Anthelmintic quinolinyl acylhydrazones, method of use and compos

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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546153, 546176, 546122, 544235, 544238, 544283, 544333, 544349, 544405, 514247, 514253, 514255, 514256, 514259, 514300, A61K 3147, C07D40112, C07D21550, C07D21554

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048700827

DESCRIPTION:

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 quinolinyl acylhydrazones, to new anthelmintic formulations comprising the same, and to new quinolinyl acylhydrazones.
The anthelmintic quinolinyl 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 warm-blooded 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 Dictyocaulus, Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Bunostomum, Oesophagostomum, Chabertia, Strongyloides, Trichuris, Fasciola, Dicrocoelium, Enterobius, Ascaris, Toxascaris, Toxocara, Ascaridia, Capillaria, Heterakis, Ancylostoma, Uncinaria, Dirofilaria, Onchocerca, Taenia, Moniezia, Dipylidium, Metastrongylus, Triodontophorus, Macracanthorhynchus, Hyostrongylus, 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 quinolinyl acylhydrazones has not been previously reported.


DETAILED DESCRIPTION OF THE INVENTION

The quinolinyl acylhydrazones of the invention, including hydrates or pharmaceutically acceptable salts thereof, are represented by Formula I wherein X is (a) hydrogen; (b) C.sub.1 -C.sub.10 alkyl; (c) C.sub.2 -C.sub.6 akenyl; (d) C.sub.2 -C.sub.6 alkynyl; (e) cyclo(C.sub.3 -C.sub.10)alkyl optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, trifluoromethyl, or halo; (f) pyrrolidinyl; (g) piperidinyl; (h) 1-methylpyrrolidinyl; (i) 1-methylpiperidinyl; (j) C.sub.2 -C.sub.6 alkoxyalkyl; (k) cyclo(C.sub.3 -C.sub.10)alkyl(C.sub.1 -C.sub.4)alkyl; (m) phenoxy(C.sub.1 -C.sub.4)alkyl optionally substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, or trifluoromethyl; (n) uredio(C.sub.1 -C.sub.4)alkyl; (o) C.sub.2 -C.sub.6 alkoxy; (p) diphenylmethoxy; (s) benzyloxy optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, or trifluoromethyl; (t) heteroaromatic optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, halo, C.sub.1 -C.sub.3 alkylthio, or trifluoromethyl; (u) phenyl optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, halo, hydroxy, trifluoromethyl, C.sub.2 -C.sub.6 dialkylamino, C.sub.1 -C.sub.3 alkylthio or nitro; or (v) phenyl optionally substituted with the divalent C.sub.1 -C.sub.2 alkylenedioxy;
wherein R.sub.1 and R.sub.2, being the same or different, are hydrogen; hydroxy C.sub.1 -C.sub.4 alkyl; C.sub.1 -C.sub.3 alkoxy; C.sub.1 -C.sub.3 alkylthio; halo or trifluoromethyl;
wherein R.sub.3 is hydrogen; C.sub.1 -C.sub.4 alkyl; cyclo(C.sub.3 -C.sub.6)alkyl optionally substituted with one, 2 or 3 C.sub.1 -C.sub.3 alkyl, preferably cyclo(C.sub.3 -C.sub.5)alkyl optionally substituted; phenyl optionally substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, halo, trifluoromethyl, or C.sub.1 -C.sub.3 alkoxy; phenyl(C.sub.1 -C.sub.3)alkyl optionally

REFERENCES:
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Bobarenic B. et al, Glasnik Hemicara & Technologia BiH, Sarajivo, 13/14. pp. 47-50 (1965).

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