Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-03-01
2001-09-25
Ford, John M. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C544S182000
Reexamination Certificate
active
06294536
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a new triazine derivative, a method of its production, and use thereof. More specifically, the present invention relates to a new triazine derivative that is useful for the control of parasitic protozoa such as coccidia, or a salt thereof, a method of its production, and an anti-protozoal containing it.
BACKGROUND ART
Parasitic protozoa are widely parasitic to animals, such as mammals, fowls, fish, and insects. They mainly parasitize animal internal organs, or skin, eyes, etc., and significantly damage the host, resulting in vast economic loss in domestic animal and poultry and fish industries. Coccidiosis, a parasitic protozoal disease in poultry, is caused mainly by several parasitic protozoa of the genus Eimeria, such as
E. tenella, E. necatrix, E. acervulina, E. maxima, E. brunetti
, and
E. mivati
. For example,
E. tenella
parasitizes the walls of the chicken cecum and other intestines to fatally affect the host. Specifically, this infection is manifested as symptoms such as intestinal wall erosion, inflammation and bleeding due to a broad range of intestinal invasion, cecal blood retention, and associated appetite loss and poor growth. Internal parasitic protozoa are generally transmitted orally. In the case of coccidiosis, in particular, oocyst inactivation is impossible even by potent disinfestation with potassium bichromate solution. In addition, because of the generation cycle of as short as about 7 days, there is no effective countermeasure against its rapid infection and onset in large-scale animal breeding.
In the case of fish, protozoa that mainly parasitize external organs are of concern; their parasitization damages the fish skin and gills, and weakens their essential resistance to infectious diseases, which in turn can cause death. In large-scale fish culture, parasitic protozoa spread rapidly over the whole fish in culture, posing a significant problem of economic loss due to such damage.
The same applies to insects. In the case of honeybees, for example, protozoa, such as
Nosema apis
, have heavily damaged commercial beekeeping all over the world. This parasitic protozoon makes the host less resistant and more susceptible to other diseases, by destroying the host's internal organs.
Traditionally, a large number of chemicals against parasitic protozoa have been known, which, for the most part, are narrow in target and action spectrum, and some have been reported to be ineffective against protozoa that have acquired resistance. In addition, these chemicals are required to be administered at high doses because of their low activity, and are therefore unsatisfactory in terms of economic and environmental aspects. For these reasons, there is strong need for the development of a new chemical that can be widely used with excellent action in the control of parasites in vertebrates, such as mammals, fowls and fish, and insects.
As such drugs, 2-phenyl-6-azauracil derivatives were found to have anti-coccidium action [Journal of Medicinal Chemistry, Vol. 22, p. 1483 (1979)]; various 6-azauracil derivatives were synthesized and investigated but proved to be teratogenic and failed to come into practical application. Later, as nonteratogenic compounds, 2-phenyl-1,2,4-triazinedione compounds, such as a 2-(4-phenoxyphenyl)-1,2,4-triazine derivative [DE-A-2532363] and 2-[4-(1-cyano-1-phenylmethyl)phenyl]-1,2,4-triazine derivative [U.S. Pat. No. 4,631,278), have been developed, some of which have been used to control coccidia in some European countries, Australia, and others but have not been approved for use in Japan, the Unites States and other countries.
DISCLOSURE OF INVENTION
Against the above-described technical background, the present inventors made extensive investigations and found that a series of new triazine derivatives exhibit excellent action against parasitic protozoa. After further investigations, the inventors found that this series of derivatives are suited for the control of various parasitic protozoa encountered in animal breeding (vertebrates, such as mammals, fowls, and fish, and insects), that they are low in toxicity and retention tendency in animals, that they have very high biological effects on strains that are resistant to conventional drugs, and that are excellent in terms of safety. The inventors thus developed the present invention.
Namely, the present invention relates to:
[1] a compound represented by the formula:
wherein ring H represents an optionally substituted aromatic heterocyclic group or an optionally substituted alicyclic hydrocarbon group; X and Y independently represent a single bond, —O—, a group of the formula: —S(O)
m
— wherein m is 0, 1 or 2, a group of the formula: —NR
8
— wherein R
8
represents a hydrogen atom, an alkyl group or an acyl group, —CO— or an optionally substituted methylene group; —A—B— represents —N═CH—, —CH═N—, —N═N— or —CH═CH—; R
1
represents a hydrogen atom, a halogen atom, an optionally substituted alkyl group which may be bonded through a hetero atom or an acyl group; R
2
and R
3
independently represent a hydrogen atom, a halogen atom or an optionally substituted alkyl group; R
4
represents a hydrogen atom or a halogen atom; R
5
represents a hydrogen atom, an optionally substituted alkyl group or an acyl group; R
6
and R
7
independently represent a hydrogen atom or R
6
and R
7
may form a chemical bond together with each other; and D represents —CH
2
— or —CO— (hereinafter referred to briefly as the compound (I)), or a salt thereof,
[II] a compound represented by the formula:
wherein ring H′ is a phenyl group which may optionally be substituted with halogen and/or hydroxy; X′ is a methylene group which may optionally be substituted with a substituent selected from the group consisting of a C
1-6
alkyl group and hydroxy; and the other symbols have the same meanings as defined in [I] above (hereinafter referred to briefly as the compound (II)), or a salt thereof,
[III] a compound represented by the formula:
wherein ring H′ has the same meaning as defined in [II] above, R
1
′ is a C
1-6
alkyl group, and the other symbols have the same meanings as defined in [I] above (hereinafter referred to briefly as the compound (III)), or a salt thereof,
[IV] a compound represented by the formula:
wherein ring H″ is a phenyl group which is substituted with one to three substituents selected from the group consisting of a C
1-6
alkyl group and a C
1-6
alkylcarbonyl group, and the other symbols have the same meanings as defined in [I] above (hereinafter referred to briefly as the compound (IV)), or a salt thereof, their production and use.
Specifically the present invention relates to:
[1] a compound represented by the formula:
wherein ring H represents an optionally substituted aromatic heterocyclic group or an optionally substituted alicyclic hydrocarbon group; X and Y independently represent a single bond, —O—, a group of the formula: —S(O)
m
— wherein m is 0, 1 or 2, a group of the formula: —NR
8
— wherein R
8
represents a hydrogen atom, an alkyl group or an acyl group, —CO— or an optionally substituted methylene group; —A—B— represents —N═CH—, —CH═N—, —N═N— or —CH═CH—; R
1
represents a hydrogen atom, a halogen atom, an optionally substituted alkyl group which may be bonded through a hetero atom or an acyl group; R
2
and R
3
independently represent a hydrogen atom, a halogen atom or an optionally substituted alkyl group; R
4
represents a hydrogen atom or a halogen atom; R
5
represents a hydrogen atom, an optionally substituted alkyl group or an acyl group; R
6
and R
7
independently represent a hydrogen atom or R
6
and R
7
may form a chemical bond together with each other; and D represents —CH
2
— or —CO—; or a salt thereof,
[2] the compound as described in [1] above or a salt thereof, wherein ring H is a 5-
Aoki Isao
Hayashi Toshikatsu
Miki Hideki
Balasubramanian Venkataraman
Ford John M.
Merchant & Gould P.C.
Takeda Schering-Plough Animal Health K.K.
LandOfFree
Triazine derivatives, their production and use does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Triazine derivatives, their production and use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Triazine derivatives, their production and use will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2481956