US3839330A

US3839330A - 2-alkoxy-4,5-azimidobenzamides

Info

Publication number: US3839330A
Application number: US00117836A
Authority: US
Inventors: M Thominet
Original assignee: Ile De France
Current assignee: SOC D ETUDE SCIENTIFIGUES ET INDUSTRIELLES de l ILE DE FR FR
Priority date: 1967-08-17
Filing date: 1971-02-22
Publication date: 1974-10-01
Anticipated expiration: 1991-10-01
Also published as: DE1795110A1; FR6787M; GB1232836A; CH496007A; DE1795653A1; DE1795653B2; FR1572168A; DE1795653C3; OA03879A; DE1795110B2; BE719048A

Abstract

The azimidobenzamides of this invention are useful in the control of emesis. Such azimidobenzamides administered to mammals in a dosage of 250 Mu mg. (as the base) per kilogram of body weight effectuate 100 percent protection against emesis.

Description

United States Patent n 1 Thominet 1 Oct. 1,1974

[ 2-ALKOXY-4,5-AZIMIDOBENZAMIDES [75] Inventor: Michael Leon Thominet, Paris,

France [63] Continuation-impart of Ser. No. 751,737, Aug. 12,

[30] Foreign Application Priority Data Aug. 17, 1967 France 67.118l6l Nov. 6, 1967 France 67.127131 52] us. Cl ..260/247.2 A, 260/268 BC, 260/293.59, 260/306.7, 260/308 B.

[51] int. Cl C07d 87/42 [58] Field of Search 260/308 B, 29359, 306.7, 260/268 BC, 247.2 A

Primary ExaminerDonald G. Dans Assistant ExaminerJose Tovar Attorney, Agent, or FirmFrank M/Nolan [5 7] ABSTRACT The azimidobenzamides of this invention are useful in the control of emesis. Such azimidobenzamides administeredto mammals in a dosage of 250 p, mg. (as the base) per kilogram of body weight effectuate 100 percent protection against emesis.

13 Claims, No Drawings 1 2-ALKOXY-4.5-AZIMIDOBENZAMIDES This is a continuation-in-part application of pending U.S. patent application, Ser. No. 751,737 filed Aug. 12, 1968.

NNH

in which n is 1 or 2 B is alkyl or alkenyl of one to five carbon atoms; and A is a monovalent radical having either of the formulas:

in which m isa whole number less than 4, R is an alkyl group of one to five carbon atoms, R. and R are hydrogen or 1 or 2 alkyl radicals of one to five carbon atoms or each is linked together through at least three carbon atoms to form with the nitrogen to which they are attached a heterocyclic radical with or without oxygen, sulfur or an additional nitrogen atom. The nitrogen atom has attached thereto hydrogen or an alkyl radical of one to five carbon atoms.

Examples of monovalent radicals when formula (2) comprises a heterocyclic radical are pyrrolidinyl, piperidinyl, imidazolidinyl, piperazino and thiazolidinyl.

' Examples of monovalent radicals of formula (3) are pyrrolidinyl and piperidinyl.

The pharmaceutically acceptable salts of the bases described herein may be acid addition salts or quaternary ammonium salts. Examples of acid addition salts are those of the bases and mineral acids, such as hydrochloric acid, hydrobromic acid or phosphoric acid or those of bases and organic acids, such as citric acid, tartaric acid, lactic acid or acetic acid. Examples of quaternary ammonium salts are those obtained by reacting the bases described herein with aliphatic or aromatic alkylating agents such as methyl chloride, methyl bromide, dimethyl sulfate, or methyl p-toluenesulfonate.

The compositions of this invention are useful as antiemetics, antispasmodics and analgesics.

It is understood that where the compounds of the invention have one or more asymmetric carbon atoms, the compound may be the dextro stereo isomer alone, the levo stereo isomer alone or mixtures of both stereo isomers, such as a racemic mixture of both stereo isomers. If an inactive meso form exists, this invention contemplates such meso form with or without either or both the dextro or levo stereo isomers.

The compounds of this invention are produced by reacting in an acid medium, such as a mineral acid, a nitrite with a 2-alkoxy-4,5-diaminobenzamide having the formula:

in which n, B and A have the same meaning as heretofore defined. The nitrite may be an organic or inorganic nitrite. Amyl nitrite is an example of an organic nitrite, while a metallic nitrite, such as an alkali metal nitrite (e.g. sodium or potassium nitrite) is an example of an inorganic nitrite.

Amore comprehensive understanding of this invention is obtained by reference to the following examples.

EXAMPLE I N-(DIETHYLAMINOETHYL )-2-METH OXY-4,5-

' AZIMIDOBENZAMIDE Methyl Stage A nitrobenzoate In a 2 liter flask equipped with an agitator, a thermometer and a dropping funnel, there are introduced 223 g. (1 mol) of methyl 2-methoxy-4- acetaminobenzoate, 350 ml. of acetic acid and 337 g. of acetic anhydride. The mixture is heated to 40 C. to obtain a clear solution. It is cooled to l520 C. and 105 g. (1 mol 50 percent excess) of nitric acid (d=1.49) are poured drop by drop from the dropping funnel. When the introduction is completed the mixture is again agitated for 1/2 hour at 40 C., cooled and the reaction mixture poured into 5 liters of water.

There are obtained 182 g. (yield 68 percent) of methyl 2-methoxy-4-acetamino-5-nitrobenzoate (m.p. l63-l65 C.).

Stage B N-(diethylaminoethyl)-2-methoxy-4-amino- 5-nitrobenzamidev Into a 2 liter flask equipped with an agitator and a thermometer there are introduced 182 g. (0.68 mol) of methyl 2-methoxy-4-acetamino-S-nitrobenzoate and 600 ml. of glycol, and then 236 g. (0.68 mol X 3) of diethylaminoethylamine are added. The reaction is slightly exothermic (T 31 C.). A suspension is obtained which is heated at 55 C. and at the end of 3/4 of an hour, dissolution is complete and U2 hour later the formation of an abundant preprecipitate is observed.

The reaction mixture is maintained for hours at 55 C. All is then soluble in dilute acetic acid.

Then 600 ml. of water at 40-45 C. are added, under agitation. Then the mixture is cooled, the product obtained is dried, washed with 1.3 liters of water and dried at 60 C. 152 G. (yield 63.5 percent) of N- (diethylaminoethyl)-2-methoxy-4-amino-5- nitrobenzamide (m.p. 206208 C.) are obtained. Stage C N-(diethylaminoethyl)-2-methoxy-4,5- diaminobenzamide Into a 2 liter flask equipped with an agitator, a thermometer and a dropping funnel, there are introduced 152 g. (0.49 mol) of N-(diethylaminoethyl)-2- methoxy-4-amino-S-nitrobenzamide, 230 ml. of water and 49 ml. of concentrated hydrochloric acid. A thick mass is obtained to which are added 94 g. of tin. The

2-methoxy-4-acetamino-5- mixture is then heated to 50 C. and 390 ml. of hydrochloric acid are introduced in portions. The reaction is strongly exothermic. The temperature reaches 80 to 100 C. It is cooled if necessary.

When the introduction is complete, it is heated on a water bath until all the tin is dissolved.

into a 3 liter flask equipped with an agitator, a thermometer and a dropping funnel, there are introduced 915 ml. of washing soda. Then little by little the preceding solution is added at about 40 C. The base separates in the form of a brown oil. After cooling, it is decanted and the aqueous solution is extracted with methylene chloride. The organic solution obtained is washed once with water and dried with potassium carbonate. The methylene chloride is then distilled under vacuum to a constant weight. 137 G. (yield about 100 percent) of N-(diethylaminoethyl)-2-methoxy-4,5- diaminobenzamide are obtained.

Stage D N-(diethylaminoethyl)-2-methoxy-4,5-

, azimidobenzamide Into a 2 liter flask equipped with an agitator, a thermometer and a dropping funnel, there are placed 116 g. (0.284 mol) of dihydrochloride of N- (diethylaminoethyl)-2-methoxy-4,5- diaminobenzamide, 568 ml. of water and 28 ml. of concentrated hydrochloric acid. The mixture is heated at about 40-45 C. to dissolve the mixture. It is cooled to C. and 20 g. (0.284 mol) of sodium nitrate in water are poured drop by drop from the dropping funnel. When the addition is completed, agitation is continued for 1 hour and the temperature allowed to rise to 20 C. The solution obtained is treated with charcoal, filtered and evaporated to dryness. The solid residue is recovered in 400 ml. of boiling ethanol. The remaining sodium chloride is filtered by heat. With cooling and concentration of the alcohol solution, the hydrochloride of N-(diethylaminoethyl)-2-methoxy-4,5- azimidobenzamide crystallizes. It is dried and washed in alcohol. it is a white solid (m.p. 189191 C) (yield 77.5%).

EXAMPLE II N-(1-ETH YL-2-PYRROLIDYLMETHYL)-2- METHOXY-4,S-AZIMIDOBENZAMIDE Stage A is the same as that described in Example I.

Stage B N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy- 4-amino-5-nitro benzamide Into a 2 liter flask equipped with an agitator and a thermometer, there are introduced 140 g. (0.52 mol) of methyl 2-methoxy-4-acetamino-S-nitro benzoate, 500 ml. of glycol and 201 g. (0.52 mol X 3) of l-ethyl- 2-aminomethylpyrrolidine. A thick yellow suspension is obtained which is heated to 55C. and maintained at 55 C. for 120 hours. No apparent transformation of the initial precipitate is observed but at the end of the reaction a sample showed complete solubility in dilute acetic acid.

It is then cooled to about 40 C. and 500 ml. of water are added under agitation. The cooling is completed at about 20 C., the product obtained is dried, washed with a liter of water and dried at 50 C. 134 G. (yield 80 percent) of N-(1-ethyl-2-pyrrolidylmethyl)-2- methoxy-4-amino-S-nitrobenzamide are obtained. (m.p. 188-l90 C.)'

Stage C N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy- 4,5-diaminobenzamide Into a 2 literflask equipped with an agitator, a thermometer and a dropping funnel, there are introduced g. (0.372 mol) of N-(l-ethyl-2-pyrrolidylmethyl)- 2-methoxy-4-amino-S-nitrobenzamide, 170 ml. of waterand 37 ml. of concentrated hydrochloric acid, the mixture being heated at 50 C. The hydrochloride formed is completely soluble. 71 G. of tin are added and then 290 ml. of concentrated hydrochloric acid are added. The reaction is slightly exothermic. The temperature reaches 65 C. At the end of the addition, a thick precipitate forms. It is then heated on a water bath until all the tin is dissolved.

Into a 2 liter flask equipped with an agitator and a thermometer, there are introduced 680 ml. of washing soda and then, little by little, the above mixture without exceeding 40 C. The base separates in the form of a brown oil and some tin salts are precipitated. 200 Ml. of methylene chloride are added to dissolve the base and filter the mineral salts.

The organic solution is decanted and the aqueous solution is extracted once with 200 ml. of methylene chloride and once with 100 ml.

The organic solution is washed once with 100 ml. of water and dried withpotassium carbonate. The methylene chloride is thn distilled under vacuum to a-constant weight. 100 G. (yield 93 percent) of N-(1-ethyl-2- pyrrolidylmethyl)-2-methoxy-4,5-diamino benzamide are obtained.

Stage D N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy- 4,5-azimidobenzamide In a 2 liter flask equipped with an agitator, a thermometer and a dropping funnel, there are introduced 112 g. (0.278 mol) of hydrochloride of N-(l-ethyl-Z- pyrrolidylmethyl)-2-methoxy-4,5-diamino benzamide, 580 ml. of water and 28 ml. of concentrated hydrochlo ric acid. The mixture is heated to 40-45 C. to achieve complete dissolution and then cooled to 0 C. 19 G. of sodium nitrite dissolved in 28 ml. of water are added drop by drop through the dropping funnel. Agitation continues for 1 hour at 0 C. and then the temperature is allowed to rise. to 20 C. It is evaporated to dryness and the solid residue recovered in 400 m1. of absolute alcohol, and the sodium chloride formed is filtered with heat. The alcohol solution is concentrated. The hydrochloride of N-( l-ethyl-2-pyrrolidylmethyl)-2-methoxy- 4,5-azimidobenzamide' formed crystallizes. It is dried, washed with alcohol and then with ether. 55 G. (yield: 85 percent) of product in the form of white crystals are obtained. (m.p. 197-200 C.)

To produce N-(1-ethyl-2-pyrrolidylmethyl)-2- vinyloxy-4,5 azimidobenzamide, Example I1 is followed except that the addition of 146 g. (0.52 mol) of 2- vinyloxy-4-acetamino-S-nitromethyl benzoate is employed instead of the g. of 2-methoxy-4-acetamino- 5-nitromethyl benzoate.

To produce N-(1-ethyl-2-imidazolidylmethyl)-2- methoxy-4,5-azimidobenzamide, Example II is followed except that the addition of 202 g. (0.52 mol X 3) of l-ethyl-2-aminomethylimidazolidine is employed instead of the 201 g. of 1-ethyl-2-aminomethylpyrrolidine.

To produce N-(3-ethyl-2-thiazolidylmethyl)-2- methoxy-4,5-azimidobenzamide, Example II is followed except that the addition of 229 g. (0.52 mol X 3) of 3-ethyl-2-aminomethylthiazolidine is employed instead of the 201 g. of 1-ethyl-2-aminomethyl pyrrolidine.

EXAMPLE III DEXTRO N-(1-ETHYL-Z-PYRROLIDYLMETHYL)-2- METHOXY-4,5-AZIMIDOBENZAMIDE Stage A is similar to that described in Example I. Stage B Dextro N-(1-ethyl-2-pyrrolidylmethyl)-2- methoxy-4-amino-5-nitrobenzamide In a 2 liter flask equipped with anagitator and a thermometer, there are introduced 80 g. (0.3 mol) of methyl 2-methoxy-4-acetamino-5-nitrobenzoate, 285 ml. of glycol and 84 g. (2.2 X 0.3 mol) of dextro 1- ethyl-2-amino-methylpyrrolidine.

A yellow suspension is obtained which is heated at 55 C. and maintained at that temperature for 216 hours.

Then it is cooled to 40 C. and 500 ml. of water are added with agitation. Cooling is completed at about 20 C., the product obtained is dried, washed with 1 liter of water and dried at 50 C. 45 G. of dextro N-( 1-ethyl-2- pyrrolidylmethyl)-2-methoxy-4-amino-5- nitrobenzamide (mp. 185-187C.) are obtained. Stage C Dextro N-(1-ethyl-2-pyrrolidylmethyl)-2- methoxy-4,S-diaminobenzamide The reduction of 150 g. (0.4 mol) of hydrochloride of dextro N-( l-ethyl-2-pyrrolidylmethyl)-2-methoxy-4- amino-S-nitrobenzamide is effectuated in an autoclave with alcohol at 95 C. and in the presence of Raney nickel as a catalyst. The reaction lasts 1 hour. The hydrogen pressure at the beginning is 64 kg. at 45 C.

At the end of the reaction, the temperature reached 83 C. The nickel is filtered with heat and the dihydrochloride is prepared with the aid of 40 ml. of concentrated hydrochloric acid. After recrystallization in alcohol, 100 g. of hydrochloride of dextro N-(l-ethyl-2- pyrrolidylmethyl)-2-methoxy-4,5-diaminobenzamide are obtained. (Yield: 70 percent) (mp. 215 C.) Stage D Dextro N-(1-ethyl-2-pyrrolidylmethyl)-2- methoxy-4,5-azimidobenzamide In a 1 liter flask equipped with an agitator, a thermometer, and a dropping funnel, there are introduced 43 g. (0.107 mol) of hydrochloride of dextro N-(lethyl-Z-pyrrolidylmethyl)-2-methoxy-4,5-- azimidobenzamide, 215 ml. of water and 11 ml. of concentrated hydrochloric acid. The mixture is heated to 55 C. to achieve complete dissolution. Then it is cooled to 0C. 7.5 G. (0.107 mol) of sodium nitrite dissolved in ml. of water are added drop by drop from the dropping funnel. Agitation is continued for 1 hour at 0 C. and then the mixture is allowed to return to room temperature.

The alcohol solution is concentrated. The hydrochloride of benzamide formed crystallizes, is dried, washed with alcohol and then with ether. There are obtained 23 g. (yield 63 percent) of hydrochloride of dextro N- 6 1-ethyl-2-pyrrolidylmethyl )-2-methoxy-4,5- azimidobenzamide (m.p. l-172 C. )-[a],, =+5 (5 percent aqueous solution).

EXAMPLE IV LEVO N-(1-ETI-IYL-2-PYRROLIDYLMETHYL)-2- METHOXY-4,S-AZIMIDOBENZAMIDE Following the procedure in Example III, but replacing the dextro-amine with the levo-amine,there is obtained the dihydrochloride of levo N-( l-ethyl-2- pyrrolidylmethyl)-2-methoxy-4,5-azimidobenzamide, with the following characteristics:

(m.p. 170172 C.)

[04],, 5 4 (5 percent aqueous solution) EXAMPLE V N-(ETHYL-PROPYLAMINOETI-IYL)-2- METHOXY-4,5-AZIMIDOBENZAMIDE Stage A is the same as in Example I.

Stage B N-(ethyl-propylaminoethyl)-2-methoxy-4- amino-5-nitrobenzamide In a 2 liter flask equipped with an agitator and a thermometer, there are introduced 188 g. (0.7 mol) of methyl 2-methoxy-4-acetamino-5-nitrobenzoate and 700 ml. of glycol, and then 273 g. (0.7 mol X 3) of ethyl-propylethylene diamine are added.

The suspension obtained is heated at 55 C. and that temperature is maintained for 72 hours.

The ester dissolves partially at the beginning of the reaction andthe benzamide formed begins to precipitate. At the end of the reaction, there is total solubility.

added. The mixture is heated at 55 C. and 390 ml. of I concentrated hydrochloric acid are added in small portions. The reaction is strongly exothermic. When the introduction is terminated, the mixtureis heated on a water bath until the tin is totally dissolved.

Into a 3 liter flask equipped with an agitator, a thermometer and a dropping funnel, there are introduced 915 ml. of washing soda and then, little by little, the preceding solution without exceeding 40 C. The base separates in the form of a paste which is redissolved in 150 ml. of methylene chloride. The aqueous solution is extracted with methylene chloride. The organic solution obtained is washed with water and dried with potassium carbonate. The methylene chloride is then distilled under vacuum to a constant weight. 131 G. (yield percent) of-N-(ethyl-propylaminoethyl)-2-methoxy- 4,5-diaminobenzamide are obtained.

Stage D N-(ethyhpropylaminoethyl)-2-methoxy- 4,5-azimidobenzamide Into a 2 liter flask equipped with an agitator, a thermometer and a dropping funnel, there are introduced 106 g. (0.258 mol) of dihydrochloride-of N-(ethylpropylaminoethyl )-2-methoxy-4,5-diaminobenzamide, 516 ml. of water and 26 ml. of concentrated hydrochloric acid. It is heated to dissolve the mixture. It is then cooled at C. and 18 g. (0.258 mol) of sodium nitrite dissolved in 20 ml. of water is poured drop by drop from the dropping funnel. When the addition is completed, the mixture is maintained under agitation at 0 C. for 1 hour, and then allowed to return to room temperature.

The solution is then treated with charcoal, filtered 8 taken'up with 200 ml. of boiling absolute alcohol. The sodium chloride is filtered off and alcohol is distilled. The hydrochloride crystallizes. It is drained, washed with alcohol, and dried, to yield 35 g. of N- (piperidinoethyl)-2-methoxy-4,5-azimidobenzamide LD in mg/kg of composition in base state COMPOSITIONS by intraintraperisubcutamouth venously toneally neously N-(diethylaminoethyl) I500 l43-l46 387-400 600-576 -2-methoxy-4,5- (30% azimidobenzamide mortality) N-( l -ethyl-2-pyrl5 17 69 2 l 4-2l6 330-32] rolidylmethyl)-2- methoxy-4,5-azimidobenzamide Dextro-N-( l-ethyl-2- 84-85 248 339 pyrrolidylmethyl)-2- methoxy-4,5-azimidobenzamide Levo-N-(l-ethyl-2- 83-84 207 243 pyrrolidylmethyh- 2-methoxy-4,5- azimidobenzamide and evaporated to dryness. The solid residue is recov ered with 300 ml. of boiling ethanol. The remaining sodium chloride is filtered with heat. After cooling and concentration of the alcohol solution, the hydrochloride of N-(ethyl-propylaminoethyl)-2-methoxy-4,5- azimidobenzamide crystallizes. It is dried and washed with alcohol. It is a white solid (mp. 155 C.).

EXAMPLE VI IODOMETHYLATE OF N-( DIETHYLAMINOETHYL )-2-METHOXY-4,5- AZIMIDOBENZAMIDE Into a 250 ml. flask, there are introduced 33 g. (0.113 mol) of N-(diethylaminoethyl)-2-methoxy-4,5- azimidobenzamide dissolved in 66 ml. of methyl alcohol and 19 g. (0.113 mol 20 percent) of methyl iodide dissolved in 38 ml. of methyl alcohol. These are mixed and the flask is left securely closed for 136 hours. The product crystallizes. It is dried and then recrystallized in acetone and there is finally obtained iodomethylate of N-(diethylaminoethyl)-2-methoxy- 4,5-azimidobenzamide (mp. 205 C.).

EXAMPLE VII N-( PlPERIDlNOETl-IYL)-2-METHOXY-4,5- AZIMIDOBENZAMIDE HYDROCHLORIDE In a 1 liter flask are mixed N-piperidinoethyl-2- methoxy-4,5-diaminobenzamide dihydrochloride (53 g.), 288 ml. of water and 14 ml. of hydrochloric acid (d= 1.18). The mixture is warmed at 45 C. to dissolve and then cooled to 0 C. Sodium nitrite g.) dissolved in ml. of water is introduced while the temperature is maintained at 0 C. Stirring is continued for one hour and the temperature is then allowed to rise to 18 C. Water is distilled under vacuum and the residue The anti-emetic action of these compositions on the Rate of protection in dose of 250 u/kg (base) COMPOSITIONS N-(diethylaminoethyl)-2- methoxy-4,5-azimidohenzamide N-( l-ethyl-2-pyrrolidylmethyl) 2-methoxy-4,5 -azimidobenzamide Dextr0-N-( l-ethyl-Z-pyrrolidylmethyl)-2-methoxy-4,5- azimidobenzamide Levo-N-( l-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5- azimidobenzamide The compositions of this invention have the interesting pharmacological property of being anti-cataleptic. For two compositions of this invention, the cataleptic activity of the product showed the following results: (results measured at the maximum of the effect, such as after 300 to 360 minutes) azimidobenzamide The experimental results were clinically confirmed, the products being administered in the form of tablets or ampules of a pharmaceutically acceptable salt.

The treatments were given only under clinical conditions corresponding to pharmacodynamics, with no manifestation of medicinal intolerance. The vomitings stopped quickly and did not recur after cessation of treatment. For example, to a 70 year old man with serious recto-colitis having repeated attacks of vomiting at the time of feeding, 2 ampules daily of mg. of hydrochloride of N-(diethylaminoethyl)-2-methoxy-4,5- azimidobenzamide were adminstered. The tolerance was excellent and in 2 days there was a very great diminution of vomiting, allowing the feeding of the patient. Vomiting stopped completely after 4 days of treatment.

In a 55 year old woman afflicated with mammary cancer and treated with other medication, severe vomiting stopped in two days after the administration of 3 ampules per day of 10 mg. of the hydrochloride of N- 1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5- azimidobenzamide.

The antiemetic compositions of this invention can be administered in the form of a pharmaceutically acceptable salt in coated pills, injectable ampules or aerosols, suppositories, granulated saccharine or sweetened syrup. 7

What is claimed is:

l. A compound of the formula:

' M cosh-Ema N NH in which n is 1 when A is a heterocyclic radical or 2 when A is a non-heterocyclic radical; B is methyl; and A is:

3-ethyl-2-thiazolidyl-,

l-ethyfi-imidazolidyb,

4-ethyl-2-morpholinyl-, or l-ethyl-2-piperazinyl-, R is alkyl of one to five carbon atoms, R and R are ethyl or propyl or pharmaceutically acceptable salts thereof.

2. A compound of claim 1 which is a dextro isomer.

9. A compound of claim 1 which is iodomethylate of N-(diethylaminoethyl )-2-methoxy-4,5- azimidobenzamide.

10. A compound of claim 1 which is N-(1-ethyl-2- imidazolidylmethyl)-2-methoxy-4,5- azimidobenzamide.

11. A compound of claim 1 which is N-(3-ethyl-2- thiazolidylmethyl)-2-methoxy-4,5-azimidobenzamide.

12. A compound of claim 1 which is N-(4-ethyl-2- morpholinylmethyl)-2-methoxy-4,5- azimidobenzamide.

13. A compound of claim 1 which is N-(l-ethyl-2- piperazinylmethyl)-2-methoxy-4,5-azimidobenzamide.

Claims

1. A COMPOUND OF THE FORMULA:

2. A compound of claim 1 which is a dextro isomer.

3. A compound of claim 1 which is a levo isomer.

4. A compound of claim 1 which is N-(diethylaminoethyl)-2-methoxy-4,5-azimidobenzamide.

5. A compound of claim 1 which is N-(1-ethyl-2-pyrrolidyl-methyl)-2-methoxy-4,5-azimidobenzamide.

6. A compound of claim 1 which is dextro N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-azimidobenzamide.

7. A compound of claim 1 which is levo N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-azimidobenzamide.

8. A compound of claim 1 which is N-(ethyl-propylaminoethyl)-2-methoxy-4,5-azimidobenzamide.

9. A compound of claim 1 which is iodomethylate of N-(diethylaminoethyl)-2-methoxy-4,5-azimidobenzamide.

10. A compound of claim 1 which is N-(1-ethyl-2-imidazolidylmethyl)-2-methoxy-4,5-azimidobenzamide.

11. A compound of claim 1 which is N-(3-ethyl-2-thiazolidylmethyl)-2-methoxy-4,5-azimidobenzamide.

12. A compound of claim 1 which is N-(4-ethyl-2-morpholinylmethyl)-2-methoxy-4,5-azimidobenzamide.

13. A compound of claim 1 which is N-(1-ethyl-2-piperazinylmethyl)-2-methoxy-4,5-azimidobenzamide.