IP Library Granted Patent US 8,377,942
Granted Patent B2
US 8,377,942 · App. 13/133,432 · Granted Feb 19, 2013

Isoxazolines derivatives and their use as pesticide

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Quick Facts
Patent No.
US 8,377,942
App. No.
13/133,432
Granted
Feb 19, 2013
Kind
B2
Abstract

Novel isoxazoline compounds, compositions containing the compounds and methods for making the compounds are disclosed. The compounds and compositions have pesticidal properties and are suitable for controlling ectoparasites on non-human animals.

Claims (50)

1. A compound of formula

including geometric and stereoisomers, N-oxides, and salts thereof, wherein

A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are each independently selected from the group consisting of CR 3 ′ and N;

n is an integer from 0 to 4;

B 1 , B 2 and B 3 are each independently selected from the group consisting of CR 2 ′ and N;

each R 2 ′ is independently of the other H or R 2 ; each R 3 ′ is independently of the other H or R 3 ;

R 1 is C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 7 -alkylcycloalkyl or C 4 -C 7 -cycloalkylalkyl, each unsubstituted or substituted with one or more substituents independently selected from R 4 ;

each R 2 is independently halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -haloalkylsulfonyl, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 2 -C 6 alkoxycarbonyl, cyano (—CN) or nitro (—NO 2 );

each R 3 is independently halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 alkyl-sulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -haloalkylsulfonyl, amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 1 -C 6 -alkoxycarbonyl, —CN or —NO 2 ;

R 4 is halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, —CN or —NO 2 ;

Q is a 5- or 6-membered heterocyclic ring, or a C 6 -C 10 -carbocyclic ring system or a 8-, 9- or 10-membered fused hetero-bicyclic ring system, each of them being unsubstituted or substituted with one or more substituents independently selected from halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 1 -C 6 -alkoxy, C 3 -C 6 -cycloalkoxy, C 1 -C 6 -haloalkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -haloalkylsulfonyl, —CN, —NO 2 , amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, CO 2 H, C 1 -C 6 -alkoxycarbonyl, sulfonamido, N-mono- or N,N,di-C 1 -C 6 -alkylsulfonamido, CONH 2 , N-mono- or N,N,di-C 1 -C 6 -alkylaminocarbonyl, N-mono- or N,N,di-C 1 -C 6 -haloalkylaminocarbonyl, N—C 1 -C 2 -haloalkylaminocarbonyl-C 1 -C 2 -alkylaminocarbonyl, C 1 -C 6 -alkylcarbonylamino, C 2 -C 6 -alkanoyl, C 2 -C 6 -haloalkanoyl, CH 2 R 5 , a group C(O)N═CHN(CH 3 ) 2 , a group C(O)N═CHNHOCH 3 , pyrrolidonylcarbonyl, and unsubstituted or halogen-, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, nitro- or cyano-substituted phenyl, benzyl, phenethyl, pyridyl, pyridinylmethyl, pyrimidinyl, pyrimidinylmethyl, benzoyl or phenoxy; and

R 5 is CO 2 H, C 1 -C 6 -alkoxycarbonyl, CONH 2 , N-mono- or N,N,di-C 1 -C 6 -alkylaminocarbonyl, N-mono- or N,N,di-C 1 -C 6 -haloalkylaminocarbonyl, C 1 -C 6 -alkylcarbonylamino, pyridinylaminocarbonyl or tetrahydrofuranyl.

2. A compound of formula (I) according to claim 1 , wherein

A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are each independently selected from the group consisting of CR 3 ′ and N;

n is an integer from 0 to 4;

B 1 , B 2 and B 3 are each independently selected from the group consisting of CR 2 ′ and N;

each R 2 ′ is independently of the other H or R 2 ;

each R 3 ′ is independently of the other H or R 3 ;

R 1 is C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 7 -alkylcycloalkyl or C 4 -C 7 -cycloalkylalkyl, each unsubstituted or substituted with one or more substituents independently selected from R 4 ;

each R 2 is independently halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -haloalkylsulfonyl, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 2 -C 6 -alkoxycarbonyl, cyano (—CN) or nitro (—NO 2 );

each R 3 is independently halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 alkyl-sulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -haloalkylsulfonyl, amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 2 -C 6 -alkoxycarbonyl, —CN or —NO 2 ;

R 4 is halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, —CN or —NO 2 ; and

Q is a 5- or 6-membered heterocyclic ring, or a C 6 -C 10 -carbocyclic ring system or a 8-, 9- or 10-membered fused hetero-bicyclic ring system, each of them being unsubstituted or substituted with one or more substituents independently selected from halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -haloalkylsulfonyl, —CN, —NO 2 , amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 2 -C 6 -alkoxycarbonyl, sulfonamido, N-mono- or N,N,di-C 1 -C 4 -alkylsulfonamido, N-mono- or N,N-di-C 1 -C 6 -alkylcarbonylamino, C 2 -C 6 -alkanoyl and unsubstituted or halogen-, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, nitro- or cyano-substituted phenyl, benzyl, benzoyl or phenoxy.

3. A compound according to claim 1 of formula (I), wherein B 1 , B 2 and B 3 are each CR 2 ′.

4. A compound according to claim 1 , wherein A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are each CH.

5. A compound according to claim 1 , wherein R 1 is C 1 -C 3 -haloalkyl.

6. A compound according to claim 1 of formula

wherein R 1 , R 2 , R 3 , Q and n are as defined in claim 1 , and m is an integer from 0 to 4.

7. A compound according to claim 1 , wherein Q is a 5- or 6-membered heterocyclic ring having from 1 to 4 same or different heteroatoms selected from the group consisting of N, O and S, which is further unsubstituted or substituted by one or more substituents selected from the group consisting of C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkylthio, C 1 -C 4 -alkylsulfinyl, C 1 -C 4 -haloalkylsulfinyl, C 1 -C 4 -alkylsulfonyl, C 1 -C 4 -haloalkylsulfonyl, —CN, —NO 2 , C 1 -C 4 -alkoxycarbonyl, sulfonamido, N-mono- or N,N-di-C 1 -C 4 -alkylcarbonylamino, C 2 -C 3 -alkanoyl and unsubstituted or halogen- or C 1 -C 4 -alkyl-substituted phenyl, benzyl, benzoyl and phenoxy.

8. A compound according to claim 1 , wherein Q is a radical of formula

wherein r is an integer from 0 to 3 and R is independently selected from the group consisting of halogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, C 1 -C 2 -haloalkylthio, —CN, —NO 2 , and C 1 -C 4 -alkoxycarbonyl.

9. A compound according to claim 8 , wherein Q is the radical Q-34, Q-43 or Q-47, wherein r is in each case 0.

10. A compound of formula (Ia) according to claim 6 , wherein

n is an integer from 1 to 3, R 1 is C 1 -C 3 -haloalkyl, each R 2 and R 3 is independently selected from the group consisting of halogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, C 1 -C 2 -haloalkylthio, —CN and —NO 2 , m is an integer from 0 to 2, and Q is either (i) phenyl, which is unsubstituted or substituted by 1 to 3, same or different substituents selected from the group consisting of halogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, C 1 -C 2 -haloalkylthio, —CN, —NO 2 , and unsubstituted or halogen-, C 1 -C 2 -alkyl-, C 1 -C 2 -haloalkyl-, C 1 -C 2 -alkoxy-, C 1 -C 2 -haloalkoxy-, —CN and —NO 2 -substituted phenyl or phenoxy, or is

(ii) a 5- or 6-membered heterocyclic ring having from 1 to 3 same or different heteroatoms selected from the group consisting of N, O and S, which is further unsubstituted or substituted by halogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, C 1 -C 2 -haloalkylthio, —CN, —NO 2 or C 1 -C 4 -alkoxycarbonyl, or is

(iii) a fused hetero-bicyclic ring system comprising a 5- or 6-membered heterocyclic ring having from 1 to 3 same or different heteroatoms selected from the group consisting of N, O and S, to which is attached an annulated ring, and which is further unsubstituted or substituted by halogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, C 1 -C 2 -haloalkylthio, —CN, —NO 2 or C 1 -C 4 -alkoxycarbonyl.

11. A compound of formula (Ia) according to claim 6 , wherein

n is an integer from 1 to 3, R 1 is CF 3 , each R 2 is independently selected from the group consisting of halogen, C 1 -C 2 -haloalkyl, C 1 -C 2 -haloalkoxy and —CN, m is 0 and Q is either

(ii) a 5- or 6-membered heteroaromatic ring selected from the group consisting of the radicals given in claim 7 , or is

(iii) a fused hetero-bicyclic ring system selected from the group consisting of the radicals

12. A compound of formula (Ia) according to claim 6 , wherein

n is an integer from 1 to 3, R 1 is CF 3 , each R 2 is independently selected from the group consisting of halogen, C 1 -C 2 -haloalkyl, C 1 -C 2 -haloalkoxy and —CN, m is 0 and Q is a radical

wherein r is an integer of 0 or 1, and R is independently selected from the group consisting of C 1 -C 2 -alkyl, halo-C 1 -C 2 -alkyl, halo-C 1 -C 2 -alkylcarbonyl, cyano, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkoxycarbonylmethyl, carboxy-C 1 -C 2 -alkyl, aminocarbonyl, N-mono- or N,N-di-C 1 -C 2 -alkylaminocarbonyl, halo-C 1 -C 2 -alkylaminocarbonylmethyl, halo-C 1 -C 2 -alkylaminocarbonylmethylaminocarbonyl, halovinyl, —C(O)N═CHN(CH 3 ) 2 , —C(O)N═CHNHOCH 3 , unsubstituted or halogen- or C 1 -C 2 -alkoxy-substituted phenyl, benzyl and phenylethyl, unsubstituted and halogen-substituted 2-, 3- and 4-pyridyl and pyridylmethyl, pyridylcarbonylaminomethyl, pyrrolidinecarbonyl, and 2-tetrahydrofuranylmethyl.

13. A compound according to claim 5 , wherein R 1 is CF 3 .

14. A compound according to claim 7 , wherein Q is a 5- or 6-membered heterocyclic ring having from 1 to 3 same or different heteroatoms.

15. A compound according to claim 10 , wherein m is 0.

16. A compound according to claim 10 , wherein Q is phenyl, which is substituted by 1 or 2 same or different substituents.

17. A compound according to claim 12 , wherein Q is the radical Q-24, Q-26, Q-30, Q-32, Q-34, Q-44 or Q-47.

18. Composition for the control of parasites, comprising as active ingredient at least one compound of the formula (I) according to claim 1 , in addition to a carrier and/or a dispersant.

19. Method of controlling parasites in and on warm-blooded animals, which comprises applying to the animals a pharmaceutical effective amount of at least one compound of formula (I) according to claim 1 .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 10, 2015
From: NOVARTIS AG
To: NOVARTIS TIERGESUNDHEIT AG
Reel/Frame 034927/0017 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 13, 2011
From: NANCHEN, STEVE; GAUVRY, NOELLE; PAUTRAT, FRANCOIS
To: NOVARTIS AG
Reel/Frame 026431/0091 →