Anthelmintic acylhydrazones, method of use and compositions

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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514255, 514365, 514459, 544336, 544405, 544408, 544409, 544410, 546207, 546209, 548187, 549426, A61K 31495, A61K 3135, A61K 31425, C07D24102

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050495615

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BRIEF SUMMARY
SUMMARY OF THE INVENTION

This invention pertains to a new method for killing and controlling worms (Helminths), and new formulations for killing and controlling worms in animals, and new chemical compounds. The invention is more particularly directed to a new method for killing and controlling parasitic worms in animals with certain acylhydrazones, to new anthelmintic formulations comprising the same and to new acylhydrazones.
The anthelmintic acylhydrazones have the general structural formula I.


BACKGROUND OF THE INVENTION

The diseases or groups of diseases described generally as helminthiasis are due to infection of the animal with parasitic worms known as helminths. Helminthiasis and helminthosis are prevalent and may lead to serious economic problems in valuable domestic warmblooded animals such as sheep, swine, cattle, goats, dogs, cats, horses, poultry and man. Among the helminths, the groups of worms known as nematodes, trematodes and cestodes cause widespread and often-times serious infections in various species of animals including man. The most common genera of nematodes, trematodes and cestodes infecting the animals referred to above are Dictvocaulus, Haemonchus, Ostertazia Nematodirus, Cooreria, Bunostomum, Oesoohazostomum, Chabertia, Stronzvloides Trichuris, Fasciola, Dicrocoelium, Enterobius, Ascaris, Toxascaris Toxocara, Ascaridia, Caoillaria, Heterakis, Ancvlostoma, Uncinaria Dirofilaria, Onchocerca Taenia, Moniezia, Diovlidium Metastronzvlus, Triodontoohorus, Macracanthorhvnchus, Hvostronzvlus, and Strongylus. Some of these genera attack primarily the intestinal tract while others, inhabit the stomach, lungs, liver and subcutaneous tissues. The parasitic infections causing helminthiasis and helminthosis lead to anemia, malnutrition, weakness, weight loss, unthriftiness, severe damage to the gastrointestinal tract wall and, if left to run their course, may result in death of the infected animals.
The anthelmintic activity of acylhydrazones of formula I has not been previously reported.
The anthelmintic activity of pyridinyl acylhydrazones is disclosed in PCT Application U.S. 86/00072, filed Jan. 23, 1986 and published Aug. 14, 1986 (Case 4199.P); a continuation-in-part of U.S. patent application Ser. No 715,425, filed Mar. 25, 1985 (Case 4199.1); a continuation-in-part of U.S. patent application Ser. No. 700,375, filed Feb. 11, 1985 (Case 4199).
The anthelmintic activity of quinolinyl acylhydrazones is disclosed in PCT Application Ser. No. PCT/US86/00714, filed Apr. 7, 1986, and published Oct. 23, 1986 (Case 4132.P); a continuation-in-part of U.S. patent application Ser. No. 722,104, filed Apr. 11, 1985 (4132).
The anthelmintic activity of quaternaryalkyl acylhydrazones, including pyrazinyl and thiazolyl quaternaryalkyl acylhydrazones, is disclosed in PCT Application U.S. 87/00697, filed Apr. 3, 1987 (Case 4498.P); a continuation-in-part of U.S. patent application Ser. No 849,039, filed Apr. 7, 1986.
The anthelmintic activity of indolinyl, benzofuryl and benzylindolinyl acylhydrazones is disclosed in PCT application Ser. No. PCT/US87/00698, filed Apr. 3, 1987 (Case 4186.P); a continuation-in-part of patent application Ser. No. 849,034, filed Apr. 7, 1986.
The anthelmintic activity of thienyl, furanyl and pyrrolyl acylhydrazones is disclosed in PCT application Ser. No. PCT/US87/00699, filed Apr. 3, 1987 (Case 4237.P); a continuation-in-part of U.S. patent application Ser. No. 849,035, filed Apr. 7, 1986.


DETAILED DESCRIPTION OF THE INVENTION

The acylhydrazones of this invention, including hydrates or pharmaceutically acceptable salts thereof, are represented by Formula I wherein W is selected from the group consisting of one or two C.sub.1 -C.sub.4 alkyl, preferably C.sub.1 -C.sub.3 alkyl; C.sub.1 -C.sub.3 alkoxy; C.sub.1 -C.sub.3 alkylthio; halo; trifluoromethyl; or hydroxy; with the proviso that when substituted with two substituents only one substituent is hydroxy;
wherein X is (a) hydrogen; (b) C.sub.1 -C.sub.10 alkyl; (c) C.sub.2 -C.sub.6 alkenyl, preferably C.sub.2 -C.sub.4 alke

REFERENCES:
patent: 4870082 (1989-09-01), Rector et al.
K. Kakemi et al., Yakugaku Zasshi, 81, pp. 1609-14 (1961).
Chemical Abstracts, 56:10142h.
H. Rutner and P. E. Spoerri, J. Org. Chem., 28, pp. 1898-1899 (1963).
R. L. Frank and C. Weatherbee, J. Am. Chem. Soc., 70, pp. 3482-3483 (1948).
N. B. Mahishi et al., J. Indiana Chem. Soc., 42, pp. 67-74 (1965).
M. Ogata and H. Kano, Chem. Pharm. Bull. (TokyoO, 11, p. 32 (1963).

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