1; 1 L) and extracted with dichloromethane (CH2CI2; 3x). The combined organic extracts were dried over magnesium sulfate (MgS04) and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether-EtOAc = 10: 1- 1: 1) to give the title compound as a yellow solid (11.4 g, 51.5%): ]H NMR (300 MHz, CDCI3) δ 11.175 (s, 1H), 6.929 (s, 1H), 4.466 (q, 2H, / = 7.2 Hz), 2.697 (s, 3H), 1.425 (t, 3H, J = 7.2 Hz); ESIMS m/z 250 ([M+l]+).
The following compounds were made in accordance with the procedures disclosed in
Example 2.
Ethyl 6-(fluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinate (1-3)
Figure imgf000046_0001
The product was isolated as a yellow solid (11.1 g, 47%): ]H NMR (300 MHz, CDC13) δ 7.399 (s, 1H), 5.599 (d, / = 46.2 Hz, 2H), 4.632 (q, / = 7.2 Hz, 2H,), 1.578 (t, J = 7.2 Hz, 3H); ESIMS m/z 268 ([M+l]+).
Ethyl 6-(difluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinate (1-4)
Figure imgf000046_0002
The product was isolated as a yellow solid (11.8 g, 65%): ]H NMR (300 MHz, CDCI3) δ 11.466 (s, 1H), 7.429 (s, 1H), 6.599 (t, / = 54.9 Hz, 1H), 4.523 (q, J = 7.2 Hz, 2H), 1.456 (t, J = 7.2 Hz, 3H); ESIMS m/z 286 ([M+l]+). Ethyl 6-(chlorodifluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinate (1-5)
Figure imgf000046_0003
The product was isolated as a yellow solid (15.0 g, 94%): ]H NMR (300 MHz, CDCI3) δ 11.601 (s, 1H), 7.430 (s, 1H), 4.531 (q, / = 7.2 Hz, 2H), 1.463 (t, / = 7.2 Hz, 3H); ESIMS m/z 320 ([M+l]+).
Example 3: Preparation of ethyl 4-hydroxy-2,6-bis(trifluoromethyl)nicotinate (1-6)
Figure imgf000047_0001
To a dried, 3-L, three-necked flask equipped with nitrogen inlet, low temperature thermometer, and 500 mL addition funnel was charged diisopropylamine (118.4 g, 1.17 mol) and dry THF (500 mL). The resulting solution was cooled to -78 °C using an acetone-dry ice bath. To this was slowly added n-BuLi (2.5 M in hexane; 468 mL, 1.17 mol) at such a rate that the reaction temperature was kept below -60 °C. After stirring at -78 °C for 1 h, a solution of ethyl 2-acetyl-3-amino-4,4,4-trifluoro-2-butenoate (88 g, 0.39 mol) in dry THF (350 mL) was added dropwise. After 1 h of stirring at -78 °C, the reaction mixture was treated with ethyl trifluoroacetate (166.7 g, 1.17 mol) at such a rate that the reaction temperature was kept below -60 °C. The reaction mixture was left at -78 °C for 1 h, then was warmed to room temperature and stirred for 18 h. The resulting solution was poured into 10% HC1 (1.5 L) and was extracted with CH2CI2 (3x). The combined organic extracts were dried over MgS04 and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether-EtOAc = 10: 1-1: 1) to give the title compound as a yellow solid (95 g, 80%): mp 41.3-42.1 °C; ]H NMR (300 MHz, DMSO-d6) δ 7.527 (s, 1H), 4.375 (q, / = 7.2 Hz, 2H), 1.281 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDC13) δ 168.841, 167.192, 150.236, 149.756, 148.386, 122.466, 118.829, 113.290, 64.088, 13.811; ESIMS m/z 302 ([M-l]"). Example 4: Preparation of 4-hydroxy-6-methyl-2-(trifluoromethyl)nicotinic acid (1-7)
Figure imgf000047_0002
A solution of ethyl 4-hydroxy-6-methyl-2-(trifluoromethyl)nicotinate (11.4 g, 0.045 mol) in methyl alcohol (CH3OH; 100 mL) was treated with a saturated (satd) aqueous (aq) solution of sodium hydroxide (NaOH; 100 mL). The reaction mixture was stirred overnight at room temperature. The mixture was adjusted to pH 2 with 10% HC1 and was extracted with EtOAc (3 x 200 mL). The combined organic extracts were dried over MgS04, filtered, and concentrated in vacuo to give the title compound as a yellow oil (6.8 g, 67.2%): ]H NMR (300 MHz, DMSO-rfe) δ 13.400 (br, IH), 6.930 (s, IH), 2.405 (s, 3H); ESIMS m/z 222 ([M+l]+).
The following compounds were made in accordance with the procedures disclosed Example 4.
4-Hydroxy-6-(methoxymethyl)-2-(trifluoromethyl)nicotinic acid (1-8)
Figure imgf000048_0001
The product was isolated as a yellow oil (9.6 g, 97%): ]H NMR (300 MHz, CDC13) δ 11.281 (br IH), 7.123 (s, IH), 4.606 (s, 2H), 3.533 (s, 3H); 13C NMR (75 MHz, CDC13) δ 173.833, 167.471, 156.840, 122.147, 118.497, 114.480, 71.780, 59.527; ESIMS m/z 252 ([M+l]+).
6-(Difluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinic acid (1-9)
Figure imgf000048_0002
The product was isolated as a yellow oil (10.5 g, 99%): ESIMS m/z 256 ([M-l] ).
6-(Chlorodifluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinic acid (1-10)
Figure imgf000048_0003
The product was isolated as a yellow oil (13.7 g, 100%)
d6) δ 7.265 (s, 1H); ESIMS m/z 290 ([M-l] ).
4-Hydroxy-2,6-bis(trifluoromethyl)nicotinic acid (1-11)
Figure imgf000049_0001
The product was isolated as a yellow oil (70 g, 81 ): ]H NMR (300 MHz, DMSO-d6) δ 8.954 (br s, 1H), 7.432 (s, 1H); 13C NMR (75 MHz, DMSO- ) δ 170.218, 168.902, 164.734, 145.307, 121.798, 121.634, 119.486, 112.770; ESIMS m/z 274 ([M-l]").
Example 5: Preparation of 4-hydroxy-6-methyl-2-(trifluoromethyl)nicotinamide (1-12)
Figure imgf000049_0002
A mixture of 4-hydroxy-6-methyl-2-(trifluoromethyl)nicotinic acid (6.8 g, 0.031 mol) in thionyl chloride (70 mL) was stirred at reflux for 3 h. After removing the thionyl chloride, the residue was dissolved in dry CH2CI2 (30 mL) and the solution was added dropwise into ammonia (NH3; 100 mL). The reaction mixture was stirred for 2 h at room temperature and, then was extracted with EtOAc (3 x 400 mL). The combined organic extracts were dried over MgS04, filtered, and concentrated in vacuo to give the title compound as yellow solid, which was used in the next step without further purification (3.5 g, crude): ]H NMR (300 MHz, DMSO- ) δ 11.372 (s, 1H), 7.805 (s, 1H), 7.553 (s, 1H), 6.936 (s, 1H), 2.435 (s, 3H);
ESIMS m/z 221 ([M+l]+).
The following compounds were made in accordance with the procedures disclosed in Example 5.
4-Hydroxy-6-(methoxymethyl)-2-(trifluoromethyl)nicotinamide (1-13)
Figure imgf000050_0001
The product was isolated as a yellow solid (6.1 g, 100%): mp 141.5-143.2 °C; ]H NMR (300 MHz, DMSO-rf6) δ 8.014 (br, 2H), 7.177 (s, 1H), 4.269 (s, 2H), 3.308 (s, 3H); 13C NMR (75 MHz, DMSO- ) δ 170.594, 169.288, 168.250, 157.911, 114.113, 75.130, 58.696; ESIMS m/z 251 ([M+l]+).
6-(Difluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinamide (1-14)
Figure imgf000050_0002
The product was isolated as a yellow solid (10.4 g, 100%): ]H NMR (300 MHz, CDC13) δ 7.181 (br, 2 H), 7.179 (s, 1H), 6.686 (t, / = 54.2 Hz, 1H); ESIMS m/z 255 ([M-1]").
6-(Chlorodifluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinamide (1-15)
Figure imgf000050_0003
The product was isolated as a yellow solid (13.6 g, 99%): ESIMS m/z 289 ([M-1]").
Example 6: Preparation of 4-hydroxy-2,6-bis(trifluoromethyl)nicotinamide (1-16)
Figure imgf000051_0001
A mixture of 4-hydroxy-2,6-bis(trifluoromethyl)nicotinic acid (70 g, 0.255 mol) in thionyl chloride (500 mL) was stirred at reflux overnight. After removing the thionyl chloride, the residue was dissolved in dry CH2CI2 (100 mL) and the solution was added dropwise into NH3 (500 mL). The reaction mixture was stirred for 2 h at room temperature and was then extracted with EtOAc (3 x 400 mL). The combined organic extracts were dried over MgS04, filtered, and concentrated in vacuo to give the title compound as a white solid, which was used in the next step without further purification (70 g, crude): ]H NMR (300 MHz, DMSO-de) δ 7.974 (s, 1H), 7.583 (s, 1H), 7.291 (s, 2H); 13C NMR (75 MHz, DMSO- d6) δ 167.763, 165.148, 143.692, 125.057, 122.010, 120.264, 112.126; ESIMS m z 273 ([M- 1]~).
Example 7: Preparation of 4-chloro-6-methyl-2-(trifluoromethyl)nicotinonitrile (1-17)
Figure imgf000051_0002
A solution of 4-hydroxy-6-methyl-2-(trifluoromethyl)nicotinamide (3.5 g, 0.016 mol) in phosphorus oxychloride (30 mL) was stirred at reflux for 2 h. The phosphorus oxychloride was removed by vacuum distillation. The residue was poured into water (H20), adjusted to pH 11 with 1 N NaOH, and extracted with EtOAc (3 x 50 mL). The combined organic extracts were dried over MgS04, filtered and concentrated in vacuo to give a residue.
Purification by column chromatography (petroleum ether-EtOAc = 30: 1) gave the title compound as a yellow oil (1.46 g, 41.7%): ]H NMR (300 MHz, DMSO-d6) δ 8.193 (s, 1H), 2.674 (s, 3H); 13C NMR (75 MHz, CDC13) δ 163.867, 149.054, 126.812, 121.892, 118.237, 111.369, 25.024; EIMS m/z 220.
Example 8: Preparation of 4-chloro-6-(difluoromethyl)-2-(trifluoromethyl)nicotino- nitrile (1-18)
Figure imgf000052_0001
To a solution of 6-(difluoromethyl)-4-hydroxy-2-(trifluoromethyl)nicotinamide (10.4 g, 0.041 mol) in phosphorus oxychloride (50 mL) was added l,8-diazabicyclo[5.4.0]undec-7- ene (DBU; 18.5 g, 0.121 mol). The reaction mixture was stirred at reflux for 2 h. Then the phosphorus oxychloride was removed by vacuum distillation. The residue was poured into H20, adjusted to pH 11 with 1 N NaOH and extracted with EtOAc (3 x 100 mL). The combined organic extracts were dried over MgS04, filtered and concentrated in vacuo to give a residue. Purification by column chromatography (petroleum ether-EtOAc = 30: 1) gave the title compound (5 g, 48.1%) as a yellow oil: ]H NMR (300 MHz, CDC13) δ 8.061 (s, 1H), 6.712 (t, 7 = 54 Hz, 1H); 13C NMR (300 MHz, CDC13) δ 155.737, 151.562, 124.278, 121.465, 117.806, 111.815, 108.600; EIMS m/z 256. The following compounds were made in accordance with the procedures disclosed in
Example 8.
4-Chloro-6-(methoxymethyl)-2-(trifluoromethyl)nicotinonitrile (1-19)
Figure imgf000052_0002
The product was isolated as a yellow oil (3.7 g, 60%): ]H NMR (300 MHz, CDC13) δ 7.887 (s, 1H), 4.656 (s, 2H), 3.535 (s, 3H); 13C NMR (300 MHz, CDC13) δ 172.325, 164.219, 150.193, 124.185, 124.133, 111.265, 90.054, 74.021, 59.650; EIMS m/z 249.
4-Chloro-6-(chlorodifluoromethyl)-2-(trifluoromethyl)nicotinonitrile (1-20)
Figure imgf000053_0001
The product was isolated as a yellow oil (4.5 g, 33%): ]H NMR (300 MHz, CDC13) δ 8.058 (s, 1H); 13C NMR (75 MHz, CDC13) δ 151.986, 126.261, 122.825, 121.303, 118.563, 117.645, 110.157; EIMS m/z 291.
4-Chloro-2,6-bis(trifluoromethyl)nicotinonitrile (1-21)
Figure imgf000053_0002
The product was isolated as a yellow oil (11 g, 15%): ]H NMR (300 MHz, DMSO-d6) δ 8.870 (s, 1H); 13C NMR (75 MHz, CDC13) δ 152.065, 128.971, 121.534, 117.752, 114.262, 113.605, 111.953, 110.061 ; EIMS mJz 274. Example 9: Preparation of 4-chloro-6-(hydroxymethyl)-2-(trifluoromethyl)- nicotinonitrile (1-22)
Figure imgf000053_0003
To a solution of 4-chloro-6-(methoxymethyl)-2-(trifluoromethyl)nicotinonitrile (3.7 g,
0.015 mol) in CH2CI2 (30 mL) was added dropwise a solution of 1M boron tribromide(lM BBr3 in CH2C12; 7.4 g, 0.030 mol) at -40 °C. The mixture was stirred for 2 h at room temperature. The reaction mixture was quenched with H20 (50 mL) and extracted with EtOAc (3 x 50 mL). The combined organic extracts were dried over MgS04 and evaporated to give a residue. Purification by column chromatography (petroleum ether-EtOAc = 8: 1) gave the title compound as a yellow oil (2.64 g, 75.6%): ]H NMR (CDC¾): δ 7.912 (s, 4.925 (s, 2H). 19F NMR (CDC13): δ-66.306; EIMS mJz 235 ([M-l]").
Example 10: Preparation of 4-chloro-6-(fluoromethyl)-2-(trifluoromethyl)nicotinonitrile (1-23)
Figure imgf000054_0001
To a solution of 4-chloro-6-(hydroxymethyl)-2-(trifluoromethyl)nicotinonitrile (2.64 g, 0.011 mol) in dry CH2CI2 (20 mL) was added dropwise diethylaminosulfur trifluoride (DAST; 1.92 g, 0.012 mol) at 0 °C under a nitrogen (N2) atmosphere. The reaction mixture was warmed to room temperature and poured into ice-H20 (20 mL). The organic layer was separated, and the aqueous phase was extracted with CH2C12 (2x). The combined organic phase was washed with H20 (20 mL), dried over MgS04, and concentrated in vacuo to give a residue. Purification by column chromatography (petroleum ether-EtOAc = 30: 1) gave the title compound as a yellow oil (2.11 g, 79.3%): ]H NMR (300 MHz, CDC13) δ 7.901 (s, 1H), 5.595 (d, / = 46 Hz, 2H); 13C NMR (75 MHz, CDC13) δ 161.674, 161.362, 150.759, 123.424, 123.373, 110.931, 108.081, 82.745; EIMS m/Z 238. Example 11: Preparation of 2-hydroxy-4,6-bis(trifluoromethyl)nicotinamide (1-24)
Figure imgf000054_0002
This procedure was adapted from Umemoto and Tomisawa, JP 10168061 A, June 23, 1998. In a 250 mL round bottom flask, a suspension of malonamide (9.81 g, 96 mmol) and l,l,l,5,5,5-hexafluoropentane-2,4-dione (20 g, 96 mmol) in tetrahydrothiophene 1,1-dioxide (Sulfolane; 40 mL, 420 mmol) was heated at 80 °C for 2 h forming a clear, colorless solution. To the flask was added a short path distillation head equipped with a 20 mL receiver, and the mixture was heated at 155 °C for 5 h. The hot solution was poured into ice-H20 (400 mL), and the mixture was stirred vigorously to form a white solid suspension. After stirring for 30 min, the suspension was filtered over a Biichner funnel, and the white solid was washed with distilled water (a total of 500 mL). The solid was air-dried and then dried in a vacuum oven at 50 °C for 72 h to give the title compound as a white solid (20.1 g, 75%): ]H NMR (400 MHz, CD3CN) δ 9.62 (s, 1H), 7.56 (s, 1H), 6.69 (s, 1H), 6.54 (s, 1H); 19F NMR (376 MHz, CD3CN) δ -62.46 (s), -69.14 (s); ESIMS mJz 273.6 ([M-l]").
The following compound was made in accordance with the procedures disclosed in Example 11.
2-Hydroxy-6-(perfluoroethyl)-4-(trifluoromethyl)nicotinamide (1-25)
Figure imgf000055_0001
The product was purified by reverse phase chromatography (H20-Acetonitrile; 415 g column) to give a white solid (4.35 g, 38%): ]H NMR (400 MHz, DMSO-d6) δ 13.04 (s, 1H), 8.05 (s, 1H), 7.84 (s, 1H), 7.61 (s, 1H); 19F NMR (376 MHz, DMSO- ) δ -60.62 (s), -82.36 (s), -116.56 (s); ESIMS m/z 325.8 ([M+l]+).
Example 12: Preparation of 2-hydroxy-6-methyl-4-(trifluoromethyl)nicotinonitrile (I- 26)
Figure imgf000055_0002
To a solution of 2-cyanoacetamide (10 g, 0.119 mol) and l,l,l-trifluoropentane-2,4- dione (16.6 g, 0.108 mol) in EtOH (70 mL) was added diethylamine (3.95 g, 0.054 mol). The reaction mixture was stirred for 8 h at 70 °C. After cooling, the mixture was allowed to stand overnight at 0 °C. The yellow crystals formed were collected on a filter and dried at 80 °C to give the title compound (21 g, 96.4%): mp 234.7-236.4 °C; ]H NMR (300 MHz, DMSO-d6) δ 6.560 (s, IH), 2.358 (s, 3H); ESIMS m/z 201 ([M-l]").
The following compounds were made in accordance with the procedures disclosed in Example 11.
2-Hydroxy-6-isopropyl-4-(trifluoromethyl)nicotinonitrile (1-27)
Figure imgf000056_0001
The product was isolated as yellow crystals (19.3 g, 78%): mp 156.2-157.7 °C; ]H NMR (300 MHz, DMSO-d6) δ 10.025 (br, IH), 6.425 (s, IH), 2.864 (m, IH), 1.214 (d, / = 6.9 Hz, 6H); ESIMS m/z 229 ([M-l]").
6-(4-Chlorophenyl)-2-hydroxy-4-(trifluoromethyl)nicotinonitrile (1-28)
Figure imgf000056_0002
The product was isolated as yellow crystals (9.1 g, 85%): mp 267.6-268.3 °C; ]H NMR (300 MHz, CDC13) δ 8.044 (d, J = 8.4 Hz, 2H), 7.649 (d, J = 8.4 Hz, 2H), 7.391 (s, IH); ESIMS m/z 297 ([M-l]").
Example 13: Preparation of 2-chloro-6-methyl-4-(trifluoromethyl)nicotinonitrile (1-29)
Figure imgf000056_0003
Using the procedure of Example 7 with 2-hydroxy-6-methyl-4- (trifluoromethyl)nicotinonitrile as the starting material, the product was isolated as a yellow oil (6.4 g, 58%): ]H NMR (300 MHz, CDC13) δ 7.492 (s, 1H), 2.727 (s, 3H); 13C NMR (75 MHz, CDCI3) δ 165.504, 154.358, 122.752, 119.008, 111.962, 104.325, 25.418; EIMS m/z 220.
Example 14: Preparation of 2-chloro-6-isopropyl-4-(trifluoromethyl)nicotinonitrile (I- 30)
Figure imgf000057_0001
Using the procedures disclosed in Example 7 with 2-hydroxy-6-isopropyl-4- (trifluoromethyl)nicotinonitrile as the starting material, the product was isolated as a yellow oil (9.0 g, 84%): ]H NMR (300 MHz, CDC13) δ 7.492 (s, 1H), 3.195 (m, 1H), 1.350 (d, / = 6.9 Hz, 6H); 13C NMR (75 MHz, CDC13) δ 174.192, 154.553, 122.866, 119.229, 116.677, 104.486, 37.337, 22.142; EIMS m/z 248.
Example 15: Preparation of 2-chloro-6-(4-chlorophenyl)-4-(trifluoromethyl)- nicotinonitrile (1-31)
Figure imgf000057_0002
A mixture of 6-(4-chlorophenyl)-2-hydroxy-4-(trifluoromethyl)nicotinonitrile (9 g, 0.03 mol) and N,N-diethylbenzenamine (8.94 g, 0.06 mol) in phosphorus oxychloride (80 mL) was stirred at reflux for 2 h. After removal of the phosphorus oxychloride, the residue was poured into H20, and the pH was adjusted to 11 with 1 Ν NaOH. The mixture was extracted with EtOAc (3 x 100 mL), and the combined organic extracts were dried over MgS04 and concentrated in vacuo to give a residue. Purification by column chromatography (petroleum ether-EtOAc = 30: 1) gave the title compound as a yellow solid (3.6 g, 38%): mp 146.7-148.5 °C; ]H NMR (300 MHz, CDC13) δ 8.070 (d, / = 8.7 Hz, 2H), 7.997 (s, 1H), 7.541 (d, / = 8.7 Hz, 2H); 13C NMR (75 MHz, CDC13) δ 172.321, 160.435, 155.133, 144.324s 143.867, 139.106, 133.341, 129.917, 129.267, 122.825, 112.065, 119.181, 114.809; ESIMS m/z 318 ([M+l]+).
Example 16: Preparation of 2-chloro-4,6-bis(trifluoromethyl)nicotinonitrile (1-32)
Figure imgf000058_0001
To a suspension of 2-hydroxy-4,6-bis(trifluoromethyl)nicotinamide (1-24; 1.0 g, 3.65 mmol) in phosphorus oxychloride (POCI3, 2.80 g, 18.24 mmol) was added triethylamine (1.017 mL, 7.30 mmol) causing the mixture to turn orange in color. The mixture was heated at 125 °C for 1.5 h, forming a dark red solution that was then cooled and poured slowly into distilled H20 with vigorous stirring, quenching the excess POCI3. After 5 minutes (min), the mixture was poured into a separatory funnel containing EtOAc (250 mL) and washed with distilled H20 (1 x 150 mL) and then with brine (2 x 100 mL). The aqueous layer was extracted with EtOAc (2 x 100 mL), and the combined organic layers were dried (Na2S04), filtered and concentrated in vacuo to give a gold/brown residue. Purification by column chromatography (Hexane-EtOAc gradient; 24 g column) gave the title compound as a clear oil (630 mg, 62%): ]H NMR (400 MHz, CDC13) δ 7.99 (s, 1H); 19F NMR (376 MHz, CDC13) δ -63.87 (s), -68.51 (s); EIMS m/z 21 A.
The following compound was made in accordance with the procedures disclosed
Example 16 above.
2-Chloro-6-(perfluoroethyl)-4-(trifluoromethyl)nicotinonitrile (1-33)
Figure imgf000059_0001
The product was isolated as a gold oil (1.97 g, 49%): ]H NMR (400 MHz, CDC13) δ 8.01 (s, 1H); 19F NMR (376 MHz, CDC13) δ -63.87 (s), -82.48 (s), -117.34 (s); EIMS m/z 324.
Example 17: Preparation of 4-chloro-2,6-bis(trifluoromethyl)pyrimidine-5-carbonitrile
(1-34)
Figure imgf000059_0002
To a solution of 5-cyano-4-oxo-2,6-bis(trifluoromethyl)-4H-pyrimidin-3-ide potassium salt (prepared as in Parker, M. Η. et al. Synth. Commun. 2004, 34, 903-907; 23 g, 78 mmol) in acetonitrile (CH3CN, 250 mL) was added POCI3 (10.89 mL, 117 mmol), which formed an off-white suspension. The mixture was heated at 65 °C for 2 h and then was cooled to room temperature. The mixture was filtered over a Biichner funnel, and the white solid material washed with CH3CN (4 x 25mL). The filtrate was concentrated in vacuo at 35°C to give a gold oil which was diluted with CH2CI2 (300 mL) and washed with warm distilled H20 (35 °C) and brine. The organic layer was dried with MgS04, filtered and concentrated in vacuo to give a gold oil. The oil was Kugelrohr distilled (pot at 95 °C; approx 5 mbar) to give a light yellow oil (18.36 g 81%): 13C NMR (101 MHz, CDC13) δ 167.48, 160.80, 160.41, 160.03, 159.64, 158.77, 157.87, 157.45, 157.06, 122.58, 121.89, 119.87, 119.14, 117.10, 116.38, 114.33, 113.63, 109.69, 108.85; 19F NMR (376 MHz, CDC13) δ -67.25 (s), -70.54 (s); EIMS m/z 275.
Example 18: Preparation of (2,6-dichloro-4-(trifluoromethoxy)phenyl)hydrazine
Figure imgf000060_0001
This procedure was adapted from Critcher, D. J. et al. WO 2005/090313. To a 50 mL round-bottomed flask were added sulfuric acid (95-98%; 1 mL, 18.76 mmol) and sodium nitrite (0.297 g, 4.31 mmol), which formed a viscous mixture that was cooled to between 5- 10 °C with an ice bath. To this mixture was added a solution of 2,6-dichloro-4- (trifluoromethoxy) aniline (1.0 g, 4.06 mmol) in glacial acetic acid (4 mL, 69.9 mmol) dropwise over 10 min, and the viscous mixture was warmed to ambient temperature and stirred for 30 min. The orange suspension was heated at 60 °C for 1 h and then cooled to 5 °C with an ice bath. To the mixture was added a solution of tin (II) chloride (3.16 g, 16.67 mmol) in hydrochloric acid (37%; 2.5 mL, 82 mmol) dropwise causing an exotherm and forming a thick white precipitate. After 20 min, the precipitate was filtered over a fritted glass funnel, and the solid was transferred in portions to a mixture of ammonium hydroxide (NH4OH, 28% in H20; 30 mL, 770 mmol) and ice (50 g). The white suspension was stirred for 30 min and then diluted with Et20 (300 mL). The organic layer was washed with brine (1 x lOOmL), and the combined aqueous layers were extracted with Et20 (2 x 200mL) to give a pale yellow solution. The solution was dried with MgS04, filtered and concentrated in vacuo to give a white solid (892 mg, 80%): mp 62-64 °C; ]H NMR (400 MHz, CDC13) δ 7.20 (d, J = 0.7 Hz, 2H), 5.56 (s, 1H), 3.95 (s, 2H); EIMS m/z 261.
Hydrazine compounds 2,6-dichloro-4-(trifluoromethylthio)phenyl)hydrazine and [2,6- dichloro-4-(pentafluoro- 6-sulfanyl)phenyl] were also prepared in this manner.
Example 19: Preparation of fert-butyl l-(4-(trifluoromethyl)benzyl)hydrazine- carboxylate (1-36)
Figure imgf000060_0002
A 25 mL round-bottomed flask was charged with (4-(trifluoromethyl)benzyl)- hydrazine (1 g, 5.26 mmol) and THF (5 mL), followed by triethylamine (0.806 mL, 5.78 mmol) and distilled H20 (1.0 mL, 55.5 mmol), and the mixture was cooled to 0 °C with an ice bath. To the mixture was added a solution of di-ieri-butyl dicarbonate (1.587 mL, 6.84 mmol) in THF (5 mL) dropwise over 10 min (as in Menon, S. et al., Combinatorial
Chemistry & High Throughput Screening 2003, 6, 471-480). After the addition, the mixture was allowed to stir cold for 10 min and was warmed to ambient temperature over 2 h. The mixture was concentrated in vacuo, diluted with EtOAc (70 mL) and washed with brine (2 x 50mL). The organic layer was dried (Na2S04), filtered and concentrated in vacuo to give a viscous oil. Purification by column chromatography (Hexane-EtOAc gradient; 80 g column) gave the title compound as a clear oil (750 mg, 47%): ]H NMR (400 MHz, CDC13) δ 7.60 (d, / = 8.1 Hz, 2H), 7.39 (d, / = 8.0 Hz, 2H), 4.60 (s, 2H), 4.03 (s, 2H), 1.49 (s, 9H); EIMS m/z 234 [M-(i-butyl)]. Example 20: Preparation of a library of 4-(trifluoromethyl)-2H-pyrazolo[4,3-c]- and - [3,5-6]-pyridin-3-amines
Figure imgf000061_0001
R'=R2=H
To a solution of a 4-chloro-6-(substituted)-2-(trifluoromethyl)nicotinonitrile, such as
1- 17, 1-18, 1-20 and 1-23, or a 2-chloro-6-(substituted)-4-(trifluoromethyl)nicotinonitrile, such as 1-29, 1-30, 1-31 and 1-33, (0.7 mmol) in EtOH (4 mL) was added an appropriate hydrazine, such as (4-(trifluoromethyl)phenyl)hydrazine, (4-fluoro-2-(trifluoromethyl)phenyl)hydrazine, (2-chloro-4-(trifluoromethyl)phenyl)hydrazine, (2,6-dichloro-4-(trifluoromethyl)phenyl)- hydrazine, 3,5-dichloro-2-hydrazinylpyridine, (4-chloro-2-methylphenyl)hydrazine, (2,4,6- trichlorophenyl)hydrazine, (2-chloro-6-fluoro-4-(trifluoromethyl)phenyl)hydrazine, 3-chloro-
2- hydrazinyl-5-(trifluoromethyl)pyridine and (3,4,5-trichlorophenyl)hydrazine (0.7 mmol), and triethylamine (0.7 mmol). The reaction mixture was stirred for 5 days (d) at 80 °C. After cooling, the mixture was purified by preparative thin layer chromatography (TLC) to give the 4-(trifluoromethyl)-2H-pyrazolo[4,3-c]- or -[3,5-&]-pyridin-3-amines.
Compounds 1 - 80 in Table 1 were made in accordance with the procedures disclosed in Example 20.
Example 21: Preparation of a library of 4,6-bis(trifluoromethyl)-2H-pyrazolo[4,3-c]- and -[3,5-ft]-pyridin-3-amines
Figure imgf000062_0001
R1=R2=H
To a solution of 4-chloro-2,6-bis(trifluoromethyl)nicotinonitrile (1-21) or 2-chloro- 4,6-bis(trifluoromethyl)nicotinonitrile (1-32) (150 mg, 0.55 mmol) in EtOH (4 mL) was added an appropriate hydrazine (0.55 mmol) and triethylamine (112 mg, 1.1 mmol). The reaction mixture was stirred overnight at 80 °C. After cooling, the mixture was purified by preparative TLC to give the 4,6-bis(trifluoromethyl)-2H-pyrazolo[4,3-c]- or -[3,5-&]-pyridin- 3-amines.
The hydrazines used include: (4-(trifluoromethyl)phenyl)hydrazine, (2,4- dichlorophenyl)hydrazine, (2-methoxyphenyl)hydrazine, (4-ieri-butylphenyl)hydrazine, p- tolylhydrazine, (4-(methylsulfonyl)phenyl)hydrazine, (2,6-dichlorophenyl)hydrazine, (4- chloro-2-methoxyphenyl)hydrazine, (4-chloro-2-methylphenyl)hydrazine, (2-chloro-4- methylphenyl)hydrazine, (2,6-dimethylphenyl)hydrazine, (2,6-dichloro-4- methylphenyl)hydrazine, (4-(trifluoromethoxy)phenyl)hydrazine, (2,6-dichloro-4- (methylsulfonyl)phenyl)hydrazine, 2-hydrazinyl-5-(trifluoromethyl)pyridine, 3-chloro-2- hydrazinylpyridine, 5-hydrazinyl-2-(trifluoromethyl)pyridine, (2-chloro-6-fluoro-4- (trifluoromethyl)phenyl)hydrazine, (2,6-dichloro-4-(trifluoromethyl)phenyl)hydrazine, (2,4,6-trichlorophenyl)hydrazine, (2-ethylphenyl)hydrazine, 5-chloro-2-hydrazinylpyridine, 3,5-dichloro-4-hydrazinylpyridine, 4-hydrazinyl-3-methylpyridine, 2-hydrazinyl-3- (trifluoromethyl)pyridine, (2-chloro-5-(trifluoromethyl)phenyl)hydrazine, (4-fluoro-2- (trifluoromethyl)phenyl)hydrazine, (2-chloro-4-(trifluoromethyl)phenyl)hydrazine, (2-chloro- 4-(methylsulfonyl)phenyl)hydrazine, (2-(trifluoromethoxy)phenyl)hydrazine, (4-methoxy-2- methylphenyl)hydrazine, 2-hydrazinyl-6-methyl-4-(trifluoromethyl)pyridine, 3,5-dichloro-2- hydrazinylpyridine, 3-chloro-2-hydrazinyl-5-(trifluoromethyl)pyridine, and 2-hydrazinyl-3- methylpyridine.
Compounds 81 - 148 in Table 1 were made in accordance with the procedures disclosed in Example 21. Example 22: Preparation of 4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-</]pyrimidin-3- amines - Method A
Figure imgf000063_0001
R'=R2=H To a solution of 4-chloro-2,6-bis(trifluoromethyl)pyrimidine-5-carbonitrile (1-34; 1 equivalent (equiv)) in 1 ,4-dioxane (3 mL) was added an appropriate solution of hydrazine (1.0 equiv) dissolved in 1 ,4-dioxane (2-5 mL). When hydrazine hydrochlorides were used, they were pre-treated with triethylamine (1.0 equiv). The mixture was stirred at ambient temperature from 30 min to 24 h. The resulting suspension was then treated with
triethylamine (2 equiv) and heated at 95 °C from 2 h to 24 h. After cooling, the mixture was purified by column chromatography to give the 4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4- <i]pyrimidin-3 -amines.
The hydrazines used include: [2,6-dichloro-4-(pentafluoro- 6- sulfanyl)phenyl]hydrazine (prepared as in Critcher, D. J. et al. WO 2005/090313), (2,3,5,6- tetrafluoro-4-(trifluoromethyl)phenyl)hydrazine, (2,6-dichloro-3,5-difluoro-4-
(trifluoromethyl)phenyl)hydrazine, (2,6-dichloro-4-(trifluoromethyl)phenyl)hydrazine, (2- chloro-6-fluoro-4-(trifluoromethyl)phenyl)hydrazine, (2,4-dichlorophenyl)hydrazine, (2,5- dichlorophenyl)hydrazine, (2,4-difluorophenyl)hydrazine hydrochloride, (3- (trifluoromethyl)phenyl)hydrazine, (2-(trifluoromethyl)phenyl)hydrazine, (4- nitrophenyl)hydrazine, (2-chloro-5-(trifluoromethyl)phenyl)hydrazine, (4-chloro-3- (trifluoromethyl)phenyl)hydrazine hydrochloride, (3,5-bis(trifluoromethyl)phenyl)hydrazine, (3,5-dichlorophenyl)hydrazine hydrochloride, (3,4-dichlorophenyl)hydrazine hydrochloride, 2,3,5,6-tetrachloro-4-hydrazinylpyridine, 3,5-dichloro-4-hydrazinyl-2- (trichloromethyl)pyridine, 2,3,5-trichloro-4-hydrazinylpyridine, 3-chloro-2-hydrazinyl-5- (trifluoromethyl)pyridine, 2-hydrazinyl-5-(trifluoromethyl)pyridine, (2,4- dimethylphenyl)hydrazine hydrochloride, (4-chloro-2-methylphenyl)hydrazine
hydrochloride, (2-(trifluoromethoxy)phenyl)hydrazine hydrochloride, (2,6- dimethylphenyl)hydrazine hydrochloride, (2,4,6-trichlorophenyl)hydrazine, (4-fluoro-2- (methylsulfonyl)phenyl)hydrazine, (4-(2,2,2-trifluoroethoxy)phenyl)hydrazine hydrochloride, 2-hydrazinyl-3-(trifluoromethyl)pyridine, (2,6-dichloro-4-
((trifluoromethyl)thio)phenyl)hydrazine (as prepared in Example 18), (2,6-dichloro-4- (trifluoromethoxy)phenyl)hydrazine (as prepared in Example 18) (3,4,5- trichlorophenyl)hydrazine hydrochloride, (2,6-dichloro-4-(methylsulfonyl)phenyl)hydrazine hydrochloride, (2,6-dichloro-3-methylphenyl)hydrazine hydrochloride, (2- phenoxyphenyl)hydrazine hydrochloride, (3-chloro-2-methylphenyl)hydrazine hydrochloride, (5-chloro-2-methoxyphenyl)hydrazine hydrochloride, 5-chloro-2-hydrazinylpyridine, 5- hydrazinyl-2-(trifluoromethyl)pyridine, mesitylhydrazine hydrochloride, (4-bromo-2- chlorophenyl)hydrazine hydrochloride, (2-chloro-4-iodophenyl)hydrazine hydrochloride, (4- ((trifluoromethyl)sulfonyl)phenyl)hydrazine, 4-hydrazinyl-3-(trifluoromethyl)quinoline, (2,6- dichlorophenyl)hydrazine.
Compounds 149 - 192 and 208 in Table 1 were made in accordance with the procedures disclosed in Example 22. Example 23: Preparation of 4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3- amines - Method B
Figure imgf000064_0001
R'=R2=H To a solution of 4-chloro-2,6-bis(trifluoromethyl)pyrimidine-5-carbonitrile (1-34; 1.88 mmol, 1 equiv) in CH2CI2 (2 mL) was added an appropriate solution of hydrazine (2.01 mmol, 1.07 equiv) dissolved in EtOH (2-5 mL). When hydrazine hydrochlorides were used, triethylamine (2.01 mmol, 1.07 equiv) was added dropwise to the mixture. The mixture was stirred at ambient temperature from 30 min to 24 h. The solvents were removed under a stream of nitrogen (N2). The residue was dissolved in CH2CI2 and the mixture was washed with H20. The organic layer was dried, filtered and concentrated. Purification by column chromatography gave the 4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-(i]pyrimidin-3-amines.
The hydrazines used include: (2-chlorophenyl)hydrazine hydrochloride, (4- (trifluoromethyl)phenyl)hydrazine, (2-chloro-4-(trifluoromethyl)phenyl)hydrazine, 3,6- dichloro-4-hydrazinylpyridazine.
Compounds 193 - 195 in Table 1 were made in accordance with the procedures disclose in Example 23.
Example 24: Preparation of 4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3- amines - Method C
Figure imgf000065_0001
R'=R2=H
To twelve separate 7 mL vials each charged with a solution of 4-chloro-2,6- bis(trifluoromethyl)pyrimidine-5-carbonitrile (1-34; 0.20 mmol, 1 equiv) in dry DMF (1 mL), was added an appropriate solution of hydrazine (0.24 mmol, 1.2 equiv) in dry DMF (1 mL), and triethylamine (0.22 mmol, 1.1 equiv) in dry DMF (0.20 mL). The vials were sealed with Teflon screw caps and then were heated at 100 °C on an orbital shaker for 1 h. The samples were allowed to cool to ambient temperature. Argonaut PS-CHO resin (1.08 mmol/g; 100- 120 mg, 0.108-0.130 mmol) was added to scavenge the remaining hydrazine. The samples were heated at 50 °C for 1 h. The liquid was removed by pipette and filtered into a plate.
The hydrazines used include: 3,6-dichloro-4-hydrazinylpyridazine, 2-hydrazinyl-5- phenyl-l,3,4-thiadiazole, 3,5-dichloro-2-hydrazinylpyridin-4-amine, 4-hydrazinyl- benzenesulfonamide, 2-hydrazinylpyrimidine, 3,5,6-trichloro-4-hydrazinylpicolinonitrile, 5- hydrazinyl-6-methyl-3-(methylthio)-l,2,4-triazine, 6-hydrazinyl-l,3-dimethylpyrimidine- 2,4(lH,3H)-dione, 2-chloro-4-hydrazinyl-5-methoxypyrimidine, (4-chlorophenyl)hydrazine, (2-methoxyphenyl)hydrazine, 2-hydrazinylpyridine.
Compounds 196 - 207 in Table 1 were made in accordance with the procedures disclosed in Example 24.
Example 25: Preparation of 4,6-bis(trifluoromethyl)-2-(4-(trifluoromethyl)benzyl)-2H- pyrazolo[3,4-rf]pyrimidin-3-amine (Compound 209)
Figure imgf000066_0001
To a solution of 4-chloro-2,6-bis(trifluoromethyl)pyrimidine-5-carbonitrile (1-34; 150 mg, 0.544 mmol) in 1,4-dioxane (3 mL) was added ieri-butyl l-(4-
(trifluoromethyl)benzyl)hydrazinecarboxylate (1-36; 174 mg, 0.599 mmol), and after a few min, an off-white suspension formed. The reaction mixture was concentrated in vacuo and the residue was diluted with EtOAc (125 mL) and washed with satd sodium chloride (NaCl; 2 x 50 mL). The organic layer was dried (Na2S04), filtered and concentrated in vacuo to give a white residue which was stored under high vacuum for 12 h. The residue was dissolved in CH2O2 (30 mL), and triethylsilane (0.5 mL, 3.13 mmol) was added, followed by
trifluoroacetic acid (TFA; 5 mL, 64.9 mmol). The mixture was heated at reflux for 1 h. More TFA (3 mL) was added, and heating was continued for 90 min. The mixture was concentrated in vacuo and diluted with CH2C12 (150 mL). The organic layer was washed with brine (2 x 150 mL) and water (50 mL) mixed with satd aq sodium bicarbonate (NaHCC^) solution. The organic layer was dried (MgS04), filtered and concentrated to give a yellow solid residue. Purification by column chromatography (Hexanes-EtOAc; 40 g column) yielded the title compound (174 mg, 73%) as a yellow solid: mp 201-203 °C; ]H NMR (400 MHz, DMSO- d6) δ 7.74 (d, J = 8.2 Hz, 2H), 7.47 (d, 7 = 8.1 Hz, 2H), 7.33 (s, 2H), 5.70 (s, 2H); ESIMS m/z 431 ([M+H]+).
Example 26: Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-jV-methyl-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-amine (Compound 210)
Figure imgf000067_0001
To a solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- 2H-pyrazolo[3,4-<i]pyrimidin-3-amine (0.15 g, 0.31 mmol, 1 equiv) in C¾CN (3-5 mL) was added potassium phosphate tribasic (K3PO4, 0.066 g, 0.31 mmol, 1 equiv) forming a dark brown solution. To the mixture was added iodomethane (0.097g, 0.68 mmol, 2.2 equiv), and the mixture was heated at 60 °C from 1 h forming a light red/orange color. The mixture was diluted with EtOAc (50-150 mL) and washed with satd aq NaCl (3 x 25 mL) and distilled H20 (1 x 25 mL). The combined aqueous layers were extracted with EtOAc (1 x 20 mL). The combined organic layers were dried with Na2SC>4, filtered and concentrated in vacuo to give a yellow/orange solid residue. Purification by column chromatography (CH2C12; 24 g column) gave the title compound as a yellow solid (108 mg, 69%): mp 250-252 °C; ]H NMR (400 MHz, DMSO- ) δ 8.38 - 8.35 (m, 2H), 7.36 (s, 1H), 2.69 (s, 3H); ESIMS m/z 498.91 ([M+H]+).
The electrophiles (1-9 equiv) used include: iodoethane, 2-iodopropane,
(bromomethyl)cyclopropane, 2-(bromomethyl)- 1 , 1 -difluorocyclopropane, (2- chloroethyl) (methyl) sulfane, 1 -iodopentane, (iodomethyl)cyclopentane. Compounds 211 - 214 and 216 - 218 in Table 1 were made in accordance with the procedures disclosed in Example 26:
Example 27: Preparation of 2-(2,6-dichloro-4-(pentafluoro-λ6-sulfan l)phen l)- V- methyl-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-amine (Compound 219)
Figure imgf000068_0001
Using the procedure of Example 26 with 2-(2,6-dichloro-4-(pentafluoro- 6- sulfanyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-J|pyrimidin-3-amine as the starting material, the product was isolated as an orange solid (0.96 g, 61%): mp 242-245 °C; ]H NMR (400 MHz, DMSO- ) δ 8.59 (s, 2H), 7.40 (s, 1H), 2.74 (m, 3H); ESIMS m/z 557.13 ([M+H]+).
Example 28: Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-jV-(2,6- difluorobenzyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-amine
(Compound 220)
Figure imgf000068_0002
To a stirred solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-J|pyrimidin-3-amine (200 mg, 0.413 mmol) in CH3CN (4.1 iriL) was added 2,6-difluorobenzyl bromide (103 mg, 0.496 mmol) followed by K3PO4 (88 mg, 0.413 mmol). The mixture was heated at 70 °C for 5 h. The mixture was diluted with EtOAc (20 iriL), and the organic solution was washed with H20 and brine. The solution was dried over MgSOzi, filtered and concentrated. The residue was purified via radial chromatography (6: 1 - 1: 1 hexane-EtOAc). The fraction isolated at Rf = 0.25 was the expected mono-addition product (137 mg, 54%): ]H NMR (400 MHz, CDC13) δ 7.83 (s, 2H), 7.32 (ddd, / = 15.0, 8.4, 6.6 Hz, 1H), 6.89 (t, / = 8.0 Hz, 2H), 5.31 (s, 1H), 4.22 (d, / = 6.2 Hz, 2H); 19F NMR (376 MHz, CDCI3) δ -63.25, -66.45, -70.58, -115.55; ESIMS m/z 610 ([M+H]+). Compounds 221 - 223 in Table 1 were made in accordance with the procedures disclosed in Example 28.
Example 29: Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-N,N-dimethyl- 4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-</]pyrimidin-3-amine (Compound 224)
Figure imgf000069_0001
To a solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- 2H-pyrazolo[3,4-<i]pyrimidin-3-amine (500 mg, 1.033 mmol) in C¾CN (3 mL) was added K3PO4 (435 mg, 2.06 mmol) forming a dark brown solution. To the mixture was added iodomethane (0.582 mL, 9.30 mmol) and the mixture was heated at 60 °C for 5 h. The mixture turned a light red/orange color during this time. The reaction mixture was diluted with diethyl ether (Et20; 150 mL) and washed with a mixture of satd aq NaCl (50 mL) and H20 (50 mL). The combined aqueous layer was extracted with Et20 (1 x 25 mL). The combined organic layer was dried with Na2S04, filtered and concentrated in vacuo to give a viscous orange/yellow material. Purification by column chromatography (Hexane-EtOAc; 24 g column) gave the title compound as a yellow solid (214 mg, 40.5%): mp 183-185 °C; JH NMR (400 MHz, CDC13) δ 7.88 - 7.85 (m, 2H), 2.92 (s, 6H); ESIMS m/z 512.98 ([M+H]+).
Compound 215 in Table 1 was made in accordance with the procedures disclosed in Example 29.
Example 30: Preparation of 2-(2,6-dichloro-4-(pentafluoro^6-sulfanyl)phenyl)-jV,jV- dimethyl-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-amine (Compound 225)
Figure imgf000069_0002
Using the procedure of Example 29 with 2-(2,6-dichloro-4-(pentafluoro- 6- sulfanyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-(i]pyrimidin-3-amine as the starting material, the product was isolated as an orange solid (0.036 g, 22%): mp 176-180 °C; ]H NMR (400 MHz, DMSO- ) δ 8.66 (s, 2H), 2.92 (s, 6H); ESIMS m/z 571.16 ([M+H]+).
Example 31: Preparation of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-jV-(3,3- dimethylbutyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-amine
(Compound 226)
Figure imgf000070_0001
To a mixture of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- 2H-pyrazolo[3,4-<i]pyrimidin-3-amine (100 mg, 0.21 mmol, 1 equiv), l-bromo-3,3- dimethylbutane (69.3 mg, 0.42 mmol, 2 equiv) in C¾CN (3.0 mL) was added potassium iodide (KI; 34.9 mg, 0.21 mmol, 1 equiv) and K3P04 (89.2 mg, 0.42 mmol, 2 equiv). The dark mixture was heated at 60 °C for 5 h. The cooled mixture was diluted with EtOAc and washed with ¾0 (10 mL). The organic phase was concentrated in vacuo to give a residue, which was purified by preparative TLC to give the title compound (23 mg, 19.6%) as a yellow solid: ]H NMR (300 MHz, CDC13) δ 7.84 (s, 2H), 5.20 (br s, 1H), 2.91 - 2.84 (m, 2H), 1.46 - 1.41 (m, 2H), 0.77 (s, 9H); ESIMS m/z 568 [(M+H)]+.
Electrophiles used in the above reaction: 5-bromopentanenitrile, 5-bromopentan-l-ol, l-bromo-4-methoxybutane, 4-bromobut-l-ene, l-bromopent-2-yne.
Compounds 227 - 231 in Table 1 were made in accordance with the procedures disclosed in Example 31. Example 32: Preparation of V-(5-(tert-butyldimethylsilyloxy)pentyl)-2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-amine (Compound 232)
Figure imgf000071_0001
A solution of 5-((2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- 2H-pyrazolo[3,4-<i]pyrimidin-3-yl)amino)pentan-l-ol (Compound 228; 100 mg, 0.18 mmol) in CH2CI2 (5 mL) was treated with imidazole (12 mg, 0.18 mmol) and tert- butylchlorodimethylsilane (TBS-Cl; 33 mg, 0.22 mmol). The mixture was stirred at ambient temperature for 6 h. The mixture was concentrated in vacuo to give a residue, which was purified by column chromatography to yield the title compound (60 mg, 49%) as a yellow solid: mp 98.6-99.9 °C; ]H NMR (300 MHz, CDC13) δ 7.82 (s, 2H), 5.26 (br s, 1H), 3.57 (t, J = 6.6 Hz, 2H), 2.90 - 2.84 (m, 2H), 1.60 - 1.55 (m, 2H), 1.46 - 1.39 (m, 2H), 1.35 - 1.26 (m, 2H), 0.87 (s, 9H), 0.02 (s, 6H); ESIMS m/z 684 [(M+H)]+.
Example 33: Preparation of 5-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis (trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-ylamino)pentyl acetate (Compound 233)
Figure imgf000072_0001
A solution of 5-((2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- 2H-pyrazolo[3,4-<i]pyrimidin-3-yl)amino)pentan-l-ol (Compound 228; 100 mg, 0.18 mmol) in CH2CI2 (5 mL) was treated with triethylamine (36 mg, 0.35 mmol) and acetyl chloride (21 mg, 0.26 mmol). The mixture was stirred at 0 °C for 30 min. The mixture was concentrated in vacuo to give a residue that was purified by column chromatography to yield the title compound (90 mg, 82%) as a yellow oil: ]H NMR (300 MHz, CDC13) δ 7.84 (s, 2H), 5.21 (br s, 1H), 4.03 (t, / = 6.6 Hz, 2H), 2.89 - 2.87 (m, 2H), 2.04 (s, 3H), 1.61 - 1.55 (m, 4H), 1.34 - 1.29 (m, 2H); ESIMS m/z 612 ([M+H]]+).
Example 34: Preparation of V-acetyl- V-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-yl)acetamide (Compound 234)
Figure imgf000072_0002
To a 10 mL round-bottomed flask was added 2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-(i]pyrimidin-3-amine (100 mg, 0.207 mmol) and acetic anhydride (2 mL, 0.207 mmol), and the mixture was stirred at ambient temperature for 10 min. The mixture was then heated at 55 °C for 4 h. Triethylamine (0.058 mL, 0.413 mmol) was added causing the yellow solution to turn deep orange in color, and the mixture was stirred for 1.5 h. At this time, more triethylamine (4 drops) was added, and the mixture was stirred at ambient temperature overnight. Some solvent was removed in vacuo, and the mixture was diluted with distilled H20 (10 mL) and poured into a separatory funnel containing EtOAc (100 mL). Washed organic phase with H20 (2 x 25 mL), saturated aqueous NaHCC^ (1 x 25mL). The organic layer was dried (Na2S04), filtered and concentrated to give a gold oil that was purified by column chromatography (Hexane-EtOAc gradient; 40 g column) to provide the title product (34.7 mg, 28%) as a white solid.mp 198— 200 °C; ]H NMR (400 MHz, CDC13) δ 7.93 - 7.75 (m, 2H), 2.35 (s, 6H); ESIMS m/z 570.39 «M+H]+).
Example 35: Preparation of V-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-yl)acetamide (Compound 235)
Figure imgf000073_0001
To a solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- 2H-pyrazolo[3,4-<i]pyrimidin-3-amine (300 mg, 0.620 mmol) and N,N-dimethylpyridin-4- amine (DMAP; 3.79 mg, 0.031 mmol) in THF (2 mL) was added pyridine (10.02 μΐ,, 0.124 mmol), and the mixture was stirred at ambient temperature. To this mixture was added dropwise acetic anhydride (0.117 mL, 1.239 mmol), and the mixture was heated at 60 °C for 1 h. The mixture was cooled to ambient temperature, diluted with EtOAc (150 mL) and washed with brine (2 x 50 mL). The organic layer was dried (Na2S04), filtered and concentrated in vacuo to give a gold oil. Purification by column chromatography (Hexane- EtOAc gradient; 24 g column) gave the title compound (283 mg, 82%) as a yellow solid: mp 266-268 °C; ]H NMR (400 MHz, DMSO-rf6) δ 11.04 (s, 1H), 8.42 (s, 2H), 2.03 (s, 3H); ESIMS m/z 526.4 ([M+H]+).
Example 36: Preparation of V-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-yl)pentanamide (Compound 236)
Figure imgf000074_0001
To a solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)- 2H-pyrazolo[3,4-d]pyrimidin-3-amine (100 mg, 0.21 mmol) and triethylamine (60 mg, 0.59 mmol) in anhydrous CH2CI2 (2.5 mL) was added DMAP (61 mg, 0.49 mmol) and pentanoyl chloride (30.4 mg, 0.25 mmol). The reaction mixture was stirred for 2 h under N2 at ambient temperature. The mixture was diluted with distilled H20 (10 mL) and extracted with EtOAc (2 x 15 mL). The combined organic phase was concentrated in vacuo to give a residue, which was purified by preparative TLC to give the title compound (60 mg, 51.1%) as a yellow solid: mp 169.4-171.8 °C; ]H NMR (300 MHz, DMSO-i¾: δ 11.00 (s, 1H), 8.44 (s, 2H), 2.31 (t, / = 7.2 Hz, 2H), 1.43 - 1.38 (m, 2H), 1.11 - 1.03 (m, 2H), 0.79 (t, / = 7.2 Hz, 3H); ESIMS m/z 566 ([M-H]").
Example 37: Preparation of V-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-</]pyrimidin-3-yl)- V-(3,3-dimethylbutanoyl)-3,3- dimethylbutanamide (Compound 237) and V-(2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-yl)- 3,3-dimethylbutanamide (Compound 238).
Figure imgf000074_0002
To stirred solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-J|pyrimidin-3-amine (100 mg, 0.207 mmol) in CH2C12 (2.1 mL) was added di-ieri-butyl carbonate (54 mg, 0.248 mmol) followed by DMAP (25 mg 0.207 mmol). The reaction mixture was stirred at room temperature for 3 h. 1 N HC1 (4 mL) was added, and the mixture was stirred for an additional 15 min. The solution was extracted with EtOAc and washed with H20 and brine. The solution was dried over MgSOzi, filtered and concentrated. The residue was purified via radial chromatography (6: 1 hexane-EtOAc). The first fraction isolated (Rf = 0.41) was shown to be N-(2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-J|pyrimidin-3-yl)-N-(3,3- dimethylbutanoyl)-3,3-dimethylbutanamide (97 mg; 69%) as a yellow solid: ]H NMR (400 MHz, CDC13) δ 7.82 (s, 2H), 1.43 (s, 18H); ESIMS m/z 684 ([M+H]+). The second fraction isolated (Rf = 0.30) was shown to be N-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-(i]pyrimidin-3-yl)-3,3-dimethylbutanamide (32 mg; 27%) as a yellow solid: ]H NMR (400 MHz, CDC13) δ 7.85 (s, 2H), 6.51 (s, 1H), 1.36 (s, 9H); ESIMS m/z 584 ([M+H]+).
Example 38: Preparation of bis-2,2,2-trichloroethyl (2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3- yl)carbamate (Compound 239).
Figure imgf000075_0001
To a 0 C solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-J|pyrimidin-3-amine (107 mg, 0.221 mmol) and
Hunig's base (96 μΕ, 0.553 mmol) in THF (2.2 mL) was added dropwise 2,2,2-trichloroethyl carbonochloridate (38 μΕ, 0.276 mmol), and the mixture was stirred at room temperature for 3 h. TLC analysis indicated mostly starting material. Another equivalent of Hunig's base and the chloroformate was added, and the mixture was heated at 50 °C for 3 h. The mixture was diluted with EtOAc (10 mL), and the organic layer was washed with H20 and brine, dried (MgS04) and evaporated. The residue was triturated with hexane-EtOAc solution (6: 1), filtered and dried to give the title compound as a tan solid (103 mg, 56%): ]H NMR (400 MHz, CDCI3) δ 7.83 (s, 2H), 4.98 (d, / = 11.8 Hz, 2H), 4.71 (d, / = 11.8 Hz, 2H); 19F NMR (376 MHz, CDCI3) δ -63.32, -66.71, -70.03; ESIMS m/z 835 ([M+H]+). Example 39: Preparation of methyl (2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3-yl)carbamate (Compound 240)
Figure imgf000076_0001
To a stirred solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-J|pyrimidin-3-amine (110 mg, 0.227 mmol) in CH2C12 (2.3 mL) was added methyl chloroformate (18 μί, 0.227 mmol) followed by DMAP (28 mg, 0.227 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was diluted with CH2C12 (20 mL) and washed with 1 N HC1, satd aq NaHC03, H20 and brine. The solution was dried with MgS04, filtered and concentrated. The residue was purified via radial chromatography (4: 1 hexane-EtOAc; Rf = 0.25) to afford the title compound (57 mg, 46%) as a tan solid.: ]H NMR (400 MHz, CDC13) δ 7.86 (s, 2H), 7.25 (br s, 1H), 3.69 (s, 3H); 19F NMR (376 MHz, CDC13) δ -63.30, -67.17, -70.14; ESIMS m/z 542 «M+H]+).
Example 40: Preparation of 2,2,2-trichloro- V-((2-(2,6-dichloro-4- (trifluoromethyl)phenyl)-4,6-bis(trifluoromethyl)-2H-pyrazolo[3,4-rf]pyrimidin-3- yl)carbamoyl)acetamide (Compound 241)
Figure imgf000076_0002
To a stirred solution of 2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-(i]pyrimidin-3-amine (100 mg, 0.207 mmol) in CH2C12 (2.1 mL) was added 2,2,2-trichloroacetyl isocyanate (27 \iL, 0.227 mmol) followed by K2CO3 (121 mg, 0.878 mmol). The reaction mixture was stirred at room temperature overnight. TLC analysis indicated starting material remained. Added isocyanate (15 \lL, 0.5 equiv) and the mixture was stirred at room temperature for 14 h. The solvent was removed under reduced pressure to yield the title compound (79 mg, 70%) as a yellow solid: ]H NMR (400 MHz, CDCI3) δ 10.04 (s, 1H), 8.76 (s, 1H), 7.87 (s, 2H); 19F NMR (376 MHz, CDC13) δ -63.23, -67.08, -70.11; ESIMS m/z 672 ([M+H]+).
Example 41: Preparation of l-(2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6-bis- (trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-3-yl)urea (Compound 242)
Figure imgf000077_0001
To a solution of 2,2,2-trichloro-N-((2-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4,6- bis(trifluoromethyl)-2H-pyrazolo[3,4-J|pyrimidin-3-yl)carbamoyl)acetamide (141 mg, 0.21 mmol) in CH3OH (2 mL) was added K2CO3 (123 mg, 0.891 mmol), and the reaction mixture was stirred at ambient temperature for 1 h. The solvent was evaporated and H20 (15 mL) was added. The aqueous solution was extracted with EtOAc, and the organic layer was dried over MgSOzi, filtered and concentrated. The residue was purified via radial chromatography (95:5 CHCI3/CH3OH; Rf = 0.25) to afford the title compound (53 mg; 48%) as a yellow solid: ]H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 2H), 8.01 (s, 1H), 6.48 - 6.25 (br s, 2H); 19F NMR (376 MHz, DMSO- ) δ -61.12, -61.47, -64.91, -65.90, -68.17, -69.03 (Rotational isomers); ESIMS m/z 527 ([M+H]+).
Example A: BIOASSAYS ON BEET ARMYWORM ("BAW") AND CORN EARWORM ("CEW") BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants. CEW is also known to be resistant to certain insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.
Certain molecules disclosed in this document were tested against BAW and CEW using procedures described in the following examples. In the reporting of the results, the "BAW & CEW Rating Table" was used (See Table Section). Bio ASSAYS ON BAW (Spodoptera exigua)
Bioassays on BAW were conducted using a 128-well diet tray assay, one to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm2 of the test compound (dissolved in 50 μΕ of 90: 10 acetone- water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25 °C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in Table 3 in the column entitled "BAW Results" (See Table Section). BIOASSAYS ON CEW (Helicoverpa zed)
Bioassays on CEW were conducted using a 128-well diet tray assay. One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg /cm2 of the test compound (dissolved in 50 μL· of 90: 10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25 °C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in Table 3 in the column entitled "CEW Results" (See Table Section). Example B: Bio ASSAYS ON GREEN PEACH APHID ("GPA") (Myzus persicae).
GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed resistance to many pesticides.
Certain molecules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the "GPA Rating Table" was used (See Table Section).
Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/methanol (1 : 1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5X with 0.025% Tween 20 in H20 to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/methanol (1: 1) solvent. Treated plants were held in a holding room for three days at approximately 25 °C and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W.S. Abbott, "A Method of Computing the Effectiveness of an
Insecticide" J. Econ. Entomol. 18 (1925), pp.265-267) as follows.
Corrected % Control = 100 * (X - Y) / X
where
X = No. of live aphids on solvent check plants and
Y = No. of live aphids on treated plants The results are indicated in Table 3 in the column entitled "GPA Results" (See Table Section).
Example C: BIOASSAYS ON Yellow Fever Mosquito "YFM" (Aedes aegypti).
YFM prefers to feed on humans during the daytime and is most frequently found in or near human habitations. YFM is a vector for transmitting several diseases. It is a mosquito that can spread the dengue fever and yellow fever viruses. Yellow fever is the second most dangerous mosquito-borne disease after malaria. Yellow fever is an acute viral hemorrhagic disease and up to 50% of severely affected persons without treatment will die from yellow fever. There are an estimated 200,000 cases of yellow fever, causing 30,000 deaths, worldwide each year. Dengue fever is a nasty, viral disease; it is sometimes called
"breakbone fever" or "break-heart" because of the intense pain it can produce. Dengue fever kills about 20,000 people annually.
Certain molecules disclosed in this document were tested against YFM using procedures described in the following paragraph. In the reporting of the results, the "YFM Rating Table" was used (See Table Section).
Master plates containing 400 μg of a molecule dissolved in 100 \L of dimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used. A master plate of assembled molecules contains 15 \L per well. To this plate, 135 \L of a 90: 10 watenacetone mixture is added to each well. This solvent addition is completed shortly before actual run time on the Sagian to minimize any molecules incompatibility or stability issues. The Sagian robot is programmed to dispense 15 \L aspirations from the master plate into an empty 96- well shallow plate ("daughter" plate). There are 6 reps ("daughter" plates) created per master. The created daughter plates are then immediately infested with YFM larvae.
The day before plates are to be treated, mosquito eggs are placed in Millipore water containing liver powder to begin hatching (4 g. into 400 ml). After the daughter plates are created using the Sagian robot, they are infested with 220 \L of the liver powder/larval mosquito mixture (about 1 day-old larvae). After plates are infested with mosquito larvae, a non-evaporative lid is used to cover the plate to reduce drying. Plates are held at room temperature for 3 days prior to grading. After 3 days, each well is observed and scored based on mortality. The results are indicated in Table 3 in the column entitled "YFM Results" (See Table Section). PESTICIDALLY ACCEPTABLE ACID ADDITION SALTS, SALT DERIVATIVES, SOLVATES, ESTER DERIVATIVES, POLYMORPHS, ISOTOPES AND
RADIONUCLIDES
Molecules of Formula One may be formulated into pesticidally acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally, by way of a non-limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesium.
Molecules of Formula One may be formulated into salt derivatives. By way of a non- limiting example, a salt derivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a salt. A free base may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it to its dimethylamine salt..
Molecules of Formula One may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as "solvates." However, it is particularly desirable to form stable hydrates with water as the solvent.
Molecules of Formula One may be made into ester derivatives. These ester derivatives can then be applied in the same manner as the invention disclosed in this document is applied.
Molecules of Formula One may be made as various crystal polymorphs.
Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.
Molecules of Formula One may be made with different isotopes. Of particular importance are molecules having 2H (also known as deuterium) in place of ]Η. Molecules of Formula One may be made with different radionuclides. Of particular importance are molecules having 14C.
STEREOISOMERS
Molecules of Formula One may exist as one or more stereoisomers. Thus, certain molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molecules disclosed in this document can exist as two or more isomers. The various isomers include geometric isomers, diastereomers, and enantiomers. Thus, the molecules disclosed in this document include geometric isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the present disclosure are drawn in only one geometric form for clarity, but are intended to represent all geometric forms of the molecule.
COMBINATIONS
Molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties. Additionally, the molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists. Examples of such compounds in the above groups that may be used with the Molecules of Formula One are - (3-ethoxypropyl)mercury bromide, 1 ,2-dichloropropane, 1,3- dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri- iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6- TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5- T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T- sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D- 2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB- dimethylammonium, 2,4-DB-isoctyl, 2,4-DB -potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4- D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D- dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D- isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D- meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D- sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2- hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2- phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA- sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8 -hydroxy quinoline sulfate, 8- phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorf en- sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, α/ρΛα-cypermethrin, α/ρ/ζα-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2- hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium a-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam- sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos- methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin- ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone- sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox- ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate,
benzyladenine, berberine, berberine chloride, ^eta-cyfluthrin, ^eto-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium,
brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac- ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2- hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam- methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, J-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O- methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, J-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos,
diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba- diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba- isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba- sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P- dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,
difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate,
dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d- limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal- dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdepallethrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen- ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl a-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl,
fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop- butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop- potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon- potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop- ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M- isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop- P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron- methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl,
flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCR, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop- methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox- ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin- sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron,
iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim- methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin,
MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA- 2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA- olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2- ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop- sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide,
methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p- toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nomicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene,
orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid,
oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride,
phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram- methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2- hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone- sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos- methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium a-naphthaleneacetate, ρρ'-ΌΌΎ, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione- calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone,
propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac- sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P- tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium a-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, toi/-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA- calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,
terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap- monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin,
transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop- methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, a-chlorohydrin, a-ecdysone, a-multistriatin, and a-naphthaleneacetic acid. For more information consult the "COMPENDIUM OF PESTICIDE COMMON NAMES" located at http://www.alanwood.net pesticides/index.html. Also consult "THE PESTICIDE MANUAL" 14th Edition, edited by C D S Tomlin, copyright 2006 by British Crop Production Council, or its prior or more recent editions.
BIOPESTICIDES
Molecules of Formula One may also be used in combination (such as in a
compositional mixture, or a simultaneous or sequential application) with one or more biopesticides. The term "biopesticide" is used for microbial biological pest control agents that are applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and
Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents have also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on:
1. entomopathogenic fungi {e.g. Metarhizium anisopliae);
2. entomopathogenic nematodes (e.g. Steinernema feltiae); and
3. entomopathogenic viruses (e.g. Cydia pomonella granulo virus).
Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the genetically modified organism. In one embodiment, the molecules of Formula One may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology -based control) products. Copping L.G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.
OTHER ACTIVE COMPOUNDS
Molecules of Formula One may also be used in combination (such as in a
compositional mixture, or a simultaneous or sequential application) with one or more of the following:
1. 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec-3-en-2-one;
2. 3-(4'-chloro-2,4-dimethyl[l,l '-biphenyl]-3-yl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec- 3-en-2-one;
3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;
4. 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;
5. 3-chloro-N2-[(15')-l-methyl-2-(methylsulfonyl)ethyl]-Nl-[2-methyl-4-[l,2,2,2- tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]- 1 ,2-benzenedicarboxamide;
6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;
7. 2-cy ano-N-ethyl- 3 -methoxy-benzenesulf onamide ;
8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;
9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;
10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;
11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;
12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;
13. 3 -(difluoromethyl)-N- [2-(3 ,3-dimethylbutyl)phenyl] - 1 -methyl- lH-pyrazole-4- carboxamide;
14. N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-/?-tolyl) hydrazone;
15. N-ethyl-2,2-dichloro-l-methylcyclopropane-carboxamide-2-(2,6-dichloro-a,a,a- trifluoro-/?-tolyl) hydrazone nicotine;
16. 0-{(E-)-[2-(4-chloro-phenyl)-2-cyano-l-(2-trifluoromethylphenyl)-vinyl] } S-methyl thiocarbonate;
17. (E)-Nl-[(2-chloro-l,3-thiazol-5-ylmethyl)]-N2-cyano-Nl-methylacetamidine;
18. l-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-l,2,3,5,6,7-hexahydro-imidazo[l,2- a]pyridin-5-ol;
19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and
20. N-Ethyl-2,2-dichloro-l-methylcyclopropanecarboxamide-2-(2,6-dichloro- alpha, alpha, a/p za-trifluoro-p-tolyl)hydrazone. SYNERGISTIC MIXTURES
Molecules of Formula One may be used with certain active compounds to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the molecules of Formula One are the same, similar, or different. Examples of modes of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs). Generally, weight ratios of the molecules of
Formula One in a synergistic mixture with another compound are from about 10:1 to about 1:10, in another embodiment from about 5:1 to about 1:5, and in another embodiment from about 3:1, and in another embodiment about 1: 1. FORMULATIONS
A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra low volume solutions. For further information on formulation types see "Catalogue of Pesticide Formulation Types and International Coding System" Technical Monograph n°2, 5th Edition by CropLife International (2002).
Pesticides are applied most often as aqueous suspensions or emulsions prepared from concentrated formulations of such pesticides. Such water-soluble, water- suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually from about 10% to about 90% by weight. The carrier is usually selected from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed
naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.
Emulsifiable concentrates of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are selected from conventional anionic and non-ionic surfactants.
Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.
Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.
Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine. It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.
Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure- generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.
Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.
Fumigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest' s respiratory system or being absorbed through the pest's cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in special chambers.
Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.
Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.
Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non- ionic hydrophilic surface-active agent and (3) at least one ionic surface- active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. Further information on the embodiment is disclosed in U.S. patent publication 20070027034 published February 1, 2007, having Patent Application serial number 11/495,228. For ease of use, this embodiment will be referred to as "OrWE".
For further information consult "Insect Pest Management" 2nd Edition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult "Handbook of Pest Control - The Behavior, Life History, and Control of Household Pests" by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
OTHER FORMULATION COMPONENTS
Generally, when the molecules disclosed in Formula One are used in a formulation, such formulation can also contain other components. These components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.
A wetting agent is a substance that when added to a liquid increases the spreading or penetration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading. Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrates for soluble liquids or suspension concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable powders and to improve the penetration of water into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.
A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from
reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrates, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene oxide condensates and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as dispersing agents. These have very long hydrophobic 'backbones' and a large number of ethylene oxide chains forming the 'teeth' of a 'comb' surfactant. These high molecular weight polymers can give very good long-term stability to suspension concentrates because the hydrophobic backbones have many anchoring points onto the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.
An emulsifying agent is a substance which stabilizes a suspension of droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil- soluble calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance ("HLB") values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.
A solubilizing agent is a surfactant which will form micelles in water at
concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobic part of the micelle. The types of surfactants usually used for solubilization are non- ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.
Surfactants are sometimes used, either alone or with other additives such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target. The types of surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.
A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and water- dispersible granules.
Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil- in-water emulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and CIO aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.
Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed particles or droplets.
Thickening, gelling, and anti-settling agents generally fall into two categories, namely water- insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and attapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.
Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p- hydroxybenzoate; and l,2-benzisothiazolin-3-one (BIT).
The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non- silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface.
"Green" agents {e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodegradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources. Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides.
For further information, see "Chemistry and Technology of Agrochemical
Formulations" edited by D.A. Knowles, copyright 1998 by Kluwer Academic Publishers. Also see "Insecticides in Agriculture and Environment - Retrospects and Prospects" by A.S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer- Verlag.
PESTS
In general, the molecules of Formula One may be used to control pests e.g. beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
In another embodiment, the molecules of Formula One may be used to control pests in the Phyla Nematoda and/or Arthropoda.
In another embodiment, the molecules of Formula One may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.
In another embodiment, the molecules of Formula One may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta. In another embodiment, the molecules of Formula One may be used to control pests of the Order Anoplura. A non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.
In another embodiment, the molecules of Formula One may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica,, Sitona lineatus,
Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Dermaptera. In another embodiment, the molecules of Formula One may be used to control pests of the Order Blattaria. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum,
Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinellafrit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp.,
Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus hews, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva jrimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitifoliae, Physokermes piceae,, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera,
Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Hymenoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A non-exhaustive list of particular species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Isoptera. A non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp.,
Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus,
Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp.,
Synanthedon spp., and Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaeajanata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera,
Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae,
Maruca testulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera pyrina.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis,
Ctenocephalides felis, and Pulex irritans.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non- exhaustive list of particular sp. includes, but is not limited to, Frankliniella fusca,
Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips t abaci.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Thermobia spp.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus lotus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.
In another embodiment, the molecules of Formula One may be used to control pest of the Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.
In another embodiment, the molecules of Formula One may be used to control pests of the Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus reniformis.
For additional information consult "HANDBOOK OF PEST CONTROL - THE
BEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS" by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
APPLICATIONS
Molecules of Formula One are generally used in amounts from about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.
The area to which a molecule of Formula One is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder species, vines, turf and ornamental plants, are growing; where domesticated animals are residing; the interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used in building (such as impregnated wood), and the soil around buildings. Particular crop areas to use a molecule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use ammonium sulfate with a molecule of Formula One when growing various plants. Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area. This can come about when: pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent. Generally, the area is not in or on a human; consequently, the locus is generally a non-human area.
The molecules of Formula One may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1- methylcyclopropene (also known as 1-MCP). Furthermore, such molecules may be used during times when pest activity is low, such as before the plants that are growing begin to produce valuable agricultural commodities. Such times include the early planting season when pest pressure is usually low.
The molecules of Formula One can be applied to the foliar and fruiting portions of plants to control pests. The molecules will either come in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The molecules of Formula One can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.
Generally, with baits, the baits are placed in the ground where, for example, termites can come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with, and/or be attracted to, the bait. Baits can comprise a molecule of Formula One.
The molecules of Formula One can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).
Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the molecules of Formula One may be desirable to control newly emerged larvae. Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the molecules of Formula One to a different portion of the plant. For example, control of foliar- feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.
Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as "Roundup Ready" seed, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other beneficial traits.
Furthermore, such seed treatments with the molecules of Formula One may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time. Generally, about 1 gram of the molecules of Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits, amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.
It should be readily apparent that the molecules of Formula One may be used on, in, or around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition- enhancement, or any other beneficial traits.
The molecules of Formula One may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The molecules of Formula One are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.
The molecules of Formula One may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animals. Suitable formulations are administered orally to the animals with the drinking water or feed. The dosages and formulations that are suitable depend on the species.
The molecules of Formula One may also be used for controlling parasitic worms, especially of the intestine, in the animals listed above.
The molecules of Formula One may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.
Pests around the world have been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The molecules of Formula One may also be used on such new invasive species to control them in such new environment.
The molecules of Formula One may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molecules in such area is to benefit the plants being grown in the area. Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients), improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.
Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy evaluation processes by various governmental authorities (local, regional, state, national, and international). Voluminous data requirements are specified by regulatory authorities and must be addressed through data generation and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and supported, such user or seller may use or sell such pesticide.
A molecule according to Formula One can be tested to determine its efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties. The headings in this document are for convenience only and must not be used to interpret any portion hereof.
TABLE SECTION
Figure imgf000112_0001
Table 1: Structures for Compounds
Figure imgf000113_0001
Figure imgf000114_0001
113
Figure imgf000115_0001
114
Figure imgf000116_0001
115
Figure imgf000117_0001
116
Figure imgf000118_0001
117
Figure imgf000119_0001
118
Figure imgf000120_0001
119
Figure imgf000121_0001
120
Figure imgf000122_0001
121
Figure imgf000123_0001
ı22
Figure imgf000124_0001

Figure imgf000125_0001

Figure imgf000126_0001

Figure imgf000127_0001

Figure imgf000128_0001

Figure imgf000129_0001

Figure imgf000130_0001

Figure imgf000131_0001
130
Figure imgf000132_0001
131
Figure imgf000133_0001
ı32
Figure imgf000134_0001
ı33
Figure imgf000135_0001

Figure imgf000136_0001

Figure imgf000137_0001

Figure imgf000138_0001

Figure imgf000139_0001

Figure imgf000140_0001

Figure imgf000141_0001
140
Figure imgf000142_0001
141
Figure imgf000143_0001
ı42
Figure imgf000144_0001
ı43
Figure imgf000145_0001
ı44
Figure imgf000146_0001
Figure imgf000147_0001

Figure imgf000148_0001

Figure imgf000149_0001

Figure imgf000150_0001

Figure imgf000151_0001
Figure imgf000152_0001
151
Figure imgf000153_0001
Figure imgf000153_0002
(300 MHz, CDC13) 8.44 (d, J = 2.2 Hz,
210.1- 361.8 IH), 8.11 - 8.00 (m,
Yellow Solid
211.9 ([M+H]+) IH), 6.98 (s, IH),
5.44 (s, 2H), 2.69 (s, 3H)
Figure imgf000154_0001
7.50 - 7.31 (m, 3H),
197.9- 340.9
Yellow Solid 7.02 (s, IH), 4.36 (s,
200.8 «M+H]+)
2H), 2.71 (s, 3H), 2.16 (s, 3H)
Figure imgf000154_0002
212.0- 394.8 7.56 (s, 2H), 7.02 (s,
Yellow Solid
213.3 ([M+H]+) IH), 4.35 (s, 2H),
2.71 (s, 3H)
Figure imgf000154_0003
7.74 (s, IH), 7.56 (d,
210.8- 412.9
Yellow Solid 7 = 8.5 Hz, IH), 7.06
213.4 «M+H]+)
(s, IH), 4.45 (s, 2H), 2.74 (s, 3H)
(300 MHz, CDCI3) 8.72 (s, IH), 8.27 (d,
182.9- 395.8
Yellow Solid 7 = 1.7 Hz, IH), 6.99
184.0 ([M+H]+)
(s, IH), 5.78 (s, 2H), 2.72 (s, 3H)
Figure imgf000154_0004
7.94 (d, 7 = 8.4 Hz, 2H), 7.84 (d, 7 = 8.5
219.3- 389 Hz, 2H), 7.05 (s,
Yellow Solid
220.4 ([M+H]+) IH), 4.63 (s, 2H),
3.20 (dt, 7 = 13.8, 6.8 Hz, IH), 1.39 (d, 7 = 6.9 Hz, 6H)
Figure imgf000154_0005
7.92 (s, IH), 7.76 (s, 2H), 7.09 (s, IH),
208.9- 422.9
Yellow Solid 4.44 (s, 2H), 3.25
210.6 «M+H]+)
(dt, 7 = 13.9, 7.1 Hz, IH), 1.40 (d, 7 = 6.9 Hz, 6H)
Figure imgf000154_0006
7.83 (s, 2H), 7.10 (s,
235.3- 456.8 IH), 4.43 (s, 2H),
Yellow Solid
236.6 ([M+H]+) 3.32 (dt, 7 = 13.7,
6.9 Hz, IH), 1.41 (d, 7 = 6.9 Hz, 6H) (300 MHz, CDC13) 8.44 (d, 7 = 1.9 Hz, IH), 8.06 (d, 7 = 1.8
207.1- 389.8 Hz, IH), 7.05 (s,
Yellow Solid
208.4 «M+H]+) IH), 5.57 (s, 2H),
3.57 - 3.38 (m, IH), 1.42 (d, 7 = 6.9 Hz, 6H)
Figure imgf000155_0001
7.39 (m, 3H), 7.06
208.0- 369.0 (s, IH), 4.44 (s, 2H),
Yellow Solid
210.4 «M+H]+) 3.38 (m, IH), 2.15
(s, 3H), 1.40 (d, 7 =
6.8 Hz, 6H)
Figure imgf000155_0002
7.56 (s, 2H), 7.04 (s,
208.6- 422.9 IH), 4.32 (s, 2H),
Yellow Solid
209.4 ([M+H]+) 3.19 (dt, 7 = 13.8,
6.9 Hz, 2H), 1.38 (d, 7 = 6.9 Hz, 6H)
Figure imgf000155_0003
7.74 (s, IH), 7.55 (d, 7 = 8.3 Hz, IH), 7.09
203.8- 440.8
Yellow Solid (s, IH), 4.43 (s, 2H),
205.6 «M+H]+)
3.23 (dt, 7 = 13.8, 6.9 Hz, IH), 1.40 (d, 7 = 6.9 Hz, 6H)
Figure imgf000155_0004
8.70 (s, IH), 8.26 (s, IH), 7.01 (s, IH),
205.3- 423.9
Yellow Solid 5.71 (s, 2H), 3.23
207.8 ([M+H]+)
(dt, 7 = 13.7, 6.8 Hz, IH), 1.38 (d, 7 = 6.9 Hz, 6H)
Figure imgf000155_0005
8.15 (d, 7 = 8.7 Hz, 2H), 7.95 (d, 7 = 8.3
242.9- 457.0
Yellow Solid Hz, 2H), 7.86 (d, 7 =
244.1 ([M+H]+)
8.7 Hz, 2H), 7.60 (s, IH), 7.49 (d, 7 = 8.7 Hz, 2H), 4.73 (s, 2H)
Figure imgf000155_0006
8.17 (d, 7 = 8.5 Hz,
243.6- 490.8 2H), 7.95 (s, IH),
Yellow Solid
245.1 «M+H]+) 7.80 (s, 2H), 7.64 (s,
IH), 7.51 (d, 7 = 8.4 Hz, 2H), 4.51 (s, 2H)
Figure imgf000156_0001
(300 MHz, CDC13)
395.9 8.77 (s, IH), 8.29 (s,
Yellow Oil
«M+H]+) IH), 6.14 (s, 2H),
2.66 (s, 3H)
Figure imgf000157_0001
209.8- 444.8 7.53 - 7.30 (m, 4H),
Yellow Solid
211.8 «M+H]+) 4.54 (s, 2H), 2.16 (s,
3H)
(300 MHz, CDCI3) 7.80 (s, 2H), 7.55 (s,
225.8- 412.9
Yellow Solid IH), 5.54 (d, 7 =
227.4 «M+H]+)
46.6 Hz, 2H), 5.00 (s, 2H)
Figure imgf000157_0002
208.9- 378.9 7.74 - 7.33 (m, 3H),
Yellow Solid
210.4 «M+H]+) 7.01 (3, IH), 4.33 (s,
2H), 2.68 (s, 3H)
Figure imgf000157_0003
226.2- 465.0 8.0 - 7.83 (m, 4H),
Yellow Solid
228.0 «M+H]+) 7.44 (s, IH), 4.84 (s,
2H)
Figure imgf000157_0004
8.77 (s, IH), 8.31 (d,
145.2- 413.9 7 = 1.6 Hz, IH), 7.57
Yellow Solid
147.2 «M+H]+) (s, IH), 6.01 (s, 2H),
5.54 (d, 7 = 46.5 Hz, 2H)
Figure imgf000157_0005
10.21 (s, IH), 7.92 (d, 7 = 8.4 Hz, 2H),
360.9
Yellow Oil 7.82 (d, 7 = 8.4 Hz,
«M+H]+)
2H), 7.37 (s, IH), 5.32 (s, 2H), 2.68 (s, 3H)
Figure imgf000157_0006
7.75 - 7.39 (m, 3H), 7.06 (s, IH), 4.29 (s,
407.3
Yellow Oil 2H), 3.21 (dt, 7 =
«M+H]+)
13.6, 6.9 Hz, IH), 1.38 (d, 7 = 6.9 Hz, 6H)
(300 MHz, CDCI3)
202.7- 532.7
Yellow Solid 7.86 (s, 2H), 7.45 (s,
204.5 ([M+H]+)
IH), 4.59 (s, 2H)
Figure imgf000157_0007
8.78 (d, 7 = 1.1 Hz,
466.9
Yellow Oil IH), 8.32 (d, 7 = 1.9
([M+H]+)
Hz, IH), 7.83 (s, IH), 6.09 (s, 2H) (300 MHz, CDC13) 7.67 (dd, 7 = 8.2, 2.6
199.9- 483.0
Yellow Solid Hz, IH), 7.61 - 7.47
202.8 «M+H]+)
(m, 2H), 7.44 (s, IH), 4.51 (s, 2H)
Figure imgf000158_0001
198.6- 499.8 8.76 (s, IH), 8.32 (s,
Yellow Solid
200.0 «M+H]+) IH), 7.38 (s, IH),
5.86 (s, 2H)
Figure imgf000158_0002
229.7- 428.9 7.84 (s, 2H), 7.26 (s,
Yellow Solid
231.4 «M+H]+) IH), 4.68 (s, 2H),
2.63 (s, 3H)
Figure imgf000158_0003
226.2- 412.9 7.69 - 7.52 (m, 3H),
Yellow Solid
229.1 ([M+H]+) 5.54 (d, 7 = 46.6 Hz,
2H), 4.73 (s, 2H)
Figure imgf000158_0004
217.0- 412.8 7.76 (s, IH), 7.57 (d,
Yellow Solid
217.9 «M+H]+) 7 = 8.3 Hz, IH), 4.81
(s, 2H), 2.63 (s, 3H)
Figure imgf000158_0005
204.6- 432.6 7.81 (s, IH), 7.62 (s,
Yellow Solid
207.0 ([M+H]+) 2H), 6.74 (t, 7 = 55.5
Hz, IH), 4.79 (s, 2H)
Figure imgf000158_0006
222.5- 448.9 7.81 (s, 1H), 7.75 -
Yellow Solid
224.0 ([M+H]+) 7.43 (m, 3H), 4.77
(s, 2H)
Figure imgf000158_0007
7.96 (s, 1H), 7.86 -
155.8- 430.9
Yellow Solid 7.69 (m, 3H), 6.74 (t,
157.2 «M+H]+)
7 = 55.5 Hz, IH), 4.84 (s, 2H)
(301 MHz, CDCI3) 7.95 (s, 1H), 7.86 -
464.7
Yellow Oil 7.76 (m, 2H), 7.72
([M+H]+)
(d, 7 = 8.3 Hz, IH), 4.94 (s, 2H)
Figure imgf000158_0008
7.86 (s, 2H), 7.60 (s,
196.4- 447.0
Yellow Solid IH), 5.55 (d, 7 =
198.6 «M+H]+)
46.6 Hz, 2H), 4.75 (s, 2H)
Figure imgf000158_0009
171.2- 410.9 7.82 (s, 1H), 7.57 -
Yellow Solid
173.9 ([M+H]+) 7.27 (m, 3H), 4.77
(s, 2H), 2.12 (s, 3H)
Figure imgf000159_0001
Figure imgf000160_0001
Figure imgf000161_0001
(300 MHz, CDC13)
8.79 (s, IH), 8.32 (s,
163.0- 431.9
80 Yellow Solid IH), 7.80 (s, IH),
163.9 «M+H]+)
6.72 (t, 7 = 55.5 Hz, IH), 6.05 (s, 2H)
(300 MHz, DMSO- d6) 8.09 (s, IH), 8.02
134.4- 415
81 Yellow Solid (d, 7 = 8.6 Hz, 2H),
137.0 «M+H]+)
7.94 (d, 7 = 8.5 Hz, 2H), 6.76 (s, 2H)
(300 MHz, DMSO- d6) 8.04 (s, IH), 8.00
194.6- 414.9 (d, 7 = 2.1 Hz, IH),
82 Yellow Solid
195.4 «M+H]+) 7.77 - 7.72 (m, IH),
7.72 - 7.66 (m, IH), 6.82 (s, 2H)
(300 MHz, DMSO- d6) 8.01 (s, IH), 7.70 - 7.55 (m, 1H), 7.46
120.6- 376.9 (d, 7 = 7.7 Hz, IH),
83 Yellow Solid
121.8 «M+H]+) 7.33 (d, 7 = 8.4 Hz,
IH), 7.17 (t, 7 = 7.6 Hz, IH), 6.32 (s, 2H), 3.81 (s, 3H)
(300 MHz, DMSO- d6) 8.05 (s, IH), 7.61
157.5- 403.0
84 Yellow Solid (q, 7 = 8.6 Hz, 4H),
158.9 ([M+H]+)
6.45 (s, 2H), 1.34 (s, 9H)
(301 MHz, DMSO- d6) 8.05 (s, IH), 7.52
141.9- 361.0 (d, 7 = 8.3 Hz, 2H),
85 Yellow Solid
143.4 ([M+H]+) 7.43 (d, 7 = 8.3 Hz,
2H), 6.40 (s, 2H), 2.42 (s, 3H)
(301 MHz, DMSO- ) 8.17 (d, 7 = 8.5
216.9- 425.0 Hz, 2H), 8.09 (s,
86 Yellow Solid
218.4 «M+H]+) IH), 7.97 (d, 7 = 8.5
Hz, 2H), 6.81 (s, 2H), 3.33 (s, 3H)
(300 MHz, DMSO-
206.7- 414.9 d6) 8.05 (s, IH), 7.86
87 Yellow Solid
207.9 ([M+H]+) - 7.59 (m, 3H), 7.00
(s, 2H) (300 MHz, DMSO- d6) 8.00 (s, IH), 7.74
182.4- 410.9 - 7.55 (m, 2H), 7.35
88 Yellow Solid
183.5 ([M+H]+) (d, 7 = 9.0 Hz, IH),
6.54 (s, 2H), 3.80 (s, 3H)
(300 MHz, CDC13)
193.7- 395.0 7.87 (s, 1H), 7.60 -
89 Yellow Solid
194.9 «M+H]+) 7.30 (m, 3H), 4.78
Figure imgf000163_0001
7.87 (s, IH), 7.49 (s,
394.9 IH), 7.43 (d, 7 = 8.0
90 Yellow Solid 105.1- 105.8 ([M+H]+) Hz, IH), 7.33 (d, 7 =
8.0 Hz, IH), 4.83 (s, 2H), 2.49 (s, 3H)
(301 MHz, DMSO- d6) 8.08 (s, IH), 7.49
167.1- 374.9 - 7.40 (m, 1H), 7.33
91 Yellow Solid
167.7 ([M+H+) (d, 7 = 7.7 Hz, 2H),
6.43 (s, 2H), 1.94 (s, 6H)
Figure imgf000163_0002
214.8- 428.8 7.84 (s, 1H), 7.51 -
92 Yellow Solid
216.3 ([M+H]+) 7.36 (m, 2H), 4.84
(s, 2H), 2.44 (s, 3H)
(300 MHz, DMSO- d6) 8.08 (s, IH), 7.88
159.2- 430.9
93 Yellow Solid - 7.77 (m, 2H), 7.64
161.4 ([M+H]+)
(d, 7 = 8.3 Hz, 2H), 6.67 (s, 2H)
(300 MHz, DMSO-
289.0- 492.9 d6) 8.3 l (s, 2H), 8.08
94 Yellow Solid
291.1 «M+H]+) (s, lH), 7.18 (s, 2H),
Figure imgf000163_0003
8.79 (s, IH), 8.49 (d,
157.3- 415.9 7 = 8.8 Hz, IH), 8.21
95 Yellow Solid
158.9 ([M+H]+) (d, 7 = 8.7 Hz, IH),
7.78 (s, IH), 7.67 (s, 2H)
Figure imgf000163_0004
8.53 (d, 7 = 3.9 Hz, IH), 8.07 (dd, 7 =
144.8- 381.9
96 Yellow Solid 8.1, 1.3 Hz, IH),
145.7 «M+H]+)
7.88 (s, IH), 7.49 (dd, 7 = 8.1, 4.7 Hz, IH), 5.84 (s, 2H)
Figure imgf000164_0001
Figure imgf000165_0001
(300 MHz, CDC13)
8.42 (s, IH), 7.81 (s,
107.9- 429.9
112 Yellow Solid IH), 7.70 (s, 2H),
109.1 ([M+H]+)
7.43 (s, IH), 2.76 (s,
3H)
Figure imgf000166_0001
8.53 (d, J = 2.2 Hz,
153.2- 415.8
113 Yellow Solid IH), 8.13 (d, J = 2.2
155.9 ([M+H]+)
Hz, 1H), 7.91 (s, IH), 5.81 (s, 2H)
Figure imgf000166_0002
159.7- 449.9 8.80 (s, IH), 8.34 (s,
114 Yellow Solid
160.9 ([M+H]+) IH), 7.89 (s, IH),
Figure imgf000166_0003
8.46 (d, 7 = 4.0 Hz, IH), 7.93 - 7.83 (m,
164.0- 361.9
115 Yellow Solid 2H), 7.42 (dd, 7 =
166.3 ([M+H]+)
7.7, 4.6 Hz, IH), 6.20 (s, 2H), 2.58 (s, 3H)
Figure imgf000166_0004
211.1- 141.9 8.01 - 7.80 (m, 4H),
116 Yellow Solid
213.0 ([M+H]+) 7.42 (s, IH), 4.83 (s,
Figure imgf000166_0005
157.9- 448.9 7.94 (s, IH), 7.87 -
117 Yellow Solid
159.7 ([M+H]+) 7.67 (m, 2H), 7.43
Figure imgf000166_0006
7.42 (s, IH), 7.33 (d,
152.0- 391.1 7 = 8.5 Hz, IH), 7.00
118 Yellow Solid
153.7 ([M+H]+) - 6.86 (m, 2H), 4.57
(s, 2H), 3.91 (s, 3H), 2.13 (s, 3H)
(300 MHz, DMSO- d6) 7.65 - 7.52 (m,
2H), 7.51 - 7.37 (m,
147.7- 375
119 Yellow Solid 3H), 6.06 (s, 2H),
149.9 ([M+H]+)
2.41 - 2.25 (m, 2H), 1.04 (t, 7 = 7.5 Hz, 3H)
Figure imgf000166_0007
7.62 - 7.52 (m, 2H),
170.9- 377.0
120 Yellow Solid 7.41 (s, IH), 7.25 - 172.3 ([M+H]+)
7.14 (m, 2H), 4.73 (s, 2H), 3.92 (s, 4H)
Figure imgf000167_0001
(300 MHz, CDC13)
180.7- 394.8 7.55 - 7.31 (m, 4H),
131 Yellow Solid
182.9 ([M+H]+) 4.57 (s, 2H), 2.18 (s,
3H)
(300 MHz, DMSO- d6) 7.52 - 7.39 (m,
176.4- 375.0
132 Yellow Solid 2H), 7.37 - 7.29 (m,
178.2 ([M+H]+)
2H), 6.11 (s, 2H), 1.93 (s, 6H)
Figure imgf000168_0001
221.0- 428.9 7.59 - 7.37 (m, 3H),
133 Yellow Solid
222.3 ([M+H]+) 4.56 (s, 2H), 2.51 (s,
3H)
(300 MHz, DMSO- d6) 7.92 - 7.79 (m,
203.4- 431.0
134 Yellow Solid 2H), 7.71 - 7.59 (m,
205.5 ([M+H]+)
2H), 7.54-7.48 (m, IH), 6.36 (s, 2H)
(300 MHz, DMSO-
267.3- 492.9 d) 8.30 (s, 2H), 7.47
135 Yellow Solid
269.1 ([M+H]+) (s, IH), 6.85 (s, 2H),
Figure imgf000168_0002
194.9- 430.0 8.60 (s, IH), 7.49 -
136 Yellow Solid
195.8 ([M+H]+) 7.37 (m, 3H), 7.31
Figure imgf000168_0003
181.2- 415.8 8.50 (s, IH), 8.12 (s,
137 Yellow Solid
183.9 ([M+H]+) IH), 7.39 (s, IH),
5.63 (s, 2H)
(300 MHz, DMSO-
167.9- 449.9 ck) 9.14 (s, IH), 8.97
138 Yellow Solid
168.7 ([M+H]+) (s, IH), 7.50 (s, IH),
Figure imgf000168_0004
8.80 (s, IH), 8.64 (d,
180.3- 416.0 7 = 8.9 Hz, IH), 8.25
139 Yellow Solid
181.3 ([M+H]+) (d, 7 = 8.9 Hz, IH),
7.43 (s, 2H), 7.30 (s, IH)
(300 MHz, DMSO-
186.5- 381.9 ck) 8.72 (s, IH), 8.35
140 Yellow Solid
188.8 ([M+H]+) - 8.22 (m, 2H), 7.81
(s, 2H), 7.44 (s, IH)
Figure imgf000169_0001
Figure imgf000170_0001
Figure imgf000171_0001
343- 485.0 (400 MHz, DMSO-
165 Yellow Solid
345 ([M-H]-) d6) 7.80 (s, 2H)
(400 MHz, DMSO-
235- 534.92
166 Yellow Solid d6) 9.13(s, IH), 7.84
238 «M+H]+)
(s, 2H)
(400 MHz, DMSO-
254- 483.1
167 Yellow Solid d6) 8.92 (s, IH), 7.78
256 ([M-H]")
(s, 2H)
(400 MHz, DMSO-
232- 449.1 )9.16-9.10
168 Yellow Solid 4
233 ([M-H]") (m, IH), 8.98-8.92
(m, IH), 7.65 (s, 2H)
(400 MHz, DMSO- d6) 9.10-9.06 (m,
194- 415.2 IH), 8.85 (s, 2H),
169 Orange Solid
196 ([M-H]) 8.58 (dd, 7=8.9, 2.3
Hz, IH), 8.37 (d,7 = 8.8 Hz, IH)
(400 MHz, CDC13)
231- 372.93 7.34-7.15 (m, 4H),
170 Yellow Solid
233 ([M-H]) 5.04 (s, 2H), 2.44 (s,
3H), 2.11 (s, 3H)
(400 MHz, DMSO- J = 2.2
263- 396.7 4)7.65 (d,
171 Yellow Solid Hz, IH), 7.55-7.47
265 «M+H]+)
(m, 2H),7.13(s, 2H), 2.05 (s, 3H)
(400 MHz, DMSO-
186- 432.38 d6) 7.83 - 7.74 (m,
172 Yellow Solid
188 «M+H]+) 2H), 7.74 - 7.63 (m,
2H), 7.39 (s, 2H)
(400 MHz, DMSO- d6) 7.48-7.41 (m,
179- 374.33
173 Yellow Solid IH), 7.33 (d, 7 = 7.8
181 ([M-H])
Hz, 2H), 7.02 (s, 2H), 1.96 (s, 6H)
(400 MHz, DMSO-
270- 449.21
174 Yellow Solid d6) 8.08 (s, 2H), 7.65
272 ([M-H])
(s, 2H)
(400 MHz, DMSO- 4)7.98 (dt, 7 = 8.1,
225- 444.9 1.6 Hz, IH), 7.89
175 Yellow Solid
228 «M+H]+) (dd, 7=6.2, 1.3 Hz,
2H), 7.38 (s, 2H), 3.36 (s, 3H)
Figure imgf000173_0001
(400 MHz, DMSO- 4) 8.73 (dd, 7 = 2.6,
0.5 Hz, IH), 8.64 (s,
236- 483.4
186 Yellow Solid 2H), 8.30 (dd, 7 =
238 «M+H]+)
8.9, 2.6 Hz, IH),
8.19 (dd, 7 = 9.0, 0.4
Hz, IH)
(400 MHz, DMSO- ) 9.12 (d, 7 = 2.4
235- 417.8 Hz, IH), 8.45 (dd, 7
187 Yellow Solid
236 «M+H]+) = 8.4, 2.1 Hz, IH),
8.23 (d, 7 = 8.3 Hz,
IH), 7.56 (s, 2H)
(400 MHz, DMSO- d6) 7.23 - 7.08 (m,
227- 390
188 Yellow Solid 2H), 6.97 (s, 2H),
229 «M+H]+)
2.36 (s, 3H), 1.92 (s,
6H)
(400 MHz, DMSO- ) 8.13 (d, 7 = 2.1
262- 459.02 Hz, IH), 7.84 (dd, 7
189 Yellow Solid
266 ([M-H]-) = 8.5, 2.1 Hz, IH),
7.67 (d, 7 = 8.5 Hz,
IH), 7.40 (s, 2H)
(400 MHz, DMSO- 4) 8.21 (d, 7 = 1.8
256- 508.6 Hz, IH), 7.98 (dd, 7
190 Yellow Solid
260 «M+H]+) = 8.3, 1.9 Hz, IH),
7.46 (d, 7 = 8.3 Hz,
IH), 7.38 (s, 2H)
(400 MHz, CDC13)
187- 480 8.40 - 8.30 (m, IH),
191 Yellow Solid
192 ([M+H]+) 8.18 - 8.07 (m, IH),
Figure imgf000174_0001
8.48 - 8.43 (d, 7 =
8.6 Hz, IH), 8.06 -
465.1
192 Yellow Solid 80-90 7.97 (m, 2H), 7.86 - ([M-H]")
7.80 (m, 1H), 7.76 - 7.71 (m, IH), 5.22
(s, 2H)
Anal. Calcd for
(300 MHz, CDCI3) C13H6C1F6N5: C,
382 7.35 (m, IH), 7.65 40.9; H, 1.58; N,
193 Orange Solid 181- 182 «M+H]+) (m, IH), 7.58 (m, 18.4. Found: C,
2H), 5.20 (br s, 2H) 40.5; H, 1.70; N,
18.0.
Figure imgf000175_0001
Anal. Calcd for
CiaHsCWJs: C,
(300 MHz, CDC13)
Dark Yellow 180- 416 37.5; H, 1.21; N,
208 7.60 (m, 3H), 5.20
Solid 182 ([M+H]+) 16.8. Found: C,
(br s, 2H)
37.6; H, 1.37; N, 16.4
(400 MHz, DMSO- d6)T 4 (d, 7=8.2
201- 431
209 Yellow Solid Hz, 2H), 7.47 (d, 7 =
203 ([M+H]+)
8.1 Hz, 2H),7.33 (s,
2H), 5.70 (s, 2H)
(400 MHz, DMSO-
250- 498.91 d6) 8.38 - 8.35 (m,
210 Yellow Solid
252 ([M+H]+) 2H), 7.36 (s, IH),
2.69 (s, 3H)
(400 MHz, DMSO- ck) 8.40 (s, 2H), 7.00
153- 413.01 (t, 7=5.9 Hz, IH),
211 Orange Solid
156 ([M+H]+) 3.09 (p, 7 = 7.0 Hz,
2H), 1.05 (t, 7 = 7.1
Figure imgf000176_0001
7.89-7.81 (m, 2H),
146- 528.7 4.93 (d, 7 = 7.3 Hz,
212 Yellow Solid
148 ([M+H]+) IH), 3.22-3.05 (m,
IH), 1.14 (d,7 = 6.4
Hz, 6H)
(400 MHz, DMSO- d6) 8.46 - 8.33 (m,
2H), 7.00 (t,7 = 5.8
141- 538.9 Hz, 1H),2.91 (t,7 =
213 Yellow Solid
144 ([M+H]+) 6.5 Hz, 2H), 0.99 - 0.87 (m, IH), 0.48 - 0.33 (m, 2H), 0.20 - 0.05 (m, 2H)
(400 MHz, CDCI3)
7.86 (s,2H), 5.14 (s,
IH), 3.16-2.92 (m,
131- 573.4
214 Yellow Solid 2H), 1.88- 1.68 (m,
133 ([M+H]+)
IH), 1.61 - 1.47 (m,
IH), 1.19-1.03 (m,
Figure imgf000176_0002
7.77 (s, 2H), 3.93 - 3.80 (m, 2H), 3.16 (t,
Brown Solid 104- 633.21
215 7 =6.8 Hz, 2H), 2.88
Residue 110 ([M+H]+)
- 2.75 (m, 2H), 2.65
(t, 7 =6.8 Hz, 2H),
2.11-2.0 (m, 6H)
Figure imgf000177_0001
Figure imgf000178_0001
Figure imgf000179_0001
Figure imgf000180_0001
Table 3: Biological Results
Figure imgf000180_0002
24 D A D A
25 A A C B
26 C C C C
27 D D C C
28 D D C C
29 D D C C
30 D D C C
31 D D C C
32 D D C C
33 D D C C
34 D D C C
35 D D C D
36 D D C D
37 D D C D
38 D A D A
39 D D C D
40 A A B D
41 D D C D
42 D D C D
43 D D C D
44 A D C D
45 D D C D
46 D D B A
47 A A C B
48 D D C D
49 A D C D
50 A A B D
51 D D C D
52 D D D A
53 D D C D
54 D D C D
55 B B D D
56 D D C D
57 D D C D
58 D D C D
59 D D C D
60 A D C D
61 D D C D
62 D D C D
63 B D C D
64 D D D A
65 D D C D 66 D D C D
67 D D C D
68 D A C B
69 A A D B
70 D D C D
71 D D C D
72 D D C D
73 C C C C
74 D D C C
75 D D C C
76 A A C C
77 D D C C
78 D D C D
79 D D B D
80 D D C D
81 A A C B
82 A D C C
83 D D C D
84 B D C D
85 D D C D
86 A B C D
87 A A C D
88 D D C D
89 A D C D
90 D D C D
91 B D C D
92 D D C D
93 A A D B
94 D D C D
95 B D C D
96 A D C D
97 A B C D
98 A A C D
99 A A B D
100 A A B D
101 A D C D
102 A A D D
103 A B C D
104 D D C C
105 A A C C
106 A A C D
107 D D C D 108 B A C B
109 D D C D
110 A D C D
111 D D C B
112 B D C D
113 A D B D
114 A A D A
115 D D C D
116 A A D D
117 A A B A
118 D D C C
119 D D C C
120 D D C D
121 D D C D
122 D D C D
123 D D C D
124 D D C D
125 A A C C
126 B B C D
127 D D C C
128 A D D D
129 D D C D
130 C C C C
131 B D D D
132 D D C D
133 D D C D
134 A D D D
135 D D C C
136 D D C C
137 A A C D
138 A A D D
139 A A C C
140 A D C D
141 D D B C
142 D D C C
143 D D B C
144 A A C D
145 A A C D
146 A A B A
147 A A D B
148 A A C D
149 A A B B 150 A A D A
151 A D B D
152 A A D A
153 A A B B
154 A A B D
155 A A B D
156 A A C B
157 A A B D
158 A A C D
159 A D C B
160 A A B D
161 A A C D
162 A A B A
163 A A B D
164 A A C D
165 D D C D
166 A D D D
167 A D C D
168 A A D D
169 D D C B
170 D D D D
171 A A D D
172 A A B B
173 A D D D
174 A A B A
175 D D B B
176 A D D D
177 A D B D
178 A A D B
179 A A D A
180 A A B A
181 A D D D
182 A A D D
183 A A D D
184 A A D D
185 A B D D
186 A D D D
187 A A D D
188 B D C D
189 A A D D
190 A A B D
191 A A D A 192 D D C C
193 A B B B
194 A A B D
195 A D B D
196 A B C D
197 D D B D
198 D D D D
199 D D B D
200 D D D D
201 B D C C
202 D D B D
203 C C D D
204 D D C D
205 A A D A
206 D D B D
207 B D C D
208 A A D D
209 A A B D
210 A A B B
211 A A D A
212 A A B A
213 A A B A
214 A A B A
215 A A C C
216 A A D A
217 A A D B
218 B A D D
219 A A D D
220 A A B A
221 A A C B
222 A A B A
223 A A D A
224 A A C B
225 A A B D
226 A A C A
227 A A B D
228 D D C B
229 A A B A
230 A A D B
231 A A C D
232 D D C D
233 A A C D 234 D D B D
235 D D C D
236 B D C D
237 A D C D
238 D D C A
239 D B B A
240 D A D D
241 D A D D
242 D D C D

Claims

WE CLAIM
1. A composition comprisin a molecule according to Formula One:
Figure imgf000187_0001
wherein
(A) (Al) X1 is selected from N and CR6;
(A2) X2 is selected from N and CR5;
(B) (Bl) R1 and R2 are (each independently) selected from
(a) H, OH, SH,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000187_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C3- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, S- heterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g) N(R8)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, and
(h) C3-C8 cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d), and (h) of (Bl) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(bl)
Figure imgf000188_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a2) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000188_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b3)
Figure imgf000189_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, (h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a4) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000190_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000190_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Bl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000191_0001
C8)alkyl, S(0)(CrC8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, C(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl, (B2) optionally R1 and R2 along with N1 can instead form a 5- or 6- membered ring, where said ring may be saturated or unsaturated, where the additional atoms in said ring (ring atoms) are selected from C, S, S(O), S(0)2, N, or O (provided that two oxygen atoms are not bonded to each other), and where each C or N ring atom that can have non-ring bonds is bonded to one or more of the following excluding N-F, N-Cl, N-Br and N-I
(a) H, F, CI, Br, I, CN, N02, OH, SH, (=0),
(b) (C C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000192_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C3- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl,
C(=S)0(C3-C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl,
Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g) N(R8)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), and (d) of
(B2) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000192_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (B2) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000193_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl, (C) (CI) R3 and R4 are (each independently) selected from
(a) H, F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000194_0001
C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2- C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl,
(d) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C3-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, S(C3-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2- C8)alkynyl, OC(=0)0(C3-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C3-C8)alkenyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl,
(g) N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=S)N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (h) of (CI) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000194_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (CI) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000195_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Cl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b3)
Figure imgf000196_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Cl) may (each independently) be substituted with one or more substituents selected from
(a4) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000196_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (CI) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000197_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(d-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and (h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (CI) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000198_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl,
(D) (Dl) R5 and R6 are (each independently) selected from
(a) H, F, CI, Br, I, CN, OH, OSi((C C8)alkyl)3,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000198_0002
C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C3- C8)alkenyl, OC(=0)(C2-C8)alkenyl, S(C3-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-
C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, (d) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C3- C8)alkynyl, OC(=0)(C2-C8)alkynyl, S(C3-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2- C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl,
(g) N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=S)N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d), and (h) of (Dl) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000199_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and (hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000200_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b3)
Figure imgf000200_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a4) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000201_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b5)
Figure imgf000202_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Dl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000202_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl, (d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl,
(E) (El) R7 is selected from
(a) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, S(0)(C
C8)alkyl, S(0)2(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl,
(b) (C3-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, (0)(C2- C8)alkenyl, S(0)2(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl,
(c) (C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C2-C8)alkynyl,
(d) phenyl, C(=0)phenyl, C(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, S(0)phenyl, S(0)2phenyl,
(e) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(f) C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (a), (b), (c), and (h) of (El) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3, (bl)
Figure imgf000204_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (d) and (e) of (El) may (each independently) be substituted with one or more substituents selected from
(a2) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (C C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000204_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-
C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, (f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (El) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b3)
Figure imgf000205_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl,
OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (El) may (each independently) be substituted with one or more substituents selected from
(a4) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3, (b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000206_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (El) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000206_0002
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMQ-QOalkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, (f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (El) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000207_0001
C8)alkyl, S(0)(CrC8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl, (F) (Fl) R8 (each independently) is selected from
(a) H, CN, OH, (b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, C(=0)NH(C
C8)alkyl, C(=S)NH(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, C(=0)NH(C2- C8)alkenyl, C(=S)NH(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(0)(C2-
C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C3-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, C(=0)NH(C2- C8)alkynyl, C(=S)NH(C2-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(0)(C3- C8)alkynyl, S(0)2(C3-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, C(=0)NHphenyl, C(=S)NHphenyl,
C(=S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)2phenyl,
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, C(=0)NH- heterocyclyl, C(=S)NH-heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl,
S(0)heterocyclyl, S(0)2heterocyclyl, and
(h) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl in (b), (c), (d) and (g) of (Fl) may (each independently) be substituted with one or more substituents selected from
(al) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(bl)
Figure imgf000208_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, SCOMd-CgJalkyl
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl, (gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a2) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (C C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000209_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and
S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b3)
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(Ci-C8)alkyl, (c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a4) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000210_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl, (g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2,
C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3),
(c4), (d3), (d4), (h3), and (h4) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5)
Figure imgf000211_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2- C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl,
OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3- C8)alkynyl, S(C2-C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Fl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000211_0002
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl, (c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl,
C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl; and
(G) (Gl) R9 (each independently) is selected from
(a) H, CN, OH, OSi((Ci-C8)alkyl)3,
(b) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000212_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C3- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl,
C(=S)0(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C2-C8)alkynyl, 0(C3-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(0)(C3-C8)alkynyl, S(0)2(C3-C8)alkynyl,
(e) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl, C(=S)phenyl, C(=S)Ophenyl, S(0)phenyl, S(0)2phenyl
(f) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, C(=S)heterocyclyl, C(=S)Oheterocyclyl, S(0)heterocyclyl,
S(0)2heterocyclyl, and
(g) (C3-C8)cycloalkyl, wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b), (c), (d) and (g) of (Gl) may (each independently) be substituted with one or more substituents selected from (al) F, CI, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(bl)
Figure imgf000213_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(cl) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2- C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2- C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(dl) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2-
C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(el) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(fl) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl,
OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(gl) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(hi) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e) and (f) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a2) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3,
(b2) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl, OC(=0)(C C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl , S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c2) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d2) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-
C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl, (e2) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f2) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g2) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, C(=S)N(R9)2, ON(R9)2, OC(=0)N(R9)2, SN(R9)2, S(0)N(R9)2, and S(0)2N(R9)2, and
(h2) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (bl), (b2), (cl), (c2), (dl), (d2), (hi), and (h2) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a3) F, Cl, Br, I, CN, N02, OH, OSi((Ci-C8)alkyl)3,
(b3)
Figure imgf000214_0001
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c3) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2- C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2- C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d3) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2- C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e3) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f3) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g3) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h3) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (el), (e2), (fl), and (f2) of (Gl) may
(each independently) be substituted with one or more substituents selected from
(a4) F, Cl, Br, I, CN, N02, OH, SF5, OSi((C C8)alkyl)3, (b4) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000215_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c4) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d4) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e4) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f4) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g4) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2,
ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h4) (C3-C8)cycloalkyl,
wherein each said alkyl, alkenyl, alkynyl, and cycloalkyl, in (b3), (b4), (c3), (c4), (d3), (d4), (h3), and (h4) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a5) F, CI, Br, I, CN, N02, OH, OSi((C C8)alkyl)3,
(b5) C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl, OC(=0)(C
C8)alkyl, OC(=0)0(C C8)alkyl, C(=S)(C C8)alkyl, C(=S)0(C C8)alkyl, S(C C8)alkyl, S(0)(C C8)alkyl, S(0)2(C1-C8)alkyl,
(c5) C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2-C8)alkenyl, OC(=0)(C2-
C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2- C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d5) C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2-C8)alkynyl, OC(=0)(C2- C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)(C2-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e5) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl, (f5) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g5) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2 , SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h5) (C3-C8)cycloalkyl,
wherein each said phenyl and heterocyclyl in (e3), (e4), (f3), and (f4) of (Gl) may (each independently) be substituted with one or more substituents selected from
(a6) F, CI, Br, I, CN, N02, OH, SF5, OSi((Ci-C8)alkyl)3,
(b6) (Ci-C8)alkyl, C(=0)(C C8)alkyl, C(=0)0(C C8)alkyl, 0(C C8)alkyl,
Figure imgf000216_0001
C8)alkyl, S(0)(C C8)alkyl, S(0)2(C C8)alkyl,
(c6) (C2-C8)alkenyl, C(=0)(C2-C8)alkenyl, C(=0)0(C2-C8)alkenyl, 0(C2- C8)alkenyl, OC(=0)(C2-C8)alkenyl, OC(=0)0(C2-C8)alkenyl, C(=S)(C2-C8)alkenyl, C(=S)0(C2-C8)alkenyl, S(C2-C8)alkenyl, S(0)(C2-C8)alkenyl, S(0)2(C2-C8)alkenyl,
(d6) (C2-C8)alkynyl, C(=0)(C2-C8)alkynyl, C(=0)0(C3-C8)alkynyl, 0(C2- C8)alkynyl, OC(=0)(C2-C8)alkynyl, OC(=0)0(C3-C8)alkynyl, C(=S)0(C3-C8)alkynyl, S(C2- C8)alkynyl, S(0)(C2-C8)alkynyl, S(0)2(C2-C8)alkynyl,
(e6) phenyl, C(=0)phenyl, C(=0)Ophenyl, Ophenyl, OC(=0)phenyl,
OC(=0)Ophenyl, C(=S)Ophenyl, C(=S)phenyl, Sphenyl, S(0)phenyl, S(0)2phenyl,
(f6) heterocyclyl, C(=0)heterocyclyl, C(=0)Oheterocyclyl, Oheterocyclyl, OC(=0)heterocyclyl, OC(=0)Oheterocyclyl, C(=S)Oheterocyclyl, C(=S)heterocyclyl, Sheterocyclyl, S(0)heterocyclyl, S(0)2heterocyclyl,
(g6) N(R9)2, NHC(=0)N(R9)2, NHC(=S)N(R9)2, C(=0)N(R9)2, C(=0)ON(R9)2, ON(R9)2, OC(=0)N(R9)2, C(=S)N(R9)2, SN(R9)2, S(0)N(R9)2, S(0)2N(R9)2, and
(h6) (C3-C8)cycloalkyl.
2. A molecule according to claim 1 wherein R1 and R2 are independently selected from one, or any combinations of more than one, of the following, - (Ci-C8)alkyl, (C2-C8)alkenyl, (Ci-C8)alkylS(Ci-C8)alkyl, (C2-C8)alkynyl, (Ci-C8)alkylO(C C8)alkyl, (C
Figure imgf000216_0002
C8)alkyl, C(=0)N(R8)2, C(=0)0(C C8)alkyl, C(=0)0(C C8)substituted alkyl, (C C8)alkyl(C3-C8)cycloalkyl, (Ci-C8)alkyl(C3-C8)substituted cycloalkyl, (C Cs)alkyl(substituted phenyl), H, and 0(Ci-Cs)substituted alkyl.
3. A molecule according to claim 1 wherein R1 and R2 are independently selected from one, or any combinations of more than one, of the following, - (CH2)2C(CH3)3,
(CH2)2CH=CH2, (CH2)2SCH3, (CH2)4C≡CH, (CH2)4CH3, (CH2)4OCH3, (CH2)5OC(=0)CH3, (CH2)5OH, (CH2)5OSi(CH3)2(C(CH3)3), C(=0)(CH2)3CH3, C(=0)CH3,
C(=0)N(H)(C(=0)CC13), C(=0)NH2, C(=0)OC(CH3)3, C(=0)0CH2CC13, C(=0)OCH3, CH(CH3)2, CH2C≡CCH2CH3, CH2CH3, CH2-cyclopentyl, CH2-cyclopropyl, CH2- halocyclopropyl, CH2-halomethylphenyl, CH2-halophenyl, CH3, and H;.
4. A molecule according to claim 1 wherein R1 and R2 are the same.
5. A molecule according to claim 1 wherein R1 and R2 are different.
6. A molecule according to claim 1 wherein R3 is (Ci-Cs)alkyl, which may optionally be substituted with one or more of - F, CI, Br, and I.
7. A molecule according to claim 1 wherein R3 is CF3.
8. A molecule according to claim 1 wherein R4 is (Ci-Cs)alkyl or phenyl, where said alkyl and said phenyl may optionally be substituted with one or more of - F, CI, Br, and I.
9. A molecule according to claim 1 wherein R4 is selected from one, or any
combinations of more than one, of the following, - CF2CF3, CF2C1, CF3, CH(CH3)2, CH2F, CH3, CHF2, and chlorophenyl.
10. A molecule according to claim 1 wherein R4 is CF3.
11. A molecule according to claim 1 wherein R3 and R4 are both CF3.
12. A molecule according to claim 1 wherein R7 is (Ci-Cs)alkyl where said alkyl may optionally be substituted with one or more phenyls, where said phenyl may optionally be substituted with one or more of - F, CI, Br, I, and (Ci-Cs)alkyl (which may optionally be substituted with one or more of - F, CI, Br, and I).
13. A molecule according to claim 1 wherein R7 is a phenyl, where said phenyl may optionally be substituted with one or more of - F, CI, Br, I, N02, (Ci-C8)alkyl, S(0)2(Cr
Cs)alkyl, 0(Ci-Cs)alkyl, halothio, S(0)2N(R8)2, and Ophenyl, where each of said alkyls may optionally be substituted with one or more of - F, CI, Br, and I.
14. A molecule according to claim 1 wherein R7 is a heterocyclyl selected from one, or any combinations of more than one, of the following, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, oxiranyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl, 1,2,3,4-tetrahydroquinolinyl, 4,5- dihydro-oxazolyl, 4,5-dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[l,3,4]- oxadiazolyl, thietanyl, and thietanyl-dioxide.
15. A molecule according to claim 1 wherein R7 is a heterocyclyl selected from one, or any combinations of more than one, of the following, - pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrazolyl, imidazolyl, thienyl, quinolinyl, and thiadiazolyl, where said heterocyclyls may optionally be substituted with one or more of - F, CI, Br, I, CN, 0=, (Cr Cs)alkyl, 0(Ci-Cs)alkyl, N(R8)2, and phenyl, where each of said alkyls may optionally be substituted with one or more of - F, CI, Br, and I.
16. A molecule according to claim 1 wherein R7 is a phenyl that has one or more substituents, where said substituent are selected from one, or any combinations of more than one, of the following, - C(CH3)3, CF3, CH2CH3, CH3, OCH3, F, CI, Br, I, S(0)2CH3, OCF3, SCF3, SF5, N02, OCH2CF3, Ophenyl, and S(0)2CF3.
17. A molecule according to claim 1 wherein R7 is selected from one, or any
combinations of more than one, of the following, - pyridyl, pyrimidinyl, pyridazinyl, triazinyl, quinolinyl, and thiadiazolyl, each of which may optionally be substituted, where said substituents are selected from one, or any combinations of more than one, of the following, - CF3, CC13, NH2, CN, CH3, OCH3, 0=, F, CI, Br, I, SCH3, and phenyl.
18. A molecule according to claim 1 wherein R7 is (Ci-Cs)alkyl, aryl, or heterocyclyl and where R7 has 1, 2, 3, 4, or 5 substituents.
19. A molecule accordin to claim 1 having one of the following structures.
Figure imgf000219_0001
20. A composition according to claim 1 further comprising:
(a) one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties; or
(b) one or more compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists; or
(c) both (a) and (b).
21. A composition according to claim 1 wherein further comprising one or more compounds selected from: (3 -ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3- dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri- iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6- TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5- T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T- sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D- 2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB- dimethylammonium, 2,4-DB-isoctyl, 2,4-DB -potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4- D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D- dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D- isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D- meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D- sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2- hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2- phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA- sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8 -hydroxy quinoline sulfate, 8- phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorf en- sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, α/ρΛα-cypermethrin, α/ρ ζα-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2- hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium a-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam- sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos- methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin- ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone- sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox- ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate,
benzyladenine, berberine, berberine chloride, ^eta-cyfluthrin, ^eto-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium,
brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac- ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2- hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam- methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, J-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O- methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, J-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos,
diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba- diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba- isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba- sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P- dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,
difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d- limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal- dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdepallethrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen- ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl a-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl,
fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop- butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop- potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon- potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop- ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M- isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop- P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron- methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl,
flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCR, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop- methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox- ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin- sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron,
iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim- methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA- 2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA- olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2- ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop- sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide,
methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p- toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene,
orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid,
oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride,
phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram- methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2- hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone- sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos- methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium a-naphthaleneacetate, ρρ'-ΌΌΎ, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione- calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone,
propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac- sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P- tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium a-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, toi/-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA- calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,
terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap- monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin,
transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop- methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, a-chlorohydrin, a-ecdysone, a-multistriatin, and a-naphthaleneacetic acid.
22. A composition according to claim 1 further comprising an agriculturally acceptable carrier.
23. A composition according to claim 1 wherein said molecule is in the form of a pesticidally acceptable acid addition salt.
24. A composition according to claim 1 wherein said molecule is in the form of a salt derivative.
25. A composition according to claim 1 wherein said molecule is in the form a hydrate.
26. A composition according to claim 1 wherein said molecule is in the form an ester derivative.
27. A composition according to claim 1 wherein said molecule is in the form a crystal polymorph.
28. A composition according to claim 1 wherein said molecule has a 2H in place of ]H.
29. A composition according to claim 1 wherein said molecule has a 14C in place of a 12C.
30. A composition according to claim 1 further comprising a biopesticide.
31. A composition according to claim 1 further comprising one or more of the following compounds:
(a) 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec-3-en-2- one;
(b) 3 -(4' -chloro-2,4-dimethyl[ 1 , 1 ' -biphenyl] -3 -yl)-4-hydroxy-8-oxa- 1 - azaspiro[4,5]dec-3-en-2-one;
(c) 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;
(d) 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;
(e) 3-chloro-N2-[(15')-l-methyl-2-(methylsulfonyl)ethyl]-Nl-[2-methyl-4- [ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]- 1 ,2-benzenedicarboxamide;
(f) 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;
(g) 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; (h) 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;
(i) 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;
(j) 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;
(k) 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; (1) 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;
(m) 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-l-methyl-lH-pyrazole-4- carboxamide; (n) N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-/?-tolyl) hydrazone;
(o) N-ethyl-2,2-dichloro- 1 -methylcyclopropane-carboxamide-2-(2,6-dichloro- α,α,α-trifluoro-p-tolyl) hydrazone nicotine;
(p) 0-{(E-)-[2-(4-chloro-phenyl)-2-cyano-l-(2-trifluoromethylphenyl)-vinyl] } S- methyl thiocarbonate;
(q) (E)-Nl-[(2-chloro-l,3-thiazol-5-ylmethyl)]-N2-cyano-Nl-methylacetamidine;
(r) l-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro- 1,2,3,5, 6,7-hexahydro- imidazo[l,2-a]pyridin-5-ol;
(s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and
(t) N-Ethyl-2,2-dichloro-l-methylcyclopropanecarboxamide-2-(2,6-dichloro- alpha, alpha, a/p za-trifluoro-p-tolyl)hydrazone.
32. A composition according to claim 1 further comprising a compound having one or more of the following modes of action: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs).
33. A composition according to claim 1 further comprising a seed.
34. A composition according to claim 1 further comprising a seed that has been genetically modified to express one or more specialized traits.
35. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule.
36. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule, wherein said capsule has a diameter of about 100-900 nanometers or about 10-900 microns.
37. A process comprising applying a composition according to claim 1, to an area to control a pest, in an amount sufficient to control such pest.
38. A process according to claim 37 wherein said pest is selected from beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
39. A process according to claim 37 wherein said pest is from the Phyla Nematoda or Arthropoda.
40. A process according to claim 37 wherein said pest is from the Subphyla Chelicerata, Myriapoda, or Hexapoda.
41. A process according to claim 37 wherein said pest is from the Class of Arachnida, Symphyla, or Insecta.
42. A process according to claim 37 wherein said pest is from the Order Anoplura, Order Coleoptera, Order Dermaptera, Order Blattaria, Order Diptera, Order Hemiptera, Order
Hymenoptera, Order Isoptera, Order Lepidoptera, Order Mallophaga, Order Orthoptera, Order Siphonaptera, Order Thysanoptera, Order Thysanura, Order Acarina, or Order Symphyla.
43. A process according to claim 37 wherein said pest is BAW, CEW, or GPA.
44. A process according to claim 37 wherein said amount is from about 0.01 grams per hectare to about 5000 grams per hectare.
45. A process according to claim 37 wherein said amount is from about 0.1 grams per hectare to about 500 grams per hectare.
46. A process according to claim 37 wherein said amount is from about 1 gram per hectare to about 50 grams per hectare.
47. A process according to claim 37 wherein said area is an area where apples, corn, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans, are growing, or the seeds thereof are going to be planted.
48. A process according to claim 37 further comprising applying said composition to a genetically modified plant that has been genetically modified to express one or more specialized traits.
49. A process according to claim 37 where said composition further comprise ammonium sulfate.
50. A process comprising: orally administering; or topically applying; a composition according to claim 1, to a non-human animal, to control endoparasites, ectoparasites, or both.
51. A process comprising applying a composition according to claim 1 to a plant to enhance the plant's health, yield, vigor, quality, or tolerance, at a time when pest activity is low.
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