CA1171782A - Anticoccidial combinations comprising polyether antibiotics and carbanilides - Google Patents
Anticoccidial combinations comprising polyether antibiotics and carbanilidesInfo
- Publication number
- CA1171782A CA1171782A CA000367322A CA367322A CA1171782A CA 1171782 A CA1171782 A CA 1171782A CA 000367322 A CA000367322 A CA 000367322A CA 367322 A CA367322 A CA 367322A CA 1171782 A CA1171782 A CA 1171782A
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- carbanilide
- trifluoromethyl
- bis
- nitro
- chloro
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Abstract
Abstract The present invention is directed to novel anticoccidial compositions and methods of employing the same to control coccidiosis in poultry. These compositions comprise a polyether antibiotic and a second component which is a selected carbanilide.
Description
7~,~
ANTICOCCIDIAL COMBINATIONS COMPRISING
POLYETHER ANTIBIOTICS AND CARBANILIDES
Brief SummarY of the Invention The present invention is directed to the control-ling of coccidiosis in poultry and, more particularly, to an orally administerable feedstuff comprising a first component which is a polyether antibiotic and a second component which is selected ~rom a group of carbanilides.
Detailed Description The polyether antibiotics are a class of anti-biotics produced by the Streptomyces genus of microorgan-isms. They are characterized by comprising a multiplicityof cyclic ethers in their structures. The class is reviewed in Kirk-Othmer: EncYcloPedia of Chemical Technoloqy, Vol. 3, Third Edition (John Wiley ~ Sons, Ind., 1978), page 47 et seq.; in Annual RePorts in Medicinal Chemistry Volume 10 (Academic Press, N.Y. 1975), page 246 et seq.; and in ~. Chrom. Lib., Vol. 15 (Elsevier Scientific Publishing Co., N.Y. 1978), page 488 et seq.
Like other products of fermentation origin, many of the polyether antibiotics comprise more than one factor. The various factors are all usable in the present invention. Further, many of these antibiotics readily form ethers, esters, salts, or other derivatives, which are either active as such or are ~ 1';'17~
converted _ vivo to the basic antibiotic. Such derivatives can also be employed in the present in-vention. All that is necessary is that an active moiety of a polyether antibiotic be delivered in vivo.
Representative polyether antibiotics in-clude the following: monensin (factors ~, B, and C), laidlomycin, nigericin, grisorixin, dianemycin, lenoremycin, salinomycin, narasin, lonomycin, anti-biotic X206, alborixin, septamycin, antibiotic 204A, A32887 (K41), etheromycin, lasalocid (factors A, B, C, D, and E), isolasalocid A, lysocellin, and anti-biotic A23187.
Preferred polyether antibiotics include monensin, narasin, lasalocid, salinomycin, A-204, lonomycin, X-206, nigericin, and dianemycin, and especially monensin, narasin, lasalocid, and A-204.
Many of the carbanilides to be employed in the present combinations are known compounds, and some of them are known to exhibit anticocidial activity.
The carbanilides can be divided into three groups. A first group consists of the following compounds (literature references, where known, are included):
A. ~iscellaneous Carbanilide Compounds A.l. 3,3'-bis(trifluoromethyl)-4,4'-dichlorocar-banilide (CAS registry #370-50-3: C.A.
68:2655v) -A.2. 3,3',5,5'-tetrakis(trifluoromethyl)car-banilide (CAS registry #3824-74-6; C.A.
66: P646444, C.A. 68: 2655v, and C.A.
71: P91052y) 11;'17~
A.3. 3-chloro-4'-fluorocarbanilide (C.A. 65: 12792c) A.4. 2-chloro-2'-fluorocarbanilide A.5. 3,4',5-tris(trifluoromethyl)carbanilide (CAS
registry #23747-71-9; C.A. 71: P91056c) A.6. 3,4,5-trichlorocarbanilide A.7. 2-chloro-5-(trifluoromethyl)-4'-(ethoxy-carbonyl)carbanilide 10 A.8. 2,6-dimethyl-4'-(N-methylacetamido)carbanilide A.9. 2-methoxy-4'-acetamidocarbanilide A.10. 3-(~rifluoromethyl)-4'-iodothiocarbanilide A.ll. 2-fluoro-4'-(aminosulfonyl)carbanilide A.12. 2-methoxy-4'-isopropylcarbanilide A.13. 2-methyl-2',5'-diethoxycarbanilide A.14. 4-ethyl-2'-methoxycarbanilide A.15. 2-methyl-5-chloro-2',5'-dimethoxycarbanilide A.16. 2,4,4'-trimethyl-3'-nitrocarbanilide A.17. 2-amino-3-nitro-5-(trifluoromethyl)-2',4'-dimethylcarbanilide A.18. 2-amino-3,4'-dinitro-5-(trifluoromethyl)-2'-chlorocarbanilide A.l9. 2-amino-3,5'-dinitro-5-(trifluoromethyl)-2'-fluorocarbanilide A.20. 2-amino-3-nitro-5-(trifluoromethyl)-2'-(ethoxycarbonyl)carbanilide A.21. 2-ethyl-6-sec-butylcarbanilide ~'i'l7~
A.22. 2-isopropyl-2',4',6'-trimethylcarbanilide A.23. 2-amino-3-nitro-3',5-bis(trifluoromethyl)-4'-chlorocarbanilide A.24. 2-ethyl-6-sec-butyl-4'-n-butoxycarbanilide A.25. 2-amino-3-nitro-5-(trifluoromethyl)-2',4',5'-trichlorocarbanilide A.26. 2-amino-3,3'-dinitro-5-(trifluoromethyl)-4'-chlorocarbanilide A.27. 2-amino-3-nitro-5-ttrifluoromethyl)-2'-methyl-4'-bromocarbanilide A.28. 2-amino-3-nitro-5-(trifluoromethyl)-2',6'-dibromo-4'-fluorocarbanilide A.29. 2-amino-3-nitro-2',5-bis(trifluoromethyl)-4'-chlorocarbanilide A.30. 3,3',5,5'-tetrakis(trifluoromethyl)thio-carbanilide (CAS registry #1060-92-0; C.A.
66: 64644H) A.31. 2,4-dimethoxy-4'-(ethoxycarbonyl)carbanilide A.32. 4-(ethoxycarbonyl)-2'-methyl-6'-ethylcarbanilide A.33. 2,2'-dinitro-4,4'-bis(trifluoromethyl)car-banilide (CAS re~istry #16588-81-1; C.A.
68: 2655v) A.34. 3,3',4,4',5,5'-hexachlorocarbanilide A.35. 3-nitro-4 chloro-4'-(trifluoromethyl)car-banilide A.36. 4-chloro-3,4'-bis(trifluoromethyl)carbanilide (CAS registry #23747-70-8; C.A. 71: P91056c) 7~
A.37. 4,4'-dinitro-2,2'-bis(trifluoromethyl)car-banilide (CAS registry #16588-84-4; C.A.
68: 2655v) A.38. 4,4'-bis(trifluoromethyl)carbanilide (CAS
registry #1960-88-9; C.A. 71: 91056c) A.39. 3-bromo-3',5'-dimethylcarbanilide A.40. 2,5-dichloro-4'-methyl-N2-ethylcarbanilide A.41. 2,5-dichloro-2',4'-difluorocarbanilide A.42. 2-amino-3-nitro-3',5,5'-tris(trifluoromethyl)-carbanilide A.43. 2,6-diethyl-4'-(ethoxycarbonyl)carbanilide A.44. 3-ethyl-3'-chloro-4'-methyl-N2-ethylcarbanilide A.45. 2,6-dimethyl-4'-(ethoxycarbonyl)carbanllide A.46. 4-methoxy-3'-acetamidocarbanilide A.47. 2-methoxy-4'-(n-butoxycarbonyl)carbanilide 20 A.48. 4-(isobutoxycarbonyl)carbanilide A.49. 2,4'-bis(methoxycarbonyl)carbanilide A.50. 2',4-dichloro-3-nitro-3'-(trifluoromethyl)-carbanilide A.51. 3,4,4',5-tetrachloro-3'-(trifluoromethyl)-carbanilide (C.A. 63: P440f) A.52. 4-chloro-3-nitro-3',5'-bis(trifluoromethyl)-carbanilide A.53. 2,4,6-trimethyl-4'-(ethoxycarbonyl)carbanilide A.54. 2-~trifluoromethyl)-2'-ethyl-6'-isopropyl-carbanilide 1 71~
A.55. 4-chloro-3,3',5'-tris(trifluoromethyl)car-banilide (CAS registry ~t4528-83-0; C.A.
71: 91052y and 66: 64644h) A.56. 3,4,4',5-tetrachloro-3'-nitrocarbanilide A.57. 2,6-dimethyl-4'-benzoylcarbanilide A.58. 3,4-dimethyl-2'-ethoxycarbanilide A.59. 2-chloro-4,4'-bis(methylthio)carbanilide 10 A.60. 2-methyl-~'-ethoxycarbanilide A.61. 4-chloro-2-methoxythiocarbanilide A.62. 4,4'-dinitro-N,N'-dimethylcarbanilide 5CAS
registry #34594-47-3; C.A. 83: 36180m and C.A. 85: 20476t) A.63. 4-(trifluoromethyl)-4'-nitrocarbanilide (CAS
registry #23747-76-4 U.S. 3,867,544) A.64. 3,3',5,5'-tetrakis(trifluoromethyl)-N,N'-dimethylcarbanilide A second group of carbanilides to be employed in the present combinations is the group of carbanilides described by U.S. patent 3,284,433. These compounds are of the formula X~ ---NH--CO-NH~ X
Formula I
wherein each X is independently selected from the group consisting of chlorine, bromine, and nitro radicals;
and (2) compounds of the same formula as (I) except that a hydrogen of at least one of the rings of (I) is replaced by a substituent ~elected from the groupconsisting of chlorine, bromine, nitro and lower alkyl radicals.
Representative compo~nds of this group include the following:
B. Phenoxycarbanilides of U.S. Patent 3,284,433 B.l. 4-nitro-4'-(4-chlorophenoxy)carbanilide B.2. 4-nitro-4'-(3,4-dichlorophenoxy)carbanilide B.3. 4-nitro-3'-chloro-4'-(4-chlorophenoxy) carbanilide B.4. 4-nitro-3',5'-dichloro-4'-(4-chlorophenoxy)-carbanilide B.5. 4-nitro-3'-chloro-4'-(3,4-dichlorophenoxy)-carbanilide B.6. 4-nitro-4'-(2,4-dichlorophenoxy)carbanilide B.7. 4-nitro-4'-(4-nitrophenoxy)carbanilide B.8. 4-nitro-3'.nitro-4'-(4-chlorophenoxy)-carbanilide B.9. 4-nitro-3'-methyl-4'-(4-chlorophenoxy)-carbanilide B.10. 4-nitro-2'-nitro-4'-(4-chlorophenoxy)-carbanilide B.ll. 4-nitro-4'-(2,4-dinitrophenoxy)carbanilide B.12. 4-nitro-3'-chloro-4'-(2-tert-butyl-4-chloro-phenoxy)carbanilide 3~
B.13. 4-nitro-4'-(2-methyl-4-chlorophenoxy)-carbanilide l l'J'1 7~2 B.14. 4-nitro-3'-bromo-4'-(4-bromophenoxy)carbanilide B.15. 4-nitro-3'-bromo-4'-(4-chlorophenoxy)-carbanilide B.16. 4-nitro-3'-chloro-4'-(4-bromophenoxy)-carbanilide B.17. 3,3',4'-trichloro-4-(4-chlorophenoxy)-carbanilide B.18. 3,4'-dichloro-4-(4-chlorophenoxy)carbanilide B.l9. 3,4-dichloro-4'-(4-chlorophenoxy)carbanilide B.20. 2-methyl-4-nitro-3'-chloro-4'-(4-chloro-phenoxy)carbanilide A third group of carbanilides to be employed lS in the present combin~tions is the group of carbanilides described by German Patent 2,334,355. These compounds include the following:
C. Carbanilides of German 2,334,355 20 C.l. 3,3',5'-tris(trifluoromethyl)-4-methoxy-carbanilide C.2. 3-(trifluoromethoxy)-3',5'-bis(trifluoro-methyl)carbanilide 25 C.3. 4-ttrifluorom~thoxy)-3',5'-bis(trifluoro-methyl)carbanilide C.4. 2,3',5'-tris(trifluoromethyl)-4-(trifluoro-methoxy)carbanilide C.5. 4-~methylthio)-3',5'-bis(trifluoromethyl)-carbanilide C.6. 4-(methylthio)-3',5'-bis(trifluoromethyl)-thiocarbanilide C.7. 3-chloro-4-(methylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.8. 3-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.9. 4-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.10. 2-chloro-4-~trifluoromethylthio)-3',5'-bis(trifluoromethyl)carbanilide C.ll. 4-(trifluoromethylthio)-3'-(trifluoromethyl~-5'-nitrocarbanilide C.12. 4-(trifluoromethylthio)-2',5'-bis(trifluoro-methyl)-4'-nitrocarbanilide C.13. 4,4'-bis(trifluoromethylthio)carbanilide C.14. 4-(trifluoromethylthio)-4'-(chloromethyl-sulfonyl)carbanilide C.15. 3-(difluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.16. 4-(ethylthio)-3',5r-bis(trifluoromethyl)-carbanilide C.17. 3-chloro-4-(ethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.18. 4-ethoxy-3,3',5'-tris(trifluoromPthyl)car-banilide C.l9~ 3-(trifluoromethyl)-4-ethoxy-4'-(trifluoro-methylthio)carbanilide -'17~Z
C.20. 3-(trifluoromethyl)-4-ethoxy-3'-(trifluoro-methylthio)carbanilide C.21. 4-methyl-3-~2-chloroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.22. 4-(1,2-dichlorovinyloxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.23. 4-(1,2-dichlorovinyloxy)-3',5'-bis(trifluoro-methyl)carbanilide C.24. 4-(2,2,2-trichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.25. 2-,2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.26. 3-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.27. 3-(2,2-dichloro~ difluoroethoxy)-4-bromo-3',5'-bis(trifluoromethyl)carbanilide C.28. 4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.29. 4-(2,~ichloro-1,1-difluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.30. 3-methoxy-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.31. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.32. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-4'-isopropylcarbanilide C.33. 3-nitro-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.34. 2-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.35. 4-(2,2-dichloro-1,1-difluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.36. 3-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide 1 1 f 1>~2 C.37. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.38. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)thiocarbanilide C.39. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.40. 4,4'-bis(2-chloro-1,1,2-trifluoroethoxy)-carbanilide C.41. 4-(2-chloro-1,1,2-trifluoroethoxy)-4'-(trifluoromethylthio)carbanilide C.42. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.43. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3'-bis(trifluoromethyl)-5'-nitrocarbanilide C.44. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.45. 3-(1,1,2-trifluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.46. 3-(1,1,2,2-tetrafluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.47. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(chlorodi~luoromethyl)carbanilide C.48. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.49. 3-(trifluoro~ethyl)-4-(1,1,2,2-tetrafluoro-ethoxy)-4'-bromocarbanilide C.50. 3-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)carbanilide ,.a.7~
C.51. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)carbanilide C.52. 3-chloro-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.53. 3-methyl-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.54. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.55. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.56. 4-(methoxycarbonylthio)-3',5'-bis(tri-fluoromethyl)carbanilide C.57. 4-(4-chlorophenoxy)-4'-(trifluoromethyl-thio)thiocarbanilide C.58. 4-(4-chlorophenoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.59. 3-chloro-4-(4-cnlorophenoxy)-3',5'-bis(trifluoromethyl)carbanilide C.60. 4-(4-chlorophenoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.61. 4-(3,5-bis(trifluoromethyl)phenoxy-3',5'-bis(trifluoromethyl)carbanilide C.62. 4-~4-methylphenoxycarbonyl)-3',5'-3~ bis(trifluoromethyl)carbanilide C.63. 4-(4-methylphenoxycarbonyl)-4'-(tri-fluoromethylthio)carbanilide C.64. 3,5-bis(trifluoromethyl)-2',4',6'-trichlorocarbanilide C.65. 3,5-bis(trifluoromethyl)-2',4',~'-tri-chlorocarbanilide C.66. 3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.67. 3,3',5-tris(trifluoromethyl)-5'-nitro-carbanilide C.68. 2',3,5,6'-tetrakis(trifluoromethyl)-4'-nitrocarbanilide C.69. 3-~chlorodifluoromethyl)-3',5'-bis(tri-fluoromethyl)carbanilide C.70. 3-(1,1,2,2-tetrafluoroethyl)-3',~'-bis(trifluoromethyl)carbanilide C.71. 4-phenyl-3',.5'-bis(trifluoromethyl)-.
carbanilide C.72. 3-[fluorosulfonyl)-3',5'-bis(trifluoro-methyl)carbanilide C.73. 4-(fluorosulfonyl)-4'-(trifluoromethyl-thio)carbanilide C.74. 4-(fluorosulfonyl)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.75. 4-(chloromethylsulfonyl)-3',5'-bis(tri-fluoromethyl)carbanilide ~l'f~ ~7 C.76. ~-(ethylsulfonyl)-3',5,5'-tris(trifluoro-methyl)carbanilide C.77. 2-(ethylsulfonyl)-3',5-bis(trifluoro-methyl)-5'-nitrocarbanilide C.78. 4-(trifluoromethylsulfonyl)-3',5'-bisttrifluoromethyl)carbanilide C.79. 4-(trifluoromethylsulfonyl)-3'-(tri-fluoromethyl)-4'-methoxycarbanilide C.80. . 4-(trifluoromethylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.81. 4-(4-nitrophenylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.82. 4-(4-acetamidophenylsulfonyl)-4'-(trifluoromethylthio)carbanilide C.83. 4-(4-(isopropylideneamino)phenylsul-fonyl)-4'-(trifluoromethylthio)car-banilide C.84. 4,4-sulfonylbis(3'-(trifluoromethylthio)-carbanilide) C.85. 4,4-sulfonylbis(4'-(1,2-dichlorovinyl-oxy)carbanilide) C.86. 4,4-sulfonylbis(3'-(1,1,2,2-tetra-fluoroethoxy)carbanilide) C.87. 4,4-sulf~nylbis(4'-(2-chloro-1,1,2-trifluoroethoxy)carbanilide) C.88. 4,4-sulfonylbis(4'-(trifluoromethyl-thio)carbanilide) 7t~
All of the carbanilides to be employed in accordance with the present invention are prepared in classic synthetic procedures, such as those exempli-fied by U.S. Patent 3,284,433 and German Patent 2,334,355.
The following examples illustrate the synthesis of the carbanilides.
ANTICOCCIDIAL COMBINATIONS COMPRISING
POLYETHER ANTIBIOTICS AND CARBANILIDES
Brief SummarY of the Invention The present invention is directed to the control-ling of coccidiosis in poultry and, more particularly, to an orally administerable feedstuff comprising a first component which is a polyether antibiotic and a second component which is selected ~rom a group of carbanilides.
Detailed Description The polyether antibiotics are a class of anti-biotics produced by the Streptomyces genus of microorgan-isms. They are characterized by comprising a multiplicityof cyclic ethers in their structures. The class is reviewed in Kirk-Othmer: EncYcloPedia of Chemical Technoloqy, Vol. 3, Third Edition (John Wiley ~ Sons, Ind., 1978), page 47 et seq.; in Annual RePorts in Medicinal Chemistry Volume 10 (Academic Press, N.Y. 1975), page 246 et seq.; and in ~. Chrom. Lib., Vol. 15 (Elsevier Scientific Publishing Co., N.Y. 1978), page 488 et seq.
Like other products of fermentation origin, many of the polyether antibiotics comprise more than one factor. The various factors are all usable in the present invention. Further, many of these antibiotics readily form ethers, esters, salts, or other derivatives, which are either active as such or are ~ 1';'17~
converted _ vivo to the basic antibiotic. Such derivatives can also be employed in the present in-vention. All that is necessary is that an active moiety of a polyether antibiotic be delivered in vivo.
Representative polyether antibiotics in-clude the following: monensin (factors ~, B, and C), laidlomycin, nigericin, grisorixin, dianemycin, lenoremycin, salinomycin, narasin, lonomycin, anti-biotic X206, alborixin, septamycin, antibiotic 204A, A32887 (K41), etheromycin, lasalocid (factors A, B, C, D, and E), isolasalocid A, lysocellin, and anti-biotic A23187.
Preferred polyether antibiotics include monensin, narasin, lasalocid, salinomycin, A-204, lonomycin, X-206, nigericin, and dianemycin, and especially monensin, narasin, lasalocid, and A-204.
Many of the carbanilides to be employed in the present combinations are known compounds, and some of them are known to exhibit anticocidial activity.
The carbanilides can be divided into three groups. A first group consists of the following compounds (literature references, where known, are included):
A. ~iscellaneous Carbanilide Compounds A.l. 3,3'-bis(trifluoromethyl)-4,4'-dichlorocar-banilide (CAS registry #370-50-3: C.A.
68:2655v) -A.2. 3,3',5,5'-tetrakis(trifluoromethyl)car-banilide (CAS registry #3824-74-6; C.A.
66: P646444, C.A. 68: 2655v, and C.A.
71: P91052y) 11;'17~
A.3. 3-chloro-4'-fluorocarbanilide (C.A. 65: 12792c) A.4. 2-chloro-2'-fluorocarbanilide A.5. 3,4',5-tris(trifluoromethyl)carbanilide (CAS
registry #23747-71-9; C.A. 71: P91056c) A.6. 3,4,5-trichlorocarbanilide A.7. 2-chloro-5-(trifluoromethyl)-4'-(ethoxy-carbonyl)carbanilide 10 A.8. 2,6-dimethyl-4'-(N-methylacetamido)carbanilide A.9. 2-methoxy-4'-acetamidocarbanilide A.10. 3-(~rifluoromethyl)-4'-iodothiocarbanilide A.ll. 2-fluoro-4'-(aminosulfonyl)carbanilide A.12. 2-methoxy-4'-isopropylcarbanilide A.13. 2-methyl-2',5'-diethoxycarbanilide A.14. 4-ethyl-2'-methoxycarbanilide A.15. 2-methyl-5-chloro-2',5'-dimethoxycarbanilide A.16. 2,4,4'-trimethyl-3'-nitrocarbanilide A.17. 2-amino-3-nitro-5-(trifluoromethyl)-2',4'-dimethylcarbanilide A.18. 2-amino-3,4'-dinitro-5-(trifluoromethyl)-2'-chlorocarbanilide A.l9. 2-amino-3,5'-dinitro-5-(trifluoromethyl)-2'-fluorocarbanilide A.20. 2-amino-3-nitro-5-(trifluoromethyl)-2'-(ethoxycarbonyl)carbanilide A.21. 2-ethyl-6-sec-butylcarbanilide ~'i'l7~
A.22. 2-isopropyl-2',4',6'-trimethylcarbanilide A.23. 2-amino-3-nitro-3',5-bis(trifluoromethyl)-4'-chlorocarbanilide A.24. 2-ethyl-6-sec-butyl-4'-n-butoxycarbanilide A.25. 2-amino-3-nitro-5-(trifluoromethyl)-2',4',5'-trichlorocarbanilide A.26. 2-amino-3,3'-dinitro-5-(trifluoromethyl)-4'-chlorocarbanilide A.27. 2-amino-3-nitro-5-ttrifluoromethyl)-2'-methyl-4'-bromocarbanilide A.28. 2-amino-3-nitro-5-(trifluoromethyl)-2',6'-dibromo-4'-fluorocarbanilide A.29. 2-amino-3-nitro-2',5-bis(trifluoromethyl)-4'-chlorocarbanilide A.30. 3,3',5,5'-tetrakis(trifluoromethyl)thio-carbanilide (CAS registry #1060-92-0; C.A.
66: 64644H) A.31. 2,4-dimethoxy-4'-(ethoxycarbonyl)carbanilide A.32. 4-(ethoxycarbonyl)-2'-methyl-6'-ethylcarbanilide A.33. 2,2'-dinitro-4,4'-bis(trifluoromethyl)car-banilide (CAS re~istry #16588-81-1; C.A.
68: 2655v) A.34. 3,3',4,4',5,5'-hexachlorocarbanilide A.35. 3-nitro-4 chloro-4'-(trifluoromethyl)car-banilide A.36. 4-chloro-3,4'-bis(trifluoromethyl)carbanilide (CAS registry #23747-70-8; C.A. 71: P91056c) 7~
A.37. 4,4'-dinitro-2,2'-bis(trifluoromethyl)car-banilide (CAS registry #16588-84-4; C.A.
68: 2655v) A.38. 4,4'-bis(trifluoromethyl)carbanilide (CAS
registry #1960-88-9; C.A. 71: 91056c) A.39. 3-bromo-3',5'-dimethylcarbanilide A.40. 2,5-dichloro-4'-methyl-N2-ethylcarbanilide A.41. 2,5-dichloro-2',4'-difluorocarbanilide A.42. 2-amino-3-nitro-3',5,5'-tris(trifluoromethyl)-carbanilide A.43. 2,6-diethyl-4'-(ethoxycarbonyl)carbanilide A.44. 3-ethyl-3'-chloro-4'-methyl-N2-ethylcarbanilide A.45. 2,6-dimethyl-4'-(ethoxycarbonyl)carbanllide A.46. 4-methoxy-3'-acetamidocarbanilide A.47. 2-methoxy-4'-(n-butoxycarbonyl)carbanilide 20 A.48. 4-(isobutoxycarbonyl)carbanilide A.49. 2,4'-bis(methoxycarbonyl)carbanilide A.50. 2',4-dichloro-3-nitro-3'-(trifluoromethyl)-carbanilide A.51. 3,4,4',5-tetrachloro-3'-(trifluoromethyl)-carbanilide (C.A. 63: P440f) A.52. 4-chloro-3-nitro-3',5'-bis(trifluoromethyl)-carbanilide A.53. 2,4,6-trimethyl-4'-(ethoxycarbonyl)carbanilide A.54. 2-~trifluoromethyl)-2'-ethyl-6'-isopropyl-carbanilide 1 71~
A.55. 4-chloro-3,3',5'-tris(trifluoromethyl)car-banilide (CAS registry ~t4528-83-0; C.A.
71: 91052y and 66: 64644h) A.56. 3,4,4',5-tetrachloro-3'-nitrocarbanilide A.57. 2,6-dimethyl-4'-benzoylcarbanilide A.58. 3,4-dimethyl-2'-ethoxycarbanilide A.59. 2-chloro-4,4'-bis(methylthio)carbanilide 10 A.60. 2-methyl-~'-ethoxycarbanilide A.61. 4-chloro-2-methoxythiocarbanilide A.62. 4,4'-dinitro-N,N'-dimethylcarbanilide 5CAS
registry #34594-47-3; C.A. 83: 36180m and C.A. 85: 20476t) A.63. 4-(trifluoromethyl)-4'-nitrocarbanilide (CAS
registry #23747-76-4 U.S. 3,867,544) A.64. 3,3',5,5'-tetrakis(trifluoromethyl)-N,N'-dimethylcarbanilide A second group of carbanilides to be employed in the present combinations is the group of carbanilides described by U.S. patent 3,284,433. These compounds are of the formula X~ ---NH--CO-NH~ X
Formula I
wherein each X is independently selected from the group consisting of chlorine, bromine, and nitro radicals;
and (2) compounds of the same formula as (I) except that a hydrogen of at least one of the rings of (I) is replaced by a substituent ~elected from the groupconsisting of chlorine, bromine, nitro and lower alkyl radicals.
Representative compo~nds of this group include the following:
B. Phenoxycarbanilides of U.S. Patent 3,284,433 B.l. 4-nitro-4'-(4-chlorophenoxy)carbanilide B.2. 4-nitro-4'-(3,4-dichlorophenoxy)carbanilide B.3. 4-nitro-3'-chloro-4'-(4-chlorophenoxy) carbanilide B.4. 4-nitro-3',5'-dichloro-4'-(4-chlorophenoxy)-carbanilide B.5. 4-nitro-3'-chloro-4'-(3,4-dichlorophenoxy)-carbanilide B.6. 4-nitro-4'-(2,4-dichlorophenoxy)carbanilide B.7. 4-nitro-4'-(4-nitrophenoxy)carbanilide B.8. 4-nitro-3'.nitro-4'-(4-chlorophenoxy)-carbanilide B.9. 4-nitro-3'-methyl-4'-(4-chlorophenoxy)-carbanilide B.10. 4-nitro-2'-nitro-4'-(4-chlorophenoxy)-carbanilide B.ll. 4-nitro-4'-(2,4-dinitrophenoxy)carbanilide B.12. 4-nitro-3'-chloro-4'-(2-tert-butyl-4-chloro-phenoxy)carbanilide 3~
B.13. 4-nitro-4'-(2-methyl-4-chlorophenoxy)-carbanilide l l'J'1 7~2 B.14. 4-nitro-3'-bromo-4'-(4-bromophenoxy)carbanilide B.15. 4-nitro-3'-bromo-4'-(4-chlorophenoxy)-carbanilide B.16. 4-nitro-3'-chloro-4'-(4-bromophenoxy)-carbanilide B.17. 3,3',4'-trichloro-4-(4-chlorophenoxy)-carbanilide B.18. 3,4'-dichloro-4-(4-chlorophenoxy)carbanilide B.l9. 3,4-dichloro-4'-(4-chlorophenoxy)carbanilide B.20. 2-methyl-4-nitro-3'-chloro-4'-(4-chloro-phenoxy)carbanilide A third group of carbanilides to be employed lS in the present combin~tions is the group of carbanilides described by German Patent 2,334,355. These compounds include the following:
C. Carbanilides of German 2,334,355 20 C.l. 3,3',5'-tris(trifluoromethyl)-4-methoxy-carbanilide C.2. 3-(trifluoromethoxy)-3',5'-bis(trifluoro-methyl)carbanilide 25 C.3. 4-ttrifluorom~thoxy)-3',5'-bis(trifluoro-methyl)carbanilide C.4. 2,3',5'-tris(trifluoromethyl)-4-(trifluoro-methoxy)carbanilide C.5. 4-~methylthio)-3',5'-bis(trifluoromethyl)-carbanilide C.6. 4-(methylthio)-3',5'-bis(trifluoromethyl)-thiocarbanilide C.7. 3-chloro-4-(methylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.8. 3-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.9. 4-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.10. 2-chloro-4-~trifluoromethylthio)-3',5'-bis(trifluoromethyl)carbanilide C.ll. 4-(trifluoromethylthio)-3'-(trifluoromethyl~-5'-nitrocarbanilide C.12. 4-(trifluoromethylthio)-2',5'-bis(trifluoro-methyl)-4'-nitrocarbanilide C.13. 4,4'-bis(trifluoromethylthio)carbanilide C.14. 4-(trifluoromethylthio)-4'-(chloromethyl-sulfonyl)carbanilide C.15. 3-(difluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.16. 4-(ethylthio)-3',5r-bis(trifluoromethyl)-carbanilide C.17. 3-chloro-4-(ethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.18. 4-ethoxy-3,3',5'-tris(trifluoromPthyl)car-banilide C.l9~ 3-(trifluoromethyl)-4-ethoxy-4'-(trifluoro-methylthio)carbanilide -'17~Z
C.20. 3-(trifluoromethyl)-4-ethoxy-3'-(trifluoro-methylthio)carbanilide C.21. 4-methyl-3-~2-chloroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.22. 4-(1,2-dichlorovinyloxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.23. 4-(1,2-dichlorovinyloxy)-3',5'-bis(trifluoro-methyl)carbanilide C.24. 4-(2,2,2-trichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.25. 2-,2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.26. 3-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.27. 3-(2,2-dichloro~ difluoroethoxy)-4-bromo-3',5'-bis(trifluoromethyl)carbanilide C.28. 4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.29. 4-(2,~ichloro-1,1-difluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.30. 3-methoxy-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.31. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.32. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-4'-isopropylcarbanilide C.33. 3-nitro-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.34. 2-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.35. 4-(2,2-dichloro-1,1-difluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.36. 3-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide 1 1 f 1>~2 C.37. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.38. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)thiocarbanilide C.39. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.40. 4,4'-bis(2-chloro-1,1,2-trifluoroethoxy)-carbanilide C.41. 4-(2-chloro-1,1,2-trifluoroethoxy)-4'-(trifluoromethylthio)carbanilide C.42. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.43. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3'-bis(trifluoromethyl)-5'-nitrocarbanilide C.44. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.45. 3-(1,1,2-trifluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.46. 3-(1,1,2,2-tetrafluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.47. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(chlorodi~luoromethyl)carbanilide C.48. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.49. 3-(trifluoro~ethyl)-4-(1,1,2,2-tetrafluoro-ethoxy)-4'-bromocarbanilide C.50. 3-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)carbanilide ,.a.7~
C.51. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)carbanilide C.52. 3-chloro-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.53. 3-methyl-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.54. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.55. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.56. 4-(methoxycarbonylthio)-3',5'-bis(tri-fluoromethyl)carbanilide C.57. 4-(4-chlorophenoxy)-4'-(trifluoromethyl-thio)thiocarbanilide C.58. 4-(4-chlorophenoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.59. 3-chloro-4-(4-cnlorophenoxy)-3',5'-bis(trifluoromethyl)carbanilide C.60. 4-(4-chlorophenoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.61. 4-(3,5-bis(trifluoromethyl)phenoxy-3',5'-bis(trifluoromethyl)carbanilide C.62. 4-~4-methylphenoxycarbonyl)-3',5'-3~ bis(trifluoromethyl)carbanilide C.63. 4-(4-methylphenoxycarbonyl)-4'-(tri-fluoromethylthio)carbanilide C.64. 3,5-bis(trifluoromethyl)-2',4',6'-trichlorocarbanilide C.65. 3,5-bis(trifluoromethyl)-2',4',~'-tri-chlorocarbanilide C.66. 3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.67. 3,3',5-tris(trifluoromethyl)-5'-nitro-carbanilide C.68. 2',3,5,6'-tetrakis(trifluoromethyl)-4'-nitrocarbanilide C.69. 3-~chlorodifluoromethyl)-3',5'-bis(tri-fluoromethyl)carbanilide C.70. 3-(1,1,2,2-tetrafluoroethyl)-3',~'-bis(trifluoromethyl)carbanilide C.71. 4-phenyl-3',.5'-bis(trifluoromethyl)-.
carbanilide C.72. 3-[fluorosulfonyl)-3',5'-bis(trifluoro-methyl)carbanilide C.73. 4-(fluorosulfonyl)-4'-(trifluoromethyl-thio)carbanilide C.74. 4-(fluorosulfonyl)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.75. 4-(chloromethylsulfonyl)-3',5'-bis(tri-fluoromethyl)carbanilide ~l'f~ ~7 C.76. ~-(ethylsulfonyl)-3',5,5'-tris(trifluoro-methyl)carbanilide C.77. 2-(ethylsulfonyl)-3',5-bis(trifluoro-methyl)-5'-nitrocarbanilide C.78. 4-(trifluoromethylsulfonyl)-3',5'-bisttrifluoromethyl)carbanilide C.79. 4-(trifluoromethylsulfonyl)-3'-(tri-fluoromethyl)-4'-methoxycarbanilide C.80. . 4-(trifluoromethylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.81. 4-(4-nitrophenylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.82. 4-(4-acetamidophenylsulfonyl)-4'-(trifluoromethylthio)carbanilide C.83. 4-(4-(isopropylideneamino)phenylsul-fonyl)-4'-(trifluoromethylthio)car-banilide C.84. 4,4-sulfonylbis(3'-(trifluoromethylthio)-carbanilide) C.85. 4,4-sulfonylbis(4'-(1,2-dichlorovinyl-oxy)carbanilide) C.86. 4,4-sulfonylbis(3'-(1,1,2,2-tetra-fluoroethoxy)carbanilide) C.87. 4,4-sulf~nylbis(4'-(2-chloro-1,1,2-trifluoroethoxy)carbanilide) C.88. 4,4-sulfonylbis(4'-(trifluoromethyl-thio)carbanilide) 7t~
All of the carbanilides to be employed in accordance with the present invention are prepared in classic synthetic procedures, such as those exempli-fied by U.S. Patent 3,284,433 and German Patent 2,334,355.
The following examples illustrate the synthesis of the carbanilides.
2-~MINO-3-NIT~0-5-(TRIFLVOROMETHYL)-2',4'-DIMETHYLCAR-BANILIDE
3-Nitro-5-(trifluoromethyll-o-phenylenediamine (2.2 grams; 0.01 mole) and 2,4-dimethylphenyl isocyanate (1.5 grams; 0.01 mole) were taken up in 40 ml. of methyl-ene chloride, and 1 ml. of pyridine was added. The reaction mixture was maintained at 23C. for 16 hours.
The yellow precipitate was filtered and dried, m.p., >300C. Elemental analysis showed the following:
16 15 3 43: C, 52.17; H, 4.08; N, 15.22.
Found: C, 53.01; H, 4.05; N, 16.44.
Additional carbanilides were prepared in essen-tially the same procedures as Example 1.
2-Amino-3,3'-dinitro-5-(trifluoromethyl)-4'-chlorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine(2.2 grams; 0.01 mole) and 3-nitro-4-chlorophenyl isocyanate (2.0 grams; 0.01 mole).
The product, 3.3 grams, melted at 214-216C. ~lemental analysis showed the following:
Calculated for C14HgClF3N5O5: C, 40.06; H, 2.16; N, 16.96.
Found: C, 40.33; H, 1.88; N, 16.45.
2-Amino-3-nitro-5-(trifluoromethyl)-2',4',5'-trichlorocarbanilide was prepared ~y reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (2.2 gra~s; 0.1 mole) and 2,4,5-trichlorophenyl isocyanate (2.2 ~rams;
0.01 mole). The product melted at 225-227C. Elemental analysis showed the following:
~ ~ î'l7~
Calculated for C14H8C13F3N4O3: C, 37.91; H, 1.82; N, 12.63.
Found: C, 37.83; H, 1.55; N, 12.40.
2-Amino-3-nitro-5-(txifluoromethyl)-2'-(ethoxy-carbonyl)carbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (1.1 grams; Q.005 mole) and 2-(ethoxycarbonyl)phenyl isocyanate (1.0 grams; 0.005 mole). The product, 1.4 grams, melted at 186-188C. Ele-mental analysis showed the following:
Calculated for Cl~H15F3N4O5: C, 49.52; H, 3.67: N, 13.59.
Found: C, 49.75i H, 3.59; N, 13.50.
2-Amino-3,5'-dinitro-5-(trifluoromethyl)-2'-fluorocarbanilide was prepared from 3-nitro~5-(trifluoro-methyl) o-phenylenediamine (1.1 grams; 0.005 mole) and 2-fluoro-5-nitrophenyl isocyanate (0.8 gram; 0.005 mole).
The product, 1.2 grams, melted at 218-220C. Elemental analysis showed the following:
Calculated for C14HgF4N5O5: C, 41.70; H, 2.25; N, 17.37.
Found: C, 41.91; H, 1.98; N, 17.27.
2-Amino-3,4'-dinitro-5-(trifluoromethyl)-2'-chlorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (1.1 grams; 0.005 2S mole) and 2-chloro-4-nitrophenyl isocyanate (1.0 gram;
0.005 mole). The product, 1.2 grams, melted at 220-222C.
Elemental analysis showed the following:
Calculated for C14HgClF3N5O5: C, 40.06; H, 2.16; N, 16.67.
Found: C, 40.11; H, 2.11; N, 16.48.
2-Amino-3-nitro-3',5-bis(trifluoromethyl)-4'-chlorocarbanilide was prepared by reacting 2-amino-3-nitro-7~Z
5-(trifluoromethyl)-o-phenylenediamine (2.2 grams; 0.01 mole) and 4-chloro-3-(trifluoromethyl)phenyl isocyanate (2.2 grams; 0.01 mole). The product, 1.8 grams, melted at 214-216C. Elemental analysis showed the following:
Calculated for C15HgClF6N4O3: C, 40.70; H, 2.05; N, 12.66.
Found: C, 40.90; H, 2.04; N, 12.67.
E ~ IPLE 8 2-Amino--3-nitro-3',5,5'-tris(trifluoromethyl)-carbanilide was prepared by reacting 3-nitro-5-(trifluoro-methyl)-o-phenylenediamine (1.1 grams; 0.005 mole) and (3,5-bis(trifluoromethyl)phenyl)carbamoyl chloride (1.4 grams; 0.005 mole). Elemental analysis of the product showed the following:
Calculated for C16HgFgN4O3: C, 40.35; H, 1.92; N, 11.76.
Found: C, 40.52; H, 1.82; N, 11.78.
EX~MPLE 9 2-Amino-3-nitro-2',5-bis(trifluoromethyl)-4'-chlorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (2.2 grams; 0.01 mole) and 4-chloro-2-(trifl~oromethyl)phenyl isocyanate (2.2 grams; 0.01 mole). The product melted at 245-247C.
Elemental analysis showed the following:
Calculated for C15HgClF6N4O3: C, 40.70; H, 2.05; N, 12.66.
Found: C, 40.94; H, 1.88; ~J, 12.55.
~ EXAMPLE 10 2-Amino-3-nitro-5-(trifluoromethyl)-2'-methyl-
The yellow precipitate was filtered and dried, m.p., >300C. Elemental analysis showed the following:
16 15 3 43: C, 52.17; H, 4.08; N, 15.22.
Found: C, 53.01; H, 4.05; N, 16.44.
Additional carbanilides were prepared in essen-tially the same procedures as Example 1.
2-Amino-3,3'-dinitro-5-(trifluoromethyl)-4'-chlorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine(2.2 grams; 0.01 mole) and 3-nitro-4-chlorophenyl isocyanate (2.0 grams; 0.01 mole).
The product, 3.3 grams, melted at 214-216C. ~lemental analysis showed the following:
Calculated for C14HgClF3N5O5: C, 40.06; H, 2.16; N, 16.96.
Found: C, 40.33; H, 1.88; N, 16.45.
2-Amino-3-nitro-5-(trifluoromethyl)-2',4',5'-trichlorocarbanilide was prepared ~y reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (2.2 gra~s; 0.1 mole) and 2,4,5-trichlorophenyl isocyanate (2.2 ~rams;
0.01 mole). The product melted at 225-227C. Elemental analysis showed the following:
~ ~ î'l7~
Calculated for C14H8C13F3N4O3: C, 37.91; H, 1.82; N, 12.63.
Found: C, 37.83; H, 1.55; N, 12.40.
2-Amino-3-nitro-5-(txifluoromethyl)-2'-(ethoxy-carbonyl)carbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (1.1 grams; Q.005 mole) and 2-(ethoxycarbonyl)phenyl isocyanate (1.0 grams; 0.005 mole). The product, 1.4 grams, melted at 186-188C. Ele-mental analysis showed the following:
Calculated for Cl~H15F3N4O5: C, 49.52; H, 3.67: N, 13.59.
Found: C, 49.75i H, 3.59; N, 13.50.
2-Amino-3,5'-dinitro-5-(trifluoromethyl)-2'-fluorocarbanilide was prepared from 3-nitro~5-(trifluoro-methyl) o-phenylenediamine (1.1 grams; 0.005 mole) and 2-fluoro-5-nitrophenyl isocyanate (0.8 gram; 0.005 mole).
The product, 1.2 grams, melted at 218-220C. Elemental analysis showed the following:
Calculated for C14HgF4N5O5: C, 41.70; H, 2.25; N, 17.37.
Found: C, 41.91; H, 1.98; N, 17.27.
2-Amino-3,4'-dinitro-5-(trifluoromethyl)-2'-chlorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (1.1 grams; 0.005 2S mole) and 2-chloro-4-nitrophenyl isocyanate (1.0 gram;
0.005 mole). The product, 1.2 grams, melted at 220-222C.
Elemental analysis showed the following:
Calculated for C14HgClF3N5O5: C, 40.06; H, 2.16; N, 16.67.
Found: C, 40.11; H, 2.11; N, 16.48.
2-Amino-3-nitro-3',5-bis(trifluoromethyl)-4'-chlorocarbanilide was prepared by reacting 2-amino-3-nitro-7~Z
5-(trifluoromethyl)-o-phenylenediamine (2.2 grams; 0.01 mole) and 4-chloro-3-(trifluoromethyl)phenyl isocyanate (2.2 grams; 0.01 mole). The product, 1.8 grams, melted at 214-216C. Elemental analysis showed the following:
Calculated for C15HgClF6N4O3: C, 40.70; H, 2.05; N, 12.66.
Found: C, 40.90; H, 2.04; N, 12.67.
E ~ IPLE 8 2-Amino--3-nitro-3',5,5'-tris(trifluoromethyl)-carbanilide was prepared by reacting 3-nitro-5-(trifluoro-methyl)-o-phenylenediamine (1.1 grams; 0.005 mole) and (3,5-bis(trifluoromethyl)phenyl)carbamoyl chloride (1.4 grams; 0.005 mole). Elemental analysis of the product showed the following:
Calculated for C16HgFgN4O3: C, 40.35; H, 1.92; N, 11.76.
Found: C, 40.52; H, 1.82; N, 11.78.
EX~MPLE 9 2-Amino-3-nitro-2',5-bis(trifluoromethyl)-4'-chlorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (2.2 grams; 0.01 mole) and 4-chloro-2-(trifl~oromethyl)phenyl isocyanate (2.2 grams; 0.01 mole). The product melted at 245-247C.
Elemental analysis showed the following:
Calculated for C15HgClF6N4O3: C, 40.70; H, 2.05; N, 12.66.
Found: C, 40.94; H, 1.88; ~J, 12.55.
~ EXAMPLE 10 2-Amino-3-nitro-5-(trifluoromethyl)-2'-methyl-
4'-bromocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (2.2 grams; 0.01 mole) and 2-methyl-4~bromophenyl isocyanate (2.1 grams;
0.01 mole). The product melted at 230-231C. Elemental analysis showed the following:
Calculated fox C15HllBrF3N4O3: C, 41.59: H, 2.79; N, 12.93.
Found: C, 41.40; H, 2.65; N, 12.71.
7~3~
2-Amino-3-nitro-5-(trifluoromethyl)-2',6'-dibromo-4'-fluorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (2.2 grams; 0.~1 mole) and 2,6-dibromo-4-fluorophenyl iso-cyanate. The product melted at 249-251C. Elemental analysis showed the following:
Calculated for C14H~Br2F4N4O3: C, 32.59; H, 1.56; N, 10.86.
Found: C, 32.64; H, 1.39; N, 10.76.
The methods and compositions of the present invention can be used with all species of poultry.
Because of their economic importance, chickens and turkeys are the principal species requiring anticoccidial treatment. However, the present invention can be prac-ticed with other poultry, such as ducks, geese, pheasants, and quail.
The present invention is practiced in the usual manner of anticoccidials. Since coccidiosis affects the intestinal tract, the compositions of the present invention are. those which are suited for oral administration. The polyether antibiotics are gen-erally of low solubility in water, even in the sodium or other salt form. Therefore, the present invention is preferably practiced by administering the subject com~inations in a feedstuff rather than in drinking water. Furthermore, it is the practice of the industry to supply poultry with only one source of feed, constituting the entire food supply of the poultry.
Therefore, in a preferred practice of the present invention. the anticoccidial combinations are supplied in a total feed, with concentrations adjusted accord-ingly. Those skilled in the art, however, will recog-nize that concentrations are to be adjusted upward, f should it be desired to supply poultry with multiple sources of food only one of which contains the combi-nations of the present invention.
The components of the present combinations can be employed in a wide range of concentrations in the feed administered to poultry. In general, for those components which are known anticoccidials, the maxima to be employed in accordance with the present invention are the same as the maxima for anticoccidial treatment by the individual components. The lower limits in accordance with the present invention are generally less than for therapy by the individual components, especially where the components are being used to minimize side effects of either individual component.
Representative amounts of selected polyether antibiotics are as follows:
from about 20 to about 120 ppm of monensin;
from about 25 to about 100 ppm of narasin;
from about 35 to about 125 ppm of lasalocid;
from about 25 to about lOO ppm of salinomycin;
from about 5 to about 15 ppm of A-204;
from about 25 to about 100 ppm of lonomycin.
from about 25 to about 100 ppm of X-206;
- 30 from about 50 to about 200 ppm of nigericin; and from about 10 to about 50 ppm of - dianemycin.
11~17~f"
The carbanilide is generally employed in a concentration of from about 10 to about 250 ppm, preferably from about 50 to about 100 ppm. Amounts will be adjusted downward where more than one polyether, or more than one carbanilide, is employed.
Since the polyether antibiotics, alone, are active as anticoccidials, the present combinations are useful regardless of the exact concentration of the carban-ilide. As noted above, certain of the carbanilides, alone, exhibit anticoccidial activity. Therefore, preferred embodiments of the present invention are those wherein the carbanilide is employed in a concentration that potentiates the anticoccidial activity of the polyether (where the carbanilide is, itself, lacking anticoccidial activity); or in a concentration that is synergistic with the anticoccidial activity of the polyether (where the carbanilide also exhibits anticoccidial activity).
The Group A compounds include both compounds exhibiting no independent anticoccidial activity, at typical rates, as well as compounds exhibiting indepen-dent anticoccidial activity. Each of the GrOup A compounds has been found to potentiate or synergize, respectively, the activity of a representative polyether antibiotic, monensin. The potentiating and synergizing effect of the Group A compounds is shown in Tables I and IV, below.
The Group B compounds are taught in 3,284,433 to exhibit anticoccidial activity. Therefore, they are preferably employed in amounts which are synergistic as to the anticoccidial activity of the polyethers.
The Group C compounds are taught in German Patent No. 2,334,355 to exhibit anticoccidial activity.
They are likewise preferably employed in amounts which are synergistic as to the anticoccidial activity of the ~ 1 ~'17~2 polyethers. Data on the effects of the Group C
compounds is shown in Tables I, II, and III, below.
As will be noted, not all Group C compounds are syner-gistic in the specific rates and against the specific Eimeria organisms reported below. Compounds C.13., C.58., C.65., and C.86. are regarded as synergistic, whereas compounds C.l., C.5., C.6., C.8., C.ll., C.62., and C.76. are regarded as not synergistic in the tests reported below. However, simple range-finding experi-ments as to any of the carbanilides to be employed inthe present invention will enable those skilled in the art to determine the preferred potentiating or svner-gistic amounts of the respective carbanilide.
Poultry feedstuffs of all types and formulae in the poultry industry may be used in administering the combinations of the present invention. The follow-ing formulae are exemplary only.
Broiler Starter ~-~
Ingredients Percent _ _ Corn, Yellow, Ground50.0 Soybean Oil Meal, Solvent Extracted Dehulled (50%) 30.9 Animal Fat 6.5 Fish Meal with Solubles (60~) 5.0 Corn Distillers Dried Solubles 4.0 Dicalcium Phosphate, Feed Grade 1.8 Calcium Carbonate (Ground Limestone) 0.8 Vitamin Premix TK-01 (1.03)1/ 0.5 - Salt (NaCl) 0.3 Trace Mineral Premix TK-01 (1.02)2/ 0.1 Methionine Hydrox~ Analog 0.1 Total 100.0 l.~.'; 1.7~
Broiler Grower .
Ingredients Percent Corn, Yellow, Ground 57.7 Soybean Meal, Solvent, Extracted, Dehulled (50%)31.7 Animal ~at (Beef tallow) 6.0 Dicalcium Phosphate, Feed Grade 2.7 Calcium Carbonate (Ground Limestone) 0.9 Vitamin Premix TK-01 (1.03)1/ 0.5 Salt (NaCl) 0.2 Methionine Hydroxy Analog 0.2 Trace Mineral Premix TK-01 (1.02)2/ 0.1 ~otal 100.0 Chick Starter, Light Breeds Ingredients Percent .
Corn, Yellow, Ground 56.3 Soybean Meal, Solvent Extracted, Dehulled (50%)17.9 Wheat Middlings 10.0 Corn Distillers Dried Solubles 5.0 Fish Meal with Solubles 5.0 Alfalfa Meal, Dehydrated (17%) 2.5 Dicalcium Phosphate, Feed Grade 1.3 Calcium Carbon~ate 0.9 Vitamin Premixl 0.5 Salt (NaCl) 0.3 Methionine Hydroxy A~alog 0.2 Trace Mineral Premix 0.1 Total 100.0 .t .1 ';'171~
Pullet Grower Ingredients Percent Corn, Yellow, Ground 73.5 Soybean Meal, Solvent Extracted, Dehulled (50%)21.9 Dicalcium Phosphate, Feed Grade 2.5 Calcium Carbonate 1.0 Vitamin Premixl 0 5 Salt (NaCl) 0 3 Methionine Hydroxy Analog0 2 Trace Mineral Premix2 0.1 Total 100.0 Pullet Developer Ingredients Percent Corn, Yellow, Ground 67.5 Oats, Ground Whole 15.0 Soy~ean Meal, Solvent Extracted, Dehulled (50~).13.4 Dicalcium Phosphate, ~eed Grade 2 1 Calcium Carbonate 1 0 Vitamin Premixl 0.5 Methionine Hydroxy Analog0.3 Salt (NaCl) 2 0.2 Trace Mineral Premix 0.1 Total 100.0 1 1', ~7~
Turkey Starter Ingredients Percent Soybean Meal, Solvent Extracted, Dehulled 40.7 Corn, Yellow, Ground 39.7 Fish Meal with Solubles 5.0 Beef Tallow 5.0 Corn Distillers Dried Solubles 2 5 Alfalfa Meal, Dehydrated (17~) 2 5 Dicalcium Phosphate, ~eed Grade 2.5 Calcium Carbon~te 1.2 Vitamin Premixl 0.5 Salt (NaCl) 2 0.2 Trace Mineral Premix 0.1 Methionine Hydroxy Analog0.1_ Total 100.0 Turkey Finisher Ingredients Percent Corn, Yellow, Ground 71.2 Soybean Meal, Solvent Extracted, Dehulled (50%) 9.9 Corn Distillers Dried Solubles 5.0 Alfalfa Meal, Dehydrated (17~3 5.0 Animal Fat 3.0 Fish Meal With Solubles 2.5 Dicalcium Phosphate, Feed ~rade 1.7 Calcium Carbonate o.5 Vitamin Premixl 0 5 Salt (~aCl) 0.4 Methionine Hydroxy Anzalog0.2 Trace Mineral Premix 0.1 Total 100.0 1/ .
- Vitamin premix provides 3000 IU of vitamin A, 900 ICU
of vitamin D, 40 mg. of vitamin E, 0.7 mg. of vitamin K, 1000 mg. of choline, 70 mg. of niacin, 4 mg. of pantothenic acid, 4 mg. of riboflavin, 0.10 mg. of vitamin B12, 0.10 mg. of biotin and 125 mg. of ethoxy-quin per kg. of complete feed.
-/Trace mineral premix provides 75 mg. of manganese,
0.01 mole). The product melted at 230-231C. Elemental analysis showed the following:
Calculated fox C15HllBrF3N4O3: C, 41.59: H, 2.79; N, 12.93.
Found: C, 41.40; H, 2.65; N, 12.71.
7~3~
2-Amino-3-nitro-5-(trifluoromethyl)-2',6'-dibromo-4'-fluorocarbanilide was prepared by reacting 3-nitro-5-(trifluoromethyl)-o-phenylenediamine (2.2 grams; 0.~1 mole) and 2,6-dibromo-4-fluorophenyl iso-cyanate. The product melted at 249-251C. Elemental analysis showed the following:
Calculated for C14H~Br2F4N4O3: C, 32.59; H, 1.56; N, 10.86.
Found: C, 32.64; H, 1.39; N, 10.76.
The methods and compositions of the present invention can be used with all species of poultry.
Because of their economic importance, chickens and turkeys are the principal species requiring anticoccidial treatment. However, the present invention can be prac-ticed with other poultry, such as ducks, geese, pheasants, and quail.
The present invention is practiced in the usual manner of anticoccidials. Since coccidiosis affects the intestinal tract, the compositions of the present invention are. those which are suited for oral administration. The polyether antibiotics are gen-erally of low solubility in water, even in the sodium or other salt form. Therefore, the present invention is preferably practiced by administering the subject com~inations in a feedstuff rather than in drinking water. Furthermore, it is the practice of the industry to supply poultry with only one source of feed, constituting the entire food supply of the poultry.
Therefore, in a preferred practice of the present invention. the anticoccidial combinations are supplied in a total feed, with concentrations adjusted accord-ingly. Those skilled in the art, however, will recog-nize that concentrations are to be adjusted upward, f should it be desired to supply poultry with multiple sources of food only one of which contains the combi-nations of the present invention.
The components of the present combinations can be employed in a wide range of concentrations in the feed administered to poultry. In general, for those components which are known anticoccidials, the maxima to be employed in accordance with the present invention are the same as the maxima for anticoccidial treatment by the individual components. The lower limits in accordance with the present invention are generally less than for therapy by the individual components, especially where the components are being used to minimize side effects of either individual component.
Representative amounts of selected polyether antibiotics are as follows:
from about 20 to about 120 ppm of monensin;
from about 25 to about 100 ppm of narasin;
from about 35 to about 125 ppm of lasalocid;
from about 25 to about lOO ppm of salinomycin;
from about 5 to about 15 ppm of A-204;
from about 25 to about 100 ppm of lonomycin.
from about 25 to about 100 ppm of X-206;
- 30 from about 50 to about 200 ppm of nigericin; and from about 10 to about 50 ppm of - dianemycin.
11~17~f"
The carbanilide is generally employed in a concentration of from about 10 to about 250 ppm, preferably from about 50 to about 100 ppm. Amounts will be adjusted downward where more than one polyether, or more than one carbanilide, is employed.
Since the polyether antibiotics, alone, are active as anticoccidials, the present combinations are useful regardless of the exact concentration of the carban-ilide. As noted above, certain of the carbanilides, alone, exhibit anticoccidial activity. Therefore, preferred embodiments of the present invention are those wherein the carbanilide is employed in a concentration that potentiates the anticoccidial activity of the polyether (where the carbanilide is, itself, lacking anticoccidial activity); or in a concentration that is synergistic with the anticoccidial activity of the polyether (where the carbanilide also exhibits anticoccidial activity).
The Group A compounds include both compounds exhibiting no independent anticoccidial activity, at typical rates, as well as compounds exhibiting indepen-dent anticoccidial activity. Each of the GrOup A compounds has been found to potentiate or synergize, respectively, the activity of a representative polyether antibiotic, monensin. The potentiating and synergizing effect of the Group A compounds is shown in Tables I and IV, below.
The Group B compounds are taught in 3,284,433 to exhibit anticoccidial activity. Therefore, they are preferably employed in amounts which are synergistic as to the anticoccidial activity of the polyethers.
The Group C compounds are taught in German Patent No. 2,334,355 to exhibit anticoccidial activity.
They are likewise preferably employed in amounts which are synergistic as to the anticoccidial activity of the ~ 1 ~'17~2 polyethers. Data on the effects of the Group C
compounds is shown in Tables I, II, and III, below.
As will be noted, not all Group C compounds are syner-gistic in the specific rates and against the specific Eimeria organisms reported below. Compounds C.13., C.58., C.65., and C.86. are regarded as synergistic, whereas compounds C.l., C.5., C.6., C.8., C.ll., C.62., and C.76. are regarded as not synergistic in the tests reported below. However, simple range-finding experi-ments as to any of the carbanilides to be employed inthe present invention will enable those skilled in the art to determine the preferred potentiating or svner-gistic amounts of the respective carbanilide.
Poultry feedstuffs of all types and formulae in the poultry industry may be used in administering the combinations of the present invention. The follow-ing formulae are exemplary only.
Broiler Starter ~-~
Ingredients Percent _ _ Corn, Yellow, Ground50.0 Soybean Oil Meal, Solvent Extracted Dehulled (50%) 30.9 Animal Fat 6.5 Fish Meal with Solubles (60~) 5.0 Corn Distillers Dried Solubles 4.0 Dicalcium Phosphate, Feed Grade 1.8 Calcium Carbonate (Ground Limestone) 0.8 Vitamin Premix TK-01 (1.03)1/ 0.5 - Salt (NaCl) 0.3 Trace Mineral Premix TK-01 (1.02)2/ 0.1 Methionine Hydrox~ Analog 0.1 Total 100.0 l.~.'; 1.7~
Broiler Grower .
Ingredients Percent Corn, Yellow, Ground 57.7 Soybean Meal, Solvent, Extracted, Dehulled (50%)31.7 Animal ~at (Beef tallow) 6.0 Dicalcium Phosphate, Feed Grade 2.7 Calcium Carbonate (Ground Limestone) 0.9 Vitamin Premix TK-01 (1.03)1/ 0.5 Salt (NaCl) 0.2 Methionine Hydroxy Analog 0.2 Trace Mineral Premix TK-01 (1.02)2/ 0.1 ~otal 100.0 Chick Starter, Light Breeds Ingredients Percent .
Corn, Yellow, Ground 56.3 Soybean Meal, Solvent Extracted, Dehulled (50%)17.9 Wheat Middlings 10.0 Corn Distillers Dried Solubles 5.0 Fish Meal with Solubles 5.0 Alfalfa Meal, Dehydrated (17%) 2.5 Dicalcium Phosphate, Feed Grade 1.3 Calcium Carbon~ate 0.9 Vitamin Premixl 0.5 Salt (NaCl) 0.3 Methionine Hydroxy A~alog 0.2 Trace Mineral Premix 0.1 Total 100.0 .t .1 ';'171~
Pullet Grower Ingredients Percent Corn, Yellow, Ground 73.5 Soybean Meal, Solvent Extracted, Dehulled (50%)21.9 Dicalcium Phosphate, Feed Grade 2.5 Calcium Carbonate 1.0 Vitamin Premixl 0 5 Salt (NaCl) 0 3 Methionine Hydroxy Analog0 2 Trace Mineral Premix2 0.1 Total 100.0 Pullet Developer Ingredients Percent Corn, Yellow, Ground 67.5 Oats, Ground Whole 15.0 Soy~ean Meal, Solvent Extracted, Dehulled (50~).13.4 Dicalcium Phosphate, ~eed Grade 2 1 Calcium Carbonate 1 0 Vitamin Premixl 0.5 Methionine Hydroxy Analog0.3 Salt (NaCl) 2 0.2 Trace Mineral Premix 0.1 Total 100.0 1 1', ~7~
Turkey Starter Ingredients Percent Soybean Meal, Solvent Extracted, Dehulled 40.7 Corn, Yellow, Ground 39.7 Fish Meal with Solubles 5.0 Beef Tallow 5.0 Corn Distillers Dried Solubles 2 5 Alfalfa Meal, Dehydrated (17~) 2 5 Dicalcium Phosphate, ~eed Grade 2.5 Calcium Carbon~te 1.2 Vitamin Premixl 0.5 Salt (NaCl) 2 0.2 Trace Mineral Premix 0.1 Methionine Hydroxy Analog0.1_ Total 100.0 Turkey Finisher Ingredients Percent Corn, Yellow, Ground 71.2 Soybean Meal, Solvent Extracted, Dehulled (50%) 9.9 Corn Distillers Dried Solubles 5.0 Alfalfa Meal, Dehydrated (17~3 5.0 Animal Fat 3.0 Fish Meal With Solubles 2.5 Dicalcium Phosphate, Feed ~rade 1.7 Calcium Carbonate o.5 Vitamin Premixl 0 5 Salt (~aCl) 0.4 Methionine Hydroxy Anzalog0.2 Trace Mineral Premix 0.1 Total 100.0 1/ .
- Vitamin premix provides 3000 IU of vitamin A, 900 ICU
of vitamin D, 40 mg. of vitamin E, 0.7 mg. of vitamin K, 1000 mg. of choline, 70 mg. of niacin, 4 mg. of pantothenic acid, 4 mg. of riboflavin, 0.10 mg. of vitamin B12, 0.10 mg. of biotin and 125 mg. of ethoxy-quin per kg. of complete feed.
-/Trace mineral premix provides 75 mg. of manganese,
5~ mg. of zinc, Z5 mg. of iron and 1 mg. of iodine per kg. of complete feed.
~ 1717~
The foregoing compositions are typical of feed-stuffs actually administered to poultry. ~remixes are commonly used in the poultry industry, and the combinations of the present invention can also be formulated as pre-mixes. Such premixes typically comprise the polyetherantibiotic, the selected carbanilide, and a solid sub-stance acceptable as a feedstuff, such as corn meal, rice hulls, crushed limestone, soybean meal, soya grits, distillers' dried grains, citrus meal, wheat middlings, clays and the like. Such a premix is mixed or blended with other substances to constitute either an inter-mediate premix or the finished feed.
" A representative premix in accordance with the present invention is as follows:
monensin: 45 grams activity a selected carbanilide in accordance with the present invention: 45 grams rice hulls q.s. ad 454 grams This formulation is mixed thoroughly and can be added to one ton of fini,shed feed to sl~pply suitable amounts of the components in accordance with the present invention.
The present invention was evaluated in chickens as follows: one-week-old broiler chicks were fed a medi-cated or control ration, typically for one day, prior to infection (by gavage) with oocysts of a coccidiosis-causing organism, generally 750,000 oocysts of Eimeria acerwlin_ and 75,000 oocysts of Eimeria tenella. The chicks were maintained on their respective rations for an additional period of time, typically six days. There were five chicks in a group and generally two replicates per treatment. Anticoccidial efficacy was determined by lesion scores. To determine lesion scores, the birds were sacrificed and the severity of lesions scored on a 0-4 scale, with lesion-free birds scored as 0, extremely ~ .1.';'1.7~Z
severe infections scored as 4, and intermediate degrees of infection scored as 1, 2, or 3. The scores of all birds which received a given treatment were averaged.
Most of the compounds were tested in a preli-minary test "A"; in this test, monensin was tested alone at S0 ppm and the carbanilide compound was tested in combination with monensin, each at 50 ppm. In a secon-dary test "B", monensin and the carbanilide compound were each tested alone, at 50 ppm, and the two were tested in combination, each at 50 ppm. Additional tests at more varied concentrations were also conducted with certain of the compounds.
The results are reported in the following tables.
The concentration of monensin and the carbanilide~ is expressed as the parts per million (ppm) of the total feed provided to the chicks.
TABLE I
LESION SCORES
Eimerla acervuIina Eimerla tenella monensln monensin ComPound -~
Number 0 50 050 .
A.3. A 0 2.8 1.6 2.0 1.9 0.7 0.9 B 0 3.0 1.2 2.0 1.2 50 3.0 1.2 2.5 0.7 A.4. ~ A 0 2.8 1.6 2.0 0.9 B 0 3.0 1.2 2.0 1.2 50 3.0 0.9 2.4 0.6 A.5. A 0 2.4 1.2 2.5 1.4 0.3 0.4 B 0 3.0 1.2 2.0 1.2 50 3.0 1.1 2.2 0 A.6. A 0 2.8 1.6 2.0 0.9 1.6 0.6 B 0 3.0 1.2 2.0 1.2 50 2.9 0.8 2.5 0.5 A.7. A 0 2.5 1.6 2.4 2.3 0.9 0.4 B 0 3.0 1.2 2.0 1.2 50 3.0 1.4 1.8 0.6 A.8. A 0 3.0 1.2 2.1 0.9 0.4 0.2 B 0 3.3 1.3 3.0 2.2 50 2.6 0.8 3.0 1.0 z TABLE I (cont'd) _ LESION SCORES
Eimeria acervulina Eimeria tenella monensin monensin Compound Number 0 50 _ 0 50 A.9. A 0 3.01.2 2.1 0.9 0.7 0.9 B 0 3.31.3 3.0 2.2 2.8G.8 2.9 1.3 A.10. A 0 2.71.7 3.0 1.0 0.5 0.6 B 0 3.31.3 3.0 2.2 2.40.9 2.7 1.7 A.ll. A 0 3.61.2 3.0 1.2 0.6 0.8 B 0 3.31.3 3.0 2.2 2.61.4 2.8 1.1 A.12. A 0 2.81.1 2.3 1.0 1.1 0.6 B 0 3.31.3 3.Q 2.2 2.50.9 2.9 0.8 A.13. A 0 3.01.2 2.1 0.9 S0 0.9 0.5 B 0 3.31.3 3.0 2.2 2.91.4 3.0 1.2 A.14. A 0 3.01.2 2.1 0.9 1.2 0.6 B 0 3.31.3 3.0 2.2 5a 2.6 1.1 3.0 1.0 C.8. A 0 2.7 1.7 3.0 1.0 - 1.2 0.4 B 0 3.3 1.3 3.0 2.2 5Q 2.3 1.1 3.0 0.3 1 ~';'17~
TABLE I (cont'd) LESION SCORES
E~imeria acervulina Eimeria eenella monensin monensin Compound -- - -Number 0 50 0 50 A.15. A 0 3.2 1.5 2.4 1.9 1.8 1.0 B 0 3.3 1.3 3.0 2.2 2.6 1.6 2.6 1.1 A.16. A 0 3.0 1.1 2.6 1.0 0.9 0.5 B 0 3.3 1.3 3.0 2.2 2.8 1.0 2.8 1.1 A.17. A 0 2.8 1.4 2.6 0.8 0.9 0.9 B 0 2.6 1.0 2.5 1.5 2.4 0.6 2.6 1.3 A.lB. A 0 2.8 1.4 2.6 0.8 0.1 0.3 B 0 2~6 1.0 2.5 1.5 2.7 0.6 2.0 0.7 A.19. A 0 2.8 1.4 2.6 0.8 0.4 0.4 B 0 2.6 1.0 2.5 1.5 2.7 0.4 2.4 0.7 A.20. A 0 2.8 1.4 2.6 0.8 0.5 0.8 B 0 2.6 1.0 2.5 1.5 2.4 0.4 1.4 0.1 .... ..... ......................................................................................................................................... ............. .......
1 1717~Z
X-5472 ~30-TABLE I (cont'd) LESION SCORES
Eimeria acervulina Eimeria tenella monen~ln monensin Compound ---- - -Number O _ _50 0 50 A.21. A 0 2.5 0.9 2.4 1.7 1.3 1.0 B 0 2.6 1.0 2.5 1.5 2.3 1.0 2.2 0.7 A.22. A 0 3.2 2.3 3.0 1.8 1.3 0.8 B 0 2.6 1.0 2.5 1.5 2.7 1.3 2.2 0.6 A.23. A 0 2.6 0.6 2.7 0.9 0.5 0.6 B 0 2.6 1.0 2.5 1.5 2.8 0.6 2.0 0.4 A.24. A 0 2.5 0.9 2.4 1.7 0.9 0.6 B 0, 2.6 1.0 2.5 1.5 2.8 0.8 2.2 0.7 A.25. A 0 2.7 0.6 2.7 0.9 1.1 0.3 B 0 2.6 1.0 2.5 1.5 2.9 0.9 1.8 0.6 A.26. A 0 2.6 0.6 2.7 0.9 0.7 0.4 B 0 2.6 1.0 2.5 1.5 2.8 ~.3 2.3 0.8 ~ ~ ~ 17~Z
TABLE I (cont'd) LESION SCORES _, Eimerla acervulina Eimeria tenella Compound monensin monensin Number 0 50 050 A.27. A 0 2.6 0.6 2.7 0.9 0.3 0.7 B 0 2.6 1.2 2.6 1.5 2.8 0.9 2.6 1.2 A.28. A 0 2.6 0.6 2.7 0.9 0.4 0.9 B 0 2.6 1.2 2.6 1.5 2.7 0.8 2.2 0.7 A.29. A 0 2.6 0.6 2.7 0.9 0.8 0.4 B 0 2.6 1.2 2.6 1.5 1.7 1.4 1.2 0.6 A.30. A 0 2.5 0.9 2.4 1.7 0.8 0,4 O~ 2.6 1.2 Z.6 1.5 2.9 0.2 2.0 0.2 A.31. A 0 2.7 1.6 2.5 1.6 0.3 0.7 B 0 2.6 1.2 2.6 1.5 2.8 0.8 2.7 1.2 B 0 2.4 1.2 2.2 1.8 2.7 0.9 3.0 1.6 A.32. A O 2.7 1.6 2.5 1.6 0.4 0.6 B 0 2.6 1.2 2.6 1.5 2.8 0.7 2.1 0.9 - B 0 2.4 1.2 2.2 1.8 2.5 1.0 2.9 1.0 . . .... .. . .. . . .. . . .. .. .
1 7~12 TABLE I (cont'd) LESION SCORES
Eimeria acervulina Eimeria tenella monensin monensin Compound - -Number O_ 50 0 50 A.33. B 0 2.8 1.2 2.7 1.6 2.8 0.5 2.6 1.0 A.34. B 0 2.8 1.2 2.7 1.6 2.9 0.3 2.2 0.3 A.35. B 0 2.8 1.2 2.7 1.6 2.8 0.2 3.0 0.9 A.36. B 0 2.8 1.2 2.7 1.6 2.2 0 2.6 0.1 A.37. B 0 2.8 1.2 2.7 1.6 2.0 0.4 2.9 1.2 A.38. B 0 2.8 1.2 2.7 1.6 2.6 0.4 2.9 1.3 A.39. A 0 3.6 1.6 2.8 1.2 1.4 0.5 B 0 3.6 2.0 2.9 1.3 3.1 0.5 3.0 0.8 A.40. A 0 3.6 1.6 2.8 1.2 1.3 0.3 B 0 3.6 2.0 2.9 1.3 - 50 2.6 0.8 2.6 0.8 _ _ _ _ . . . .. . ... .. ........ ....... .. . . ................................ ....... . ..
7~;~
X-5472 ~33~
TABLE I (cont'd~
LESION SCOR~S
Eimeria acervullna m~ cenella monensin ~onensin Compound -- --Number 0 50 0 50 A.41. A 0 3.6 1.6 2.8 1.2 1.3 0.2 B 0 3.6 2.0 2.9 1.3 2.1 0 2.2 0.4 A.42. A 0 2.7 1.6 2.6 1.6 0.3 0.7 B 0 3.6 2.0 2.9 1.3 3.2 2.5 2.1 0 A.43. A 0 2.7 1.6 2.6 1.6 1.3 0.4 B 0 3.2 1.1 1.9 0.8 3.1 0.8 2.3 0.4 A.44. A 0 3.6 1.6 2.8 1.2 1.2 0.4 B, 0 3.2 1.1 1.9 0.8 2.g 0.5 2.6 0.6 A.45. A 0 3.0 0.9 2.8 0.5 0.8 0.3 B 0 3.2 1.1 1.9 0.8 2.7 1.0 2.1 0.2 : ... . : .-.. - :: -:- .. -.-. -.. :. .::
'17~12 TABLE I (cont'd) _ LESION SCORES
Eimerla acervulina Eimeria tenella monensin monensin Com~_und - -- - -- -~umber 0 50 0 50 _ _ --A.46. A 0 3.0 0.7 2.8 0.2 1.0 0.2 B 0 3.2 1.1 1.9 0.8 2.9 0.9 2.1 0.2 A.47. A 0 2.8 1.0 3.0 1.2 1.4 0.7 B 0 3.2 1.1 1.9 0.8 2.7 0.g 2.4 0.5 A.48. A 0 2.8 1.0 3.0 1.2 0.9 0.7 B 0 3.2 1.1 1.9 0.B
3.3 1.0 2.3 0.4 A.49. A 0 3.0 0.7 2.8 0.2 0.6 0.4 B 0 3.2 1.1 1.9 0.8 50 3.1 0.3 2.8 0.2 A.50. B 0 2.8 1.0 1.7 0.5 3.0 0 2.0 0 .
1.7~Z
TABLE I _(cont'd) _LESION SCORES
Eimerla acervulina Eimeria tenella . .
monensin monensin Com~und - -- -Number 0 _ 50 _ 0 50 A.51. B 0 2.8 1.0 1.7 0.5 1.3 0 1.1 0 A.52. B 0 2.8 1.0 1.7 0.5 2.8 0 2.1 0.2 A.53. A 0 2.7 1.6 2.5 1.6 0.8 0.9 B 0 2.4 1.2 2.2 1.8 2.8 0.8 2.6 1.4 A.54. A 0 3.1 2.0 2.4 0.6 1.7 0.6 B 0 2.4 1.2 2.2 1.8 2.6 0.7 2.9 0.4 A.55. B 0 2.4 1.2 2.2 1.8 2.9 0.8 2,5 0.1 A.56. B, 0 2.4 1.2 2.2 1.8 2.8 0.6 2.8 0.2 A.57. A 0 2.7 1.6 2.5 1.6 0.~ 0.9 B 0 2.4 1.2 2.2 1.8 3.0 1.2 2.8 0.9 A.58. A 0 2.7 1.6 2.5 1.6 0.9 0.7 B 0 2.4 1.2 2.2 1.8 2.7 0.7 2.7 0.8 1 ~7~7~
~ABLE I (cont'd) LESION SCORCS
Eimeria acervulina Eimeria tenella monensin monensin Compound - - -N~rber 0 50 0 50 A.59. A 0 2.9 0.9 2.2 1.7 0.5 1.4 B 0 2.4 1.2 2.2 1.8 2.9 0.7 2.9 1.1 A.60. A 0 2.7 1.6 2.5 1.6 - 50 0.6 0.7 B 0 2.7 1.2 2.1 2.1 2.9 0.8 2.7 1.6 A.61. A 0 3.0 1.5 2.8 1.9 0.8 1.7 B 0 2.0 0.2 2.8 1.3 2.0 0.7 3.1 2.2 A.62. B 0 2.0 0.2 2.8 1.3 so 0.4 0 2.4 0.8 A.63. B~ 0 2.0 0.2 2.8 1.3 2.6 0.1 2.9 0.6 A.64. B 0 2.0 0.2 2.8 1.3 0.7 0 2.4 0.8 ............................... ,.......... ....... ~
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TABLE IV
LESION SCORES
Eimeria acervullna* Eimeria tenella*
Eimeria maxima*
Compound (Intestinal) (Cecal) Number . Monensin Monensin A.l. 0 4.9 2.8 .3 0 3.3 3.3 .9 0 3.7 .3 .07 3.2 .67 .13 2.1 0 0 2.7 0 .07 100 1.3 .6 A.2. 0 5.93 3.7 2.1 0 2.83 3.1 1.2 .47 1.72 .33 .13 1.78 .4 0 .45 0 0 .55 .2 0 Infected with 500,000 oocysts of Eimeria acer~ulina, 60,000 oocysts of Eimeria maxima, ant 40,000 oocysts of Elmeria tenella. Test contucted wlth three repllcates.
~ 1717~
The foregoing compositions are typical of feed-stuffs actually administered to poultry. ~remixes are commonly used in the poultry industry, and the combinations of the present invention can also be formulated as pre-mixes. Such premixes typically comprise the polyetherantibiotic, the selected carbanilide, and a solid sub-stance acceptable as a feedstuff, such as corn meal, rice hulls, crushed limestone, soybean meal, soya grits, distillers' dried grains, citrus meal, wheat middlings, clays and the like. Such a premix is mixed or blended with other substances to constitute either an inter-mediate premix or the finished feed.
" A representative premix in accordance with the present invention is as follows:
monensin: 45 grams activity a selected carbanilide in accordance with the present invention: 45 grams rice hulls q.s. ad 454 grams This formulation is mixed thoroughly and can be added to one ton of fini,shed feed to sl~pply suitable amounts of the components in accordance with the present invention.
The present invention was evaluated in chickens as follows: one-week-old broiler chicks were fed a medi-cated or control ration, typically for one day, prior to infection (by gavage) with oocysts of a coccidiosis-causing organism, generally 750,000 oocysts of Eimeria acerwlin_ and 75,000 oocysts of Eimeria tenella. The chicks were maintained on their respective rations for an additional period of time, typically six days. There were five chicks in a group and generally two replicates per treatment. Anticoccidial efficacy was determined by lesion scores. To determine lesion scores, the birds were sacrificed and the severity of lesions scored on a 0-4 scale, with lesion-free birds scored as 0, extremely ~ .1.';'1.7~Z
severe infections scored as 4, and intermediate degrees of infection scored as 1, 2, or 3. The scores of all birds which received a given treatment were averaged.
Most of the compounds were tested in a preli-minary test "A"; in this test, monensin was tested alone at S0 ppm and the carbanilide compound was tested in combination with monensin, each at 50 ppm. In a secon-dary test "B", monensin and the carbanilide compound were each tested alone, at 50 ppm, and the two were tested in combination, each at 50 ppm. Additional tests at more varied concentrations were also conducted with certain of the compounds.
The results are reported in the following tables.
The concentration of monensin and the carbanilide~ is expressed as the parts per million (ppm) of the total feed provided to the chicks.
TABLE I
LESION SCORES
Eimerla acervuIina Eimerla tenella monensln monensin ComPound -~
Number 0 50 050 .
A.3. A 0 2.8 1.6 2.0 1.9 0.7 0.9 B 0 3.0 1.2 2.0 1.2 50 3.0 1.2 2.5 0.7 A.4. ~ A 0 2.8 1.6 2.0 0.9 B 0 3.0 1.2 2.0 1.2 50 3.0 0.9 2.4 0.6 A.5. A 0 2.4 1.2 2.5 1.4 0.3 0.4 B 0 3.0 1.2 2.0 1.2 50 3.0 1.1 2.2 0 A.6. A 0 2.8 1.6 2.0 0.9 1.6 0.6 B 0 3.0 1.2 2.0 1.2 50 2.9 0.8 2.5 0.5 A.7. A 0 2.5 1.6 2.4 2.3 0.9 0.4 B 0 3.0 1.2 2.0 1.2 50 3.0 1.4 1.8 0.6 A.8. A 0 3.0 1.2 2.1 0.9 0.4 0.2 B 0 3.3 1.3 3.0 2.2 50 2.6 0.8 3.0 1.0 z TABLE I (cont'd) _ LESION SCORES
Eimeria acervulina Eimeria tenella monensin monensin Compound Number 0 50 _ 0 50 A.9. A 0 3.01.2 2.1 0.9 0.7 0.9 B 0 3.31.3 3.0 2.2 2.8G.8 2.9 1.3 A.10. A 0 2.71.7 3.0 1.0 0.5 0.6 B 0 3.31.3 3.0 2.2 2.40.9 2.7 1.7 A.ll. A 0 3.61.2 3.0 1.2 0.6 0.8 B 0 3.31.3 3.0 2.2 2.61.4 2.8 1.1 A.12. A 0 2.81.1 2.3 1.0 1.1 0.6 B 0 3.31.3 3.Q 2.2 2.50.9 2.9 0.8 A.13. A 0 3.01.2 2.1 0.9 S0 0.9 0.5 B 0 3.31.3 3.0 2.2 2.91.4 3.0 1.2 A.14. A 0 3.01.2 2.1 0.9 1.2 0.6 B 0 3.31.3 3.0 2.2 5a 2.6 1.1 3.0 1.0 C.8. A 0 2.7 1.7 3.0 1.0 - 1.2 0.4 B 0 3.3 1.3 3.0 2.2 5Q 2.3 1.1 3.0 0.3 1 ~';'17~
TABLE I (cont'd) LESION SCORES
E~imeria acervulina Eimeria eenella monensin monensin Compound -- - -Number 0 50 0 50 A.15. A 0 3.2 1.5 2.4 1.9 1.8 1.0 B 0 3.3 1.3 3.0 2.2 2.6 1.6 2.6 1.1 A.16. A 0 3.0 1.1 2.6 1.0 0.9 0.5 B 0 3.3 1.3 3.0 2.2 2.8 1.0 2.8 1.1 A.17. A 0 2.8 1.4 2.6 0.8 0.9 0.9 B 0 2.6 1.0 2.5 1.5 2.4 0.6 2.6 1.3 A.lB. A 0 2.8 1.4 2.6 0.8 0.1 0.3 B 0 2~6 1.0 2.5 1.5 2.7 0.6 2.0 0.7 A.19. A 0 2.8 1.4 2.6 0.8 0.4 0.4 B 0 2.6 1.0 2.5 1.5 2.7 0.4 2.4 0.7 A.20. A 0 2.8 1.4 2.6 0.8 0.5 0.8 B 0 2.6 1.0 2.5 1.5 2.4 0.4 1.4 0.1 .... ..... ......................................................................................................................................... ............. .......
1 1717~Z
X-5472 ~30-TABLE I (cont'd) LESION SCORES
Eimeria acervulina Eimeria tenella monen~ln monensin Compound ---- - -Number O _ _50 0 50 A.21. A 0 2.5 0.9 2.4 1.7 1.3 1.0 B 0 2.6 1.0 2.5 1.5 2.3 1.0 2.2 0.7 A.22. A 0 3.2 2.3 3.0 1.8 1.3 0.8 B 0 2.6 1.0 2.5 1.5 2.7 1.3 2.2 0.6 A.23. A 0 2.6 0.6 2.7 0.9 0.5 0.6 B 0 2.6 1.0 2.5 1.5 2.8 0.6 2.0 0.4 A.24. A 0 2.5 0.9 2.4 1.7 0.9 0.6 B 0, 2.6 1.0 2.5 1.5 2.8 0.8 2.2 0.7 A.25. A 0 2.7 0.6 2.7 0.9 1.1 0.3 B 0 2.6 1.0 2.5 1.5 2.9 0.9 1.8 0.6 A.26. A 0 2.6 0.6 2.7 0.9 0.7 0.4 B 0 2.6 1.0 2.5 1.5 2.8 ~.3 2.3 0.8 ~ ~ ~ 17~Z
TABLE I (cont'd) LESION SCORES _, Eimerla acervulina Eimeria tenella Compound monensin monensin Number 0 50 050 A.27. A 0 2.6 0.6 2.7 0.9 0.3 0.7 B 0 2.6 1.2 2.6 1.5 2.8 0.9 2.6 1.2 A.28. A 0 2.6 0.6 2.7 0.9 0.4 0.9 B 0 2.6 1.2 2.6 1.5 2.7 0.8 2.2 0.7 A.29. A 0 2.6 0.6 2.7 0.9 0.8 0.4 B 0 2.6 1.2 2.6 1.5 1.7 1.4 1.2 0.6 A.30. A 0 2.5 0.9 2.4 1.7 0.8 0,4 O~ 2.6 1.2 Z.6 1.5 2.9 0.2 2.0 0.2 A.31. A 0 2.7 1.6 2.5 1.6 0.3 0.7 B 0 2.6 1.2 2.6 1.5 2.8 0.8 2.7 1.2 B 0 2.4 1.2 2.2 1.8 2.7 0.9 3.0 1.6 A.32. A O 2.7 1.6 2.5 1.6 0.4 0.6 B 0 2.6 1.2 2.6 1.5 2.8 0.7 2.1 0.9 - B 0 2.4 1.2 2.2 1.8 2.5 1.0 2.9 1.0 . . .... .. . .. . . .. . . .. .. .
1 7~12 TABLE I (cont'd) LESION SCORES
Eimeria acervulina Eimeria tenella monensin monensin Compound - -Number O_ 50 0 50 A.33. B 0 2.8 1.2 2.7 1.6 2.8 0.5 2.6 1.0 A.34. B 0 2.8 1.2 2.7 1.6 2.9 0.3 2.2 0.3 A.35. B 0 2.8 1.2 2.7 1.6 2.8 0.2 3.0 0.9 A.36. B 0 2.8 1.2 2.7 1.6 2.2 0 2.6 0.1 A.37. B 0 2.8 1.2 2.7 1.6 2.0 0.4 2.9 1.2 A.38. B 0 2.8 1.2 2.7 1.6 2.6 0.4 2.9 1.3 A.39. A 0 3.6 1.6 2.8 1.2 1.4 0.5 B 0 3.6 2.0 2.9 1.3 3.1 0.5 3.0 0.8 A.40. A 0 3.6 1.6 2.8 1.2 1.3 0.3 B 0 3.6 2.0 2.9 1.3 - 50 2.6 0.8 2.6 0.8 _ _ _ _ . . . .. . ... .. ........ ....... .. . . ................................ ....... . ..
7~;~
X-5472 ~33~
TABLE I (cont'd~
LESION SCOR~S
Eimeria acervullna m~ cenella monensin ~onensin Compound -- --Number 0 50 0 50 A.41. A 0 3.6 1.6 2.8 1.2 1.3 0.2 B 0 3.6 2.0 2.9 1.3 2.1 0 2.2 0.4 A.42. A 0 2.7 1.6 2.6 1.6 0.3 0.7 B 0 3.6 2.0 2.9 1.3 3.2 2.5 2.1 0 A.43. A 0 2.7 1.6 2.6 1.6 1.3 0.4 B 0 3.2 1.1 1.9 0.8 3.1 0.8 2.3 0.4 A.44. A 0 3.6 1.6 2.8 1.2 1.2 0.4 B, 0 3.2 1.1 1.9 0.8 2.g 0.5 2.6 0.6 A.45. A 0 3.0 0.9 2.8 0.5 0.8 0.3 B 0 3.2 1.1 1.9 0.8 2.7 1.0 2.1 0.2 : ... . : .-.. - :: -:- .. -.-. -.. :. .::
'17~12 TABLE I (cont'd) _ LESION SCORES
Eimerla acervulina Eimeria tenella monensin monensin Com~_und - -- - -- -~umber 0 50 0 50 _ _ --A.46. A 0 3.0 0.7 2.8 0.2 1.0 0.2 B 0 3.2 1.1 1.9 0.8 2.9 0.9 2.1 0.2 A.47. A 0 2.8 1.0 3.0 1.2 1.4 0.7 B 0 3.2 1.1 1.9 0.8 2.7 0.g 2.4 0.5 A.48. A 0 2.8 1.0 3.0 1.2 0.9 0.7 B 0 3.2 1.1 1.9 0.B
3.3 1.0 2.3 0.4 A.49. A 0 3.0 0.7 2.8 0.2 0.6 0.4 B 0 3.2 1.1 1.9 0.8 50 3.1 0.3 2.8 0.2 A.50. B 0 2.8 1.0 1.7 0.5 3.0 0 2.0 0 .
1.7~Z
TABLE I _(cont'd) _LESION SCORES
Eimerla acervulina Eimeria tenella . .
monensin monensin Com~und - -- -Number 0 _ 50 _ 0 50 A.51. B 0 2.8 1.0 1.7 0.5 1.3 0 1.1 0 A.52. B 0 2.8 1.0 1.7 0.5 2.8 0 2.1 0.2 A.53. A 0 2.7 1.6 2.5 1.6 0.8 0.9 B 0 2.4 1.2 2.2 1.8 2.8 0.8 2.6 1.4 A.54. A 0 3.1 2.0 2.4 0.6 1.7 0.6 B 0 2.4 1.2 2.2 1.8 2.6 0.7 2.9 0.4 A.55. B 0 2.4 1.2 2.2 1.8 2.9 0.8 2,5 0.1 A.56. B, 0 2.4 1.2 2.2 1.8 2.8 0.6 2.8 0.2 A.57. A 0 2.7 1.6 2.5 1.6 0.~ 0.9 B 0 2.4 1.2 2.2 1.8 3.0 1.2 2.8 0.9 A.58. A 0 2.7 1.6 2.5 1.6 0.9 0.7 B 0 2.4 1.2 2.2 1.8 2.7 0.7 2.7 0.8 1 ~7~7~
~ABLE I (cont'd) LESION SCORCS
Eimeria acervulina Eimeria tenella monensin monensin Compound - - -N~rber 0 50 0 50 A.59. A 0 2.9 0.9 2.2 1.7 0.5 1.4 B 0 2.4 1.2 2.2 1.8 2.9 0.7 2.9 1.1 A.60. A 0 2.7 1.6 2.5 1.6 - 50 0.6 0.7 B 0 2.7 1.2 2.1 2.1 2.9 0.8 2.7 1.6 A.61. A 0 3.0 1.5 2.8 1.9 0.8 1.7 B 0 2.0 0.2 2.8 1.3 2.0 0.7 3.1 2.2 A.62. B 0 2.0 0.2 2.8 1.3 so 0.4 0 2.4 0.8 A.63. B~ 0 2.0 0.2 2.8 1.3 2.6 0.1 2.9 0.6 A.64. B 0 2.0 0.2 2.8 1.3 0.7 0 2.4 0.8 ............................... ,.......... ....... ~
: .. -....... . .... .. ...... ... .. . . .. . ........ .. .
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X-5472 _37_ ~ ~
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TABLE IV
LESION SCORES
Eimeria acervullna* Eimeria tenella*
Eimeria maxima*
Compound (Intestinal) (Cecal) Number . Monensin Monensin A.l. 0 4.9 2.8 .3 0 3.3 3.3 .9 0 3.7 .3 .07 3.2 .67 .13 2.1 0 0 2.7 0 .07 100 1.3 .6 A.2. 0 5.93 3.7 2.1 0 2.83 3.1 1.2 .47 1.72 .33 .13 1.78 .4 0 .45 0 0 .55 .2 0 Infected with 500,000 oocysts of Eimeria acer~ulina, 60,000 oocysts of Eimeria maxima, ant 40,000 oocysts of Elmeria tenella. Test contucted wlth three repllcates.
Claims (19)
1. A poultry feedstuff composition comprising a first component which is a polyether antibiotic and a second component which is a carbanilide, said components being present in concentrations which, in combination, exert a potentiated or synergized anti-coccidial effect as to at least one coccidiosis-causing strain of Eimeria, and said carbanilide being selected from the group consisting of A.l. 3,3'-bis(trifluoromethyl)-4,4'-dichlorocarbanilide, A.2. 3,3'-5,5'-tetrakis(trifluoromethyl)carbanilide, A.3. 3-chloro-4'-fluorocarbanilide, A.4. 2-chloro-2'-fluorocarbanilide, A.5. 3,4',5-tris(trifluoromethyl)carbanilide, A.6. 3,4,5-trichlorocarbanilide, A.7. 2-chloro-5-(trifluoromethyl)-4'-(ethoxycarbonyl)-carbanilide, A.8. 2,6-dimethyl-4'-(N-methylacetamido)carbanilide, A.9. 2-methoxy-4'-acetamidocarbanilide, A.10. 3-(trifluoromethyl)-4'-iodothiocarbanilide, A.ll. 2-fluoro-4'-taminosulfonyl)carbanilide, A.12. 2-methoxy-4'-isopropylcarbanilide, A.13. 2-methyl-2',5'-diethoxycarbanilide, A.14. 4-ethyl-2'-methoxycarbanilide, A.15. 2-methyl-5-chloro-2',5'-dimethoxycarbanilide, A.16. 2,4,4'-trimethyl-3'-nitrocarbanilide, A.17. 2-amino-3-nitro-5-(trifluoromethyl)-2',4'-dimethylcarbanilide, A.18. 2-amino-3,4'-dinitro-5-(trifluoromethyl)-2'-chlorocarbanilide, A.l9. 2-amino-3,5'-dinitro-5-(trifluoromethyl)-2'-fluorocarbanilide, A.20. 2-amino-3-nitro-5-(trifluoromethyl)-2'-(ethoxy-carbonyl)carbanilide, A.21. 2-ethyl-6-sec-butylcarbanilid, A.22. 2-isopropyl-2',4',6'-trimethylcarbanilide, A.23. 2-amino-3-nitro-3',5-bis(trifluoromethyl)-4'-chlorocarbanilide, A.24. 2-ethyl-6-sec-butyl-4'-n-butoxycarbanilide, A.25. 2-amino-3-nitro-5-(trifluoromethyl)-2',4',5'-trichlorocarbanilide, A.26. 2-amino-3,3'-dinitro-5-(trifluoromethyl)-4'-chlorocarbanilide, A.27. 2-amino-3-nitro-5-(trifluoromethyl)-2' methyl-4'-bromocarbanilide, A.28. 2-amino-3-nitro-S-(trifluoromethyl)-2',6'-dibromo-4'-fluorocarbanilide, A.29. 2-amino-3-nitro-2',5-bis(trifluoromethyl)-4'-chlorocarbanilide, A.30. 3,3',5,5'-tetrakis(trifluoromethyl)thiocarbanil-ide, A.31. 2,4-dimethoxy-4'-(ethoxycarbonyl)carbanilide, A.32. 4-(ethoxycarbonyl)-2'-methyl-6'-ethylcarbanilide, A.33. 2,2'-dinitro-4,4'-bis(trifluoromethyl)carbanil-ide, A.34. 3,3',4,4',5,5'-hexachlorocarbanilide, A.35. 3-nitro-4-chloro-4'-(trifluoromethyl)carbanilide, A.36. 4-chloro-3,4'-bis(trifluoromethyl)carbanilide, A.37. 4,4'-dinitro-2,2'-bis(trifluoromethyl)carbanil-ide, A.38. 4,4'-bis(trifluoromethyl)carbanilide, A.39. 3-bromo-3',5'-dimethylcarbanilide, A.40. 2,5-dichloro-4'-methyl-N2-ethylcarbanilide, A.41. 2,5-dichloro-2',4'-difluorocarbanilide, A.42 2-amino-3-nitto-3',5,5'-tris(trifluoromethyl)-carbanilide, A.43. 2,6-diethyl-4'-(ethoxycarbonyl)carbanilide, A.44. 3-ethyl-3'-chloro-4'-methyl-N2-ethylcarbanilide, A.45. 2,6-dimethyl-4'-(ethoxycarbonyl)carbanilide, A.46. 4-methoxy-3'-acetamidocarbanilide, A.47. 2-methoxy-4'-(n-butoxycarbonyl)carbanilide, A.48. 4-(isobutoxycarbonyl)carbanilide, A.49. 2,4'-bis(methoxycarbonyl)carbanilide, A.50. 2',4-dichloro-3-nitro-3'-(trifluoromethyl-carbanilide, A.51. 3,4,4',5-tetrachloro-3'-(trifluoromethyl)-carbanilide, A.52. 4-chloro-3-nitro-3',5'-bis(trifluoromethyl)-carbanilide, A.53. 2,4,6-trimethyl-4'-(ethoxycarbonyl)carbanilide, A.54. 2-(trifluoromethyl)-2'-ethyl-6'-isopropyl-carbanilide, A.55. 4-chloro-3,3',5'-tris(trifluoromethyl)car-banilide, A.56. 3,4,4',5-tetrachloro-3'-nitrocarbanilide, A.57. 2,6-dimethyl-4'-benzoylcarbanilide, A.58. 3,4-dimethyl-2'-ethoxycarbanilide, A.59. 2-chloro-4,4'-bis(methylthio)carbanilide, A.60. 2-methyl-2'-ethoxycarbanilide, A.61. 4-chloro-2-methoxythiocarbanilide, A.62. 4,4'-dinitro-N,N'-dimethylcarbanilide, A.63. 4-(trifluoromethyl)-4'-nitrocarbanilide, A.64. 3,3',5,5'-tetrakis(trifluoromethyl)-N,N'-dimethylcarbanilide;
B.l. 4-nitro-4'-(4-chlorophenoxy)carbanilide B.2. 4-nitro-4'-(3,4-dichlorophenoxy)carbanilide B.3. 4-nitro-3'-chloro-4'-(4-chlorophenoxy) carbanilide B.4. 4-nitro-3',5'-dichloro-4'-(4-chlorophenoxy)-carbanilide B.5. 4-nitro-3'-chloro-4'-(3,4-dichlorophenoxy)-carbanilide B.6. 4-nitro-4'-(2,4-dichlorophenoxy)carbanilide B.7. 4-nitro-4'-(4-nitrophenoxy)carbanilide B.8. 4-nitro-3' nitro-4'-(4-chlorophenoxy)-carbanilide B.9. 4-nitro-3'-methyl-4'-(4-chlorophenoxy)-carbanilide B.10. 4-nitro-2'-nitro-4'-(4-chlorophenoxy)-carbanilide B.11. 4-nitro-4'-(2,4-dinitrophenoxy)carbanilide B.12. 4-nitro-3'-chloro-4'-(2-tert-butyl-4-chloro-phenoxy)carbanilide B.13. 4-nitro-4'-(2-methyl-4-chlorophenoxy)-carbanilide B.14. 4-nitro-3'-bromo-4'-(4-bromophenoxy)carbanilide B.15. 4-nitro-3'-bromo-4'-(4-chlorophenoxy)-carbanilide B.16. 4-nitro-3'-chloro-4'-(4-bromophenoxy)-carbanilide B.17. 3,3',4'-trichloro-4-(4-chlorophenoxy)-carbanilide B.18. 3,4'-dichloro-4-(4-chlorophenoxy)carbanilide B.19. 3,4-dichloro-4'-(4-chlorophenoxy)carbanilide B.20. 2-methyl-4-nitro-3'-chloro-4'-(4-chloro-phenoxy)carbanilide C.1. 3,3',5'-tris(trifluoromethyl)-4-methoxy-carbanilide C.2. 3-(trifluoromethoxy)-3',5'-bis(trifluoro-methyl)carbanilide C.3. 4-(trifluoromethoxy)-3',5'-bis(trifluoro-methyl)carbanilide C.4. 2,3',5'-tris(trifluoromethyl)-4-(trifluoro-methoxy)carbanilide C.5. 4-(methylthio)-3',5'-bis(trifluoromethyl)-carbanilide C.6. 4-(methylthio)-3',5'-bis(trifluoromethyl)-thiocarbanilide C.7. 3-chloro-4-(methylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.8. 3-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.9. 4-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.10. 2-chloro-4-(trifluoromethylthio)-3',5'-bis(trifluoromethyl)carbanilide C.ll. 4-(trifluoromethylthio)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.12. 4-(trifluoromethylthio)-2',5'-bis(trifluoro-methyl)-4'-nitrocarbanilide C.13. 4,4'-bis(trifluoromethylthio)carbanilide C.14. 4-(trifluoromethylthio)-4'-(chloromethyl-sulfonyl)carbanilide C.15. 3-(difluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.16. 4-(ethylthio)-3',5'-bis(trifluoromethyl)-carbanilide C.17. 3-chloro-4-(ethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.18. 4-ethoxy-3,3',5'-tris(trifluoromethyl)car-banilide C.l9. 3-(trifluoromethyl)-4-ethoxy-4'-(trifluoro-methylthio)carbanilide C.20. 3-(trifluoromethyl)-4-ethoxy-3'-(trifluoro-methylthio)carbanilide C.21. 4-methyl-3-(2-chloroethoxy)-3',5'-bis(tri-fluoromethyl)chrbanilide C.22. 4-(1,2-dichlorovinyloxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.23. 4-(1,2-dichlorovinyloxy)-3',5'-bis(trifluoro-methyl)carbanilide C.24. 4-(2,2,2-trichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.25. 2-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.26. 3-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.27. 3-(2,2-dichloro-1,1-difluoroethoxy)-4-bromo-3',5'-bis(trifluoromethyl)carbanilide C.28. 4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.29. 4-(2,2-dichloro-1,1-difluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.30. 3-methoxy-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.31. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.32. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-4'-isopropylcarbanilide C.33. 3-nitro-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.34. 2-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.35. 4-(2,2-dichloro-1,1-difluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.36. 3-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.37. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.38. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)thiocarbanilide C.39. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.40. 4,4'-bis(2-chloro-1,1,2-trifluoroethoxy)-carbanilide C.41. 4-(2-chloro-1,1,2-trifluoroethoxy)-4'-(trifluoromethylthio)carbanilide C.42. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.43. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3'-bis(trifluoromethyl)-5'-nitrocarbanilide C.44. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.45. 3-(1,1,2-trifluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.46. 3-(1,1,2,2-tetrafluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.47. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(chlorodifluoromethyl)carbanilide C.48. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.49. 3-(trifluoromethyl)-4-(1,1,2,2-tetrafluoro-ethoxy)-4'-bromocarbanilide C.50. 3-(1,1,2,3,3,3-hexafluoro-n-propoxv)-3',5'-bis(trifluoromethyl)carbanilide C.51. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)carbanilide C.52. 3-chloro-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.53. 3-methyl-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.54. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3',5l-tris(trifluoromethyl)carbanilide C.55. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.56. 4-(methoxycarbonylthio)-3',5'-bis(tri-fluoromethyl)carbanilide C.57. 4-(4-chlorophenoxy)-4'-(trifluoromethyl-thio)thiocarbanilide C.58. 4-(4-chlorophenoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.59. 3-chloro-4-(4-chlorophenoxy)-3',5'-bis(trifluoromethyl)carbanilide C.60. 4-(4-chlorophenoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.61. 4-(3,5-bis(trifluoromethyl)phenoxy-3',5'-bis(trifluoromethyl)carbanilide C.62. 4-(4-methylphenoxycarbonyl)-3',5'-bis(trifluoromethyl)carbanilide C.63. 4-(4-methylphenoxycarbonyl)-4'-(tri-fluoromethylthio)carbanilide C.64. 3,5-bis(trifluoromethyl)-2',4',6'-trichlorocarbanilide C.65. 3,5-bis(trifluoromethyl)-2',4',5'-tri-chlorocarbanilide C.66. 3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.67. 3,3',5-tris(trifluoromethyl)-5'-nitro-carbanilide C.68. 2',3,5,6'-tetrakis(trifluoromethyl)-4'-nitrocarbanilide C.69. 3-(chlorodifluoromethyl)-3',5'-bis(tri-fluoromethyl)carbanilide C.70. 3-(1,1,2,2-tetrafluoroethyl)-3',5'-bis(trifluoromethyl)carbanilide C.71. 4-phenyl-3'"5'-bis(trifluoromethyl)-carbanilide C.72. 3-(fluorosulfonyl)-3',5'-bis(trifluoro-methyl)carbanilide C.73. 4-(fluorosulfonyl)-4'-(trifluoromethyl-thio)carbanilide C.74. 4-(fluorosulfonyl)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.75. 4-(chloromethylsulfonyl)-3',5'-bis(tri-fluoromethyl)carbanilide C.76. 2-(ethylsulfonyl)-3',5,5'-tris(trifluoro-methyl)carbanilide C.77. 2-(ethylsulfonyl)-3',5-bis(trifluoro-methyl)-5'-nitrocarbanilide C.78. 4-(trifluoromethylsulfonyl)-3',5'-bis(trifluoromethyl)carbanilide C.79. 4-(trifluoromethylsulfonyl)-3'-(tri-fluoromethyl)-4'-methoxycarbanilide C.80. 4-(trifluoromethylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.81. 4-(4-nitrophenylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.82. 4-(4-acetamidophenylsulfonyl)-4'-(trifluoromethylthio)carbanilide C.83. 4-(4-(isopropylideneamino)phenylsul-fonyl)-4'-(trifluoromethylthio)car banilide C.84. 4,4-sulfonylbis(3'-(trifluoromethylthio)-carbanilide) C.85. 4,4-sulfonylbis(4'-(1,2-dichlorovinyl-oxy)carbanilide) C.86. 4,4-sulfonylbis(3'-(1,1,2,2-tetra-fluoroethoxy)carbanilide) C.87. 4,4-sulfonylbis(4'-(2-chloro-1,1,2-trifluoroethoxy)carbanilide) C.88. 4,4-sulfonylbis(4'-(trifluoromethyl-thio)carbanilide).
B.l. 4-nitro-4'-(4-chlorophenoxy)carbanilide B.2. 4-nitro-4'-(3,4-dichlorophenoxy)carbanilide B.3. 4-nitro-3'-chloro-4'-(4-chlorophenoxy) carbanilide B.4. 4-nitro-3',5'-dichloro-4'-(4-chlorophenoxy)-carbanilide B.5. 4-nitro-3'-chloro-4'-(3,4-dichlorophenoxy)-carbanilide B.6. 4-nitro-4'-(2,4-dichlorophenoxy)carbanilide B.7. 4-nitro-4'-(4-nitrophenoxy)carbanilide B.8. 4-nitro-3' nitro-4'-(4-chlorophenoxy)-carbanilide B.9. 4-nitro-3'-methyl-4'-(4-chlorophenoxy)-carbanilide B.10. 4-nitro-2'-nitro-4'-(4-chlorophenoxy)-carbanilide B.11. 4-nitro-4'-(2,4-dinitrophenoxy)carbanilide B.12. 4-nitro-3'-chloro-4'-(2-tert-butyl-4-chloro-phenoxy)carbanilide B.13. 4-nitro-4'-(2-methyl-4-chlorophenoxy)-carbanilide B.14. 4-nitro-3'-bromo-4'-(4-bromophenoxy)carbanilide B.15. 4-nitro-3'-bromo-4'-(4-chlorophenoxy)-carbanilide B.16. 4-nitro-3'-chloro-4'-(4-bromophenoxy)-carbanilide B.17. 3,3',4'-trichloro-4-(4-chlorophenoxy)-carbanilide B.18. 3,4'-dichloro-4-(4-chlorophenoxy)carbanilide B.19. 3,4-dichloro-4'-(4-chlorophenoxy)carbanilide B.20. 2-methyl-4-nitro-3'-chloro-4'-(4-chloro-phenoxy)carbanilide C.1. 3,3',5'-tris(trifluoromethyl)-4-methoxy-carbanilide C.2. 3-(trifluoromethoxy)-3',5'-bis(trifluoro-methyl)carbanilide C.3. 4-(trifluoromethoxy)-3',5'-bis(trifluoro-methyl)carbanilide C.4. 2,3',5'-tris(trifluoromethyl)-4-(trifluoro-methoxy)carbanilide C.5. 4-(methylthio)-3',5'-bis(trifluoromethyl)-carbanilide C.6. 4-(methylthio)-3',5'-bis(trifluoromethyl)-thiocarbanilide C.7. 3-chloro-4-(methylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.8. 3-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.9. 4-(trifluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.10. 2-chloro-4-(trifluoromethylthio)-3',5'-bis(trifluoromethyl)carbanilide C.ll. 4-(trifluoromethylthio)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.12. 4-(trifluoromethylthio)-2',5'-bis(trifluoro-methyl)-4'-nitrocarbanilide C.13. 4,4'-bis(trifluoromethylthio)carbanilide C.14. 4-(trifluoromethylthio)-4'-(chloromethyl-sulfonyl)carbanilide C.15. 3-(difluoromethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.16. 4-(ethylthio)-3',5'-bis(trifluoromethyl)-carbanilide C.17. 3-chloro-4-(ethylthio)-3',5'-bis(trifluoro-methyl)carbanilide C.18. 4-ethoxy-3,3',5'-tris(trifluoromethyl)car-banilide C.l9. 3-(trifluoromethyl)-4-ethoxy-4'-(trifluoro-methylthio)carbanilide C.20. 3-(trifluoromethyl)-4-ethoxy-3'-(trifluoro-methylthio)carbanilide C.21. 4-methyl-3-(2-chloroethoxy)-3',5'-bis(tri-fluoromethyl)chrbanilide C.22. 4-(1,2-dichlorovinyloxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.23. 4-(1,2-dichlorovinyloxy)-3',5'-bis(trifluoro-methyl)carbanilide C.24. 4-(2,2,2-trichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.25. 2-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.26. 3-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.27. 3-(2,2-dichloro-1,1-difluoroethoxy)-4-bromo-3',5'-bis(trifluoromethyl)carbanilide C.28. 4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.29. 4-(2,2-dichloro-1,1-difluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.30. 3-methoxy-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.31. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.32. 3-methyl-4-(2,2-dichloro-1,1-difluoroethoxy)-4'-isopropylcarbanilide C.33. 3-nitro-4-(2,2-dichloro-1,1-difluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.34. 2-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.35. 4-(2,2-dichloro-1,1-difluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.36. 3-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.37. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)carbanilide C.38. 4-(2-chloro-1,1,2-trifluoroethoxy)-3',5'-bis(trifluoromethyl)thiocarbanilide C.39. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.40. 4,4'-bis(2-chloro-1,1,2-trifluoroethoxy)-carbanilide C.41. 4-(2-chloro-1,1,2-trifluoroethoxy)-4'-(trifluoromethylthio)carbanilide C.42. 4-(2-chloro-1,1,2-trifluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.43. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3'-bis(trifluoromethyl)-5'-nitrocarbanilide C.44. 4-(2-chloro-1,1,2-trifluoroethoxy)-3,3',5'-tris(trifluoromethyl)carbanilide C.45. 3-(1,1,2-trifluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.46. 3-(1,1,2,2-tetrafluoroethoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.47. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(chlorodifluoromethyl)carbanilide C.48. 3-methyl-4-(1,1,2,2-tetrafluoroethoxy)-3'-(trifluoromethyl)-4'-chlorocarbanilide C.49. 3-(trifluoromethyl)-4-(1,1,2,2-tetrafluoro-ethoxy)-4'-bromocarbanilide C.50. 3-(1,1,2,3,3,3-hexafluoro-n-propoxv)-3',5'-bis(trifluoromethyl)carbanilide C.51. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)carbanilide C.52. 3-chloro-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.53. 3-methyl-4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3',5'-bis(trifluoromethyl)-carbanilide C.54. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3',5l-tris(trifluoromethyl)carbanilide C.55. 4-(1,1,2,3,3,3-hexafluoro-n-propoxy)-3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.56. 4-(methoxycarbonylthio)-3',5'-bis(tri-fluoromethyl)carbanilide C.57. 4-(4-chlorophenoxy)-4'-(trifluoromethyl-thio)thiocarbanilide C.58. 4-(4-chlorophenoxy)-3',5'-bis(tri-fluoromethyl)carbanilide C.59. 3-chloro-4-(4-chlorophenoxy)-3',5'-bis(trifluoromethyl)carbanilide C.60. 4-(4-chlorophenoxy)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.61. 4-(3,5-bis(trifluoromethyl)phenoxy-3',5'-bis(trifluoromethyl)carbanilide C.62. 4-(4-methylphenoxycarbonyl)-3',5'-bis(trifluoromethyl)carbanilide C.63. 4-(4-methylphenoxycarbonyl)-4'-(tri-fluoromethylthio)carbanilide C.64. 3,5-bis(trifluoromethyl)-2',4',6'-trichlorocarbanilide C.65. 3,5-bis(trifluoromethyl)-2',4',5'-tri-chlorocarbanilide C.66. 3,3'-bis(trifluoromethyl)-5'-nitro-carbanilide C.67. 3,3',5-tris(trifluoromethyl)-5'-nitro-carbanilide C.68. 2',3,5,6'-tetrakis(trifluoromethyl)-4'-nitrocarbanilide C.69. 3-(chlorodifluoromethyl)-3',5'-bis(tri-fluoromethyl)carbanilide C.70. 3-(1,1,2,2-tetrafluoroethyl)-3',5'-bis(trifluoromethyl)carbanilide C.71. 4-phenyl-3'"5'-bis(trifluoromethyl)-carbanilide C.72. 3-(fluorosulfonyl)-3',5'-bis(trifluoro-methyl)carbanilide C.73. 4-(fluorosulfonyl)-4'-(trifluoromethyl-thio)carbanilide C.74. 4-(fluorosulfonyl)-3'-(trifluoromethyl)-5'-nitrocarbanilide C.75. 4-(chloromethylsulfonyl)-3',5'-bis(tri-fluoromethyl)carbanilide C.76. 2-(ethylsulfonyl)-3',5,5'-tris(trifluoro-methyl)carbanilide C.77. 2-(ethylsulfonyl)-3',5-bis(trifluoro-methyl)-5'-nitrocarbanilide C.78. 4-(trifluoromethylsulfonyl)-3',5'-bis(trifluoromethyl)carbanilide C.79. 4-(trifluoromethylsulfonyl)-3'-(tri-fluoromethyl)-4'-methoxycarbanilide C.80. 4-(trifluoromethylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.81. 4-(4-nitrophenylsulfonyl)-4'-(tri-fluoromethylthio)carbanilide C.82. 4-(4-acetamidophenylsulfonyl)-4'-(trifluoromethylthio)carbanilide C.83. 4-(4-(isopropylideneamino)phenylsul-fonyl)-4'-(trifluoromethylthio)car banilide C.84. 4,4-sulfonylbis(3'-(trifluoromethylthio)-carbanilide) C.85. 4,4-sulfonylbis(4'-(1,2-dichlorovinyl-oxy)carbanilide) C.86. 4,4-sulfonylbis(3'-(1,1,2,2-tetra-fluoroethoxy)carbanilide) C.87. 4,4-sulfonylbis(4'-(2-chloro-1,1,2-trifluoroethoxy)carbanilide) C.88. 4,4-sulfonylbis(4'-(trifluoromethyl-thio)carbanilide).
2. The composition of Claim 1 wherein the polyether antibiotic is monensin.
3. The composition of Claim 1 or 2 wherein the second component is 3,3'-bis(trifluoromethyl)-4,4'-dichlorocarbanilide.
4. The composition of Claim 1 or 2 wherein the second component is 3,3'-5,5'-tetrakis(trifluoromethyl)-carbanilide.
5. The composition of Claim 1 or 2 wherein the second component is 4-nitro-3'-chloro-4'-(4-chlorophenoxy)-carbanilide.
6. The composition of claim 1 or 2 wherein the second component is 4-nitro-3'-chloro-4'-(4-chlorophenoxy)-carbanilide.
7. The composition of Claim 1 or 2 wherein the second component is 4-nitro-3'-bromo-4'-(4-bromophenoxy)-carbanilide.
8. The composition of Claim 1 or 2 wherein the second component is 4,4'-bis(trifluoromethylthio)-carbanilide.
9. The composition of Claim 1 or 2 wherein the second component is 4-(4-chlorophenoxy)-3',5'-bis (trifluoromethyl)carbanilide.
10. The composition of Claim 1 or 2 wherein the second component is 3,5-bis(trifluoromethyl-2',4',5'-trichlorocarbanilide.
11. The composition of Claim 1 or 2 wherein the second component is 4,4-sulfonylbis-3'-(1,1,2,2-tetrafluoroethoxy)carbanilide.
12. The composition of Claim 1 wherein the polyether antibiotic is narasin.
13. The composition of Claim 1 wherein the polyether antibiotic is lasalocid.
14. The composition of Claim 1 wherein the polyether antibiotic is salinomycin.
15. The composition of Claim 1 wherein the polyether antibiotic is A-204.
16. The composition of Claim 1 wherein the polyether antibiotic is lonomycin.
17. The composition of Claim 1 wherein the polyether antibiotic is X-206.
18. The composition of Claim 1 wherein the polyether antibiotic is nigericin.
19. The composition of Claim 1 wherein the polyether antibiotic is dianemycin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10730479A | 1979-12-26 | 1979-12-26 | |
| US107,304 | 1979-12-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1171782A true CA1171782A (en) | 1984-07-31 |
Family
ID=22315944
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000367322A Expired CA1171782A (en) | 1979-12-26 | 1980-12-22 | Anticoccidial combinations comprising polyether antibiotics and carbanilides |
Country Status (2)
| Country | Link |
|---|---|
| CA (1) | CA1171782A (en) |
| PH (1) | PH21525A (en) |
-
1980
- 1980-12-22 CA CA000367322A patent/CA1171782A/en not_active Expired
- 1980-12-23 PH PH25027A patent/PH21525A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PH21525A (en) | 1987-11-16 |
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