ANTHELMINTIC ACYLHYDRAZONES, METHOD OF USE AND COMPOSITIONS

Abstract: Process for killing internal parasites, especially nematodes, trematodes, and cestodes affecting warm blooded animals such as sheep, cattle, swine, goats, dogs, cats, horses and humans as well as poultry by administering an effective amount of a compound of formula (I). The compounds are readily prepared by conventional chemical reactions.

Description: ANTHELMI TIC ACYLHYDRAZONES , METHOD OF USE AND COMPOSITIONS 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 acylhydra- zones, 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 warm-blooded domestic 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- imes 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. Trichostrongylus. Ostertagia. Nematodirus. Cooneria. Bunostomum. Oesophagostomum. Chabertia. Strongyloides. Trichuris. Fasciola. Dicrocoelium. Enterobius. Ascaris. Toxascaris. Toxocara. Ascaridia. Canillaria. Heterakis. Ancylostoma. Uncinaria. Dirofilaria. Onchocerca. Taenia. Moniezia. Dipylidium. Metastrongylus. Triodontoohorus . Macracanthorhvnchus. Hvostrongylus . 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. DETAILED DESCRIPTION OF THE INVENTION The acylhydrazones of this invention, including hydrates or pharmaceutically acceptable salts thereof, are represented by Formula 1 wherein X is (a) hydrogen; (b) C--C 10 alkyl; with the proviso that when X is n-propyl, R 3 is methyl, R χ and R 2 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (c) C 2 -C 6 alkenyl, preferably C--C 4 alkenyl; (d) C--C 6 alkynyl; (e) cyclo(C 3 -C 10 )alkyl optionally substituted with one, 2 or 3 C 1 -C !i alkyl, C 2 -C 4 alkenyl, C- -C A alkoxy, trifluoromethyl, or halo; with the proviso that when X is cyclopropyl, R 2 is 2-methyl, R χ and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (f) pyrrolidinyl; (g) piperidinyl; (h) 1-methylρyrrolidinyl; (i) 1-methylpiρeridinyl; (j) C 2 -C 5 alkoxyalkyl; (k) cyclo(C 3 -C χQ )alkyl(C χ -C )alkyl; with the proviso that when X is cyclohexylmethyl, R χ and R- are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydra¬ zone; (1) phenyl(C χ -C A )alkyl optionally substituted with one, 2 or 3 halo or C x -C 4 alkoxy, or one or 2 trifluoromethyl; (m) phenoxy(C χ - C A )alkyl optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; (n) perhalo(C 1 -C 7 )alkyl; (o) C χ -C 6 alkoxy, with the proviso that when X is t-butoxy and the compound is a 2-benzofuranyl acylhydrazone (IB) , and R χ and R- are hydrogen, R 3 is other than methyl; with the proviso that when X is ethoxy, R- , R 2 and R 3 are hydrogen, the compound Is other than a l-acetylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R- are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3- benzothiofuran acylhydrazone (IA) ; (p) diphenylmethoxy; (q) cyclo(C 3 - C 6 )alkyloxy optionally substituted with one or two C χ -C 3 alkyl; (r) phenoxy optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; with the proviso that when X is phenoxy, R χ and R 2 are hydrogen and R 3 is methyl, the compound is other than a 2-benzo¬ furanyl acyhydrazone; (s) benzyloxy optionally substituted with one, 2 or 3 halo or C χ -C A alkoxy, or one or 2 trifluoromethyl; with the provi-so that when X is benzyloxy and R χ , R 2 and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (t) heteroaromatic optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; (u) phenyl substituted with one, 2 or 3 halo, or one - 3 - or 2 trifluoromethyl, amino, alkyl(C χ -C 3 )amino, dialkyl(C χ -C 3 )amino, C χ -C 5 alkyl or C χ -C 3 alkoxy; with the proviso that when X is 4- ethoxyphenyl or 4-chlorophenyl, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3-benzothienyl acylhydrazone (IA) ; with the proviso that when X is 4-chlorophenyl, R χ and R- are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydra¬ zone; with the proviso that when X is 4-methylphenyl, 3 ,4-dimethoxy- phenyl or 3-me hoxyphenyl and R χ , R_ and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; with the proviso that when X is 4-ethoxyphenyl, R χ , R-, and R 3 are hydrogen, the compound is other than a l-acetylindol-3-yl acylhydrazone; (v) N- morpholinyl(C χ -C A )alkyl; (w) N-piperidinyl(C χ -C A )alkyl; (x) N- pyrrolidinyl(C χ -C )alkyl; (y) bridged polycyclic hydrocarbon substituents of six to 10 nuclear carbons, optionally substituted with one, 2 or 3 (C χ -C 3 ) alkyl groups (z) naphthyl(C χ -C 3 ) lkyl optionally substituted with one, 2 or 3 C χ -C alkyl, C χ -C alkoxy, halo, or trifluoromethyl; wherein Y is an oxygen atom; a sulfur atom; or a N-Z group; wherein Z is hydrogen; C χ -C A alkyl; acetyl; benzoyl; phenyl optionally substituted * with one, 2 or 3 C χ -C A alkyl, C χ -C 3 alkoxy, halo, trifluoromethyl, C 2 -C 6 dialkylamino, C χ -C 3 alkyl hio, nitro, or phenoxy optionally substituted with one, 2 or 3 C χ -C A alkyl, C χ -C 3 alkoxy, halo, or trifluoromethyl; or phenyl(C χ -C A )alkyl optionally substituted with one, 2 or 3 C χ -C A alkyl, C χ -C A alkoxy, halo, or trifluoromethyl; wherein R χ is- hydrogen; hydroxy; C χ -C alkyl, preferably C χ -C 3 alkyl; C χ -C 3 alkoxy; C χ -C 3 alkylthio; halo; nitro; benzyloxy or trifluoromethyl; with the proviso that when R χ is benzyloxy, X is other than alkyl; and wherein R 2 is hydrogen; hydroxy; C χ -C A alkyl, preferably C χ -C 3 alkyl; C χ -C 3 alkoxy; C χ -C 3 alkylthio; halo or trifluoromethyl; and wherein R- is hydrogen; 0 χ -C A alkyl; cyclo(C 3 -C 5 )alkyl optionally substituted with one, 2 or 3 C x -C 3 alkyl, preferably cyclo(C 3 -C 5 )alkyl optionally substituted; phenyl optionally substituted with one, 2 or 3 C χ -C A alkyl, halo, trifluoromethyl, or C χ -C 3 alkoxy; phenyl(C χ -C 3 )alkyl optionally substituted with one, 2 or 3 C χ -C A alkyl, halo, trifluoromethyl, or C χ -C- alkoxy; or 1,3- dioxacyclohexan-5-yl; n is 0 when Y is a sulfur atom or a N-Z group; n is 0 or 1 when Y is an oxygen atom. C - C means the carbon content of various hydrocarbon-containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety. Thus (C χ -C 3 ) alkyl refers to alkyl of one to 3 carbon atoms, inclusive or methyl, ethyl, propyl, and isopropyl. Halogen atom (halo) refers to a bro o, chloro, iodo or fluoro atom. Heteroaromatic refers to pyrrole, 3-pyridine, (pyridin-3-yl) , thiophene or furan, as well as the N-oxides, hydrates and pharmaceutically acceptable salts thereof. When Y is sulfur, the term heteroaromatic also includes 2-pyridine and 4-pyridine, preferably 4-ρyridine, as well as the N-oxides, hydrates and pharmaceutically acceptable salts thereof. Pharmaceutically acceptable refers to those properties and/or substances which are acceptable to the patient from a pharmacologically-toxicological point of view and to the manufacturing pharmaceutical chemist from a physical-chemical point of view regarding composition, formulation, stability, patient acceptance and bioavailability. Examples of C χ -C A alkyl are methyl, ethyl, propyl, butyl and isomeric forms thereof. Examples of C, -C ~ alkoxy are methoxy, ethoxy, propoxy and isomeric forms thereof. Examples of phenoxy substituted with one, 2 or 3 C χ -C A alkyl are (o-, m- , or p-)tolyl, (o-, m- , or p-)ethylphenyl, p-tert-butylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 2,4-dimethylphenyl, (2,3,4-, 2,3,5-, 2,3,6-, 2,4,6- or 2,4,5-)trimethylphenyl. Examples of C 2 -C 8 dialkylamino are dimeth lamino, dieth lamino, methylethylamino, dipropylamino and ethylpropylamino. Examples of phenyl(C χ -G 3 ) lkyl are benzyl, phenylethyl and phenylpropyl. Examples of phenyl(C χ -C 3 )alkyl substituted with halo or trifluoromethyl include 4-chlorobenzyl, 2-chlorophenyleth l or p- trifluoromethyl. Examples of naphthyl(C χ -C 3 )alkyl include 2-naphthylmethyl and 1-naphthylethyl. Examples of substituted naphthyl(C χ -C 3 ) lkyl is (3,8-dichloro-l-naphthyl)methyl; (4-chloro-l-naphthyl)methyl; and (4-methoxy-l-naphthyl)methyl. Examples of substituted naphthyl include 3,6-dichloro-l-naphthyl; 3, 5-dichloro-2-naρhthyl; 6-methyl-2- naphthyl; and 4,6-dichloro-l-naphthyl. Examples of substituted cyclo(C- -C χ - )alkyl are chrysan hemyl, 1-mechylcycloproρyl and 2-methylcyclopropyl. Examples of cyclo(C 3 -C χ0 )alkyl(C χ -C A )alkyl are 2-cyclohexylethyl and cyclohexylmethyl. An example of substituted cyclo(C 3 -C_ )alkyloxy is menthyl. Examples of bridged polycyclic hydrocarbon substituents of six to 10 nuclear carbons, optionally substituted with one, 2 or 3 (C χ -C 3 ) alkyl groups include exo or endo-2-norbonyl, bicyclo[2,2,2]oct-l-yl, and 1-adamantyl. Examples of perhalo (C- -C 7 ) alkyl include trifluoromethyl, n-heptafluoropropyl and n-undecafluoropentyl. Preferred acylhydrazones of Formula I are indolyl acylhydrazones (IC) . Preferred R x and R 2 include hydrogen, methyl or a bromo atom. R 3 is preferably hydrogen. Preferred X include C χ -C A alkyl; cyclo(C 3 -C 6 )alkyl; C χ -C A alkoxy; and 3-pyridinyl. Most preferably X includes cyclobutyl; t- butoxy; ethoxy; ethyl; and 3-pyridinyl. Z is preferably hydrogen. One embodiment of this invention includes, of course, the anthelmintic use and anthelmintic compositions of compounds of Formula I, IA, IB, IC, or ID hydrates thereof or pharmaceutically acceptable salts thereof. Still another embodiment of this invention are the novel compounds, hydrates thereof or pharmaceutically acceptable salts thereof according to Formula I, IA, IB, IC and ID. Among the acylhydrazones of Formula I: acetic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 1016-49- 5); 4-aminobenzoic acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 10245-42-8); 4-me hoxybenzoic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN 15565-86-3); 4-morpholineacetic acid (2-benzofuranylmethylene)hydrazide (CA RN 72627-58-8); (2-chlorophenoxy)acetic acid (lH-indol-3-ylmethylene)hydrazide (CA RN 81111-25-3); -6 - ( -chlorophenoxy)acetic acid (lH-indol-3-ylmethylene)hydrazide (CA RN 81111-26-4); (2-chlorophenoxy)acetic acid f (2-methoxy-lH-indol-3-yl)methyl- enejhydrazide (CA RN 81122-74-9); (4-chlorophenoxy)acetic acid [(2-methoxy-lH-indol-3-yl)methyl- ene]hydrazide (CA RN 81122-75-0); methyl (lH-indol-3-ylmethylene)carbazate (CA RN 88692-99-3); phenylmethyl [1-(lH-indol-3-yl)propylidene]carbazate (CA RN 32947-16-3); 1-piperidineacetic acid [(2-methyl-3-benzofuranyl)methylene - hydrazide (CA RN 35806-44-1); 1-pyrrolidineacetic acid (2-benzofuranylmethylene)hydrazide (CA RN 35806-70-3); 1-piperidineacetic acid (2-benzofuranylmethylene)hydrazide (CA RN 35806-85-0); 1-pyrrolidineacetic acid [(2-methyl-3-benzofuranyl)methylene] - hydrazide (CA RN 35802-00-9); formic acid [(lH-indol-2-yl)methylene]hydrazide (CA RN 50335-88- i); ethyl (lH-indol-2-ylmethylene)carbazate (CA RN 50335-89-2); ethyl [1-(2-benzofuranyl)ethylidene]carbazate (CA RN 56968-94- 6); ethyl (1-(5-chloro-2-benzofuranyl)ethylidene]carbazate (CA RN 56968-95-7); 1,1-dimethylethyl (lH-indol-3-ylmethylene)carbazate (CA RN 57699-52-2); 4-aminobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-21-1); butyric acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 15641- 24-4); propionic acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 15641- 25-5); ethyl [(1H-indol-3-yl)methylene]carbazate (CA RN 15641-27-7); formic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-28-8); acetic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-29-9); propanoic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN - 7 - 15641-30 -2) ; butanoic acid [ (l-methylindol-2-yl)methylenejhydrazide (CA RN 15641-31-3); 2-methylpropanoic acid [ (l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-32-4); phenylacetic acid [ (l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-34-6); 4-chlorobenzoic acid [ (l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-36-8); 1-naphthaleneacetic acid [ (l-methylindol-2-yl)methylene] - hydrazide (CA RN 15641-38-0); ethyl [ (l-methylindol-2-yl)methylene]carbazate (CA RN 15565-88- 5); 4-chlorobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-01-7); 2-chlorobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-03-9); 3-chlorobenzoic acid [ (lH-Indol-3-yl)methylene]hydrazide (CA RN 15641-04-0); 2,4-dichlorobenzoic acid [ (lH-indol-3-yl)me(_hylene]hydrazide (CA RN 15641-05-1); 4-bromobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-06-2); 2-methylpropanoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-12-0); 4-methoxybenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-15-3); phenylacetic acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 15641-17-5); 1-naphthaleneacetic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-18-6); 2-furoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641- 19-7); 2-naphthaleneacetic acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 15718-86-2): ethyl [l-(lH-indol-3-yl)ethylidene]carbazate (CA RN 32927-03-0); phenylmethyl 3- [ (lH-indol-3-yl)methylene]carbazate (CA RN 32927- . 05-2); phenylmethyl [1- (lH-indol-3-yl)ethylidenejcarbazate (CA RN 32927-06-3); ethyl [(l-methylindol-3-yl)methylene]carbazate (CA RN 32927-89- 2); ethyl [1-(lH-indol-3-yl) ropylidene]carbazate (CA RN 32947-13-0) are known. See S. Swamiπathan and K. Narasinhan, Indiana J. Chem., 2(10), 423-424 (1964); Chem. Abstr. 62:3995F; F. Fujikawa, et al, 86, 861-864 (1966); Chem Abstr. 65:20087b; I.P. Singh et al, Arch. Phar . 317(17), 609-614 (1985); A. Ale any et al, Bull. Soc. Chim. Fr., (3), 780-786 (1967); E. Fernandez Alvarez, et al, Span. ES 324609, 16 Dec 1966, 24 Mar 1966; Chem. Abstr. 67(7) :32590s; A. Tajana et al, Boll. Chim. Farm., 118(7), 397-406 (1979); Chem. Abstr. 92(15) :121571v; S. Misra et al, J. Chem. Soc. Pak. , 3(4), 199-202 (1981); Chem. Abstr. 96(17) :142622h; P. Benko et al, Ger. Offen. DE3316316A1, 10 Nov 1983; Chem. Abstr. 100(9) :68022x; M. Bernabe et al, Bull. Soc. Chim. Fr. , (5), 1882-1887 (1971); Chem. Abstr. 75(9):63537z; A. Tajana and R. Pozzi, J. Med. Chem., 14, 1017-1020 (1971) ;M. Robba et al, Bull. Soc. Chim. Fr., (3-4, Pt 2), 333-336 (1977); Chem. Abstr. 88(3) :22764w; M. Robba et al, Tetrehedron Lett., (35), 3235-3238 (1973); M. Robba et al, J. Heterocycl. Chem., 14(8), 1365-1368 (1977); J.P. Dusza et al, U.S. 3882149, 6 May 1975; Chem. Abstr. 83(13) :114190f; A.S. Dutta and J.S. Morley, J. Chem. Soc. Perkins Trans., 1(17), 1712-1720 (1975); N.R. El-Rayyes amd A.H. Katrib, J. Chem. Eng. Data, 28(1), 132-134 (1983); N.R. El-Rayyes and F.M. Al-Kharafi, Egypt, J. Chem., Vol. date 1980, 23(2), 151-156 (1981); Chem. Abstr. 96(17) :142575x; R. Jurado et al, Arch. Inst. Far acol. Exp., 18(2), 49-58 (1966); Chem. Abstr. 69(19) :75350x. The acylhydrazones of this invention (Formula I) are readily prepared by reacting the appropriate ketone/aldehyde (II) with the acylhydrazide/carbazate (III) (Chart A, Scheme A) or by heating the heteroaromatic ketone/aldehyde (II) with the appropriate hydrazine (IV) to form the hydrazone intermediate (V) which is then acylated with the halide or anhydride (VI) to form the acylhydrazone (I) (Chart A, Scheme B) . The reaction of Scheme A is carried out in the presence of a suitable solvent, for example, water, alcohols, ethers, halogenated hydrocarbons, hydrocarbons and include methanol, ethanol, isopropanol, propanol, hexane, tetrahydrofuran, dioxane, methylene chloride, preferably ethanol. A catalyst such as glacial acetic acid, hydrochloric acid, sulfuric acid or p-toluenesulfonic acid can be utilized to enhance the yield/rate of the reaction, particularly when R 3 is alkyl of 3 or more atoms, arylalkyl or aryl. The acylation reaction of Scheme B is carried out in the presence of a suitable base such as an organic tertiary amine or an Inorganic base, for example, triethylamine or sodium carbonate, or preferably, pyridine. The base may also be the solvent. The starting compounds are known or can be readily prepared by known methods. R. L. Frank and C. Weatherbee, J. Am. Chem. Soc, 70, 3482-3 (1948); N. B. Mahishi, et al. , J. Indian Chem. Soc, 42, 67-74 (1965) and M. Ogata and H. Kano, Chem. Pharm. Bull (Tokyo), 11, 32 (1963). The following detailed examples/procedures describe how to prepare various acylhydrazones of the invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. Those skilled in the art will promptly recognize appropriate variations from the procedures both as to reactants as well as to reaction conditions and techniques. Procedure 1 Preparation of ^-morpholinopropionyl [ (lH-indol-3-yl)- methylene]hydrazide hydrate. Compound 1. A mixture of 3.46 gm (0.02 mole) of 3-morpholinopropionyl- . hdyrazide, 2.90 gm (0.02 mole) of indole-3-carboxaldehyde and 100 ml of ethanol is refluxed 6 hr. The solvent is evaporated. The residue is dissolved in hot dimethylforma ide and filtered. The filtrate is diluted with ethyl acetate to the cloud point, cooled, then chilled. The product is collected, washed with ether and dried to yield 4.63 gm (74%) of the title compound having a melting point of 235.2°C. Analysis Calcd: C, 61.42; H, 6.81; N, 17.91 Found: C, 61.41; H, 6.71; N, 17.47 Procedure 2 Preparation of 3-chlorobenzoic acid [(lH-indol-3-yl)- ethylene]hydrazide. Compound 2. A mixture of 7.26 gm (0.05 mole) of indole-3-carboxaldehyde, 8.52 gm (0.05 mole) 3-chlorobenzoic acid hydrazide and 50 ml of ethanol is refluxed 12 hr. The reaction mixture is cooled. The product is collected, washed with water and dried to yield 11.55 gm (77%) of the title compound having a melting point of 224.3"C. Analysis Calcd: C, 64.54; H, 4.06; N, 14.11; Cl, 11.91 Found: C, 64,72; H, 4.07; N, 14.14; Cl, 11.77 Procedure 3 Preparation of 1,1-dimethylethyl [ (1H-indol-3-yl)- methylene carbazate. Compound 4. A mixture of 7.26 gm (0.05 mole) of indole-3-carboxaldehyde, 6.81 gm (0.05 mole) of tert-butylcarbazate and 50 ml of ethanol is refluxed 10 hr. The solvent is evaporated to give an oil which solidifies on standing. The product is crystallized from aqueous ethanol to yield 8.65 gm (67%) of the title compound having a melting point of 136.2°C. Analysis Calcd: C, 64.84; H, 6.61; N, 16.21 Found: C, 64.47; H, 6.52; N, 15.95 Procedure 4 Preparation of ethyl[l-(2-benzofuranyl)ethylidene] - carbazate. Compound 8. A mixture of 6.25 gm (0.06 mole) of ethyl carbazate, 9.61 gm (0.06 mole) of 2-acetylbenzofuran and 100 ml of aqueous ethanol Is refluxed 6 hr. The reaction mixture Is cooled. The crude product is collected and recrystallized from alcohol to yield 13.34 gm (90%) of the title compound having a melting point of 167.8°C. Analysis Calcd: C, 63.41; H, 5.69; N, 11.38 Found: C, 63.56; H, 5.71; N, 11.41 Procedure 5 Preparation of 2-chlorobenzoic acid [ (lH-indol-3-yl) - methylene]hydrazide. Compound 15. A mixture of 4.36 gm (0.03 mole) of indole-3-carboxaldehyde, 5.10 gm (0.03 mole) of 2-chlorobenzhydrazide, 100 ml of ethanol and 5 ml of glacial acetic acid is refluxed 3 hr. The mixture is diluted with sufficient dimethylformamide to give a solution. The hot solution is filtered. The filtrate is diluted with water to the cloud point and cooled, then chilled. The product is collected, washed with water and dried to yield 8.25 gm (93%) of the title compound having a melting point of 231.4°C. Analysis Calcd: C, 64.65; H, 4.04; N, 14.14 Found: C, 64.81; H, 3.83; N, 14.21 Procedure 6 Preparation of butanoic acid [1-(l-benzylindol-3-yl)- propylidene]hydrazide. Compound 49. A mixture of 11.85 gm (0.045 mole) of l-benzylindol-3-yl ethyl ketone, 4.6 gm (0.045 mole) of butanoic acid hydrazide, 250 ml of ethanol and 12 drops of concentrated hydrochloric acid is refluxed 6 -11- hr. The hot solution is filtered. The filtrate is cooled and chilled. This product is collected and dried to yield 2.18 gm (14%) of the title compound having a melting point of 277.4°C. Analysis Calcd: C, 7605; H, 7.25; N, 12.09 Found: C, 76.00; H, 7.42; N, 12.07 Procedure 7 Preparation of isonicotinic acid [1- (l-benzylindol-3- yl)ρropylidene]hydrazide. Compound 58. A mixture of 5.49 gm (0.04 mole) of isonicotinic acid hydrazide, 10.53 gm (0.04 mole) of l-benzylindol-3-yl ethyl ketone, 200 ml of ethanol and 12 drops of glacial acetic acid is refluxed 20 hr. The reaction mixture is cooled. The product is collected and dried to yield 6.31 gm (41%) of the title compound having a melting point of 200.8°C. Analysis Calcd: C, 75.37; H, 5.80; N, 14.65 Found: C, 75.79; H, 5.85; N, 14.08 Procedure 8 Preparation of methyl[ (2-methylindol-3-yl)methy- lene]cabazate. Compound 161. A mixture of 7.16 gm (0.045 mole) of 2-methylindol-3-carboxal- dehyde, 4.04 gm (0.045 mole) of methyl carbazate and 100 ml of absolute ethanol is refluxed 8 hr. The hot solution is diluted with water to the cloud point, then cooled. The product is collected and dried to yield 7.79 gm (71%) of the title compound having a melting point of 152.7°C. Analysis Calcd: C, 59.10; H, 5.95; N, 17.23 Found: C, 58.66; H, 5.56; N, 17.03 Procedure 9 Ethyl [1-(2-oxo-2H-l-benzopyran-3-yl)ethylidene] - carbazate. Compound 248. A mixture of 5.73 gm (0.055 mole) of ethyl carbazate, 10.34 gm (0.055 mole) of 3-ace ylcoumarin and 130 ml of aqueous ethanol is refluxed 8 hr. The mixture is chilled. The white crystals are collected and dried to give 6.98 gm (46%) of the title compound having a melting point of 170.2 β C. Analysis Calcd: C, 61.31; H, 5.11; N, 10.22 Found: C, 61.84; H, 5.14; N, 10.28 Procedure 10 Cyclohexanecarboxylic acid [l-(2-oxo-2H-l-benzopyran- 3-yl)ethylidene]hydrazide. Compound 251. A mixture of 4.0 gm (0.0213 mole) of 3-acetylcoumarin, 3.03 gm (0.0213 mole) of cyclohexamecarboxylic acid hydrazide, 100 ml of - 12- ethanol and 10 drops of glacial acetic acid is refluxed 8 hr. The reaction mixture is chilled. The product is collected, washed with water and dried to give 4.62 gm (69%) of the title compound having a melting point of 190.5°C. Analysis Calcd: C.69.22; H, 6.45; N, 8.96 Found: C, 68.94; H, 6.32; N, 8.83 The compounds prepared according to Procedures 1-10 are tabulated in Table A along with other illustrative compounds of the invention prepared following the general procedure indicated (Procedures 1-10) and making non-critical variations, except starting with the appropriate ketone/aldehyde (II) and acylhydrazide/carbazate (III). The acylhydrazones of this invention (.Formula I) are effective against parasitic worms, particularly those of valuable domestic warm-blooded animals and more particularly helminth parasites In ovines (sheep) and bovines (cattle) . Observations in sheep experimentally infected with Haemonchus contortus in accordance with Procedure A, generally confirm anthelmintic activity at 100 mg/kg of body weight upon oral and/or parenteral administration as set forth in Table I. Acylhydrazones which are toxic at 100 mg/kg are expected to exhibit anthelmintic activity at a lower non-toxic dose. Further observations in sheep naturally infected with various helminths also confirmed broad-spectrum anthelmintic activity of acylhydrazones of this invention. See Procedure B and the results as set forth in Tables IIA and IIB. Procedure No. A In individual experiments all sheep are treated identically, however non-critical variations occur between experiments. All of the sheep used in this procedure are treated twice with levamisole hydrochloride orally at 8 mg/kg or once each with ivermectin parenterally at 200 g/kg and levamisole hydrochloride orally at 8 mg/kg. The second treatment in each case is administered 4-7 days after the first treatment. Two weeks after the second treatment all sheep are inoculated per os with -3,500 to -7,500 infective larvae of H. contortus. Rectal fecal samples are taken from each sheep 26-41 days post-inoculation (PI), and these samples are examined for eggs of H. contortus using the McMaster counting chamber technique. All - 13 - sheep harboring good infections of H. contortus are randomly allocated to a treatment group; those which do not exhibit suitable infections are dropped from the study. One-three days later on days 27-42 PI each sheep remaining in the study (excluding the nontreated controls) is treated with a test compound (orally or parenterally at 100 mg/kg unless indicated otherwise) or a standard (levamisole hydrochloride orally at 8 mg/kg) or is used as an untreated control. All sheep received food and water ad lib, throughout the experiment. Prior to administration, all solid compounds are finely ground using a mortar and pestle. Oral compounds are suspended in 20-30 ml of sterile vehicle #98 (each ml contains: carboxymethylcellulose - 10 mg, polysorbate 80-4 mg, propylparaben - 0.42 mg) using a sonicator and administered along with a tap water wash via a stomach tube. The parenteral compounds are similarly suspended in 20-30 ml of the sterile vehicle and given by intraperitoneal injection using a 13 gauge, 2 inch needle and a 50 ml syringe. All test compounds are given to a single sheep/route of administration. Two or more sheep are treated with levamisole hydrochloride and five are used as nontreated controls. All animals are monitored for signs of toxicity following treatment. The sheep are sacrificed 7-12 days after treatment (days 35-49 PI), and the abomasum is ligated and removed from each sheep. Each abomasum is longitudinally sectioned and rinsed into an 80 mesh sieve. Sieve contents are collected in individual containers and fixed in for ol-alcohol. Later each sample is transferred to a 1000 or 2000 ml beaker and the volume brought to 400-1000 ml with tap water. The total number of worms in a 40-100 ml aliquot (10%) is determined. When no worms are found in the 10% aliquot, the entire sample is examined. Total worm number/sheep and percentage clearance for each treatment are calculated. Percentage clearance for -a particular test compound in a given trial is determined according to the following formula: Percentage Clearance - [(Mean number of worms recovered from non- treated control sheep - Number of worms recovered from treated sheep)/Mean number of worms recovered from nontreated control sheep] x 100. Sheep which die within 24 hr following treatment are not examined for worms (Toxic) , while any that die between 24 hr post-treatment and necropsy are examined in an identical manner as that described above. The results of various trials are combined and reported in Table I as percentage clearance. Procedure No. B Parasitized sheep are randomly assigned to groups of five animals based on parasitic burden, sex, and farm origin. Sheep are double ear-tagged, weighed, housed in a barn in community pens, fed hay supplemented with 1/2 lb corn/head/day. Water is given ad lib. Animals are allowed to acclimate for one-two weeks prior to treatment. Each group of sheep receives a test compound either orally or parenterally at a dosage rate of 100 mg/kg. A group of sheep is treated with 8 mg/kg of levamisole hydrochloride and another group serves as an untreated control group. Orally administered compounds are suspended in 20-30 ml of sterile vehicle s=98 (each ml contains: carboxymethylcellulose - 10 mg, polysorbate 80-4 mg, propylparaben - 0.42 mg) using a sonicator and administered along with a tap water wash via a stomach tube. For parenteral administration, compounds are similarly suspended in 20-30 ml of the sterile vehicle and given > by intraperitoneal injection using a 20 gauge, 1 inch needle and a 50 ml syringe. Following treatment, all animals are observed for signs of toxicity. The number and classification of helminth eggs per gram of feces (e.p.g.) are determined for each sheep during the acclimation period and in some cases at necropsy. Egg counts are made using the McMaster counting chamber technique and rectal fecal samples. Animals dying during the 24 hours immediately following dosing are not subjected to necropsy. Sheep that die 1-6 days posttreatment are posted and complete worm counts performed. All remaining animals are sacrificed on days 7-8 posttreatment. Each sheep is euthanised and bled out prior to opening the abdominal cavity. Ligatures are placed at the reticulo-omasal junction, the pyloric valve, and the ileo- cecal junction. The abomasum and small intestine are freed of fat and mesenteric attachments, longitudinally opened, and their contents placed in individual containers. The mucosal surface of each is washed with tap water, rubbed clean, and rinsed several times. Washings and ingesta for each organ are made up to 1 liter and a 10% . aliquot in formalin is stored for later examination. The cecum, - 15 - large intestine, and colon are freed of mesenteric attachments, each is longitudinally opened, and their contents washed, collected, and made up to 1 liter in 10% formalin. The entire sample is stored. All carcasses are incinerated. Ten percent of the total contents collected from the abomasum and small intestine and the entire contents of the large intestine, cecum, and colon are examined under stereoscopic magnification (40X) . All worms are identified to genus and in some instances species. Separate adult and larval counts are determined. The mean percentage clearance against specific helminths in the test sheep is calculated by subtracting the mean number of helminths observed in the treated sheep at necropsy from the mean number observed in the nontreated controls at necropsy, dividing the remainder by the latter mean number and multiplying by 100. The mean percentage clearances against the various helminths identified in the test sheep are calculated. The results for a acylhydrazone of Formula I are set forth in Tables HA and IIB. From an evaluation of the test results set forth in Tables I and IIA and IIB, it is clear that the acylhydrazones of this invention (Formula I) are broad-spectrum anthelmintic agents. DETAILED DESCRIPTION (cont'd) The acylhydrazones of Formula I can be used as the pure compounds or as mixtures of pure compounds but for practical reasons the compounds are preferably formulated as anthelmintic compositions and administered as a single or multiple dose, alone or in combination with other anthelmintics (e.g. avermectins, benzimid- azoles, levamisole, praziquantel, etc.). For example, aqueous or oil suspensions can be administered orally, or the compounds can be formulated with a. solid carrier for feeding. Furthermore, an oil suspension can be converted into an aqueous emulsion by mixing with water and injecting the emulsion intramuscularly, subcutaneously or into the peritoneal cavity. In addition, the active compound(s) can be administered topically to the animal in a conventional pour-on formulation. Pure compounds, mixtures of the active compounds, or combinations thereof with a solid carrier can be administered in the animal's food, or administered in the form of tablets, pills, boluses, wafers, pastes, and other conventional unit dosage forms, as -16- well as sustained release dosage forms which deliver the active compound over an extended period of days, weeks or months. All of these various forms of the active compounds of this invention can be prepared using physiologically acceptable carriers and known methods of formulation and manufacture. Representative solid carriers conveniently available and satisfactory for physiologically acceptable, unit dosage formulations include corn starch, powdered lactose, powdered sucrose, talc, stearic acid, magnesium stearate, finely divided bentonite, and the like. The active agent can be mixed with a carrier in varying proportions from, for example, about 0.001 percent by weight in animal feed to about 90 or 95 percent or more in a pill or capsule. In the latter form, one might use no more carrier than sufficient to bind the particles of active compound. In general, the compounds can be formulated in stable powders or granules for mixing in an amount of feed for a single feeding or enough feed for one day and thus obtain therapeutic efficacy without complication. It is the prepared and stored feeds or feed premixes that require care. A recommended practice is to coat a granular formulation to protect and preserve the active ingredient. A prepared hog-feed containing about 0.2 percent of the active compound will provide a dosage of about 100 mg per kg body weight for each 100 lb pig in its daily ration. A solid diluent carrier need not be a homogeneous entity, but mixtures of different diluent carriers can include small proportions of adjuvants such as water; alcohols; protein solutions and suspensions like skimmed milk; edible oils; solutions, e.g., syrups; and organic adjuvants such as propylene glycols, sorbitol, glycerol, diethyl carbonate, and the like. The solid carrier formulations of the inventions are conveniently prepared in unit dosage forms, to facilitate administration to animals. Accordingly, several large boluses (about 20 g weight) amounting to about 54 g of active compound would be required for a single dosage to a 900 lb horse at a dosage rate of 50 mg/kg of body weight. Similarly, a 60 lb lamb at a dosage rate of 100 mg/kg of body weight would require a pill, capsule, or bolus containing about 2.7 g of active compound. A small dog, on the other hand, weighing about 20 lbs. would require a total dosage of about - 17 - 225 mg at a dosage rate of 25 mg/kg of body weight. The solid, unit dosage forms can be conveniently prepared in various sizes and concentrations of active ingredient, to accomodate treatment of the various sizes of animals that are parasitized by worms. Liquid formulations can also be used. Representative liquid formulations include aqueous (including isotonic saline) suspensions, oil solutions and suspensions, and oil in water emulsions. Aqueous suspensions are obtained by dispersing the active compound in water, preferably including a suitable surface-active dispersing agent such as cationic, anionic, or non-ionic surface-active agents. Representative suitable ones are polyoxyalkylene derivatives of fatty alcohols and of sorbitan esters, and glycerol and sorbitan esters of fatty acids. Various dispersing or suspending agents can be Included and representative ones are synthetic and natural gums, tragacanth, acacia, alginate, dextran, gelatin, sodium carboxymethylcellulose, methylcellulose, sodium polyvinylpyrrolidone, and the like. The proportion of the active compound in the aqueous suspensions of the invention can vary from about T percent to about 20 percent or more. Oil solutions are prepared by mixing the active compound and an oil, e.g. an edible oil such as cottonseed oil, peanut oil, coconut oil, modified soybean oil, and sesame oil. Usually, solubility in oil will be limited and oil suspensions can be prepared by mixing additional finely divided compound in the oil. Oil in water emulsions are prepared by mixing and dispersing an oil solution or suspension of the active compound in water preferably aided by surface-active agents and dispersing or suspending agents as indicated above. In general, the formulations of this invention are administered to animals so as to achieve therapeutic or prophylactic levels of the active compound. At present, it is known that a dose of 100 mg/kg. of body weight in sheep of a acylhydrazone of this invention will effectively combat a wide variety of parasites. Much lower effective dosages of various compounds are contemplated, e.g., in the range of 1 to 75 mg/kg of body weight. In other animals, and for other kinds of parasitic worms, definitive dosages can be proposed. Contemplated are dosage rates of about 1 mg to about 800 mg/kg of body weight. A preferred, contemplated range of dosage rates is from about 5 mg to about 400 -18 - mg/kg of body weight. In this regard, it should be noted that the concentration of active compound in the formulation selected for administration is in many situations not critical. One can administer a larger quantity of a formulation having a relatively low concentration and achieve the same therapeutic or prophylactic dosage as a relatively small quantity of a relatively more concentrated formulation. More frequent small dosages will likewise give results comparable to one large dose. One can also administer a sustained release dosage system (protracted delivery formulation) so as to provide therapeutic and/or prophylactic dosage amounts over an extended period. Unit dosage forms in accordance with this invention can have anywhere from less than 1 mg to 500 g of active compound per unit. Although the anthelmintic agents of this invention will find their primary use in the treatment and/or prevention of helminth parasitisms in domesticated animals such as sheep, cattle, horses, dogs, swine, goats and poultry, they are also effective in treatment that occurs in other warm blooded animals including man. The optimum amount to be employed for best results will, of course, depend upon the particular compound employed, species of animal to be treated, the regimen treatment and the type and severity of helminth infection. Generally good results are obtained with compounds of Formula I by the oral or parenteral route of administration of about 1 to 300 mg/kg of animal bodyweight (such total dose being given at one time, in a protracted manner or in divided doses over a short period of time such as 1-4 days) . The technique for administering these materials to animals are known to those skilled in the veterinary and medical fields. It is contemplated that the acylhydrazones of Formula I can be used to treat various helminth diseases in humans, including those caused by Ascaris. Enterobius. Ancylostoma. Trichuris. Strongyloides. Fasciola. Taenia. and/or Onchocerca or other filaria at a dose of from 1 mg/kg to 300 mg/kg of body weight upon oral and/or parenteral administr tion. DEFINITIONS The definitions and explanations below are for the terms as used throughout the entire patent application including both the specification and claims. - 19 - All temperatures are in degrees Celsius. TLC refers to thin-layer chromatography. When solvent pairs are used, the ratio of solvents used are volume/volume (v/v) . -20- TABLE A 1 NH 3 H H H N-morpholinyl 235.2 1 CH 2 CH 2 2 NH 3 H H H 3-ClPh 224.3 2 3 NH 3 H H H CH 3 CH 2 247.5 2 4 NH 3 H H H t-C H 9 0 136.2 3 5 NH 3 H H H 2-thIenyl 272.7 2 6 NH 3 H H H 4-CH 3 CH 2 0Ph 234.6 1 7 NH 3 H H H 1-menthylO 222.2d 1 8 0 2 H H CH 3 CH 3 CH 2 0 167.8 4 9 0 2 H H CH 3 t-C A H 9 0 176.7 4 10 0 2 H H CH 3 PhCH 2 0 251.0 4 11 0 2 H H CH 3 Ph 2 CHO 222.3 4 12 NH 3 H H H CH 3 CH 2 0 147.1 2 13 NH 3 H H H 3-pyridinyl 230.8 2 14 NH 3 H H H N-morpholin l- 214.8 2 CH 2 (CH 3 )CH 15 NH 3 H H H 2-ClPh 231.4 5 16 NH 3 H H H 4-Cl?h * 230.5 5 17 NH 3 H H H 4-N0 2 Ph 247.0 5 18 NH 3 H H H 2-HOPh 256.0 5 19 NH 3 H H H 3-N0 2 Ph 101.7 5 20 NH 3 H H H CNCH 2 176.2 5 21 NH 3 H H H 3-pyridinyl 230.3 5 22 NH 3 H H H 2 - fur any 1 276.0 5 3 NH 3 H H H 3,5-(N0 2 ) 2 Ph 285.2 5 24 0 2 H H CH 3 H 185.6 3 25 0 2 H H CH 3 CH 3 178.0 3 26 0 2 H H CH 3 CH 3 CH 2 123.9 3 27 0 2 H H CH 3 CH 3 CH 2 CH 2 160.1 3 28 0 2 H H CH 3 i-C 3 H 2 139.6 3 29 0 2 H H CH 3 c-C 3 H 5 223.3 3 30 0 2 H H CH 3 PhO 176.0 3 31 NH 3 H H H H 213.7 2 32 NH 3 H H H CH 3 0 124.5 3 33 NH 3 H H H PhCH, 0 166.9 3- ■ 21- TABLE A (cont'd) 34 NH 3 H H H Ph 237.3 3 + 35 NH 3 H H H CH 3 CH 2 CH 2 227.0 3 36 NH 3 H H H PhCH- 209.9 3 - 37 NH 3 H H H 2-CH 3 Ph 273.9 3 - 38 NH 3 H H H 3,5-(CH 3 0) 2 Ph 244.2 5 - 39 NH 3 H H H 2-CH 3 OPh 144.8 3 + 40 NH 3 H H H 3-CH 3 OPh >300° 3 - 41 NH 3 H H H 4-CH 3 0Ph 255.9 5 - 42 NH 3 H H H 2-PhOPh 226.8 5 - 43 MH 3 H H H 1 - naphthyl 300°d 5 + 44 NH 3 H H H 4-PhPh 255.2 5 + 45 NH 3 H H H 3,4-(CH 3 0) 2 Ph 206.0 5 - 46 NH 3 H H H 2,5-(CH 3 0) 2 Ph 204.3 5 - 47 NH 3 H H CH 3 2-HOPh 249.7 5 - 48 NH 3 H H CH 3 Ph 232.3 5 + 49 NCH 2 Ph 3 H H CH 3 CH 2 CH 3 CH 2 CH 2 177.4 6 - 50 NH 3 5- Br H H CH 3 CH 2 CH 2 256.4 2 - 51 NH 3 H H H 4-pyridinyl 160.8 3 - 52 NH 3 5- Br H H CH 3 CH 2 0 177.8 3 - 53 NH 3 5- Br H H Ph 241.7d 3 - 54 NH 3 5- Br H H 4-pyridinyl >300 2 - 55 NH 3 5- Br H H c-C 6 H χχ 244.9 2 - 56 NCH 2 Ph 3 H H CH 3 CH 2 CH 3 CH 2 0 102.5 2 - 57 NCH 2 Ph 3 H H CH 3 CH 2 Ph 175.0 2 - 58 NCH 2 Ph 3 H H CH 3 CH 2 4-pyridinyl 200.8 7 - 59 NCH 2 Ph 3 H H CH 3 CH 2 c-C 6 H χχ CH 2 180.5 7 - 60 NCH 2 Ph 3 H H CH 3 CH 2 c-C A H 7 185.7 7 - 61 NCH 2 Ph 3 H H CH 3 CH 2 H 195.2 7 - 62 NCH 2 Ph 3 H H CH 3 CH 2 4-ClPh 138.8 2 - 63 NCH 2 Ph 3 H H CHgClL, 4-CH 3 Ph 158.7 2 - 64 NCH 2 Ph 3 H H CH 3 CH- CH 3 195.9 2 - 65 NH 3 H H H 4-CH 3 Ph >300 2 + 66 NH 3 H H H c-C A H 7 254. Od 2 + 67 NH 3 H 2- CH 3 H CH 3 CH 2 0 138.8 7 + 68 NH 3 H 2- CH 3 H 4-pyridinyl >300 2 -22- TABLE A (cont'd) c V a Ex S 2 * C) ? £3 X .D. C 69 NH 3 H 2- •CH- H CH 3 CH 2 CH 165.5 2 70 NH 3 H 2- CH 3 H CH 3 CH 2 176.0 2 71 NH 3 H 2- ■ CH 3 H c-C 3 H 5 117.2 2 72 NH 3 H 2- ■ CH 3 H i-C 3 H 7 202.2 2 73 NH 3 H H H CH 3 261.4 7 74 NH 3 H H H c-C 6 H χχ CH 2 249.3 7 75 NH 3 H H H c-C 5 H χχ CH 2 CH 2 228.8 7 76 NH 3 H H H c-C 6 H χχ CH 2 CH 2 229.7 7 77 NH 3 H H H i-C 3 H 7 >300 7 78 NH 3 H H CH 3 CH 3 CH 2 CH 2 166.5 7 79 NH 3 H H CH 3 CH 3 CH 2 0 140.7 7 80 NH 3 H H CH 3 4-pyridinyl 246.9 7 81 0 2 H H CH 3 H 185.6 3 82 0 2 H H CH 3 CH 3 178.0 3 83 0 2 H H CH 3 CH 3 CH 2 123.9 3 84 0 2 H H CH 3 CH-a CH CH 2 160.1 3 85 0 2 H H CH 3 i-C 3 H 7 139.6 3 86 0 2 H H CH 3 c-C 3 H 5 223.3 3 87 NH 3 H H H c-C 6 H χχ 220.2 7 88 NH 3 H 2- •CH 3 H c-C 6 H χx 223.6 7 89 NH 3 K 2- •CH 3 H 4-t-C A H g Ph 269.9 7 90 NH 3 H 2- • CH- H 4-CF 3 Ph 210.8 7 91 NH 3 H 2- • CH 3 H 3,4-(CH 3 0) 2 PhCH 2 119.7 7 92 NH 3 H 2- •CH 3 H PhCH 2 0 168.3 7 93 NH 3 H 2- •CH 3 H 4-CH 3 Ph 260.1 7 94 NH 3 H 2- ■ CH 3 H 2-ClPh 211.6 7 95 NH 3 H 2- ■CH 3 H 4-ClPh 284.6 7 96 NH 3 H 2- CH 3 H 3-pyridinyl 271.5 7 97 NH 3 H 2- CH 3 H t-C A H g O 131.8 7 98 NH 3 H 2- •CH 3 H 4-CH 3 0Ph 227.1 7 99 NH 3 5-Br H H i-C 3 H 7 230.4 3 100 NH 3 5-Br H H 4-t-C A H g Ph 260.7 3 101 0 2 H H CH 3 CH 3 0 154.4 2 102 0 2 H H CH 3 1-menthyl 189.7 3 103 0 2 H H CH 3 c-C 5 H lχ 209.0 3 ■ 23- TABLE A (cont'd) C X a S. s 2 s 3 X m.o.rc. P H 104 0 2 H H CH 3 c-C 6 H χχ CH 2 165.0 3 - 105 0 2 H H CH 3 c-C 6 H χχ CH 2 CH 2 153.2 3 - 106 0 2 H H CH 3 CH 3 CH 2 0CH 2 CH 2 109.0 3 - 107 0 2 H H CH 3 chrysanthemyl 154.2 3 - 108 0 2 H H CH 3 PhCH- 200.0 2 - 109 0 2 H H CH 3 4-CH 3 OPhCH 2 0 171.5 3 - 110 0 2 H H CH 3 Ph 164.0 3 - 111 0 2 H H CH 3 2-ClPh 160.6 3 - 112 0 2 H H CH 3 2-CH 3 OPh 131.9 3 - 113 0 2 H H CH 3 3-CH30Ph 146.9 3 - 114 0 2 H H CH 3 4-CH 3 OPh 194.1 3 - 115 0 2 H H CH 3 2-CH 3 Ph 159.5 3 - 116 0 2 H H CH 3 3-CH 3 Ph 160.0 3 - 117 0 2 H H CH 3 4-CH 3 Ph 210.5 3 - 118 S 3 H H CH 3 CH 3 CH2CH 2 146.5 7 - 119 s 3 H H CH 3 CH 3 CH 2 0 135.5 6 - 120 s 3 H H CH 3 Ph 185.2 6 - 121 s 3 H H CH 3 4-pyridinyl 239.3 7 - 122 s 3 H H CH 3 c-C 6 H χχ 206.1 2 - 123 s 3 H H CH 3 CH 3 CH 2 155.6 7 - 124 s 3 H H CH 3 c-C 6 H χχ CH 2 CH 2 157.7 7 - 125 s 3 H H CH 3 PhCH 2 0 149.5 6 - 126 s 3 H H CH 3 2-ClPh 197.1 6 - 127 s 3 H H CH 3 3-ClPh 190.2 6 - 128 s 3 H H CH 3 4-ClPh 186.3 6 - 129 s 3 H H GH 3 1-menthyl 0 152.3 6 - 130 s 3 H H CH 3 4-CH 3 Ph 175.7 6 - 131 s 3 H H CH 3 4-CH 3 CH 2 0Ph 163.4 6 - 132 s 3 H H CH 3 3,5-(CH 3 0) 2 Ph 167.7 6 - 133 s 3 H H CH 3 4-CF 3 Ph 184.3 6 - 134 s 3 H H CH 3 4-t-C H g Ph 162.4 6 - 135 s 3 H H CH 3 4-(CH 3 ) 2 NPh 213.2 7 - 136 s 3 H H CH 3 2 - furanyl 154.4 6 - 137 s 3 H H CH 3 2 - thienyl 172.6 6 - 138 NH 3 2-CH 3 H H Ph 224.2 7. + 139 NH 3 H H H 4-t-C A H 9 Ph 265.9 2 - •24- TABLE A (cont'd) 140 NH 3 H H H c-C 3 H 5 272.5 2 141 NH 3 H H H 3-CH 3 Ph 213.0 2 142 NH 3 H H H 2-CH 3 CH 2 OPh 209.1 2 143 NH 3 H H H l-naphthylCH 2 236.3 2 144 NH 3 H H H 4-CH 3 OPhCH 2 0 178.8 2 145 NCOCH 3 3 H H H n-C 3 H 7 199.8 2 146 NCOCH 3 3 H H H CH 3 CH 2 0 241.0 2 147 NCOCH 3 3 H H H Ph 236.9 2 148 NC0CH 3 3 H H H 4-pyridinyl 250.1 2 149 NC0CH 3 3 H H H c-C 5 H χι 271.1 2 150 NCOCH 3 3 H H H c-C 3 H 7 260.2 2 151 NCOCH 3 3 H H H i-C 3 H 7 227.6 2 152 NCOCH 3 3 H H H c-C A H 7 239.7 2 153 NC0CH 3 3 H H H t-C A H g O 215.2 2 154 NCOCH 3 3 H H H 4-CH 3 Ph 250.0 2 155 NCOCH 3 3 H H H 3-CH 3 Ph 251.9 2 156 NCOCH 3 3 H H H l-naρhthylCH 2 276.1 2 157 NCOCH 3 3 H H H 2-CH 3 CH 2 0Ph 201.6 2 158 NC0CH 3 3 H H H 4-CH 3 CH 2 OPh 232.7 2 159 NCOCH 3 3 H H H 4-t-C H 9 Ph 256.3 2 160 NCOCH 3 3 H H H 3,4-(CH 3 0) 2 PhCH 2 186.7 2 161 NH 3 H 2-CH 3 H CH 3 0 152.7 8 162 NH 3 H 2-CH 3 H 2,5-(Cl) 2 Ph 223.6 8 163 NH 3 H 2-CH 3 H 4-CH 3 CH 2 0Ph 221.0 2 164 NH 3 H 2-CH 3 H CH 3 >300 2 165 NH 3 H 2-CH 3 H c-C 6 H χι CH 2 CH 2 182.1 8 166 NH 3 H 2-CH 3 H c-C 6 H χχ CH 2 174.7 8 167 NH 3 H 2-CH 3 H PhCH 2 188.5 2 168 NH 3 H 2-CH 3 H c-G A H 7 173.8 8 169 NH 3 H 2-CH 3 H 3-CH 3 Ph >300 8 170 NH 3 H 2-CH 3 H 2-CH 3 Ph 160.4 8 171 NH 3 H 2-CH 3 H 2-PhOPh 217.8 2 172 NH 3 H 2-CH 3 H 2-CH 3 OPh >300 8 173 NC0CH 3 3 H H H CH 3 0 231.4 2 174 NC0CH 3 3 H H H 2,5-(Cl) ' 2 Ph 221.9 2 175 NGOCHg 3 H H H 3-pyridinyl 229.3 2 •25- TABLE A (cont'd) 176 NCOCH- 3 H H H 4-ClPh 253.4 2 - 177 NC0CH 3 3 H H H 2-ClPh 222.3 2 - 178 NC0CH 3 3 H H H 3-ClPh 228.2 2 - 179 NCOCH 3 3 H H H c-C 6 H χχ CH 2 CH 2 224.4 2 - 180 NCOCH- 3 H H H 4-CH 3 0Ph 228.7 2 - 181 NCOCH 3 3 H H H PhCH- 232.4 2 - 182 NCOCH 3 3 H H H 4-CF 3 Ph 258. Od 0 - 183 NCOCH 3 3 H H H 2-CH 3 Ph 244.3 2 - 184 NCOCH 3 3 H H H 2-PhOPh 216.5 2 - 185 NCOCH 3 3 H H H 2-CH 3 OPh 200.9 2 + 186 NCOCH 3 3 H H H 4-CH 3 0PhCH 2 0 236.6 2 - 187 NCOCH 3 3 H H H PhCH- O 248.0 2 - 188 NCOCH 3 3 H H H 2-thienyl 245.5 2 - 189 NCOCH 3 3 H H H 2 - fur any 1 221.4 2 + 190 NCOCH 3 3 H H H 3 - CH 3 OPh 210.9 2 - 191 NCOCH 3 3 H H H 3,5-(CH 3 0) 2 Ph 239.7 2 - 192 NCOCH 3 3 H H H 2,5-(CH 3 0) 2 Ph 212.0 2 - 193 NCOCH 3 3 H H H 4-(CH 3 ) 2 NPh 265.9 2 - 194 NH 3 5-PhCH 2 0 H H n-C 3 H 7 215.2 8 - 195 NH 3 5-PhCH 2 0 H H CH 3 CH 2 0 104.5 8 + 196 NH 3 5-PhCH 2 0 H H Ph 257.3 5 + 197 NH 3 5-PhCH 2 0 H H 4-pyridinyl 290.7 5 + 198 NH 3 5-PhCH 2 0 H H c-C 3 H 5 285.1 5 - 199 NH 3 5-PhCH 2 0 H H i-C 3 H 7 >300 5 - 200 NH 3 5-PhCH 2 0 H H l-naphthylCH 2 120.3 5 + 201 NH 3 H 2- CH 3 H l-naphth lCH 2 233.9 2 + 202 NH 3 H 2- CH 3 H 3-CH 3 0Ph 202.3 2 + 203 NH 3 H 2- CH 3 H 3,5-(CH 3 θ) 2 Ph >300 2 + 204 NH 3 H 2- CH 3 H S-CHgCH- j OPh 249.4 2 + 205 NH 3 H 2- CH 3 H 3,4-(CH 3 0) 2 Ph 291.2 2 + 206 NCOCH 3 3 H H H 3-CH 3 CH 2 0Ph 173.1 2 + 207 NH 3 H H H 4-CF 3 Ph 225.8 2 + 208 NH 3 H 5- PhCH 2 0 H c-C 6 H χχ >300 5 + 209 NH 3 H 2- CH 3 H 4-(CH 3 ) 2 NPh 182.0 2 + 210 NH 3 H 2- CH 3 H 4-CH 3 0PhCH 2 0 140.8 8 - 211 NH 3 H 2- CH 3 H 2-thienyl 245.4 2 + -26- TABLE A (cont'd) c • V_. a Si s 2 s 3 X m.p.T -C) P 212 NH 3 H 2- CH 3 H 2 -fur any 1 133.4 2 213 NH 3 H 2- CH 3 H 2,5-(CH 3 0) 2 Ph 189.9 2 214 NC0CH 3 3 H H H 3,4,5-(CH 3 0) 3 Ph 237.2 2 215 NCOCH 3 3 H H H 3,4-(CH 3 0) 2 Ph 217.4 2 216 NC0CH 3 3 H H H CH 3 CH 2 0CH 2 CH 2 177.5 2 217 NCOCH 3 3 H H H 4-H 2 NPh 269.7 2 218 NCOCHg 3 H H H CH 3 CH 2 224.6 2 219 NC0CH 3 3 H H H CH 3 269.0 2 220 NH 3 H H H CH 3 CH 2 OCH 2 CH 2 206.4 2 221 NH 3 H H H 4-H 2 NPh 290.9 2 222 0 3 H H CH 3 l-naphthylCH 2 235.2 8 223 0 3 H H CH 3 3-ClPh 186.4 8 224 0 3 H H CH 3 4-ClPh 219.8 8 225 0 2 H H CH 3 2-PhOPh 170.1 8 226 0 2 H H CH 3 2-CH 3 CH 2 0Ph 169.8 8 227 0 2 H H CH 3 4-CH 3 CH 2 0Ph 212.3 8 228 0 2 H H CH 3 4-t-C H 9 Ph 214.0 8 229 0 2 H H CH 3 4-CF 3 Ph 212.8 2 230 0 2 H H CH 3 4-(CH 3 ) 2 NPh 225.1 2 231 0 2 H H CH 3 2,5-(CH 3 0) 2 Ph 185.6 2 232 0 2 H H CH 3 3,4-(CH 3 )) 2 Ph 162.4 2 233 0 2 H H CH 3 2 - f uranyl 195.9 2 - 234 0 2 H H CH 3 3-pyridinyl 172.0 2 - 235 0 2 H H CH 3 2,5-(Cl) 2 Ph 190.3 2 - 236 0 2 H H CH 3 3,5-(CH 3 0) 2 Ph 196.0 2 - 237 0 2 H H CH 3 2-thienyl 224.9 2 - 238 0 2 H H -CH 3 4-pyridinyl 239.6 2 - 239 0 2 H H CH 3 3,4,5-(CH 3 0) 3 Ph 186.9 2 - 240 0 2 5- NO- H CH 3 CH 3 CH 2 0 208.1 2 - 241 0 2 5- NO. H CH 3 c-C 6 H χχ CH 2 CH 2 179.0 2 - 242 0 2 5- NO- H CH 3 c-C 6 H lχ 245.9 2 - 243 0 2 5- NO. H CH 3 C^CE, 238.6 2 - 244 0 2 5- N0 2 H CH 3 PhO 177.6 2 - 245 0 2 5- N0 2 H CH 3 PhCH 2 0 202.6 2 - 247 NH 3 H 2- CH 3 H 3-ClPh 219.5 8 248 0 3 H H CH 3 0CH 2 CH 3 170.2 9 - -27- TABLE A (cont'd) 249 0 3 H H CH 3 PhCH 2 0 176.6 9 250 0 3 H H CH 3 n-C 3 H 7 159.1 9 251 0 3 H H CH 3 c-C 6 H χχ 190.5 10 252 0 3 H H CH 3 CH 3 CH 2 189.9 10 253 0 3 H H CH 3 c-C 6 H χχ CH 2 CH 2 133.1 9 254 0 3 H H CH 3 4-pyridinyl 186.1 10 255 0 3 H H CH 3 2-ClPh 120.1 10 256 0 3 H H CH 3 3-ClPh 177.2 10 257 0 3 H H CH 3 4-CH 3 Ph 166.3 9 258 0 3 H H CH 3 4-CH 3 CH 2 OPh 177.6 10 259 0 3 H H CH 3 3,5-(CH 3 0) 2 Ph 217.7 10 260 0 3 H H CH 3 4-t-C A H g Ph 225.9 10 261 0 3 H H CH 3 4-(CH 3 ) 2 NPh 201.0 10 262 0 3 H H CH 3 2 - f uranyl 96.3 10 263 0 3 H H CH 3 2-thienyl 215.7 10 Note: n is 0 for compounds #1-247, inclusive; n is 1 for compounds s=248-263, inclusive. ■ 28 - TABLE 1 H. Contortus Clearance Compound No. P.O. I.P. 1 N.T. N.T. 2 26.5 N.T. 3 73.1 N.T. 4 99.5 N.T. 5 28.3 N.T. 10 6 Toxic N.T. 7 N.T. N.T. 8 N.T. N.T. 9 0 N.T. 10 N.T. N.T. 15 11 5.8 48.6 12 85.5 N.T. 13 87.5 N.T. 14 N.T. N.T. 15 48.0 N.T. 20 16 62.4 N.T. 17 N.T. N.T. 18 N.T. N.T. 19 N.T. N.T. 20 26.9 N.T. 25 21 * 22 N.T. N.T. 23 N.T. N.T. 24 N.T. N.T. 25 N.T. N.T. 30 26 N.T. N.T. 27 N.T. N.T. 28 N.T. N.T. 29 N.T. N.T. 30 0 N.T. 35 31 48.2 N.T. 32 50.0 N.T. - 29 - TABLE I (cont'd) H. Contortus % Clearance Compound No. P.O. I.P. 33 0 N.T. 34 0 N.T. 35 52.7 N.T. 36 25.5 N.T. 37 40.9 N.T. 10 38 25.5 N.T. 39 N.T. N.T. 40 0+ N.T. 41 22.7 N.T. 42 0 N.T. 15 43 0 N.T. 44 N.T. N.T. 45 1.4 N.T. 46 N.T. N.T. 47 N.T. N.T. 20 48 12.7 31.0 49 16.8 N.T. 50 49.8 N.T. 51 0 N.T. 52 80.3 N.T. 25 53 14.7 N.T. 54 0 N.T. 55 N.T. N.T. 56 0 N.T. 57 21.1 N.T. 30 58 N.T. N.T. 59 0 N.T. 60 N.T. N.T. 61 65.9 N.T. 62 0 N.T. 35 63 N.T. N.T. 64 94.9 N.T. • - TABLE I (cont'd) H. Contortus % Clearance Compound No. P.O. I.P. 65 0 N.T. 66 86.7 N.T. 67 98.6 N.T. 68 N.T. N.T. 69 99.2 N.T. 10 70 85.7 N.T. 71 0 N.T. 72 52.1 N.T. 73 44.4- N.T. 64.5 15 74 8.6 N.T. 75 N.T. N.T. 76 N.T. N.T. 77 N.T. N.T. 78 0 N.T. 20 79 99.5 N.T. 80 N.T. N.T. 81 96.0 N.T. 82 Toxic N.T. 83 49.6 N.T. 25 84 Toxic N.T. 85 * 86 * 87 N.T. N.T. 88 67.8 N.T. 30 89 24.5 N.T. 90 50.4 N.T. 91 56.7 N.T. 92 66.7 N.T. 93 39.8 N.T. 35 94 61.4 N.T. 95 44.2 N.T. 96 97.4 N.T. 00 o § oo O o 2, Tj O CM CO vt in vD 00 cr. β rv 00 cr. O O O O 0 O O 0 3 cr. cr. , cr. o P a o u ro CO vo © 00 Co Co ro ro t-n O ι_n O co o 23 2! 5 21 23 2J S3 S3 23 23 S3 23 25 2; 23 25 23 2J 23 2! 23 23 2* -3 25 23 2; H H HI H H H Hi H H H H H H H H H H H H H H ι-3 H H H H H ■ 33 - TABLE I (cont 'd) H. Contortus % Cl<sarance Compound No. P.O. I.P 166 65.1 N.T 167 97.9 N.T 168 N.T. N.T 169 N.T. N.T 170 N.T. N.T 10 171 N.T. N.T 172 N.T. N.T 173 N.T. N.T 174 N.T. N.T 175 N.T. N.T 15 176 0 N.T 177 N.T. N.T 178 N.T. N.T 179 N.T. N.T 180 N.T. N.T 20 181 N.T. N.T 182 N.T. N.T 183 N.T. N.T 184 N.T. N.T 185 N.T. N.T 25 186 N.T. N.T 187 N.T. N.T 188 N.T. N.T 189 N.T. N.T 190 N.T. N.T 30 191 N.T. N.T 192 N.T. N.T 193 N.T. N.T 194 0 N.T 195 N.T. N.T 35 196 63.9 N.T 197 N.T. N.T, 198 N.T. N.T, 199 0 N.T, ■ 34- TABLE I (cont'd) H. Contortus % Clearance Compound No. P.O. I.P. 200 N.T. N.T. 201 N.T. N.T. 202 N.T. N.T. 203 N.T. N.T. 204 N.T. N.T. 10 205 N.T. N.T. 206 N.T. N.T. 207 N.T. N.T. 208 N.T. N.T. 209 N.T. N.T. 15 210 N.T. N.T. 211 N.T. N.T. 212 N.T. N.T. 213 N.T. N.T. 214 N.T. N.T. 20 215 N.T. N.T. 216 N.T. N.T. 217 N.T. N.T. 218 53.5 N.T. 219 78.9 N.T. 25 220 N.T. N.T. 221 N.T. N.T. 222 N.T. N.T. 223 N.T. N.T. 224 71.8 N.T. 30 225 N.T. N.T. 226 N.T. N.T. 227 N.T. N.T. 228 N.T. N.T. 229 N.T. N.T. 35 230 N.T. N.T. 231 N.T. N.T. 232 N.T. N.T. 233 N.T. N.T. -35- TABLE I (cont'd) H. Contortus % CLaarance Compound No . P.O. I.P. 244 N.T. N.T. 245 N.T. N.T. 246 N.T. N.T. 247 61.5 N.T. 248 98.1 N.T. 249 62.5 N.T. 250 95.2 N.T. 251 69.4 N.T. 252 70.4 N.T. 253 N.T. N.T. 254 N.T. N.T. 255 N.T. N.T. 256 N.T. N.T. 257 N.T. N.T. 258 N.T. N.T. 259 N.T. N.T. 260 N.T. N.T. 261 N.T. N.T. 262 N.T. N.T. 263 N.T. N.T. N.T. - not tested - , means the compound was tested two or more times and the extreme values reported (for example, 23.7 - 26.6) I.P. - Intraperitoneal administration P.O. - oral administration + - 80 mgAg * Tested, Data inconclusive (due to failure of untreated controls) Toxic - Sheep died within 24 hr following treatment and were n examined for worms. - 36- TABLE IIA Anthelmintic Activity (Adult Worms) of Compound 11 in Lambs When Administered Orally at 100 mg/kg (Experiment 1 Parasite Percentage Clearance Haemonchus contortus 0 Trichuris ovis 14.5 Oesophagos omum venulosu 9.0 Trichostrongylus axei 52.7 Trichostrongylus colubriformls 0 Trichostrongylus spp. 47.9 Nematodirus spathiger 0 Thvsanosoma actinioides 54.5 - 37 - TABLE I IB Anthelmintic Activity (Adult Worms) of Compound sll in Sheep When Administered Orally at 100/mg kg (Experiment 2) Percentage Parasite Clearance Haemonchus 0 Ostertagia 0 Trichostrongylus 0 axei Trichostrongylus 42.0 colubriformis Cooperia 0 Nematodirus 7.7 Strongyloides 33.9 Trichuris 53.4 Oesphagostomum 33.3 -38- FORMULAE -39- CHA T A Scheme A: II III Scheme B: W is a halogen atom or other active group, for example, an anhydride

Claims: CLAIMS 1. A method of killing parasitic worms in humans and valuable warm¬ blooded domestic animals which comprises administering to humans or valuable warm-blooded domestic animals in need, a therapeutic or prophylactic dosage of an acylhydrazone, hydrate thereof or pharmaceutically acceptable salt thereof of the formula: wherein X is (a) hydrogen; (b) C χ -C χo alkyl; with the proviso that when X is n-propyl, R 3 is methyl, R χ and R 2 are hydrogen, the compound is other than a indol ' -3-yl acylhydrazone; (c) C 2 -C 6 alkenyl; (d) C 2 -C 6 alkynyl; (e) cyclo(C 3 -C χo )alkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C_-C 4 alkenyl, 0,-0^ alkoxy, trifluoro¬ methyl, or halo; with the proviso that when X is cyclopropyl, R_ is 2-methyl, R χ and R 3 are hydrogen, the compound is other than a indol- 3-yl acylhydrazone; (f) pyrrolidinyl; (g) piperidinyl; (h) 1- methylpyrrolidinyl; (i) 1-methylpiperidinyl; (j ) C--C- alkoxyalkyl; (k) cyclo(C 3 -C χo )alkyl(C χ -C lt ) lkyl; with the proviso that when X is cyclohexylmethyl, R χ and R 2 are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; (1) phenyl(C χ - C 4 )alkyl optionally substituted with one, 2 or 3 halo or C χ -C 4 alkoxy, or one or 2 trifluoromethyl; (m) phenoxy(C χ -C 4 )alkyl optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; (n) perhalo(C χ -C 7 )alkyl; (o) C χ -C 6 alkoxy, with the proviso that when X is t-butoxy and the compound is a 2-benzofuranyl acylhydrazone (IB) , and R χ and R- are hydrogen, R 3 is other than methyl; with the proviso that when X is ethoxy, R χ , R 2 and R 3 are hydrogen, the compound is other than a l-acetylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R 2 are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3- benzothiofuran acylhydrazone (IA) ; (p) diphenylmethoxy; (q) cyclo(C 3 - -41- C 5 )alkyloxy optionally substituted with one or two C χ -C 3 alkyl; (r) phenoxy optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; with the proviso that when X is phenoxy, R χ and R 2 are hydrogen and R 3 is methyl, the compound is other than a 2-benzo- furanyl acyhydrazone; (s) benzyloxy optionally substituted with one, 2 or 3 halo or C χ -C 4 alkoxy, or one or 2 trifluoromethyl; with the proviso that when X is benzyloxy and R χ , R 2 and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (t) heteroaromatic optionally substituted with one, 2 or 3 halo, or one or 2 trifluoro- methyl; (u) phenyl substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl, amino, alkyl(C χ -C 3 )amino, dialkyl(C χ -C 3 )amino, C χ -C 5 alkyl or C χ -C 3 alkoxy; with the proviso that when X is 4-ethoxyphenyl or 4-chloroρhenyl, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3-benzothIenyl acylhydrazone (IA) ; with the proviso that when X is 4-chlorophenyl, R χ and R 2 are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; with the proviso that when X is 4-methylphenyl, 3 ,4-dimethoxyphenyl or 3- methoxyphenyl and R χ , R- and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; with the proviso that when X Is 4- ethoxyphenyl, R χ , R- and R 3 are hydrogen, the compound is other than a l-acetylindol-3-yl acylhydrazone; (v) N-morpholinyl(C χ -C 4 )alkyl; (w) N-piperidinyl(C x -C 4 )alkyl; (x) N-pyrrolidinyl(C χ -C 4 )alkyl; (y) bridged polycyclic hydrocarbon substituents of six to 10 nuclear carbons, optionally substituted with one, 2 or 3 (C χ -C 3 ) alkyl groups (z) naphthyl(C χ -C 3 )alkyl optionally substituted with one, 2 or 3 C χ - C 4 alkyl, C χ -C 4 alkoxy, halo, or trifluoromethyl; wherein Y is an oxygen atom; a sulfur atom; or a N-Z group; wherein Z is hydrogen; C χ -C 4 alkyl; acetyl; benzoyl; phenyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C χ -C 3 alkoxy, halo, trifluoromethyl, C 2 -C 6 dialkylamino, C χ -C 3 alkylthio, nitro, or phenoxy optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C χ -C 3 alkoxy, halo, or trifluoromethyl; or phenyl(C χ -C 4 ) lkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C x -C 4 alkoxy, halo, or trifluoromethyl; wherein R χ is hydrogen; hydroxy; C χ -C 4 alkyl; C χ -C 3 alkoxy; C χ - C 3 alkylthio; halo; nitro; benzyloxy or trifluoromethyl; with the proviso that when R χ is benzyloxy, X is other than alkyl; and wherein R 2 is hydrogen; hydroxy; C x -C 4 alkyl; C x -C 3 alkoxy; C x - -42 - C 3 alkylthio; halo or trifluoromethyl; and wherein R 3 is hydrogen; C χ -C 4 alkyl; cyclo(C 3 -C- )alkyl optionally substituted with one, 2 or 3 C χ -C 3 alkyl; phenyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, halo, trifiuoro- methyl, or C, -C 3 alkoxy; phenyl(C χ -C 3 ) lkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, halo, trifluoromethyl, or C χ -C 3 alkoxy; or l,3-dioxacyclohexan-5-yl; n is 0 when Y is a sulfur atom or a N-Z group; n is 0 or 1 when Y is an oxygen atom. 2. The method according to Claim 1 wherein n is 0. 3. The method according to Claim 2 wherein the compound, hydrate or pharmaceutically acceptable salt thereof is a lH-indol-3-yl acyl- hydrazone. 4. The method according to Claim 2 wherein X is cyclobutyl, t- butoxy, ethoxy, ethyl or 3-pyridinyl. » 5. The method according to Claim 2 wherein R χ and R 2 are selected from the group consisting of hydrogen, methyl or a bromo atom. 6. The method according to Claim 2 wherein R 3 is hydrogen. 7. The method according to Claim 1 wherein the compound, hydrate or pharmaceutically acceptable salt thereof is selected from the group consis ing of: 1,1-dimeth lethy1 [(lH-indol-3-yl)methylene]carbazate (Cpd 4) ; ethyl [(lH-indol-3-yl)me hylene]carbazate (Cpd 12); nicotinic acid (lH-indol-3-yl)methylene]hydrazide (Cpd 13); ethyl [(5-bromo-lH-indol-3-yl)methylene]carbazate (Cpd 52); acetic acid [(l-phenylmethylindol-3-yl)propylidene]hydrazide (Cpd 64) ; cyclobutanecarboxylic acid [(lH-indol-3-methylene]hydrazide (Cpd 66); ethyl [(2-methyl-lH-indol-3-yl)methylene]carbazate (Cpd 67) ; butanoic acid [ (2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 69); -43 - propanoic acid [ (2-methyl-1H-indol-3-yl)methylene]hydrazide (Cpd 70); ethyl [(lH-indol-3-yl)ethylidene]carbazate (Cpd 79); formic acid [1- (3-benzofuranyl)ethylidene]hydrazide (Cpd 81); nicotinic acid [ (2-methyl-1H-indol-3-yl) ethylene]hydrazide (Cpd 96); 1,1-dimethylethyl [ (2-methyl-1H-indol-3-yl)methylene]carbazate (Cpd 97); butanoic acid [1- (3-benzothienyl)ethylidene]hydrazide (Cpd 118); propanoic acid [ (l-acetylindol-3-yl)methylene]hydrazide (Cpd 145); phenylacetic acid [ (2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 167); ethyl [1-(2-oxo-2H-l-benzopyran-3-yl)ethylidene]carbazate (Cpd 248); or butanoic acid [1-(2-oxo-2H-l-benzopyran-3-yl)ethylidene] - hydrazide (Cpd 250) . 8. A compound, hydrate thereof or pharmaceutically acceptable salt thereof of the formula wherein X is (a) hydrogen; (b) C χ -C χo alkyl; with the proviso that when X is n-propyl, R 3 is methyl, R χ and R j are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (c) C 2 -C 6 alkenyl; (d) C 2 -C 3 alkynyl; (e) eyelo(C 3 -C χo )alkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C 2 -C 4 alkenyl, C χ -C 4 alkoxy, trifluoro¬ methyl, or halo; with the proviso that when X is cyclopropyl, R 2 is 2-methyl, R χ and R 3 are hydrogen, the compound is other than a indol- 3-yl acylhydrazone; (f) pyrrolidinyl; (g) piperidinyl; (h) 1- methylpyrrolidinyl; (i) 1-methylpiperidinyl; (j) C 2 -C 6 alkox aIky1; (k) cyclo(C 3 -C χo )alkyl(C χ -C 4 )alk l; with the proviso that when X is cyclohexylmeth l, R χ and R 2 are hydrogen, R- j is ethyl, the compound -44- is other than l-benzylindol-3-yl acylhydrazone; (1) phenyl(C χ - C 4 )alkyl optionally substituted with one, 2 or 3 halo or C χ -C & alkoxy, or one or 2 trifluoromethyl; (m) phenoxy(C χ -C 4 )alkyl optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; (n) ρerhalo(C χ -C 7 )alkyl; (o) C χ -C 5 alkoxy, with the proviso that when X is t-butoxy and the compound is a 2-benzofuranyl acylhydrazone (IB), and R χ and R 2 are hydrogen, R 3 is other than methyl; with the proviso that when X is ethoxy, R χ , R 2 and R 3 are hydrogen, the compound is other than a l-acetylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R 2 are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3- benzothiofuran acylhydrazone (IA) ; (p) diphenylmethoxy; (q) cyclo(C 3 - C 5 )alkyloxy optionally substituted with one or two C χ -C 3 alkyl; (r) phenoxy optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; with the proviso that when X is phenoxy, R χ and R 2 are hydrogen and R 3 is methyl, the compound is other than a 2-benzo¬ furanyl acyhydrazone; (s) benzyloxy optionally substituted with one, 2 or 3 halo or C x -C 4 alkoxy, or one or 2 trifluoromethyl; with the proviso that when X is benzyloxy and R χ , R 2 and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (t) heteroaromatic optionally substituted with one, 2 or 3 halo, or one or 2 trifluoro¬ methyl; (u) phenyl substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl, amino, alkyl(C χ -C 3 )amino, dialkyl(C χ -C 3 )amino, C χ -C 5 alkyl or C χ -C 3 alkoxy; with the proviso that when X is 4-ethoxyphenyl or 4-chlorophenyl, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3-benzothienyl acylhydrazone (IA) ; with the proviso that when X Is 4-chlorophenyl, R χ and R 2 are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; with the proviso that when X is 4-methylphenyl, 3,4-dimethoxyphenyl or 3- methoxyphenyl and R χ , R g and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; with the proviso that when X is 4- ethoxyphenyl, R χ , R 2 and R 3 are hydrogen, the compound is other than a l-ac tylindol-3-yl acylhydrazone; (v) N-mόrpholinyl(C χ -C 4 )alkyl; (w) N-piperidinyl(C χ -C 4 )alkyl; (x) N-pyrrolidinyl(C χ -C 4 )alkyl; (y) bridged polycyclic hydrocarbon substituents of six to 10 nuclear carbons, optionally substituted with one, 2 or 3 (C χ -C 3 ) alkyl groups -45 - (z) naphthyl(C χ -C 3 )alkyl optionally substituted with one, 2 or 3 C χ - C 4 alkyl, C χ -C 4 alkoxy, halo, or trifluoromethyl; wherein Y is an oxygen atom; a sulfur atom; or a N-Z group; wherein Z is hydrogen; C- -C 4 alkyl; acetyl; benzoyl; phenyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C χ -C 3 alkoxy, halo, trifluoromethyl, C 2 -C 6 dialkylamino, C χ -C- alkylthio, nitro, or phenoxy optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C χ -C- alkoxy, halo, or trifluoromethyl; or phenyl(C x -C 4 )alkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C. -C 4 alkoxy, halo, or trifluoromethyl; wherein R χ is hydrogen; hydroxy; C- -C 4 alkyl; C χ -C- alkoxy; C χ - C 3 alkylthio; halo; nitro; benzyloxy or trifluoromethyl; with the proviso that when R χ is benzyloxy, X is other than alkyl; and wherein R- is hydrogen; hydroxy; C χ -C 4 alkyl; C χ -C- alkoxy; C χ - C 3 alkylthio; halo or trifluoromethyl; and wherein R 3 is hydrogen; C χ -C 4 alkyl; cyclo(C 3 -C 6 )alkyl optionally substituted with one, 2 or 3 C χ -C 3 alkyl; phenyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, halo, trifluoro¬ methyl, or C χ -C 3 alkoxy; phenyl(C χ -C 3 ) lkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, halo, trifluoromethyl, or C χ -C 3 alkoxy; or 1,3-dioxacyclohexan-5-yl; n is 0 when Y is a sulfur atom or a N-Z group; n is 0 or 1 when Y is an oxygen atom; other than acetic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 1016-49- 5); 4-aminobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 10245-42-8); 4-methoxybenzoic acid [ (l-methylindol-2-yl)methylene]hydrazide (CA RN 15565-86-3); 4-morpholineacetic acid (2-benzofuranylmethylene)hydrazide (CA RN 72627-58-8); (2-chlorophenoxy)acetic acid (1H-indol-3-ylmethylene)hydrazide (CA RN 81111-25-3); (4-chlorophenoxy)acetic acid (lH-indol-3-ylmethylene)hydrazide (CA RN 81111-26-4); (2-chlorophenoxy)acetic acid [(2-methoxy-lH-indol-3-yl)methyl- ene]hydrazide (CA RN 81122-74-9); (4-chloroρhenoxy)acetic acid [(2-methoxy-lH-indol-3-yl)methyl- ene]hydrazide (CA RN 81122-75-0); methyl (1H-indol-3-ylmethylene)carbazate (CA RN 88692-99-3); phenylmethyl [1- (lH-indol-3-yl)propylidene]carbazate (CA RN 32947-16-3); 1-piperidineacetic acid [(2-methyl-3-benzofuranyl)methylene] - hydrazide (CA RN 35806-44-1); 1-pyrrolidineacetic acid (2-benzofuranylmethylene)hydrazide (CA RN 35806-70-3); 1-piperidineacetic acid (2-benzofuranylmethylene)hydrazide (CA RN 35806-85-0); 1-pyrrolidineacetic acid [(2-methyl-3-benzofuranyl)methylene] - hydrazide (CA RN 35802-00-9); formic acid [ (lH-indol-2-yl)methylene]hydrazide (CA RN 50335-88- 1); ethyl (lH-indol-2-ylmethylene)carbazate (CA RN 50335-89-2); ethyl [l-(2-benzofuranyl)ethylidene]carbazate (CA RN 56968-94- 6); ethyl [1-(5-chloro-2-benzofuranyl)ethylidene]carbazatε (CA RN 56968-95-7); 1,1-dimethylethyl (lH-indol-3-ylmethylene)carbazate (CA RN 57699-52-2); 4-aminobenzoic acid [(lH-Indol-3-yl)methylene]hydrazide (CA RN 15641-21-1); butyric acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 15641- 24-4); propionic acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 15641- 25-5); ethyl [(1H-indol-3-yl)methylene]carbazate (CA RN 15641-27-7); formic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-28-8); acetic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-29-9); propanoic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-30-2); butanoic acid [(l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-31-3); 2-methylpropanoic acid [ (l-methylindol-2-yl)methylene]hydrazide -47 - (CA RN 15641 - 32 -4) ; phenylacetic acid [ (l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-34-6); 4-chlorobenzoic acid [ (l-methylindol-2-yl)methylene]hydrazide (CA RN 15641-36-8); 1-naphthaleneacetic acid [ (l-methylindol-2-yl)methylene] - hydrazide (CA RN 15641-38-0); ethyl [(l-methylindol-2-yl)methylene]carbazate (CA RN 15565-88- 5); 4-chlorobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-01-7); 2-chlorobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-03-9); 3-chlorobenzoic acid [ (1H-indol-3-yl)methylene]hydrazide (CA RN 15641-04-0); 2,4-dichlorobenzoic acid [(1H-indol-3-yl)methylene]hydrazide (CA RN 15641-05-1); 4-bromobenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-06-2); 2-methylpropanoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-12-0); 4-methoxybenzoic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-15-3); phenylacetic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-17-5); 1-naphthaleneacetic acid [ (lH-indol-3-yl)methylene]hydrazide (CA RN 15641-18-6); 2-furoic acid [(1H-indol-3-yl)methylene]hydrazide (CA RN 15641- 19-7); 2-naphthaleneacetic acid [(lH-indol-3-yl)methylene]hydrazide (CA RN 15718-86-2): ethyl [l-(lH-indol-3-yl)ethylidene]carbazate (CA RN 32927-03-0); phenylmethyl 3- [ (lH-indol-3-yl)methylene]carbazate (CA RN 32927- 05-2); phenylmethyl [l-(lH-indol-3-yl)ethylidene]carbazate (CA RN 32927-06-3); ethyl [(l-methylindol-3-yl)methylene]carbazate (CA RN 32927-89- 2); -48 - ethyl [l-(lH-indol-3-yl)propylidene]carbazate (CA RN 32947-13- 0). 9. A Compound, hydrate or pharmaceutical acceptable salt threof according to Claim 8 where n is 0. 10. A compound, hydrate or pharmaceutically acceptable salt thereof according to Claim 9 wherein X is selected from cyclobutyl, t-butoxy, ethoxy, ethyl or 3-pyridinyl. 11. A compound, hydrate or pharmaceutically acceptable salt thereof, according to Claim 9 wherein Y is N-Z and Z is hydrogen. 12. A compound, hydrate or pharmaceutically acceptable salt thereof, according to Claim 9 wherein R χ and R 2 are selected from the group consisting of hydrogen, methyl or a bromo atom. 13. A compound, hydrate or a pharmaceutically acceptable salt thereof, according to Claim 9 wherein R 3 is hydrogen. 14. A compound, hydrate or pharmaceutically acceptable salt thereof, according to Claim 8 selected from the group consisting of 1,1-dimethylethyl [(lH-indol-3-yl)methylene]carbazate (Cpd 4); ethyl [ (lH-indol-3-yl)methylene]carbazate (Cpd 12); nicotinic acid (lH-indol-3-yl)methylene]hydrazide (Cpd 13) ; ethyl [ (5-bromo-lH-indol-3-yl)methylene]carbazate (Cpd 52); acetic acid [(l-ρhenylmethylindol-3-yl)propylidene]hydrazide (Cpd 64) ; cyclobutanecarboxylic acid [ (lH-indol-3-methylene]hydrazide (Cpd 66); ethyl [ (2-methyl-lH-indol-3-yl)methylene]carbazate (Cpd 67) ; butanoic acid [ (2-methyl-1H-indol-3-yl)methylene]hydrazide (Cpd 69); propanoic acid [(2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 70); ethyl [(lH-indol-3-yl)ethylidene]carbazate (Cpd 79) ; formic acid [l-(3-benzofuranyl)ethylidene]hydrazide (Cpd 81); nicotinic acid [(2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd ■49 - 96 ) ; 1, 1-dimethylethy1 [ (2-methyl-lH-indol-3-yl)methylene]carbazate (Cpd 97); butanoic acid [1- (3-benzothienyl)ethylidene]hydrazide (Cpd 118); propanoic acid [ (l-acetylindol-3-yl)methylene]hydrazide (Cpd 145); phenylacetic acid [ (2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 167); ethyl [1-(2-oxo-2H-l-benzopyran-3-yl)ethylidene]carbazate (Cpd 248); or butanoic acid [1- (2-oxo-2H-l-benzopyran-3-yl)ethylidene] - hydrazide (Cpd 250) . 15. An anthelmintic composition for administration to animals comprising a physiologically acceptable carrier and adjuvants, and at least an effective anthelmintic amount of a acylhydrazone, hydrate or pharmaceutically acceptable salt thereof of the formula: wherein X is (a) hydrogen; (b) C χ -C χo alkyl; with the proviso that Λen X is n-propyl, R- j is methyl, R 1 and R 2 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (c) C 2 -C 6 alkenyl; (d) C 2 -C 3 alkynyl; (e) cyclo(C 3 -C χo )alkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C 2 -C 4 alkenyl, C χ -C 4 alkoxy, trifluoro- methyl, or halo; with the proviso that when X is cyclopropyl, R 2 is 2-methyl, R χ and R 3 are hydrogen, the compound is other than a indol- 3-yl acylhydrazone; (f) pyrrolidinyl; (g) piperidinyl; (h) 1- methylpyrrolidinyl; (i) 1-methylpiperidinyl; (j) C 2 -C 5 alkoxyalkyl; (k) cyclo(C 3 -C χ0 )alkyl(C χ -C 4 )alkyl; with the proviso that when X is cyclohexylmethyl, R t and R 2 are hydrogen, R j is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; (1) phenyl(C χ - C 4 )alkyl optionally substituted with one, 2 or 3 halo or C χ -C 4 alkoxy, or one or 2 trifluoromethyl; (m) phenoxy(C x -C 4 )alkyl - 50 - optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; (n) perhalo(C χ -C 7 )alkyl; (o) C χ -C 5 alkoxy, with the proviso that when X is t-butoxy and the compound is a 2-benzofuranyl acylhydrazone (IB), and R χ and R 2 are hydrogen, R- is other than methyl; with the proviso that when X is ethoxy, R. , R 2 and R 3 are hydrogen, the compound is other than a l-acetylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R- are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; with the proviso that when X is ethoxy, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3- benzothiofuran acylhydrazone (IA) ; (p) diphenylmethoxy; (q) cyclo(C 3 - C 6 )alkyloxy optionally substituted with one or two C χ -C 3 alkyl; (r) phenoxy optionally substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl; with the proviso that when X is phenoxy, R χ and R- are hydrogen and R 3 is methyl, the compound is other than a 2-benzo¬ furanyl acyhydrazone; (s) benzyloxy optionally substituted with one, 2 or 3 halo or C χ -C 4 alkoxy, or one or 2 trifluoromethyl; with the proviso that when X is benzyloxy and R χ , R 2 and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; (t) heteroaromatic optionally substituted with one, 2 or 3 halo, or one or 2 trifluoro¬ methyl; (u) phenyl substituted with one, 2 or 3 halo, or one or 2 trifluoromethyl, amino, alkyl(C χ -C 3 )amino, dialkyl(C χ -C 3 )amino, C χ -C 5 alkyl or C χ -C 3 alkoxy; with the proviso that when X is 4-ethoxyphenyl or 4-chloroρhenyl, R χ and R 2 are hydrogen, R 3 is methyl, the compound is other than a 3-benzothienyl acylhydrazone (IA) ; with the proviso that when X is 4-chlorophenyl, R χ and R-, are hydrogen, R 3 is ethyl, the compound is other than l-benzylindol-3-yl acylhydrazone; with the proviso that when X is 4-meth lphenyl, 3,4-dimethoxyphenyl or 3- methoxyphenyl and R χ , I<_- and R 3 are hydrogen, the compound is other than a indol-3-yl acylhydrazone; with the proviso that when X is 4- ethoxyphenyl, R χ , R-- and R 3 are hydrogen, the compound is other than a l-acetylindol-3-yl acylhydrazone; (v) N-morpholinyl(C x -C 4 )alkyl; (w) N-piperidinyl(C χ -C 4 )alkyl; (x) N-pyrrolidInyl(C- -C 4 )alkyl; (y) bridged polycyclic hydrocarbon substituents of six to 10 nuclear carbons, optionally substituted with one, 2 or 3 (C χ -C 3 ) alkyl groups (z) naphthyl(C χ -C 3 )alkyl optionally substituted with one, 2 or 3 C χ - C 4 alkyl, C χ -C A alkoxy, halo, or trifluoromethyl; wherein Y is an oxygen atom; a sulfur atom; or a N-Z group; - 51- wherein Z is hydrogen; C χ -C 4 alkyl; acetyl; benzoyl; phenyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C χ -C 3 alkoxy, halo, trifluoromethyl, C 2 -C 6 dialkylamino, C χ -C 3 alkylthio, nitro, or phenoxy optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C χ -C 3 alkoxy, halo, or trifluoromethyl; or phenyl(C χ -C 4 )alkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, C χ -C 4 alkoxy, halo, or trifluoromethyl; wherein R χ is hydrogen; hydroxy; C χ -C lι alkyl; C χ -C 3 alkoxy; C χ - C 3 alkylthio; halo; nitro; benzyloxy or trifluoromethyl; with the proviso that when R χ is benzyloxy, X is other than alkyl; and wherein R- is hydrogen; hydroxy; C x -C 4 alkyl; C χ -C 3 alkoxy; C χ - C 3 alkylthio; halo or trifluoromethyl; and wherein R 3 is hydrogen; C χ -C 4 alkyl; cyclo(C 3 -C 8 )alkyl optionally substituted with one, 2 or 3 C χ -C 3 alkyl; phenyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, halo, trifluoro¬ methyl, or C χ -C 3 alkoxy; phenyl(C x -C 3 )alkyl optionally substituted with one, 2 or 3 C χ -C 4 alkyl, halo, trifluoromethyl, or C χ -C 3 alkoxy; or 1, 3-dioxacyclohexan-5-yl; n is 0 when Y is a sulfur atom or a N-Z group; n is 0 or 1 when Y is an oxygen atom. 16. The composition of Claim 13 in which the compound, hydrate or pharmaceutically acceptable salt thereof is selected from the group consisting of 1,1-dimethylethyl [(lH-indol-3-yl)methylene]carbazate (Cpd 4) ; ethyl [ (1H-indol-3-yl)methylene]carbazate (Cpd 12); nicotinic acid (lH-indol-3-yl)methylene]hydrazide (Cpd 13); ethyl [(5-bromo-lH-indol-3-yl)methylene]carbazate (Cpd 52); acetic acid [ (1-phenylmethylindol-3-yl)propylidene]hydrazide (Cpd 64); cyclobutanecarboxylic acid [ (1H-indol-3-methylene]hydrazide (Cpd 66); ethyl [ (2-methyl-lH-indol-3-yl)methylene]carbazate (Cpd 67); butanoic acid [ (2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 69); propanoic acid [ (2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 70); ethyl [ (1H-indol-3-yl)ethylidene]carbazate (Cpd 79); - 52- formic acid [1-(3-benzofuranyl)ethylidene]hydrazide (Cpd 81); nicotinic acid [(2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 96); 1,1-dimethylethyl [ (2-methyl-1H-indol-3-yl)methylene]carbazate (Cpd 97); butanoic acid [1-(3-benzothienyl)ethylidene]hydrazide (Cpd 118); propanoic acid [ (l-acetylindol-3-yl)methylene]hydrazide (Cpd 145); phenylacetic acid [(2-methyl-lH-indol-3-yl)methylene]hydrazide (Cpd 167); ethyl [1-(2-oxo-2H-l-benzopyran-3-yl)ethylidene]carbazate (Cpd 248); or butanoic acid [1-(2-oxo-2H-l-benzopyran-3-yl)ethylidene] - hydrazide (Cpd 250) .

Inventors: CONDER GEORGE A, FOLZ SYLVESTER D, RECTOR DOUGLAS L, CONDER, GEORGE, A., FOLZ, SYLVESTER D., RECTOR, DOUGLAS, L.
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1987
Main classification: A61K31
IPC codes: A61K31, A61P33, C07D209, C07D307, C07D311, C07D333, C07D335, C07D401, C07D405, C07D409