Anthelminthic heterocyclic compounds
A compound of formula (I), (IA) or formula (II) or a composition comprising the compound of formula (I), (IA) or formula (II) in association with a veterinarily acceptable carrier are described. A method of controlling helminths using same is described.
1. A compound of formula (I):
wherein:
W 1 W 2 , W 3 and W 4 are independently C—H or N;
R 1 is cyano, optionally substituted alkoxy, optionally substituted haloalkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted C 3 -C 8 -cycloalkyl, optionally substituted alkenyl, optionally substituted haloalkenyl, optionally substituted alkynyl, optionally substituted haloalkynyl, optionally substituted aryl; optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted alkyl-SO n , haloalkyl-SO n , amino, NH-optionally substituted alkyl, or NR a R b wherein R a and R b are independently optionally substituted C 1 -C 4 alkyl; or R a and R b may form, with the nitrogen to which they are attached, a 3, 4, 5, 6, 7, or 8 membered-heterocyclyl group, which may be optionally substituted;
R 2 is halogen, cyano, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted C 3 -C 8 -cycloalkyl, or SO m (optionally substituted alkyl);
R 3 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl, each of which may be optionally substituted with 1, 2, 3, 4 or 5 substituents;
each R 4 is independently hydrogen, halogen, cyano, nitro, —OH, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted cycloalkyl, -amino, NH-optionally substituted alkyl, SF 5 , or NR c R d wherein R c and R d are independently optionally substituted alkyl; or R c and R d may form, with the nitrogen to which they are attached, a 3, 4, 5, 6, 7, or 8 membered-heterocyclyl group, which may be optionally substituted, SO p (optionally substituted C 1 -C 4 -alkyl);
o is 0, 1, 2, 3, or 4;
m, n, and p are independently 0, 1, or 2;
q is 0 or 1;
X and Y are independently CR 5 R 6 , O, S, or N—R 7 , wherein at least one of X and Y is CR 5 R 6 ;
R 5 and R 6 are independently hydrogen, fluorine or C 1 -C 4 -alkyl;
R 7 is hydrogen or C 1 -C 4 -alkyl; or
a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof.
2. A compound according to claim 1 , wherein the compound has the structure of formula (I-1):
wherein:
R 1 is cyano, optionally substituted alkoxy, optionally substituted haloalkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted C 3 -C 8 -cycloalkyl, optionally substituted alkenyl, optionally substituted haloalkenyl, optionally substituted alkynyl, optionally substituted aryl; optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted alkyl-SO n , haloalkyl-S(O) n , amino, NH-optionally substituted alkyl, or NR a R b wherein R a and R b are independently optionally substituted C 1 -C 4 alkyl; or R a and R b may form, with the nitrogen to which they are attached, a 3, 4, 5, 6, 7, or 8 membered-heterocyclyl group, which may be optionally substituted;
R 2 is halogen, cyano, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted C 1 -C 4 -alkyl, optionally substituted C 3 -C 6 -cycloalkyl, or SO m (optionally substituted C 1 -C 4 -alkyl);
R 3 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl, each of which may be optionally substituted with 1, 2, 3, 4 or 5 substituents;
each R 4 is independently hydrogen, halogen, cyano, nitro, —OH, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted cycloalkyl, -amino, NH-optionally substituted alkyl, SF 5 , or NR c R d wherein R c and R d are independently optionally substituted alkyl; or R c and R d may form, with the nitrogen to which they are attached, a 3, 4, 5, 6, 7, or 8 membered-heterocyclyl group, which may be optionally substituted, SO p (optionally substituted C 1 -C 4 -alkyl);
o is 0, 1, 2, 3, or 4;
m, n, and p are independently 0, 1, or 2;
q is 0 or 1;
X and Y are independently CR 5 R 6 , O, S, or N—R 7 , wherein at least one of X and Y is CR 5 R 6 ;
R 5 and R 6 are independently hydrogen, fluorine or C 1 -C 4 -alkyl;
R 7 is hydrogen or C 1 -C 4 -alkyl; or
a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof.
3. The compound according to claim 2 wherein R 1 is secondary C 1 -C 4 -alkyl.
4. The compound of claim 2 wherein R 1 is heterocyclyl.
5. The compound of claim 4 wherein R 1 is aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolyl, or morpholinyl, all of which are optionally substituted by one or more halogen.
6. The compound according to claim 1 , wherein R 2 is Alkyl or haloalkyl.
7. The compound according to claim 1 , wherein R 3 is phenyl substituted with 1 substituent which is halo, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy or haloalkenyloxy.
8. The compound according to claim 1 , wherein R 3 is dihalophenyl.
9. The compound according to claim 1 , wherein R 3 is trihalophenyl.
10. The compound according to claim 1 , wherein q is 1.
11. The compound according to claim 1 wherein q is 0.
12. The compound according to claim 1 , wherein X is CH 2 .
13. The compound according to claim 1 , wherein Y is CH 2 .
14. The compound according to claim 1 , wherein X is O.
15. A composition comprising the compound of claim 1 and a veterinarily acceptable carrier.
16. A compound of formula (IA):
wherein:
W 5 , W 6 and W 7 are independently CH, N or S;
R 1 is -cyano, optionally substituted alkoxy, optionally substituted haloalkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted C 3 -C 8 -cycloalkyl, optionally substituted alkenyl, optionally substituted haloalkenyl, optionally substituted alkynyl, optionally substituted haloalkynyl, optionally substituted aryl; optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted alkyl-SO n , haloalkyl-SO n , amino, NH-optionally substituted alkyl, or NR a R b wherein R a and R b are independently optionally substituted C 1 -C 4 alkyl; or R a and R b may form, with the nitrogen to which they are attached, a 3, 4, 5, 6, 7, or 8 membered-heterocyclyl group, which may be optionally substituted;
R 2 is halogen, cyano, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted C 3 -C 8 -cycloalkyl, or SO m (optionally substituted alkyl);
R 3 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl, each of which may be optionally substituted with 1, 2, 3, 4 or 5 substituents;
each R 4 is independently hydrogen, halogen, cyano, nitro, —OH, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted cycloalkyl, -amino, NH-optionally substituted alkyl, SF 5 , or NR c R d wherein R c and R d are independently optionally substituted alkyl; or R c and R d may form, with the nitrogen to which they are attached, a 3, 4, 5, 6, 7, or 8 membered-heterocyclyl group, which may be optionally substituted, SO p (optionally substituted C 1 -C 4 -alkyl);
o is 0, 1, 2, 3, or 4;
m, n, and p are independently 0, 1, or 2;
q is 0 or 1;
X and Y are independently CR 5 R 6 , O, S, or N—R 7 , wherein at least one of X and Y is CR 5 R 6 ;
R 5 and R 6 are independently hydrogen, fluorine or C 1 -C 4 -alkyl;
R 7 is hydrogen or C 1 -C 4 -alkyl; or
a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof.
17. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.