Antiprotozoal imidazopyridine compounds
View Patent ↗Compounds described by the Formula (I) or (II): or pharmaceutically acceptable salts, or N-oxides thereof. The compounds are useful for the treatment and prevention of protozoal diseases in mammals and birds. A method for controlling coccidiosis in poultry comprises administering an effective amount of the compound alone, or in combination with one or more anticoccidieal agent(s). A composition for controlling coccidiosis in poultry comprises the compound alone, or in combination with one or more anticoccidial agent(s). Methods for the treatment and prevention of mammalian protozoal diseases, such as, for example, toxoplasmosis, malaria. African typanosomiasis, Chagas disease, and opportunistic infections comprise administering the compound alone, or in combination with one or more antiprotozoal agent(s).
1. A compound represented by Formula (I)
or a pharmaceutically acceptable salt, or N-oxide thereof, wherein
R 1 is
(a) hydrogen,
(b) C 1 -C 6 -alkyl,
(c) halogen;
R 2 is
(a) hydrogen,
(b) C 1 -C 6 -alkyl, optionally substituted with one or more of halogen, —OH, or aryl,
(c) cycloalkyl,
(d) CF 3 ,
(e) aryl, optionally substituted with one or more of halogen or alkyl,
(f) heteroaryl, optionally substituted with one or more of alkyl or halogen;
R 3 is selected from
R c is selected from hydrogen and C 1-4 alkyl, wherein alkyl is optionally substituted with one or more of halogen or —OH;
n and m are independently 0, 1, 2, 3 or 4, provided that n+m=2, 3 or 4;
q is 1 or 2; and
R 4 is hydrogen or halogen.
2. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 2 is optionally substituted C 1 -C 6 -alkyl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 2 is cycloalkyl.
4. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 2 is CF 3 .
5. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 2 is optionally substituted aryl.
6. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 2 is optionally substituted heteroaryl.
7. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
8. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
9. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
10. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
11. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
12. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
13. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is piperidinyl.
14. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is [(C 1-4 ) alkyl]piperidinyl.
15. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is piperidin-4-yl.
16. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is [(C 1-4 )alkyl]piperidin-4-yl.
17. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is 1-methylpiperidinyl.
18. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is 1-methylpiperidin-4-yl.
19. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is 1-(3-hydroxypropyl)-4-piperidinyl.
20. The compound of claim 1 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
R 3 is 1-(3-hydroxyethyl)-4-piperidinyl.
21. A compound represented by Formula (II)
or a pharmaceutically acceptable salt, or N-oxide thereof, wherein
Het is pyridyl, puridazinyl, triazinyl, thiazolyl, or isothiazolyl, optionally substituted with one or more of amino, alkyl or halogen; and
R 1 is
(d) hydrogen,
(e) C 1 -C 6 -alkyl,
(f) halogen;
R c is selected from hydrogen and C 1-4 alkyl, wherein alkyl is optionally substituted with one or more of halogen or —OH;
n and m are independently 0, 1, 2, 3 or 4, provided that n+m =2, 3 or 4; and
q is 1 or 2.
22. The compound of claim 21 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
Het is pyridyl.
23. The compound of claim 21 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
Het is pyridazinyl.
24. The compound of claim 21 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
Het is triazinyl.
25. The compound of claim 21 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
Het is thiazolyl.
26. The compound of claim 21 , or a pharmaceutically acceptable salt, or an N-oxide thereof, wherein
Het is isothiazolyl.
27. A compound represented by
or a pharmaceutically acceptable salt, or an N-oxide thereof.
28. A method for controlling coccidiosis in poultry which comprises administering to said poultry a therapeutically effective amount, of a compound of claim 1 .
29. A composition which comprises a compound of claim 1 and a pharmaceutically acceptable carrier.
30. The composition of claim 29 further comprising a second anticoccidial agent.
31. The composition of claim 30 wherein said second anticoccidial agent is selected from the group consisting of amprolium, ethopabate, clopidol, meticlorpindol, decoquinate, dinitolmide, halofuginone, lasalocid, maduramicin, monensin, narasin, nicarbazin, chlortetracycline, oxytetracycline, robenidine, salinomycin, semduramicin, and diclazuril.
32. The composition of claim 30 wherein said second anticoccidial agent is selected from the group consisting of amprolium, ethopabate, lasalocid, monensin, salinomycin, and diclazuril.
33. The composition of claim 29 wherein said carrier is poultry feedstuff.
34. The composition of claim 33 further comprising a second coccidial agent.
35. The composition of claim 34 wherein said second anticoccidial agent is selected from the group consisting of amprolium, ethopabate, clopidol, meticlorpindol, decoquinate, dinitolmide, halofuginone, lasalocid, maduramicin, monensin, narasin, nicarbazin, chlortetracycline, oxytetracycline, robenidine, salinomycin, semduramicin, and diclazuril.
36. The composition of claim 34 wherein said second anticoccidial agent is selected from the group consisting of amprolium, ethopabate, lasalocid, monensin, salinomycin, and diclazuril.
37. The composition of claim 29 wherein said carrier is poultry feed premix.
38. The composition of claim 37 further comprising a second anticoccidial agent.
39. The composition of claim 38 wherein said second anticoccidial agent is selected from the group consisting of amprolium, ethopabate, clopidol, meticlorpindol, decoquinate, dinitolmide, halofuginone, lasalocid, maduramicin, monensin, narasin, nicarbazin, chlortetracycline, oxytetracycline, robenidine, salinomycin, semduramicin, and diclazuril.
40. A composition of claim 38 wherein said second anticoccidial agent is selected from the group consisting of amprolium, ethopabate, lasalocid, monensin, salinomycin, and diclazuril.
41. A method for controlling malaria in a mammalian patient which comprises administering to said patient a therapeutically effective amount, of the compound of claim 1 .
42. A method for controlling African trypanosomiasis in a mammalian patient which comprises administering to said patient a therapeutically effective amount, of a compound of claim 1 .
43. A method for controlling Chagas disease in a mammalian patient which comprises administering to said patient a therapeutically effective amount, of a compound of claim 1 .
44. A method for controlling toxoplasmosis in a mammalian patient which comprises administering to said patient a therapeutically effective amount, of a compound of claim 1 .
45. A method for controlling coccidiosis in poultry which comprises administering to said poultry a therapeutically effective amount, of a compound of claim 21 .
46. A method for controlling coccidiosis in poultry which comprises administering to said poultry a therapeutically effective amount, of a combination of anticoccidial agents comprising a compound of claim 21 and a second anticoccidial agent.