Pesticidal activity of functionalized alkenes

Abstract

The present invention provides non-peptide organic compounds that have a structure analogous to or reminiscent of the TMOF structure and have pesticidal activity. Thus the present invention concerns pesticidal compounds that inhibit digestion in pests by terminating or otherwise blocking synthesis of digestive enzymes by activating a TMOF receptor (collectively referred to herein as “pesticidal compounds”). The pesticidal compounds and other compounds of the present invention are usefully employed in the control of pests, particularly insect pests Such as mosquitoes, which ingest blood.

That which is claimed is:  
     
         1 . A method for controlling a pest, comprising administering to said pest a pesticidally effective amount of a pesticidal compound of formula I:  
       
         
           
           
               
               
           
         
       
       wherein: 
 X is selected from the group consisting of —CHCH—, —CH 2 CH 2 —, and —CC—;  
 Z is selected from the group consisting of —OH, —NH 2  and —OR 6  wherein R 6  is loweralkyl;  
 m≧0 and n≧1 and together total an integer from 1 to 12;  
 the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a phenyl ring or a cyclohexyl ring; and  
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, loweralkoxy and phenyl; subject to the proviso that: 
 when the ring is a phenyl ring, a pair of R 1  and R 2 , R 2  and R 3 , or R 3  and R 4  on the phenyl ring may together represent —CR 7 ═CR 8 —CR 9 ═CR 10 —, to form with the phenyl ring illustrated above a naphthyl ring system, wherein R 7 , R 8 , R 9 , and R 10  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, and loweralkoxy.  
 
 
     
     
         2 . A method according to  claim 1 , wherein X is —CH 2 CH 2 —.  
     
     
         3 . A method according to  claim 1 , wherein X is —CHCH—.  
     
     
         4 . A method according to  claim 1 , wherein X is —CC—.  
     
     
         5 . A method according to  claim 1 , wherein R 1  is selected from the group consisting of hydroxy, bromo, fluoro, methyl, methoxy, propoxy, and ethoxy;  
     
     
         6 . A method according to  claim 1 , wherein R 1  is selected from the group consisting of bromo and propoxy.  
     
     
         7 . A method according to  claim 1 , wherein Z is OH.  
     
     
         8 . A method according to  claim 1 , wherein Z is NH 2 .  
     
     
         9 . A method according to  claim 1 , wherein m is 2 to 12.  
     
     
         10 . A method according to  claim 1 , wherein m is 3 to 10.  
     
     
         11 . A method according to  claim 1 , wherein m is 4 to 8.  
     
     
         12 . A method according to  claim 1 , wherein m is 4 to 6.  
     
     
         13 . A method according to  claim 1 , wherein n is 2 to 12.  
     
     
         14 . A method according to  claim 1 , wherein n is 3 to 10.  
     
     
         15 . A method according to  claim 1 , wherein n is 4 to 8.  
     
     
         16 . A method according to  claim 1 , wherein n is 4 to 6.  
     
     
         17 . A method according to  claim 1 , wherein R 2  is H.  
     
     
         18 . A method according to  claim 1 , wherein R 3  is H.  
     
     
         19 . A method according to  claim 1 , wherein R 5  is H.  
     
     
         20 . A method according to  claim 1 , wherein R 2  and R 3  are both H.  
     
     
         21 . A method according to  claim 1 , wherein R 2  and R 5  are both H.  
     
     
         22 . A method according to  claim 1 , wherein R 3  and R 5  are both H.  
     
     
         23 . A method according to  claim 1 , wherein R 2 , R 3  and R 5  are all H.  
     
     
         24 . A method according to  claim 1 , wherein R 1  is a halogen.  
     
     
         25 . A method according to  claim 1 , wherein R 3  is a halogen.  
     
     
         26 . A method according to  claim 1 , wherein R 1  is an alkoxy.  
     
     
         27 . A method according to  claim 1 , wherein R 3  is an alkoxy.  
     
     
         28 . A method according to  claim 1 , wherein R 1  and R 3  are both a halogen.  
     
     
         29 . A method according to  claim 1 , wherein R 1  and R 3  are both an alkoxy.  
     
     
         30 . A method according to  claim 1 , wherein said pest is an insect pest.  
     
     
         31 . A method according to  claim 1 , wherein said pest is an insect selected from the group consisting of coleopterans, lepidopterans, and dipterans.  
     
     
         32 . A method according to  claim 1 , wherein said pest is a blood-sucking insect.  
     
     
         33 . A method according to  claim 1 , wherein said pest is an insect of the suborder Nematocera.  
     
     
         34 . A method according to  claim 1 , wherein said pest is an insect of the family Colicidae.  
     
     
         35 . A method according to  claim 1 , wherein said pest is an insect of a subfamily selected from the group consisting of Culicinae, Corethrinae, Ceratopogonidae and Simuliidae.  
     
     
         36 . A method according to  claim 1 , wherein said pest is an insect of a genus selected from the group consisting of Culex, Theobaldia, Aedes, Anopheles, Aedes, Forciponiya, Culicoides and Helea.  
     
     
         37 . A method according to  claim 1 , wherein said pest is an insect species selected from the group consisting of:  Aedes aegypti, Culex quinquefasciatus, Anopheles albimanus, Anopheles quadrimaculatus, Lutzomyia anthrophora, Culicoides variipennis, Stomoxys calcitrans, Musca domestica, Ctenocephalides feliz,  and  Heliothis virescens.    
     
     
         38 . A method according to  claim 1 , wherein said pest is selected from the group consisting of flies, fleas, ticks, and lice.  
     
     
         39 . A method according to  claim 1 , wherein said pest is a mosquito.  
     
     
         40 . A method according to  claim 1 , wherein said pest is selected from the group consisting of beetles, caterpillars, and mites.  
     
     
         41 . A method according to  claim 1 , wherein said pest is selected from the group consisting of ants and cockroaches.  
     
     
         42 . A method according to  claim 1 , wherein said compound of Formula I is selected from the group consisting of: 
 E-7-phenylhept-4-enoic acid;    E-7-(4-methoxyphenyl)hept-4-enoic acid;    methyl E-7-phenylhept-4-enoate;    E-7-phenylhept-4-enoic acid amide;    Z-7-phenylhept-4-enoic acid;    E-7-(2,4-difluorophenyl)hept-4-enoic acid;    E-10-phenyldec-6-enoic acid;    E-1-(4-methoxyphenyl)dec-4-enoic acid;    E-7-(4-hydroxyphenyl)hept-4-enoic acid;    E-7-(2,4-dibromophenyl)hept-4-enoic acid;    E-7-(4-methylphenyl)hept-4-enoic acid;    E-7-(2,4-diethylphenyl)hept-4-enoic acid;    E-7-(2-ethoxyphenyl)hept-4-enoic acid;    E-7-(2,4,-dipropoxyphenyl)hept-4-enoic acid:    E-10-(2,4-difluorophenyl)dec-4-enoic acid;    E-7-(2,4-difluorophenyl)hept-4-enoic acid amide;    E-7-(4-methoxyphenyl)hept-4-enoic acid amide;    E-10-phenyldec-6-enoic acid amide;    E-7-(2,4-difluorophenyl)dec-6-enoic acid amide;    E-7-(4-methoxyphenyl)dec-6-enoic acid amide;    Z-7-phenylhept-4-enoic acid amide;    Methyl E-7-(2,4-difluorophenyl)hept-4-enoate;    Methyl E-7-(4-methoxyphenyl)hept-4-enoate;    Methyl E-10-phenyldec-6-enoate;    Methyl E-7-(2,4-difluorophenyl)dec-6-enoate;    Methyl E-7-(4-methoxyphenyl)dec-6-enoate;    Methyl Z-7-phenylhept-4-enoate;    Ethyl E-7-(2,4-difluorophenyl)hept-4-enoate;    Ethyl E-7-(4-methoxyphenyl)hept-4-enoate;    Ethyl E-10-phenyldec-6-enoate;    Propyl E-7-(2,4-difluorophenyl)dec-6-enoate;    Propyl E-7-(4-methoxyphenyl)dec-6-enoate;    Propyl Z-7-phenylhept-4-enoate;    Ethyl E-7-phenylhept-4-enoate;    Propyl E-7-phenylhept-4-enoate;    Butyl E-7-phenylhept4-enoate;    Ethyl E-10-phenyldec-6-enoate;    Propyl E-10-phenyldec-6-enoate; and    Butyl E-10-phenyldec-6-enoate.    
     
     
         43 . A method of initiating a TMOF receptor-mediated biological response, comprising contacting to a TMOF receptor in vivo or in vitro for a time and in an amount sufficient to initiate a TMOF receptor-mediated biological response a compound of Formula I:  
       
         
           
           
               
               
           
         
       
       wherein: 
 X is selected from the group consisting of —CHCH—, —CH 2 CH 2 —, and —CC—;  
 Z is selected from the group consisting of —OH, —NH 2  and —OR 6  wherein R 6  is loweralkyl;  
 m≧0 and n≦1 and together total an integer from 1 to 12;  
 the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a phenyl ring or a cyclohexyl ring; and  
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, loweralkoxy and phenyl; subject to the proviso that: 
 when the ring is a phenyl ring, a pair of R 1  and R 2 , R 2  and R 3 , or R 3  and R 4  on the phenyl ring may together represent —CR 7 ═CR 8 —CR 9 ═CR 10 —, to form with the phenyl ring illustrated above a naphthyl ring system, wherein R 7 , R 8 , R 9 , and R 10  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, and loweralkoxy.  
 
 
     
     
         44 . A method according to  claim 43 , wherein said biological response is inhibition of biosynthesis of a digestive enzyme.  
     
     
         45 . A method according to  claim 43 , wherein said digestive enzyme is trypsin.  
     
     
         46 . A method according to  claim 43 , wherein said contacting step is carried out in vivo in an insect pest.  
     
     
         47 . A method according to  claim 43 , wherein X is —CH 2 CH 2 —.  
     
     
         48 . A method according to  claim 43 , wherein X is —CHCH—.  
     
     
         49 . A method according to  claim 43 , wherein X is —CC—.  
     
     
         50 . A pest control composition comprising a pesticidal carrier and a pesticidal compound of Formula I:  
       
         
           
           
               
               
           
         
       
       wherein: 
 X is selected from the group consisting of —CHCH—, —CH 2 CH 2 —, and —CC—;  
 Z is selected from the group consisting of —OH, —NH 2  and —OR 6  wherein R 6  is loweralkyl;  
 m≧0 and n≧1 and together total an integer from 1 to 12;  
 the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a phenyl ring or a cyclohexyl ring; and  
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, loweralkoxy and phenyl; subject to the proviso that: 
 when the ring is a phenyl ring, a pair of R 1  and R 2 , R 2  and R 3 , or R 3  and R 4  on the phenyl ring may together represent —CR 7 ═CR 8 —CR 9 ═CR 10 —, to form with the phenyl ring illustrated above a naphthyl ring system, wherein R 7 , R 8 , R 9 , and R 10  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, and loweralkoxy.  
 
 
     
     
         51 . A composition according to  claim 50 , wherein said composition is a liquid composition.  
     
     
         52 . A composition according to  claim 50 , wherein said pesticidal carrier is included in said composition in an amount from 0.1% to 99.9999% by weight.  
     
     
         53 . A composition according to  claim 50 , wherein said pesticidal carrier comprises an aqueous solution.  
     
     
         54 . A composition according to  claim 50 , wherein said pesticidal carrier comprises an organic solvent.  
     
     
         55 . A composition according to  claim 50 , wherein said pesticidal carrier comprises an emulsion.  
     
     
         56 . A composition according to  claim 50 , wherein said composition is a solid composition.  
     
     
         57 . A composition according to  claim 50 , wherein said composition is a bait granule.  
     
     
         58 . A composition according to  claim 50 , wherein said compound of Formula I is selected from the group consisting of: 
 E-7-phenylhept-4-enoic acid;    E-7-(4-methoxyphenyl)hept-4-enoic acid;    methyl E-7-phenylhept-4-enoate;    E-7-phenylhept-4-enoic acid amide    Z-7-phenylhept-4-enoic acid;    E-7-(2,4-difluorophenyl)hept-4-enoic acid;    E-10-phenyldec-6-enoic acid;    E-1-(4-methoxyphenyl)dec-4-enoic acid;    E-7-(4-hydroxyphenyl)hept-4-enoic acid;    E-7-(2,4-dibromophenyl)hept-4-enoic acid;    E-7-(4-methylphenyl)hept-4-enoic acid;    E-7-(2,4-di ethylphenyl)hept-4-enoic acid;    E-7-(2-ethoxyphenyl)hept-4-enoic acid;    E-7-(2,4,-dipropoxyphenyl)hept-4-enoic acid:    E-10-(2,4-difluorophenyl)dec-4-enoic acid;    E-7-(2,4-difluorophenyl)hept-4-enoic acid amide;    E-7-(4-methoxyphenyl)hept-4-enoic acid amide;    E-10-phenyldec-6-enoic acid amide;    E-7-(2,4-difluorophenyl)dec-6-enoic acid amide;    E-7-(4-methoxyphenyl)dec-6-enoic acid amide;    Z-7-phenylhept-4-enoic acid amide;    Methyl E-7-(2,4-difluorophenyl)hept-4-enoate;    Methyl E-7-(4-methoxyphenyl)hept-4-enoate;    Methyl E-10-phenyldec-6-enoate;    Methyl E-7-(2,4-difluorophenyl)dec-6-enoate;    Methyl E-7-(4-methoxyphenyl)dec-6-enoate;    Methyl Z-7-phenylhept-4-enoate;    Ethyl E-7-(2,4-difluorophenyl)hept-4-enoate;    Ethyl E-7-(4-methoxyphenyl)hept-4-enoate;    Ethyl E-10-phenyldec-6-enoate;    Propyl E-7-(2,4-difluorophenyl)dec-6-enoate;    Propyl E-7-(4-methoxyphenyl)dec-6-enoate;    Propyl Z-7-phenylhept-4-enoate;    Ethyl E-7-phenylhept-4-enoate;    Propyl E-7-phenylhept-4-enoate;    Butyl E-7-phenylhept 4-enoate;    Ethyl E-10-phenyldec-6-enoate;    Propyl E-10-phenyldec-6-enoate; and    Butyl E-10-phenyldec-6-enoate.    
     
     
         59 . A method of identifying a non-peptide TMOF agonist from a peptide TMOF agonist, said method comprising the steps of: 
 modeling in a computer a model peptide TMOF agonist selected from the group consisting of TMOF and peptide TMOF analogs;    determining in said computer spatial orientations for at least one key feature of said model peptide compound;    generating in said computer a putative non-peptide TMOF agonist structure, said structure including (i) said at least one key feature and (ii) spatial orientations for said at least one key feature corresponding to said spatial orientations for said at least one key feature of said model peptide compound; then    synthesizing said putative non-peptide TMOF agonist; and then    screening said putative non-peptide TMOF agonist to determine the presence of TMOF activity therein.    
     
     
         60 . A method according to  claim 59 , wherein said modeling step is carried out with simulated annealing.  
     
     
         61 . A method according to  claim 59 , wherein said screening step is carried out in vivo on insects.  
     
     
         62 . A method according to  claim 59 , wherein said at least one key feature of said non-peptide TMOF agonist structure comprises (i) a phenyl ring, and (ii) a carboxylate functional group.  
     
     
         63 . A method of controlling a pest, comprising administering to said pest a pesticidally effective pesticidal amount of a non-peptide TMOF analog.  
     
     
         64 . A method according to  claim 63 , wherein said non-peptide TMOF analog is an organic compound that has TMOF activity.  
     
     
         65 . A method according to  claim 64 , wherein said organic compound that has TMOF activity includes (i) a phenyl group, and (ii) a carboxylate group.  
     
     
         66 . A method according to  claim 64 , wherein said organic compound has the stricture P—R—C, where P is a phenyl group, R is an alkane, alkene, or alkyne, and C is a carboxylate group.  
     
     
         67 . A method according to  claim 1 , wherein said method is an insect repellant method, and said administering step is carried out by applying said compound of formula I to a subject or substrate from which said insect is to be repelled in an amount sufficient to repel said insect.  
     
     
         68 . A method according to  claim 1 , wherein the ring is a cyclohexyl ring.  
     
     
         69 . A method according to  claim 1 , wherein m is 0.  
     
     
         70 . A method according to  claim 1 , wherein at least one of R 1 , R 2 , R 3 , R 4  or R 5  is phenyl.  
     
     
         71 . A method according to  claim 43 , wherein the ring is a cyclohexyl ring.  
     
     
         72 . A method according to  claim 43 , wherein m is 0.  
     
     
         74 . A method according to  claim 43 , wherein at least one of R 1 , R 2 , R 3 , R 4  or R 5  is phenyl.  
     
     
         75 . A composition according to  claim 50 , wherein said composition is a topical repellant composition.  
     
     
         76 . A composition according to  claim 50 , wherein the ring is a cyclohexyl ring.  
     
     
         77 . A composition according to  claim 50 , wherein m is 0.  
     
     
         78 . A composition according to  claim 50 , wherein at least one of R 1 , R 2 , R 3 , R 4  or R 5  is phenyl.  
     
     
         79 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 X is selected from the group consisting of —CHCH—, —CH 2 CH 2 —, and —CC—;  
 Z is selected from the group consisting of —OH, —NH 2  and —OR 6  wherein R 6  is loweralkyl;  
 m≧0 and n≧1 and together total an integer from 1 to 12;  
 the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a phenyl ring or a cyclohexyl ring; and  
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, loweralkoxy and phenyl; subject to the proviso that: 
 when the ring is a phenyl ring, a pair of R 1  and R 2 , R 2  and R 3 , or R 3  and R 4  on the phenyl ring may together represent —CR 7 ═CR 8 —CR 9 ═CR 10 —, to form with the phenyl ring illustrated above a naphthyl ring system, wherein R 7 , R 8 , R 9 , and R 10  are each independently selected from the group consisting of —H, —OH, halo, loweralkyl, and loweralkoxy.  
 
 
     
     
         80 . A compound according to  claim 79 , subject to the further proviso that when: 
 the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a phenyl ring,    each of R 1 , R 2 , R 3 , R 4  and R 5  is —H, and    n and m are each 2, Z is not —OH or —OR 6 .    
     
     
         81 . A compound according to  claim 80 , which when contacted to a TMOF receptor in vivo or in vitro effects a TMOF receptor-mediated biological response.  
     
     
         82 . A compound according to  claim 80 , which when contacted to a TMOF receptor in vivo or in vitro effects inhibition of biosynthesis of a digestive enzyme.  
     
     
         83 . A compound according to  claim 80 , which when contacted to a TMOF receptor in vivo or in vitro effects inhibition of trypsin biosynthesis.  
     
     
         84 . A compound selected from the group consisting of: 
 E-7-(4-methoxyphenyl)hept-4-enoic acid;    E-7-phenylhept-4-enoic acid amide;    E-7-(2,4-difluorophenyl)hept-4-enoic acid;    E-10-phenyldec-6-enoic acid;    E-1-(4-methoxyphenyl)dec-4-enoic acid;    E-7-(4-hydroxyphenyl)hept-4-enoic acid;    E-7-(2,4-dibromophenyl)hept-4-enoic acid;    E-7-(4-methylphenyl)hept-4-enoic acid;    E-7-(2,4-diethylphenyl)hept-4-enoic acid;    E-7-(2-ethoxyphenyl)hept-4-enoic acid;    E-7-(2,4,-dipropoxyphenyl)hept-4-enoic acid:    E-10-(2,4-difluorophenyl)dec-4-enoic acid;    E-7-(2,4-difluorophenyl)hept-4-enoic acid amide;    E-7-(4-methoxyphenyl)hept-4-enoic acid amide;    E-10-phenyldec-6-enoic acid amide;    E-7-(2,4-difluorophenyl)dec-6-enoic acid amide;    E-7-(4-methoxyphenyl)dec-6-enoic acid amide;    Z-7-phenylhept-4-enoic acid amide;    Methyl E-7-(2,4-difluorophenyl)hept-4-enoate;    Methyl E-7-(4-methoxyphenyl)hept-4-enoate;    Methyl E-10-phenyldec-6-enoate;    Methyl E-7-(2,4-di fluorophenyl)dec-6-enoate;    Methyl E-7-(4-methoxyphenyl)dec-6-enoate;    Ethyl E-7-(2,4-difluorophenyl)hept-4-enoate;    Ethyl E-7-(4-methoxyphenyl)hept-4-enoate;    Ethyl E-10-phenyldec-6-enoate;    Propyl E-7-(2,4-difluorophenyl)dec-6-enoate;    Propyl E-7-(4-methoxyphenyl)dec-6-enoate;    Ethyl E-10-phenyldec-6-enoate;    Propyl E-10-phenyldec-6-enoate; and    Butyl E-10-phenyldec-6-enoate.    
     
     
         85 . A compound according to  claim 79 , wherein: 
 X is —CHCH— or —CC—;    Z is NH 2 ;    n is from 2 to 12; and    R 1 , R 2 , R 3 , R 4  and R 5  are not all —H.    
     
     
         86 . A compound according to  claim 79 , wherein: 
 X is —CC—;    Z is NH 2 ; and    R 1 , R 2 , R 3 , R 4  and R 5  are not all —H.    
     
     
         87 . A compound according to  claim 79 , wherein at least one of R 1 , R 2 , R 3 , R 4  and R 5  is not —H.  
     
     
         88 . A compound according to  claim 79 , wherein the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a cyclohexyl ring.  
     
     
         89 . A compound according to  claim 79 , wherein at least one of R 1 , R 2 , R 3 , R 4  and R 5  is selected from the group consisting of —OH and loweralkoxy.  
     
     
         90 . A compound according to  claim 79 , wherein at least one of R 1 , R 2 , R 3 , R 4  and R 5  is —OH.  
     
     
         91 . A compound according to  claim 79 , wherein at least one of R 1 , R 2 , R 3 , R 4  and R 5  is loweralkoxy.  
     
     
         92 . A compound selected from the group consisting of: 
 E-7-(4-Hydroxyphenyl)hept-4-enoic acid;    E-7-(4-M ethoxyphenyl)hept-4-enoic acid;    Ethyl E-7-(cyclohexyl)hept-4-enoate;    Ethyl E-7-((4-phenyl)phenyl)hept-4-enoate;    E-7-(cyclohexyl)hept-4-enoic acid; and    E-7-((4-phenyl)phenyl)hept-4-enoic acid.    
     
     
         93 . A compound according to  claim 79 , wherein the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a cyclohexyl ring and Z is —OH or —OR 6 .  
     
     
         94 . A compound according to  claim 79 , wherein the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a cyclohexyl ring and Z is —OH.  
     
     
         95 . A compound according to  claim 79 , wherein the ring bearing substituents R 1 , R 2 , R 3 , R 4  and R 5  is a cyclohexyl ring and Z is —OR 6 .  
     
     
         96 . A compound according to  claim 79 , wherein at least one of R 1 , R 2 , R 3 , R 4  or R 5  is phenyl.  
     
     
         97 . A compound according to  claim 79 , wherein m is 0.  
     
     
         98 . A compound according to  claim 79 , disposed in insect-repelling relationship to a locus containing or susceptible to infestation by insects that are repelled by said compound.