Abstract
Before 1938, no broadly useful drugs for the treatment of nematode infections existed. Limited activity was found in arsenicals and in various natural products such as nicotine and oil of chenopodium. The discovery of the anthelmintic activity of phenothiazine made available a moderately broadly active compound that, although not very potent, was virtually nontoxic. The benzimidazoles, reported in 1961, followed by the commercial success of thiabendazole, signaled a new era of truly broad-spectrum, safe, orally effective, antinematodal drugs. Considerable structure-activity studies in many research centers later produced a host of more potent benzimidazoles with activity expanded to lungworms, tapeworms, and liver flukes. The advent of tetramisole in 1965 followed by the L-isomer levamisole afforded a relatively safe oral or parenteral anthelmintic that has achieved widespread use, especially in cattle. Pyrantel and morantel were developed in the same period and have found their own special place, morantel as a ruminai bolus. The discovery of the avermectins in 1976 followed by the introduction of ivermectin as a broad-spectrum antiparasitic agent carried the search one stage further. Ivermectin is not only very potent and equally effective by the oral or parenteral routes but is also effective against ectoparasites. The search for better drugs continues in many research institutes, guided by mechanism of action studies and comparative biochemistry.
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References
Actor, P., Anderson, E.L., DiCuollo, C.J., Ferlauto, R.J., Hoover, J.R.E., Pagano, J.F., Ravin, L.R., Scheidy, S.F., Stedman, R.J., and Theodorides, V.J., 1967, New broad spectrum anthelmintic, methyl 5(6)-Butyl-2-benzimidazole-carbamate, Nature (Lond.) 215:321–322.
Albers-Schonberg, G., Arison, B.H., Chabala, J.C., Douglas, A.W., Eskola, P., Fisher, M.H., Lusi, A., Mrozik, H., Smith, J.L., and Tolman, R.L., 1981, Avermectins. Structure determination, J. Am. Chem. Soc. 103:4216–4221.
Austin, W.C., Courtney, W., Danilewicz, J.C., Morgan, D.H., Conover, L.H., Howes, H.L., Jr., Lynch, J.E., McFarland, J.W., Cornwell, R.L., and Theodorides, V.J., 1966, Pyrantel tartrate, a new anthelmintic effective against infections of domestic animals, Nature (Lond.) 212:1273–1274.
Averkin, E.A., Beard, C.C., Dvorak, C.A., Edwards, J.A., Fried, J.H., Kilian, J.G., Schiltz, R.A., Kistner, T.P., Drudge, J.H., Lyons, E.T., Sharp, M.L., and Corwin, R.M., 1975, Methyl 5(6)-phenylsulfinyl-2-benzimidazolecarbamate, A new, potent anthelmintic, J. Med. Chem. 18:1164–1166.
Baeder, C., Bahr, H., Christ, O., Duwel, D., Kellner, H.J,, Kirsch, R., Loewe, H., Schuhes, E., Schutz, E., and Westen, H., 1974, Fenbendazole: A new, highly effective anthelmintic, Experientia 30:753–754.
Barthel, W.F., Giang, P.A., and Hall, S.A., 1954, Dialkyl α-hydroxyphosphonates derived from chloral, J. Am. Chem. Soc. 76:4186–4187.
Bernthsen, A., 1883, Zur Kenntniss des Methylenblau und verwandter Farbstoffe, Ber. 16:2896–2904.
Broome, A.W.J., and Greenhalgh, N., 1961, A new anthelmintic with unusual properties, Nature (Lond.) 189:59–60.
Brown, H.D., Matzuk, A.R., lives, I.R., Peterson, L.H., Harris, S.A., Sarett, L.H., Egerton, J.R., Yakstis, J.J., Campbell, W.C., and Cuckler, A.C., 1961, Antiparasitic drugs. IV. 2-(4′-thiazolyl)-benzimidazole, A new anthelmintic, J. Am. Chem. Soc. 83:1764–1765.
Brown, N.C., Hollinshead, D.T., Kingsbury, P.A., and Malone, J.C., 1962, A new class of compounds showing anthelmintic properties, Nature (Lond.) 194:379.
Brugmans, J.P., Thienpont, D.C., van Wijngaarden, I., Vanparijs, O.F., Schuermans, V.L., and Lauwers, H.L., 1971, Mebendazole in enterobiasis: Radiochemical and pilot clinical study in 1,278 subjects, J. A. M. A. 217:313–316.
Burrows, R.B., and Lillis, W.G., 1962, Thenium, a new anthelmintic for dog and cat hookworms, Am.J. Vet. Res. 23:77–80.
Chabala, J.C., Mrozik, H., Tolman, R.L., Eskola, P., Lusi, A., Peterson, L.H., Woods, M.F., Fisher, M.H., Campbell, W.C., Egerton, J.R., and Ostlind, D.A., 1980, Ivermectin, a new broadspectrum antiparasitic agent, J. Med. Chem. 23:134–1136.
Copp, F.C., Standen, O.D., Scarnell, J., Rawes, D.A., and Burrows, R.B., 1958, A new series of anthelmintics, Nature (Lond.) 181:183.
Corey, J., 1955, The stereochemistry of santonin, β-santonin and artemisin, J. Am. Chem. Soc. 77:1044–1045.
Datta, R.L., and Prosad, N., 1917, Halogenation. XVI. Iodination by means of nitrogen iodide or by means of iodine in the presence of ammonia, J. Am. Chem. Soc. 39:441–457.
Dressel, O., and Kothe, R., 1961, The discovery of germanin, J. Chem. Ed. 38:620–621.
Eichler, D.A., 1973, The anthelmintic activity of thiophanate in sheep and cattle, Br. Vet.J. 129:533–543.
Gough, G. A. C., and King, H., 1930, Trypanocidal action and chemical constitution. Part IX. Aromatic acids containing an amide group, J. Chem. Soc. 669-694.
Hoff, D.R., Fisher, M.H., Bochis, R.J., Lusi, A., Waksmunski, F., Egerton, J.R., Yakstis, J.J., Cuckler, A.C., and Campbell, W.C., 1970, A new broad spectrum anthelmintic: 2-(4-thiazolyl)-5-isopropoxycarbonylaminobenzimidazole, Experientia 26:550–551.
Kendall, J. D., and Edwards, H. D., 1946, Dicarbocyanine dyes, U.S. Pat. 2,412,815.
Krueger, H.R., Casida, J.E., and Niedermeier, R.P., 1959, Bovine metabolism of organophosphorus insecticides. Metabolism and residues associated with dermal application of Co-ral to rats, a goat, and a cow, J. Agr. Food Chem. 7:182–188.
Kushner, S., Brancone, L.M., Hewitt, R.I., McEwen, W.L., and Subbarow, Y., Stewart, H.W., Turner, R.J., and Denton, J.J., 1948, Experimental chemotherapy of filariasis. V. The preparation of derivatives of piperazine, J. Org. Chem. 13:144–153.
Lieber, E., and Slutkin, R., 1962, Diisothiocyanates and derivatives, J. Org. Chem. 27:2214–2217.
Lorenz, W., and Wegler, R., 1957, Verfahren zur Herstellung von Phosphorsaure-bzw. Thiophosphor-saureestern, Ger. Pat. 962,608.
Lynch, J.E., and Nelson, B., 1959, Preliminary Anthelmintic Studies with Nematospiroides dubius in Mice, J. Parasitol. 45:659–662.
Mann, R.L., and Bromer, W.W., 1958, The isolation of a second antibiotic from Streptomyces hygroscopkus, J. Am. Chem. Soc. 80:2714–2716.
Martin, W.B., and Martell, A.E., 1948, Preparation of piperazine, J. Am. Chem. Soc. 70:1817–1818.
McFarland, J.W., and Howes, H.L., Jr., 1972, Novel anthelmintic agents. 6. Pyrantel analogs with activity against whipworm, J. Med. Chem. 15:365–368.
McFarland, J.W., Conover, L.H., Howes, H.L., Jr., Lynch, J.E., Chisholm, D.R., Austin, W.C., Cornwell, R.L., Danilewicz, J.C., Courtney, W., and Morgan, D.H., 1969, Novel anthelmintic agents. II. Pyrantel and other cyclic amidines, J. Med. Chem. 12:1066–1079.
Mishima, H., Ide, J., Muramatsu, S., and Ono, M., 1983, Milbemycins D, E, F, G, H, J and K, J. Antibiot. XXXVI(8):980–989.
Mrozik, H., Chabala, J.C., Eskola, P., Matzuk, A., Waksmunski, F., Woods, M., and Fisher, M.H., 1983, Synthesis of milbemycins from avermectins, Tetrahedron Lett. 24:5333–5336.
Nitta, I., Watase, H., and Tomiie, Y., 1958, Structure of kainic acid and its isomer, allokainic acid, Nature (Lond.) 181:761–762.
Peters, V.K., and Neumann, L., 1932, Über die Photochemische Acetylenchlorierung, Angew. Chem. 45:261–266.
Raeymaekers, A.H.M., Allewijn, F.T.N., Van den Berk, J., Demoen, P.J.A., Van Offenwert, T.T.T., and Janssen, P.A.J., 1966, Novel broad-spectrum anthelmintics. Tetramisole and related derivatives of 6-arylimidazo[2,l-b]-thiazole, J. Med. Chem. 9:545–551.
Raeymaekers, A.H.M., Van Gelder, J.L.H., Roevens, L.F.C., and Janssen, P.A.J., 1978, Synthesis and anthelmintic activity of alkyl-(5-acyl-l-H-benzimidazol-2-yl) carbamates, Arzneimittelforsch. 28:586–594.
Spicer, L. D., and Hand, J. J., 1975, Method of using 6-substituted amino phenyl-2,3,5,6-tetrahydro-[2,1-b]-thiazoles, U.S. Pat. 3,899,583.
Sugimoto, N., and Okumura, K., 1954, 3-Methyl-l-pentyn-3-ol acid phthalate, Jpn. Pat. 1833 (’54).
Takiguchi, Y., Mishima, H., Okuda, M., Terao, M., Aoki, A., and Fukuda, R., 1980, Milbemycins, a new family of macrolide antibiotics: Fermentation, isolation and physico-chemical properties, J. Antibiot. 33:1120–1127.
Theodorides, V.J., Gyurik, R.J., Kingsbury, W.D., and Parish, R.C., 1976, Anthelmintic activity of albendazole against liver flukes, tapeworms, lung and gastrointestinal roundworms, Experientia 32:702–703.
Van Lare, E., and Brooker, L. G. S., 1950, Pyrrole dimethinecyanine dyes, U.S. Pat. 2,515,912.
Walker, D., and Knight, D., 1972, The anthelmintic activity of “mebendazole”: A field trial in horses, Vet. Rec. 90:58–65.
Whaley, A.M., and Copenhaver, J.E., 1938, Preparation of some lower alkyl chlorides from the corresponding alcohols using zinc chloride and concentrated hydrochloric acid, J. Am. Chem. Soc. 60:2497–2498.
Whetstone, R. R., and Harman, D., 1960, Insecticidally active esters of phosphorus acids and preparation of the same, U.S. Pat. 2,956,073.
Wollweber, H., Rolling, H., Widdig, A., Thomas, H., Schulz, H.-P., and Murmann, P., 1978, Febantel, a new broad-spectrum anthelmintic, Arzneimittelforsch. 28:2193–2195.
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© 1986 Plenum Press, New York
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Fisher, M.H. (1986). Chemistry of Antinematodal Agents. In: Campbell, W.C., Rew, R.S. (eds) Chemotherapy of Parasitic Diseases. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1233-8_11
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DOI: https://doi.org/10.1007/978-1-4684-1233-8_11
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