Coccidiostatic

Various other properties intestinal antiseptic (932, 933), fungicide (934, 935), insecticide (895. 898), coccidiostatic activity (936), car-cinolytic activity (937), radioprotective activity (938), antimutagenic activity (939, 940). 

Nonnutrient Additives. Nonnutritional dietary additives provide antioxidants to preserve freshness, flavor enhancers to stimulate food selection, color to meet the owner s expectations, pellet biaders to minimi2e fine particles, mycostats to minimi2e mold growth, and iagredient-flow enhancers. Pet foods do not iaclude coccidiostats, antibiotics, added hormonal materials, and fly-larval iasecticides used ia other animal feeds. 

Drugs. Ring-fluotinated aromatics have found broad pharmaceutical appHcations, eg, in tranquilizers, hypnotics, sedatives, antibacterial agents (qv), etc. Representative monofluorinated dmgs are Hsted in Table 4. Arprinocid [5579-18-15] is a fluoroaromatic-based veterinary dmg that has found wide acceptance as a coccidiostat for chicken feed. 

HydroxyethyUiydrazine (11) is a plant growth regulator. It is also used to make a coccidiostat, furazoHdone, and has been proposed, as has (14), as a stabilizer in the polymerization of acrylonitrile (72,73). With excess epoxide, polysubstitution occurs and polyol chains can form to give poly(hydroxyaLkyl) hydrazines which have been patented for the preparation of cellular polyurethanes (74) and as corrosion inhibitors for hydrauHc fluids (qv) (75). DialkyUiydrazines, R2NNH2, and alkylene oxides form the very reactive amineimines (15) which react further with esters to yield aminimides (16) ... 

NihydraZone. Acetic acid [5-nitro-2-furanyl)methylene]-hydrazide has seen use in veterinary medicine both as a coccidiostat and an antibacterial (39). 

Pyrans and related compounds react with ammonia to give pyridines. A commercially useful example is the reaction of dehydroacetic acid (derived from diketene) with ammonia to give 2,6-dimethyl-4-pyridinone [7516-31 -6] via 2,6-dimethyl-4-pyridinone-3-carboxyhc acid [52403-25-5]. Chlorination of the pyridone gives clopidol [2971-90-6] (56), a coccidiostat (72,73). 

The primary use of a-picoline (2) is as a precursor of 2-vinylpyridine (23). It is also used in a variety of agrochemicals and pharmaceuticals, such as nitrapyrin [1929-82-4] (60) to prevent loss of ammonia from fertilizers picloram [1918-02-1] (61), a herbicide and amproHum [121 -25-5] (62), a coccidiostat. 

Quaternary Salts. Herbicides paraquat (20) and diquat (59) are the quaternary salts of 4,4 -bipyridine (19) and 2,2 -bipyridine with methyl chloride and 1,2-dibromoethane, respectively. Higher alkylpyridinium salts are used in the textile industry as dye ancillaries and spin bath additives. The higher alkylpyridinium salt, hexadecylpytidinium chloride [123-03-5] (67) (cetylpyridinium chloride) is a topical antiseptic. Amprolium (62), a quaternary salt of a-picohne (2), is a coccidiostat. Bisaryl salts of butylpyridinium bromide (or its lower 1-alkyl homologues) with aluminum chloride have been used as battery electrolytes (84), in aluminum electroplating baths (85), as Friedel-Crafts catalysts (86), and for the formylation of toluene by carbon monoxide (87) (see QuaternaryAA ONiUM compounds). 

Other. Dibutyltin dilaurate [77-58-7] has been successfully used for many years as a coccidiostat in the treatment of intestinal worm infections in chickens and turkeys (see Antiparasitic agents). 

Nonmedical uses claimed for pyridopyrimidines include uses as growth promoters, cytokinins, herbicides, agricultural fungicides, coccidiostats, dyestuffs intermediates, UV absorbants and corrosion inhibitors. 

Ampicillin—see Penicillin, D-n-aminobenzyl-Amprolium coccidiostat mode of action, 1, 212 as veterinary product, 2, 515 Amquinsin, 2, 517 Amylobarbitone metabolism, 1, 237 Anabasine, 2, 511 synthesis, 2, 385 Anabasine, N-methyl-N -oxide... 

Thus the requirement for the use of man-made drugs and dietary additives as veterinary medicines for the treatment of farmed animals is considerable and worth about 100 million pounds sterling annually in the UK ( 104 million in 1994j io jjjg investment in dietary additives such as vitamins, trace minerals, coccidiostats, pigmenters, enzymes and other probiotics to feed compounders in the UK is worth about 110 million, assuming an addition rate of 2.5 kg per tonne and a cost of approximately 3% of the total concentrate dietary cost (calculated from MAFF data, 1995). ° These data can be increased by a factor of about 10 when the compound feed produced within Europe is considered. 

The nature of the conditions of intensive production, however, can increase the risk of diseases and infections which can spread very rapidly and devastate large numbers of animals." Thus it is common practice for producers of poultry to add coccidiostats to their diets and vaccines to their drinking water in order to prevent coccidiosis and other infectious diseases such as bronchitis and Newcastle disease. A similar problem exists for intensively reared fish, where it is necessary to add antibiotics to their diets. A problem with intensively reared fish is that their diet is added directly into the water in which they live thus drugs and other additives in the diet are relatively easily dispersed into the local environment of fish farms, where they can increase bacterial resistance and also cause problems such as algal blooms. 

Preparation of the coccidiostat arprinocid (80) starts by protection of two of the three amino groups on the pyrimidine 74 thus, reaction of 74 with thionyl chloride leads to reaction of... 

A further aspect that may add to the development work relates to the method of administration. In addition to the standards methods of administration associated with human medicines, veterinary medicines may be introduced to animals through medicated feeds. Such practices have been most commonly associated with the use of antibiotics or other substances to enhance animal performance under intensive farming systems. The use of medicated feeds has been phased out in Europe since the end of 2005, with the exception of coccidiostats and histomonostats intended to kill or inhibit protozoa. In the U SA, however, medicated feeds are still commonplace. Thus, the developer may have to consider the stability and appropriate labelling of the drug when compounded into medicated feeds. 

Anti-protozoa agents are utilized to treat diseases such as coccidiosis, which affects many farm animals, particularly poultry. Coccidiostats include polyether monocar-boxylic acid ionophores and other types of compounds. Polyether monocarboxylic acid ionophores include monesin, narasin, lasalocid, and salinomycin. The most common of these is salinomycin. Nonionophore coccidiostats include dimetridazole and halofunginone. Stanker et al. reviewed immunoassays available for coccidio-static agents. 

Coccidiosis is an economically significant respiratory disease of fowl. During the course of studies directed toward antimalarial agents, sulfani-tran (143) was prepared and found to be a coccidiostat. It is prepared conveniently by reaction of p-aceto-amidobenzenesulfonyl chloride with p-nitroaniline in acetic acid.68... 

The triazinedione, triazuril (163) is active as a poultry coccidiostat. Diazonium salt 160, prepared from the appropriate aniline, is coupled with the active methylene group of N-carbethoxycyanoacetamide to give 161. Hydrolysis of the cyano group is accompanied by cyclization, and the resulting acid (162) is decarboxylated to triazuril (163) on heating.50... 

Bisoxatin Acetate Choleretic Piprozolin Cholinergic Agent Aceclidine Coccidiostats Oxyphenisatin Acetate... 

---