(Hetero) arylacrylamides for the control of ectoparasites

1. A compound of formula

including all geometric and stereoisomers, N-oxides, S-oxides, salts and prodrugs thereof,

R 1 is independently halogen, cyano (—CN), nitro (—NO 2 ), C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, 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 1 -C 6 alkoxycarbonyl, C 1 -C 6 -alkylcarbonyl, aminosulfonyl, C 1 -C 6 -alkylaminosulfonyl, C 1 -C 6 -alkylsulfonylamino or phenyl which is unsubstituted or substituted by halogen, cyano, nitro, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy or C 1 -C 4 -haloalkylthio; or

R 1 is a C 1 -C 4 carbon chain which optionally contains 1-2 heteroatoms from the group of N, S, and O, which is bonded to two adjacent ring positions and which forms an aliphatic, aromatic, heteroaromatic or heterocyclic ring which is optionally mono- or polysubstituted by C 1 -C 6 -alkyl or halogen, in which case n is 2;

Y is a radical of formula

where the second (right-hand) connection site in each case is connected to the C(O)NR 7 R 8 moiety;

R 7 is H, C 1 -C 6 -alkyl which is unsubstituted or substituted by halogen, C 1 -C 4 -alkoxy, C 1 -C 2 -alkylthio, cyano, nitro, amino or N-mono- or N,N-di-C 1 -C 4 alkylamino, or is C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 3 -C 6 -cycloalkyl;

R 8 is H; a group —CH═N—OR 9 ; a radical Q; a radical Q 1 ; or 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, C 4 -C 7 -cycloalkylalkyl, C 5 -C 10 -bicyclo-alkylene or C 3 -C 6 -cycloalkanone which is each unsubstituted or substituted in the alkyl, cycloalkyl, alkenyl or alkynyl moiety by halogen, hydroxy, carboxy (COOH), C 1 -C 4 -alkyl, 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 -alkylsulfonyl, cyano, nitro, amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 3 -C 6 -cycloalkylamino, C 1 -C 6 -alkoxycarbonyl, C 2 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonylamino, aminosulfonyl, N-mono- or N,N, di-C 1 -C 4 -alkylaminosulfonyl, a group —C(W′)NR 9 R 10 or a radical Q′;

or R 7 and R 8 together are a group ═C(R 11 )—NR 12 R 13 or ═C(R 11 )—C(NH 2 )—OR 12 ); or

R 7 and R 8 together with the N-atom to which they are attached, form a 3- to 7-membered ring which optionally contains a further heteroatom selected from the group consisting of N, S and O, and which ring is further unsubstituted or mono- or polysubstituted by C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, hydroxy, halogen, cyano, nitro, N,N-di-C 1 -C 2 -alkylaminomethyl or N,N-di-C 1 -C 2 -alkylaminocarbonylmethyl;

Q and Q′ are each independently a C 6 -C 10 -aryl, an aliphatic or aromatic 4-, 5- or 6-membered heterocyclic ring, or an aliphatic or aromatic 8-, 9- or 10-membered fused hetero-bicyclic ring, each of them being unsubstituted or mono- or polysubstituted by halogen, hydroxy, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 2 -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 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, cyano, nitro, amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 3 -C 6 -cycloalkylamino, COOH, C 1 -C 6 -alkoxycarbonyl, C 2 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonyl-amino, aminocarbonyl, N-mono- or N,N-di-C 1 C 6 -alkylaminocarbonyl, aminosulfonyl, N-mono- or N,N, di-C 1 -C 4 -alkylaminosulfonyl, unsubstituted or halogen- or nitro-substituted phenyl-C 1 -C 4 -alkyl, 5- or 6-membered heterocyclyl-C 1 -C 4 -alkyl or a radical Q″;

Q″ is a C 6 -C 10 -carbocyclic ring or a 4-, 5- or 6-membered heterocyclic ring, each of them being aromatic or not, each of them being unsubstituted or mono- or polysubstituted by halogen, hydroxy, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, cyano, nitro, amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 3 -C 6 -cycloalkylamino, COOH, C 1 -C 6 -alkoxycarbonyl, C 2 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonyl-amino, aminocarbonyl, N-mono- or N,N-di-C 1 C 6 -alkylaminocarbonyl, aminosulfonyl, or N-mono- or N,N, di-C 1 -C 4 -alkylaminosulfonyl;

Q 1 is a radical

wherein Z is O or CH 2 and R 14 is H, C 1 -C 4 -alkyl, or C 1 -C 1 -haloalkyl,

R 9 is H or C 1 -C 6 -alkyl;

R 10 is H, 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, which is each unsubstituted or substituted in the alkyl, alkenyl, alkynyl or cycloalkyl moiety by halogen, cyano, nitro, hydroxy, carboxy (COOH), 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 -alkylsulfonyl, amino, N-mono- or N,N-di-C 1 -C 6 -alkylamino, C 3 -C 6 -cycloalkylamino, C 1 -C 6 -alkoxycarbonyl, C 2 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonylamino, aminocarbonyl, N-mono- or N,N-di-C 1 C 6 -alkylaminocarbonyl, aminosulfonyl, N-mono- or N,N, di-C 1 -C 4 -alkylamino-sulfonyl or a radical Q″;

R 11 is H C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy, and

R 12 and R 13 are each independently of the other C 1 -C 6 -alkyl

W′ is O or S.

2. A compound according to claim 1 , wherein R 7 is H or C 1 -C 2 -alkyl.

3. A compound according to claim 2 , wherein R 8 is

(i) phenyl, which is unsubstituted or substituted by 1 or 2, 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, cyano, nitro, aminocarbonyl and unsubstituted or halogen-, C 1 -C 2 -alkyl-, C 1 -C 2 -haloalkyl-, C 1 -C 2 -alkoxy-, C 1 -C 2 -haloalkoxy-, cyano- or nitro-substituted phenyl and phenoxy; or is

(ii) 2- or 3-furanyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1- or 4-pyrazolyl, 2-, 4- or 5-thiazolyl, 1,2,4-triazol-3- or -4-yl, 1,2,3-triazin-1- or 2-yl, 2- 3- or 4-pyridyl or 4- or 5-pyrimidinyl, which is each 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, cyano, nitro, aminocarbonyl or C 1 -C 4 -alkoxycarbonyl; or is

(iii) oxetanyl, thietanyl, thietanyl-1-oxide, thietanyl-1,1-dioxide, tetrahydrofuranyl, tetrahydro-thiophenyl, pyrrolidinyl, 2- or 3-pyrrolidonyl, 1,3-dioxolanyl, 1,2- or 1,3-oxazolidinyl, tetrahydropyranyl, piperidinyl, tetrahydrothiopyranyl, tetrahydrothiopyranyl-1,1-dioxide, morpholinyl, or 1,3- or 1,4-dioxanyl, which is each unsubstituted or substituted by halogen, C 1 -C 2 -alkyl, cyclopropyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, cyano, nitro, or C 1 -C 4 -alkoxycarbonyl; or is

(iv) C 1 -C 2 -alkyl which is unsubstituted or substituted by halogen; C 1 -C 2 -alkoxy; carboxy; C 1 -C 2 -alkoxycarbonyl; a radical —C(O)NHR 10 wherein R 10 is C 1 -C 4 -alkyl, halo-C 1 -C 2 -alkyl, cyano-C 1 -C 2 -alkyl, C 2 -C 3 -alkynyl or cyclopropylmethyl; phenyl which is unsubstituted or substituted by halogen, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy; or a heterocyclic ring selected from 2- or 3-furanyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1- or 4-pyrazolyl, 2-, 4- or 5-thiazolyl, 1,2,4-triazol-3- or -4-yl, 1,2,3-triazin-1- or 2-yl, 2- 3- or 4-pyridyl, 4- or 5-pyrimidinyl, oxetanyl, thietanyl, thietanyl-1-oxide, thietanyl-1,1-dioxide and tetrahydrofuranyl, which is each 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, cyano, nitro, aminocarbonyl or C 1 -C 4 -alkoxy-carbonyl; or is

(v) C 2 -C 4 -alkenyl; (vi) C 2 -C 4 -alkynyl; (vii) C 3 -C 6 -cycloalkyl; or (viii) C 3 -C 6 -cycloalkyl-methyl.

4. A compound according to claim 3 , wherein R 8 is

(i) phenyl which is unsubstituted or substituted by halogen, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy;

(ii) 2-furanyl, 2-thiazoyl, 2- 3- or 4-pyridyl or 4- or 5-pyrimidinyl, each unsubstituted or substituted by C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 4 -alkoxycarbonyl;

(iii) oxetan-3-yl, thietan-3-yl, thietan-3-yl-1-oxide, thietan-3-yl-1,1-dioxide, or tetrahydrofuran-2- or -3-yl;

(iv) C 1 -C 2 -alkyl which is unsubstituted or substituted by chlorine; fluorine; C 1 -C 2 -alkoxy; —C(O)NHR 10 wherein R 10 is C 1 -C 4 -alkyl, 2,2,2-trifluoroethyl, cyanomethyl, propargyl or cyclopropylmethyl; 2-furanyl; 2-thiazoyl; 2- 3- or 4-pyridyl; 4- or 5-pyrimidinyl; oxetan-3-yl; thietan-3-yl; thietan-3-yl-1-oxide; thietan-3-yl-1,1-dioxide; tetrahydrofuran-2-yl; tetrahydrofuran-3-yl; or phenyl which is unsubstituted or substituted by halogen, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy;

(v) allyl; (vi) propargyl; (vii) C 3 -C 4 -cycloalkyl; or (viii) C 3 -C 4 -cycloalkylmethyl.

5. A compound according to claim 4 , wherein R 1 is halogen, CH 3 , CF 3 , OCF 3 , SCF 3 or SO 2 CH 3 , n is an integer 1 or 2, R 7 is H or C 1 -C 2 -alkyl, in particular H, and R 8 is

(i) phenyl which is unsubstituted or substituted by halogen, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy;

(ii) 2-furanyl, 2-thiazoyl, 2- 3- or 4-pyridyl or 4- or 5-pyrimidinyl, each unsubstituted or substituted by C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 4 -alkoxycarbonyl;

(iii) oxetan-3-yl, thietan-3-yl, thietan-3-yl-1-oxide, thietan-3-yl-1,1-dioxide, or tetrahydrofuran-2- or -3-yl;

(iv) C 1 -C 2 -alkyl which is unsubstituted or substituted by chlorine; fluorine; C 1 -C 2 -alkoxy; —C(O)NHR 10 wherein R 10 is C 1 -C 4 -alkyl, 2,2,2-trifluoroethyl, cyanomethyl, propargyl or cyclopropylmethyl; 2-furanyl; 2-thiazoyl; 2- 3- or 4-pyridyl; 4- or 5-pyrimidinyl; oxetan-3-yl; thietan-3-yl; thietan-3-yl-1-oxide; thietan-3-yl-1,1-dioxide; tetrahydrofuran-2-yl; tetrahydrofuran-3-yl; or phenyl which is unsubstituted or substituted by halogen, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy;

(v) allyl; (vi) propargyl; (vii) C 3 -C 4 -cycloalkyl; or (viii) C 3 -C 4 -cycloalkylmethyl.

6. A compound according to claim 1 of formula

wherein R 1 is halogen, CF 3 or OCF 3 ;

R 1′ and R 1″ are each independently H or halogen; and

R 8 is as defined in claim 1 .

7. A compound according to claim 6 , wherein R 8 is

(i) C 1 -C 3 -alkyl which is unsubstituted or substituted by fluorine or cyano;

(ii) C 3 -C 4 -cycloalkyl, which is unsubstituted or substituted by methyl, halogen or cyano;

(iii) 2-furanyl;

(iv) thietan-4-yl or thietan-3-yl-methyl; or

(v) a radical

wherein R 14 is C 1 -C 2 -alkyl or halo-C 1 -C 2 -alkyl.

8. A compound according to claim 7 , wherein R 1 is CF 3 and R 1′ and R 1″ are each H.

9. Method of controlling parasites in and on vertebrates, which comprises applying to the vertebrates a pharmaceutical effective amount of at least one compound of claim 1 .

10. The method according to claim 9 , wherein the parasites are sea lice on fish.

11. A compound according to claim 1 of formula

or a salt or an enantiomer thereof.

12. A compound according to claim 1

or a salt or an enantiomer thereof.

13. A compound according to claim 1

or a salt or an enantiomer thereof.