SPIROINDOLINE COMPOUNDS FOR USE AS ANTHELMINTHICS
This invention relates to spiroindoline compounds for the treatment of helminth infections and the treatment of parasitosis, such as caused by helminth infections. This invention also relates to uses of the compounds to make medicaments and treatments comprising the administration of the compounds to animals in need of the treatments. Moreover this invention relates to pharmaceutical compositions and kits comprising the compounds.
1 . A pharmaceutical composition comprising
a) one or more compounds of the formula (I) and pharmaceutically acceptable solvates, N-oxides and salts thereof,
wherein
Y=O, S;
Q=—CH 2 —CH(CH 3 )—, —CH 2 —CH 2 —O, —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH═CH—, —CH 2 —CH 2 —CH 2 —;
R 1 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;
R 2 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;
A 1 =H, halogen, C 1 -C 4 -alkyl;
A 2 =H, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, wherein C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio are optionally perfluorinated;
A 3 =H, halogen, C 1 -C 4 -alkyl;
A 4 =H, halogen, C 1 -C 4 -alkyl;
B 1 =H, F, Cl, CH 3 , CF 3 ;
B 2 =H, F, Cl, CH 3 , CF 3 , NO 2 ;
B 3 =H, F, Cl, CH 3 , CF 3 , CN, OCH 3 , OCF 3 ;
B 4 =H, F, Cl, CH 3 , CF 3 ;
B 5 =H, F, Cl, CH 3 , CF 3 − ; and
b) one or more pharmaceutically acceptable excipients, and/or one or more pharmaceutically acceptable active ingredients which differ in structure from component a).
2 . The pharmaceutical composition according to claim 1 , wherein in formula (I)
Y=O, S;
Q=—CH 2 —CH(CH 3 )—, —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH═CH—, —CH 2 —CH 2 —CH 2 —; preferably —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH═CH—;
R 1 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;
R 2 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;
A 1 =H, halogen, C 1 -C 4 -alkyl;
A 2 =H, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, wherein C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio are optionally perfluorinated;
A 3 =H, halogen, C 1 -C 4 -alkyl;
A 4 =H, halogen, C 1 -C 4 -alkyl;
B 1 =H, F, Cl, CH 3 , CF 3 ;
B 2 =H, F, Cl, CH 3 , CF 3 , NO 2 ;
B 3 =H, F, Cl, CH 3 , CF 3 , CN, OCH 3 , OCF 3 ;
B 4 =H, F, Cl, CH 3 , CF 3 ;
B 5 =H, F, Cl, CH 3 , CF 3 .
3 . The pharmaceutical composition according to claim 1 , wherein in formula (I),
Y=O, S, preferably O;
Q=—CH 2 —CH═CH—;
R 1 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;
R 2 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;
A 1 =H, Cl;
A 2 =H, F, Cl, Br, CH 3 , OCH 3 , OCF 3 , CF 3 , SCF 3 ;
A 3 =H, Cl;
A 4 =H, Cl;
B 1 =H, F, Cl, CH 3 , CF 3 ;
B 2 =H, F, Cl, CH 3 , CF 3 ;
B 3 =H, F, Cl, CH 3 , CF 3 , CN, OCH 3 , OCF 3 ;
B 4 =H, F, Cl, CH 3 , CF 3 ;
B 5 =H, F, Cl, CH 3 , CF 3 .
4 . The pharmaceutical composition according to claim 1 wherein in formula (I)
a) at least one of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5 is different from hydrogen, or
b) at least one of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4 is different from hydrogen, or
c) at least one of the radicals R 1 , R 2 , B 1 , B 2 , B 3 , B 4 , B 5 is different from hydrogen, or
d) at least one of the radicals A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5 is different from hydrogen, or
e) at least one of the radicals R 1 , R 2 is different from hydrogen, or
f) at least one of the radicals A 1 , A 2 , A 3 , A 4 is different from hydrogen, or
g) at least one of the radicals B 1 , B 2 , B 3 , B 4 , B 5 is different from hydrogen, or
h) at least two of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5 are different from hydrogen, or
i) at least one of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5 is F or Cl.
5 . A method of treating a parasitic infection in an animal comprising administering to the animal the pharmaceutical composition of claim 1 .
6 . The method according to claim 5 , wherein the parasitic infection is a helminth infection.
7 . The method according to claim 5 , wherein the pharmaceutical composition is administered orally.
8 . The method according to claim 5 , wherein the pharmaceutical composition is administered parenterally.
9 . A compound selected from the group consisting of
and pharmaceutically acceptable solvates, N-oxides and salts thereof.
10 . A pharmaceutical composition, wherein the composition comprises:
a) one or more compounds as defined in claim 9 , and
b) one or more pharmaceutically acceptable excipients, and/or one or more pharmaceutically acceptable active ingredients which differ in structure from component a).
11 . A method of treating a parasite infection in an animal, comprising administering to the animal a pharmaceutical composition as defined in claim 10 .
12 . The method of claim 11 , wherein the parasite infection is a helminth infection.
13 . The method of claim 12 , wherein the helminth infection is a nematode infection.
14 . A kit, wherein the kit comprises:
a) one or more compounds as defined in claim 1 , and
b) one or more other components selected from the group consisting of an excipient, an active ingredient, an apparatus for combining the compound of component a) with an excipient and/or active ingredient, an apparatus for administering the compound of component a) to an animal, and a diagnostic tool.
15 - 16 . (canceled)
17 . The method as claimed in claim 11 , wherein one or more of the parasites are resistant to one or more antiparasitic compounds.
18 . The method of claim 11 , wherein the animal is a non-human mammal.
19 . The method of claim 5 , wherein the animal is a non-human mammal.
20 . The method of claim 5 , wherein one or more of the parasites are resistant to one or more antiparasitic compounds.
21 . The method of claim 6 , wherein the helminth infection is a nematode infection.
22 . The method of claim 11 , wherein the pharmaceutical composition is administered orally.
23 . The method of claim 11 , wherein the pharmaceutical composition is administered parenterally.