US3145215A - Indazole derivatives - Google Patents

Description

United States Patent 0 3,145,215 INDAZOLE DERIVATIVES Frederick K. Kirchner, Bethlehem, N.Y., assiguor to Sterling Drug Inc, New York, N.Y., a corporation of Delaware No Drawing. Filed Dec. 19, 1961, Ser- No. 160,663 12 Ciaims. (Cl. 260--310) This invention relates to basic esters and amides.

The invention herein resides in the concept of compositions of matter having a molecular structure obtained when a 3-indazolecarbonyl group is joined through an --O or NH- bridge to the known types of tertiaryamino-lower-alkyl groups and their quaternary ammonium derivatives, together with a process for physically embodying such concept, and the utility inherent in the embodiments so produced.

The compounds of the invention are compounds of the generalized formula W-CO--XalkN:B, wherein W represents a S-indazole moiety, X represents a member of the group consisting of oxygen and imino, alk represents a member of the group consisting of alkylene having from two to six carbon atoms and having the free valences on different carbon atoms and oxa-alkylene having from four to eight carbon atoms and N=B represents a tertiaryamino group, and quaternary ammonium salts represented by the generalized formula WCOXalk-Q+An*, wherein Q represents quaternary ammonium, An represents an anion, and W, X, and alk have the same meaning as given above.

The symbol W, as used herein, represents an unsubstituted indazole or an indazole group substituted in the benzene ring by one or more substituents inert to the reaction conditions and reagents used in the process for preparing the compounds. Such inert substituents include, without limitation, lower-alkyl, lower-alkoxy, lower-alkylmercapto, lower-alkylsulfinyl, lower-alkylsulfonyl, halogen, nitro, dialkylamino and trifluoromethyl groups; as Well as additional hydrogen atoms, in which latter case the corresponding tetraliydro compounds result; and, the 3-indazolegroup can also include a lower-aliphatic hydrocarbon, monocarbocyclic aryl substituted lower-aliphatic hydrocarbon or monocarbocyclic aryl substituent on either of the nitrogen atoms of the pyrazole ring.

A particular aspect of the invention relates to basic esters and amides having, in the free base form, the formula Formula I and in the cation form the formula Formula 11 wherein Y is a member of the group consisting of hydro- Patented Aug. 18, 1964 gen, lower-alkyl, lower-alkoxy, lower-alkylmercapto, lower-alkylsulfinyl, loWer-alkylsulfonyl, nitro, halogen, trifluoromethyl, and amino; R is a member of the group consisting of hydrogen, lower-aliphatic hydrocarbon, phenyl and benzyl; X is a member of the group consisting of O and NH; alk is a member of the group consisting of alkylene having from two to six carbon atoms and having the free valences on diiierent carbon atoms and oxaalkylene having from four to eight carbon atoms; and N=B is a member of the group consisting of di-(loweralkyl)amino, l-pyrrolidinyl, lower-alkylated-l-pyrrolidinyl, piperidino, lower-alkylated-piperidino, morpholino, lower-alkylated-morpholino, thiomorpholino, loWer-alkylated-thio-morpholino, l-piperazinyl, 4-methyl-1-piperazinyl, 4-phenyl-l-piperazinyl, 1-hexamethyleniminyl, and 1- heptamethyleniminyl; and Z is lower-alkyl, lower-alkenyl or monocarbocyclic arylmethyl. The free bases of Formula I react with organic and inorganic acid to form acid-addition salts which are the full equivalents of the free bases.

In Formula I above, alk is a divalent saturated hydrocarbon bridge which joins the X atom and the nitrogen atom of N=B and intervenes two to five carbon atoms between the X and nitrogen atoms, and contains a total of two to six carbon atoms or alk is an oxaalkylene group having from four to eight carbon atoms. Thus, alk includes for example radicals such as CH CH CH(CHH )CH CH CH CH CH(CH )CH CH CH CH and the like when representing a divalent saturated hydrogen bridge and CH CHEHQCH OCH CH(CH )CH and the like when representing an oxaalkylene radical.

The radical Y in Formula I above represents a hydrogen atom or a loWer-alkyl, lower-alkoxy, lower-alkylmercapto, lower-alkylsulfinyl, lower-alkylsulfonyl, nitro, halogen, trifiuoromethyl or amino radical. The Y substituent lower-alkyl, lower-alkoxy, lower-alkylmercapto, lower-alkylsulfinyl and lower-alkylsulfonyl radicals have preferably from one to about six carbon atoms, thus including such radicals as methyl, ethyl, propyl, isopropyl, butyl, sec.- butyl, pentyl, hexyl and the like for lower-alkyl; methylmercapto, ethylmercapto, isopropylmercapto, n-hexylmercapto and the like for lower-alkylmercapto, methylsulfinyi, ethylsulfinyl, propylsulfinyl, pentylsulfinyl and the like for lower-alkylsulfinyl; methylsulfonyl, ethylsulfonyl, n-butylsulfonyl and the like for lower-alkylsulfonyl; and methoxy, ethoxy, propoxy, butoxy, isobutoxy, pentoxy, hexoxy and the like for lower-alkoxy. The halogen can be any of the halogens fluorine, chlorine, bromine or iodine.

The radical N=B in Formula I above is a basic, aliphatic-type disubstituted amino radical which contains 212 carbon atoms and includes: di-(lower-alkyl)amino wherein the two lower alkyl radicals are the same or ditierent, and each lower alkyl contains from one to six carbon atoms, for example dimethylamino, diethylamino, ethylmethylamino, isopropylmethylamino, diisopropylamino, ethyl-n-propylamino, di-(n-butyDamino, di-(nhexyl)amino, and the like; piperidino; lower-alkylatedpiperidino, that is piperidino bearing methyl and/ or ethyl substituted on the carbon atoms thereof, for example Z-methylpiperidino, 3-ethylpiperidino, 4-methylpiperidino, 2-methyl-4-ethylpiperidino, 2,6-dimethylpiperidino, and the like; morpholino; loWer-alkylated-morpholino, that is morpholino bearing methyl and/or ethyl substituted on the carbon atoms thereof, for example 2,6-dimethylmorpholino, 3-ethylrnorpholino, Z-methyl-S-ethylmorpholino and the like; thiomorpholino; lower-alkylated-thiomorpholino, that is thiomorpholino bearing methyl and/or ethyl substituted on the carbon atoms thereof, for example 2-methylthiomorpholino, 3-etliylthiomorpholino, 2,6-dirnethylthiomorpholinyl and the like; l-pyrrolidinyl; lower-alkylated-l-pyrrolidinyl, that is l-pyrrolidinyl bearing methyl and/or ethyl substituted'on the carbon atoms thereof for example 2-methyl-l-pyrrolidinyl, 3-ethyl-1- pyrrolidinyl, 3-methyl-4-ethyl-i-pyrrolidinyl, 2,5-dimethyl-l-pyrrolidinyl, and the like; l-hexamethyleniminyl; and l-heptamethyleniminyl. I

It will be understood of course that Formula I above represents the free base form of the compounds and Formula' 11 represents the quaternary ammonium salts'of the new bases when Z is lower-alkyl, lower-aikenyl or monocarbocyclic arylmethyl. As is readily apparent, the acidaddition salts (Z H) and the quaternary ammonium compounds possess the same structural nucleus as the bases, and the structure of the bases thus constitutes the common characteristic feature of the three forms of the basic esters and amides of the invention.

The quaternary ammonium salts of Formula II are obtained by the addition of lower-alkyl, lower-alkenyl, lower-alkynyl or monocarbocyclic arylmethyl esters of inorganic acids or organic sulfonic acids and having a molecular weight less than about 200 to the free base form of Formula 1. Thus Z in Formula II includes lower-alkyl containing from one to six carbon atoms, lower-alkenyl containing from three to six carbon atoms and monocarbocyclic arylmethyl containing seven to twelve carbon atoms. The quaternizing esters, which form a well-known class in the quaternary ammonium art, include such compounds as methyl chloride, methyl bromide, methyl iodide, ethyl bromide, propyl chloride, n-hexyl chloride, allyl chloride, allyl' bromide, propargyl bromide, methyl sulfate, methyl benzenesulfonate, methyl p-toluenesulfonate, benzyl chloride, benzyl bromide, pnitrobenzyl chloride, m-methoxybenzyl bromide, p-isopropylbenzyl chloride, o-chlorobenzyl chloride, and the like.

The compounds of the invention in free base form (Formula I) are produced by several different methods dependings on the particular basic ester or amide desired. The procedure of general applicability consists in interacting a tertiary-aminoalkylamine or tertiary-aminoalka- 1101 having the formula H-XAlkN=B wherein X, Alk and N:B have the meanings given above with the known diindazolo[2,3-a,2,3-d]pyrazine-7,l4-dione having the formula or its Bz-substituted derivatives and which acts as an acylating agent by virtue of the rupture of bonds indicated by the dotted lines in the above formula. The reaction is carried out under anhydrous conditions in an inert solvent as for example, benzene, toluene, xylene, chloroform, carbon tetrachloride or the like, and takes place at temperatures between about 50 C. and about 150 C., and the best mode for carrying out the reaction consists of selecting a solvent that boils in this range and conducting the reaction at the reflux temperature.

The diketopiperazine derivatives of indazole illustrated by the formula above are produced by the action of thionyl chloride on an appropriate indazole-3-carboxylic acid whereby, in effect, a molecule of water is removed from each of two indazole molecules which then condense with each other.

Another method for preparing the compounds of the invention comprises reacting an appropriately substituted lower-alkyl 3-indazolecarboxylate with a tertiary-aminoloWer-alkylamine or a tertiary-amino-lower-alkanol under conditions conventionally employed for amidation or esterification of carboxylic acids and their derivatives.

The intermediate substituted lower-alkyl 3-indazolecarboxylates are a known class of compounds which can be prepared either by treatment of selected hydrazones of lower-alkyl o-nitrophenylglyoxylates with alkali or from isatin and its derivatives.

The quaternary ammonium salts of Formula II are prepared in conventional fashion by interacting the free base and the quaternizing ester, either alone or in an inert organic solvent. Heating may be used to facilitate the reaction, but the quaternary salt formation usually takes place readily at room temperature. The quaternary ammonium salt separates directly or can be obtained by suitable concentration of the reaction solution or removal of the solvent. When the anion in a desired quaternary ammonium salt is the anion of a' Weak acid, and it is not ordinarily possible to employ direct quaternization, conversion of one quaternary ammonium salt to another in which the anion is different is carried out in the usual general fashion. Thus, a quaternary ammonium salt containing an anion which forms a water-insoluble silver salt is obtained by direct quaternization and then reacted with silver hydroxide in aqueous medium to form the corresponding quaternary ammonium hydroxide, the original anion being removed as a precipitate. The quaternary ammonium hydroxide solution produced in this fashion is then neutralized with the appropriate acid, either Weak or strong, to produce the desired new quaternary ammonium salt in which the anion is diiferent from that of the original salt. I

The acid-addition salt forms of the basic esters and amides of the invention are conveniently obtained by interacting the free bases with one equivalent of an organic or inorganic acid. The acid moieties or anions in these salt forms are in themselves neither novel nor critical and therefore can be any acid anion or acid-like substance capable of salt formation with the free base form of the compounds.

Compounds of this invention which were prepared as described in the following examples were found to be hypotensive agents. Thus, when tested in bilaterally encapsulated renal hypertensive rats having an elevated systolic blood pressure ranging between 1.62 and 193', they produced a reduction in systolic blood pressure ranging from 12 to 40 mm. of mercury. The results obtained for each of the indicated compounds were as follows: N-(2- dimethylaminoethyl)-3-indazolecarboxamide, 21, 35 and 38 mm. Hg at 1.25, 5 and 10 mg./kg. respectively; N-(3- diethylaminopropyl)-3-indazolecarboxamide, 12 and 20 mm. Hg at 1.25 and 5 mg./kg. respectively; N-(Z-dimethylaminoethyl) 4,5,6,7-tetrahydro-3-indazolecarboxamide, 33 and 25 mm. Hg at 2 and 8 mg./kg. respectively; N-[2-(l-piperidyl)ethyl]-3-indazolecarboxamide, 14 and 28 mm. Hg at 2 and 8 mg./kg. respectively; N-[2-(4- methyl l-piperazinyl)ethyl]-3-indazolecarboxamide, 18 mm. Hg at 2 mg./kg.; and N-(Z-diethylaminoethyl)-3- indazolecarboxamide, 27 and 20 mm. Hg at 2.5 and 5 mg./kg. respectively.

The structures of the compounds of this invention followed from the methods of synthesis which were used and from the elementary analyses of the products ob tained.

The invention is illustrated by the following examples without, however, being limited thereto.

EXAMPLE 1 N-(Z-Dimethylaminoethyl) -3-Indaz0lecarb0xamide To a solution of 14.4 g. of diindazolo[2,3-a,2,3'-d]- pyrazine-7,14'dione in 150 ml. of dry benzene was added dropwise 32.5 ml. of Z-dime-thylaminoethylamine with stirring. The mixture was refluxed for one-half an hour and the solid which separated was collected by filtration and washed with water. After recrystallization from nhexane there was obtained 26.4 g. of N-(Z-dimethylaminoethyl)-3-indazolecarboxamide, M.P. 117-119 C. (corn).

Analysis.-Calcd. for C H N O: C, 62.05; H, 6.94; N, 24.12. Found: C, 62.00; H, 6.94; N, 23.78.

The free base, N-(Z-dimethylaminoethyl)-3-indazolecarboxamide, was converted into its p-toluenesulfonate salt by solution in benzene followed by the addition of methyl p-toluenesulfonate. The oil which separated solidified upon cooling and the solid collected by filtration. Recrystallization from absolute ethanol gave white crystals of 3-(N-dimethylaminoethyl)indazolecarboxarnide methyl toluenesulfonate, M.P. 234-236 C. (corn).

Analysis.-Calcd. for C H N O S: C, 57.40; H, 6.26; S, 7.66. Found: C, 57.51; H, 6.12; S, 7.72.

EXAMPLE 2 3-Diethylaminopropyl-S-Indazolecarboxylate Hydrochloride A solution of 2.9 g. of 3-diethylamino-l-propanol in 20 ml. of toluene was added dropwise with stirring to a refluxing suspension of diindazolo[2,3-a,2,3'-d]pyrazine- 7,14-dione in 200 ml. of toluene. The mixture was refluxed for two hours then cooled to room temperature to cause the separation of a dark gum. The supernatant was decanted and the gum treated with ethereal hydrochloric acid. The solvent was again decanted and the tack-like gum refluxed with dry acetone. The solid which precipitated was removed by filtration and ether added to the filtrate to cause the separation of a tan solid which was collected by filtration. Recrystallization from an ethanolether mixture gave 2.7 g. of 3-diethylaminopropyl-3-indazolecarboxylate hydrochloride, M.P. 147-150 C. (corn).

AnaZysz's.Calcd. for C H ClN O Cl, 11.38; N, 13.48. Found: Cl, 11.27; N, 13.40.

EXAMPLE 3 N -(2-Dimethylamin0ethyl -4,5,6,7-Tetrahydr0- 3-Indaz0lecarb0xamide A mixture of 10 g. of tetrahydroindazole-3-carboxylic acid and 25 ml. of thionyl chloride was heated until solution was complete. The excess thionyl chloride was allowed to evaporate and the resulting solid taken up in toluene. After evaporation to dryness under reduced pressure ml. of dimethylaminoethylamine were added and the suspension heated until a clear solution resulted. The excess solvent and amine were removed by distillation under reduced pressure, and the residue dissolved in a 5% sodium bicarbonate solution. Extraction with benzene followed by evaporation of the solvent gave a solid which was recrystallized from a benzene-hexane mixture. There was thus obtained 8.7 g. of N-(Z-dimethylaminoethyl) 4,5,6,7-tetrahydro 3 indazolecarboxamide, M.P. 115-116 C. (corn).

Analysis.-C-alcd. for C H N O: C, 60.99; H, 8.53; N, 23.71. Found: C, 61.25; H, 8.33; N, 23.93.

The general procedures described in Examples 1, 2 and 3 were used to prepare the following compounds illustrative of the invention:

3-(l-piperidyD-propyl-3-indazolecarboxylate hydrochloride, M.P. l73178 C. (corr.),byreacting diindazolo[2,3- a,2,3-d]pyrazine-7,14-dione with 3-(l-piperidyl)-1-propanol followed by treatment with ethereal hydrogen chloride.

N (3-dimethylaminopropyl) 3 indazolecarboxamide, M.P. 92 C. (corr.), by reacting diindazolo[2,3-a,2,3- d]-Py1aZine-7,14-dione with 3-dirnethylaminopropylamine.

N (3 diethylaminopropyl) 3 indazolecarboxamide, M.P. 8293 C. (corr.), by reacting diindazolo [2,3-a,2,3- d]-pyrazine-7,14-dione with 3-diethylaminopropylamine.

N (l hexamethyleniminylethyl) 3 indazolecarboxamide, M.P. 126l27 C. (corr.), by reacting diindazolo[2, 3-a,2,3-d]-pyrazine-7,14-dione with 1-hexamethylenimin lyethylamine.

N (1 hexamethyleniminylethyl) 3 indazolecarboxamide methyl p-toluenesulfonate, M.P. l84185 C. (corr.), by reacting N-(l-hexamethyleniminylethyl)-3-ir1- dazolecar-boxarnide with methyl p-toluenesulfonate.

Dimethylaminoethyl 4,5,6,7 tetrahydro 3 indazolecarboxyla-te,- M.P. 114ll5 C. (corr.), by reacting 1,2,3, 4,8,9,10,11 octahydroindazolo[2,3,a-2',3'-d]pyrazine 7, 14-dione with dimethylarninoethanol.

Dimethylaminoethyl 4,5,6,7 tetrahydro 3 indazolecarboxylate methyl p-toluenesulfonate, M.P. 211-212 C. (corr.), by reacting dimethylaminoethyl 4,5 ,6,7-tetrahydro- 3-indazolecarboxylate with methyl p-toluenesulfonate.

Diethylaminoethoxyethyl 3 indazolecarboxylate hydrochloride, M.P. 108109 C. (corr.), by reacting diinda-' zolo[2,3-a,2',3-d]pyrazine-7,14-dione with diethylaminoethoxyethyl alcohol followed by treatment with ethereal hydrogen chloride.

N-(dimethylaminoethyD-S-bromo 3 indazolecarboxamide, M.P. 172173 C. (corr.), by reacting methyl 5- bromo-3-indazolecarboxylate with dimethylaminoethylamine.

N (2 dimethylaminopropyl) 3 indazolecarboxamide, M.P. -146 C. (corr.), by reacting diindazolo[2,3, a-2,3',-d]pyrazine-7,14-dione with Z-dirnethylaminopro pylamine.

N dimethylaminoethyl 1 methyl 3 indazolecarboxamide hydrochloride, M.P. 199-200 C. (corr.), by reacting 1-methyl-3-indazolecarbonyl chloride with dimethylaminoethylamine.

Z-diethylaminoethyl 3 -indazolecarboxylate hydrochloride, M.P. 147150 C. (corr.), by reacting diindazolo[2, 3-a,2',3'-d]pyrazine-7,14-dione with diethylaminoethanol followed by treatment with ethereal hydrogen chloride.

N dimethylaminoethyl 2 methyl 3 indazolecarboxamide hydrochloride, M.P. 186 C. (corr.), by reacting 2-methyl-3-indazolecarbonyl chloride with dimethylaminoethylamine.

N [3 (1 piperidyDpropyl] 3 indazolecarboxamide, M.P. l22123 C. (corr.), by reacting diindazolo[2,3-a,2, 3'-d]-Pyrazine-7,14-dione with 3-(1-piperidyl)propylamine.

N [2 (4 morpholinyDethyl]-3-indazolecarboxamide, M.P. 169170 C. (corr.), by reacting diindazolo[2,3-a,2', 3 d]pyrazine-7,l4dione with 2 (4 morpholinyDethylamine.

N [3 (4-morpholinyl)propyl]-3-indazolecarboxamide, M.P. 162-163 C. (corr.), by reacting diindazolo[2,3-a,2, 3'-d]-pyrazine-7,l4-dione with 3-(4-morpholinyl)propylamine.

N [2 (l piperidybethyl] 3 indazolecarboxamide, M.P. 157159 C. (corr.), by reacting diindazolo [2,3-'a,2', 3'-d]PYraZine-7,l4di0ne with 2-(l-piperidyDethylamine.

N- [2- 4-methyll-pipera zinyl ethyl] -3 -indazolecarboxamide, M.P. 177-l78 C. (corr.), by reacting diindazolo- [2,3-a,2,3'-d]pyrazine-7,14-dione with 2-(1-methyl-4-piperazinyl ethylamine.

N- [2- (4-phenyll-piperazinyl) ethyl] -3 -indazolecarboxamide, M.P. 236237 C. (corr.), by reacting diindazolo- [2,3-a,2',3'-d]pyrazir1e-7,14-dione with 2-(4-phenyl-1-piperazinyl)ethylamine.

N-(Z-diethylaminoethyl) 3 indazolecarboxamide hydrochloride, M.P. 169170 C. (corr.), by reacting diindazolo[2,3-a,2,3'-d]pyrazine 7,14 dione with diethylaminoethylamine followed by treatment with ethereal hydrogen chloride.

N-[2-( 1-pyrr0lidyl)e thyl] -3-indazolecarboxamide, M.P. 144-145" C. (corn), by reacting diindazolo[2,3-a,2, 3-d]pyrazine-7,l4-dione with 2-[ 1-pyrrolidyl]ethylamine.

Z-dimethylamino-l-methylethyl 3-indazolecarboxylate hydrochloride, M.P. 217-222 C. (corr.), by reacting diindazolo[2,3-a,2',3'-d]pyrazine-7,14-dione with dimethylamino-Z-propanol followed by treatment with ethereal hydrogen chloride.

(l-pyrrolidinyl)ethoxyethyl 3-indazoiecarboxylate hydrochloride, MP. 146-148 C. (corn), by reacting diindazolo[2,3-a,2',3'-d]pyarzine-7,l4-dione with (l-pyrrolidinyl)ethoxyethylalcohol followed by treatment with ethereal hydrogen chloride.

N-(Z-dimethylamino-1methylethyl) 1 methyl 3 indazolecarboxarnide hydrochloride, M.P. 215-217 C. (corr.), by reacting 1methyl-3-indazolecarbonyl chloride with dimethylamino-Z-propanol.

N (2 dimethylamino 1 methylethyl) 3 indazolecarboxamide hydrochloride, MP. 252-255 C. (corn), by reacting diindazolo[2,3-a,2,3-d]pyraZine-7,14-dione with dimethylamino-Z-propanol followed by treatment with ethereal hydrogen chloride.

(l-pyrrolidinyl)ethoxyethyl 1-methyl-3-indazolecarboxylate diphosphate, M.P. 147-148 C. (corn), by eacting 1-methyl-3-indazolecarbonyl chloride with (l-pyrrolidinyl)etho ;yethylalcohol followed by treatment with phosphoric acid.

N-(Z-dimethylaminoethyl)-5-methoxy-3-indazolecarboX- amide hydrochloride, M.P. 130-132 C. (corn), by reacting 2,9 dimethoxydiindazolo[2,3-a,2',3'-d]pyrazine-7,14- dione, M.P. 3l0 C., with dimethylaminoethylamine followed by treatment with ethereal hydrogen chloride.

N-[2-(l-pyrrolidinyl)ethyl] 5 methoxy-3-indazolecarboxamide, MP. 137-139 C. (corr.), by reacting 2,9-dimethoxydiindazolo [2,3-a,2,3 -d] pyrazine-7,14-dione with l-pyrrolidinyl)ethylalcohol.

Following the general procedures described above other basic esters and amides of B-indazolecarboxylic acids which can be prepared include for example, 4-dibutylaminobutyl-l-phenyl 3 indazolecarboxylate by reacting methyl 1-phenyl-3-indazolecarboxylate with 4-dibutylamino-l-butanol; 6-diethylaminohexyl 4-trifluoromethyl- 3-indazolecarboxylate by reacting ethyl 4-trifluoromethyl- 3-indazolecarboxylate with 6 diethylamino 1 hexanol; N-(3-thiomorpholinopropyl)-1-benzyl-3-indazolecarboxamide by reacting methyl 1-benzyl-3-indazolecarboxylate with 3-thiomorpholinopropylamine; 2,6-dimethylpiperidinoethyl 3-indazolecarboxylate by reacting diindazolo- [2,3-a,2,3'-d]pyrazine-7,14-dione with 2,6-dimethylpiperidinoethanol; 3-diethylaminopropyl 6-methyl-3-indazolecarboxylate by reacting methyl 6-methyl-3-indazolecarboxylate with 3-diethylamino-1-propanol; and N-(Z-Inethylethylaminoethyl)-5-nitro-3:indazolecarboxamide by re- S acting ethyl S-nitro-indazolecarboxylatc with N-methyl- N-ethylethylenediamine.

I claim: 1. A member of the group consisting of a compound having the structural formula in which Y is a member of the group consisting of hydrogen, lower-alkyl, lower-alkoxy, lowcr-alkylrnercapto, lower-alkylsulfinyl, lower-alkylsulfonyl, nitro, halogen, trifiuoromethyl, and amino; R is a member of the group consisting of hydrogen, lower-aliphatic hydrocarbon, phenyl and benzyl; X is a member of the group consisting of O and NH; Alk is a member of the group consisting of alkylene having from two to six carbon atoms and having the free valences on different carbon atoms and oxa-alkylene having from four to eight carbon atoms; and N:B is a member of the group consisting of di- (lower-alltynarnino, l-pyrrolidinyl, lower-alkylated-lpyrrolidinyl, piperidino, lower-alkylated-pipcridino, morpholino, lower alkylated morpholino, thiomorpholino, lower-alkylated-thiomorpholino, l-piperazinyl, 4-methyll-piperazinyl, 4-phenyl 1 piperazinyl, l-hexamethyleni minyl, and l-heptamethyleniminyl, and pharmaceutically acceptable lower-alkyl, lower-alkenyl and monocarbocyclicarylmethyl quaternary ammonium salts thereof.

2. N-(Z-dimethylaminoethyl) 3 indazolecarboxamide methyl toluenesulfonate.

3. N-[Z-(l hexamethyleniminyl)ethyl] 3 indazole carboxamide methyl toluenesulfonate.

4. N-(Z-dimethylaminoethyl)-3-indazolecarboxamide.

5. N (2dimethylarninoethyl)-2-methyl-3-indazolecarboxarnide.

6. N-(Z-dimethylaminoethyl)-4,5,6,7-tetrahydro-3-indazolecarboxamide.

7. N-[2-(1-pyrrolidinyl)ethyl]-3-indazolecarboxamide.

8. N (2 dimethylaminoethyl)-1-methyl-3-indaz0lecarboxamide.

9. Diethylaminoethoxyethyl 3-idazolecarboxylate.

10. 3-diethylaminopropyl B-indazolecarboxylate.

11. N-[di (lower-alkyDaminoalkyl]-3-indazolecarboxamide.

l2. N-[di (lower-alkyl)arninoalkyl]4,5,6,7-tetrahydro- 3-indazolecarboxamide.

References Cited in the file of this patent Smith et 211.: J. Org. Chem., vol. 23, page 621 (1958). Musante et al.: Gazz. Chim. Ital, vol. 77, pages 199- 206 (1947).

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,145,215 August 18, 1964 Frederick Kc Kirchner It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 2 line 28, for ""-CH(CHH )CH read -CH(CH -)"CH line 34, for "hydrogen" read hydrocarbon column 3, lines 51 and 52, for "dependings" read depending column 7, line 13, for "pyarzine" read pyrazine line 26, for "'eacting" read reacting Signed and sealed this 22nd day of December 1964.

(SEAL) Attest:

ERNEST W. SWIDER' EDWARD J. BRENNER Attesting Officer Commissioner of Patents

Claims (1)

1. A MEMBER OF THE GROUP CONSISTING OF A COMPOUND HAVING THE STRUCTURAL FORMULA