US3789120A - Sulfamoyl azide process and composition for lowering blood pressure - Google Patents

Abstract

This invention is concerned with a pharmaceutical process and pharmaceutical compositions for lowering blood pressure in mammals by the administration thereto sulfamoyl azides of the Formula R1R2NSO2N3 and pharmaceutical compositions thereof. R1 is alkyl, cycloalkyl, aryl, aralkyl and so on; R2 is hydrogen, alkyl, cycloalkyl, phenyl, phenylalkyl, and so on; R1 and R2 can be taken together with nitrogen to form a heterocyclic radical.

Description

United States Patent [191 Matier et al.

[ SULFAMOYL AZIDE PROCESS AND COMPOSITION FOR LOWERING BLOOD PRESSURE [75] Inventors: William L. Matier; William T.

Comer, both of Evansville, Ind.

[73] Assignee: Mead Johnson & Company,

Evansville, Ind.

[22] Filed: Jan. 8, 1973 [21] Appl. No.: 321,872

Related U.S. Application Data [62] Division of Ser. No. 16,933, March 5, 1970, Pat. No.

[52] U.S. Cl. 424/226 [51] Int. Cl A61k 27/00 [58] Field of Search 424/250, 226

[56] References Cited OTHER PUBLICATIONS Chem. Abst. Subject Index, Vol. 71, July-Dec. 19 69,

[ Jan. 29, 1974 page 585 S.

Primary Examiner-Sam Rosen Attorney, Agent, or Firm-Robert E. Carnahan et al.

[5 7] .ABSTRACT 4 Claims, N0 Drawings SULFAMOYL AZIDE PROCESS AND COMPOSITION FOR LOWERING BLOOD PRESSURE CROSS-REFERENCE TO RELATED APPLICATION This application is a divisional application of our copending application Ser. No. 16,933 filed Mar. 5, 1970 now U.S. Pat. No. 3,723,627.

SUMMARY OF THE INVENTION The present invention is concerned with a process for lowering blood pressure in warm blooded= animals which comprises administering thereto sulfamoyl azides of Formula I. This invention also relates to pharmaceutical compositions which are suitable for administering the Formula I sulfamoyl azides to mammals in the blood pressure lowering process.

In the sulfamoyl azides of Formula I, R is selected from the group comprised of alkyl of from one to eight carbon atoms inclusive, cycloalkyl of from four to seven carbon atoms inclusive, polycycloalkyl of from seven to carbon atoms inclusive, cycloalkylalkyl of from six to 10 carbon atoms inclusive, polycycloalkylalkyl of from seven to 12 carbon atoms inclusive, aryl up to 10 carbon atoms, aralkyl up to 14 carbon atoms, benzocycloalkylene of nine to 10 carbon atoms inclusive and substituted phenyl or naphthyl wherein said substituent is selected from the group comprised of lower alkyl, halogen, lower alkoxy, hydroxyl and trifluoromethyl. It is to be understood that by the terms lower alkyl and lower alkoxy as used herein is meant that the carbon chains which comprise these groups include both straight and branched chain carbon radicals of one to fourcarbon atoms inclusive. Exemplary of these radicals are carbon chains which can be methyl, ethyl, propyl, isopropyl, l-butyl, lmethylpropyl, Z-methylpropyl and tert-butyl. Alkyl groups of from one to eight carbon atoms inclusive include the aforementioned carbon chains in addition to other permutations of carbon atoms which are made possible by extending the number of carbons such as n-pentyl, n-octyl, 1,1 ,3,3-tetramethylbutyl and the like.

Examples of the term cycloalkyl groups of from four to seven carbon atoms as used herein are: cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl. The term polycycloalkyl as used herein refers to bicyclic and tricyclic groups such as 2-bycyclo[2.2.2]octyl, and ladamantyl. Among polycycloalkylalkyl groups of from seven to 12 carbon atoms inclusive are 1- adamantylmethyl, 2-bicyclo[2.2.2]octylmethyl, and the like. By way of illustration, cycloalkylalkyl groups of from six to 10 carbon atoms include such groups as cyclopentylmethyl, cyclopentylpentyl, cyclohexylmethyl, 2-cyclohexylpropyl, 2-cyclohexyl-2,2- dimethylethyl, 2-cyclohexyl-l,l-dimethylethyl and the like. Among benzocycloalkylene groups of nine to 10 carbon atoms inclusive are l-indane, Z-indane, 1-, or Z-tetrahydronaphthylene groups and the like. Included in aralkyl groups of up to 14 carbon atoms are benzyl, phenylpropyl, 2-phenylpropyl, 2,2-dimethyl-3- phenylpropyl, diphenylmethyl, ad diphenylethyl. Aryl groups are comprised of phenyl and 1-, or Z-naphthyl radicals. Said radicals may be optionally substituted in any of the available aromatic positions with halogen (including chlorine, bromine, iodine and fluorine), hydoxyl, trifluoromethyhlower alkyl and lower alkoxy.

R in the definition of the symbols in the sulfamoyl azides of Formula 1 is a member of a group consisting of hydrogen, alkyl of from one to five carbon atoms inclusive, cycloalkyl of from four to seven carbon atoms inclusive, phenyl, and phenylalkyl up to 10 carbon atoms. Included in phenylalkyl groups of up to 10 carbon atoms are benzyl, phenylpropyl, 2-phenylpropyl, phenylbutyl, l ,1-dimethyl-2-phenylethyl, lmethylphenylpropyl, Z-methylphenylpropyl and the like.

R and R can be taken together with nitrogen to form a heterocyclic radical which is a member of a group consisting of pyrrolidyl, piperidyl, morpholyl. Also R and R can be taken together with nitrogen to form a heterocyclic radical which is a member of a group consisting of N-(lower alkyl)piperazinyl and the non-toxic pharmaceutically acceptable acid addition salts thereof. The lower alkyl group of the piperazinyl heterocycle can be comprised of straight or branched carbon chains.

Illustrative of non-toxic pharmaceutically acceptable acid addition salts of alkylpiperazinyl sulfonyl azides are a variety of inorganic and organic acids such as sulfuric, phosphoric, hydrochloric, hydrobromic, hydriodic sulfamic, acetic, lactic, malic, succinic, maleic, fumaric, tartaric, citic, gluconic, glutaric, ascorbic, benzoic, cinnamic, and related acids. The salts are prepared by methods well known to the art. For example, admixture of an alkylpiperazinyl sulfonyl azide base with substatially one chemical equivalent of any of the various acids hereinabove recited provides the corresponding acid addition salt. Generally, the reaction is carried out in an inert solvent such as ethanol, benzene, ether and the like.

Particularly preferred sulfamoyl azides of Formula I which are suitable for use in the process and pharmaceutical compositions of the present invention are methylsulfamoyl azide, n-propylsulfamoyl azide, isopropylsulfamoyl azide, isobutylsulfamoyl azide, tertbutylsulfamoyl azide, l-adamantyl-sulfamoyl azide, phenylsulfamoyl azide, 4-methoxyphenylsu1famoyl azide, 4-ch1orophenylsulfamoy1 azide, 4-tolylsulfamoyl azide, mcthylphenylsulfamoyl azide, dimethylsulfamoyl azide, benzylmethylsulfamoyl azide, and 4-methylpiperazinel -sulfonyl azide hydrochloride.

Administration of the sulfamoyl azides of Formula 1 to mammalian hosts such as the dog produces a rapid lowering of blood pressure. Both systolic and diastolic blood pressure are reduced. Significant blood pressure lowering efiects are obtained by intravenous administration of the sulfamoyl azides of Formula I to anesthetized normotensive dogs at dosages ranging from about 0.0025 to 10 mgjkg. of body weight.

The compounds of Formula I also have vasodilating properties which are demonstrated by blood flow studies in the dog conducted according to the procedures of Shipley and Wilson, Proc. Soc. Exp. BioL, 78, 724 (1951); and K, Hashimoto et al., Experientia, 25, 1,155 (1969). For example, 4-ch1orophenylsulfamoyl azide and l-adamantylsulfamoyl azide injected intraarterially at a unit dose of 0.002 g. per dog (which weigh about 7 kg.) produce significant increases in bloodflow; an effect which is indicative of vasodilating action.

The oral effectiveness of the sulfamoyl azides of Formula I in lowering blood pressure can be readily demonstrated in the dog as illustrated by the intraduodenal administration of 4-chlorophenylsulfamoyl azide or 1- adamantyl sulfamoyl azide in the anesthetized dog at doses of 1.0 mg./kg. of body weight. A rapid lowering of blood pressure in from 1 to 2 minutes with maximum reduction of about 45 percent in 7 to 27 minutes is obtained. The duration of the hypotensive effect is about 1 hour. I

At effective doses which produce a desired hypotensive effect, the sulfamoyl azides of Formula I are relatively non-toxic. Oral toxicity as determined in groups of 10 mice in accordance with accepted pharmacological technique is of a low order. For example, oral administration of the sulfamoyl azides of Formula I to mice produces deaths in 50 percent of the mice at dosages ranging from 50 to greater than 2,000 mg./kg. of body weight. Side effects in 50 percent of the mice are observed at doses ranging from about to l,000 mg./kg. of body weight.

The process of the present invention for lowering blood pressure in mammals is carried out by administering thereto systemically an effective dose of a sulfamoyl azide of Formula I ranging from about 0.003 to 10 mg./kg. body weight of the mammal. Thus for a mammal weighing about 70 kilograms, a unit dose between about 0.2 to about 700 milligrams is required to produce the desired reduction in blood pressure. Acceptable forms of systemic administration are oral, pa renteral and rectal. Examples of parenteral administration are intramuscular, intravenous, intraperitoneal, and subcutaneous administration. It will be recognized by those skilled in the art that the dosage of the sulfamoyl azides of Formula I which are used in carrying out the blood pressure lowering process of the present invention will vary with the form and mode of administration and to some degree with the particular compound chosen. Generally speaking, if the blood pressure lowering process, which is also described herein as a process for producing hypotensive effects, is carried out by the oral administration of the sulfamoyl azides of Formula l to a mammal, a larger quantity of the sulfamoyl azide is required to produce the same effect as a smaller quantity thereof given parenterally. In practice the hypotensive process of the present invention is carried out by administration of a sulfamoyl azide of Formula I in a suitable pharmaceutical carrier at a concen tration level that will generally afford effective results without producing harmful or deleterious side effects. Unit doses ranging from about 0.003 to 10 milligrams per kilogram body weight of the mammalian host are recommended.

In connection with -a daily dose, the sulfamoyl azide of Formula I can be divided into several doses and administered at specified increments of time during the day. By way of example a daily dose of 12 mg./kg. of body weight of the mammalian species treated per day can be divided into as many as 12 portions and administered every two hours in order to achieve the hypotensive effect desired. Another procedure for carrying out the hypotensive process of the present invention is the administration of the sulfamoyl azides of Formula I in the form of capsules containing coated pellets of the sulfamoyl azide whereby the coating affords a slow but sustained release of the sulfamoyl azide for periods of time upwards to 12 hours.

The pharmaceutical compositions of the present invention are comprised of the sulfamoyl azides of Formula I combined with known pharmaceutical carriers to form dosage forms such as tablets, powder, granules, capsules, suspensions, solutions, suppositories, elixirs and the like. Exemplary of suitable pharmaceutical carriers are lactose, dicalcium phosphate, corn starch, microcrystalline cellulose, stearic acid, magnesium stearate, polyethylene glycol, sesame seed oil, peanut oil, propylene glycol, dimethylformamide, methylcellulose, gums and the like.

Generally solid carriers are preferred with the composition formulated as a tablet or capsule, since there is some tendency for the sulfamoyl azides of Formula I to hydrolyze in aqueous vehicles. This tendency is most pronounced at alkaline conditions and is greater for the mono-substituted sulfamoyl azides of Formula I wherein R is hydrogen than for the di-substituted sulfamoyl azides. However, these substances are sufficiently stable at slightly acid pH values to permit extemporaneous formulation for administration 'of liquid compositions, for example, by injection. Thus at pH 5 solutions may be kept for up to an hour or more before use. The di-substituted sulfamoyl azides do not undergo any demonstrable decomposition in aqueous solution at a pH of 8 or less.

DESCRIPTION OF SPECIFIC EMBODIMENTS Additional illustrations of the present invention are given below and are not intended to be limiting in any manner. Table l and Table 2 exemplify sulfamoyl azides of Formula I which are useful in the blood pressure lowering process of the present invention.

Mono-substituted sulfamoyl azides Compound number Name 1 4-methoxypheny1sulfamoyl azide 2 Phenylsultamoyl azide TABLE 1-Contlnued V m u m RJ-If-SOgNg Mono-substituted sulfamoyl azides Compound number Name R 9 l-adamantylsuliamoyl zida 10 n;9qtyl sulfamoylazide I1=CaH17 l, 7 11.. 1,1,3,3-tetramethylbutylsulfamoyl azide (0H,),CCH=C(CH;); 12 Ethylsulfamoylazide 0:115 13,... n-Butylsulfamoyl azide. n-C H 14 n-Pentylsulmmoyl azide n-C5H 1 15 Cyclopentylsuflamoyl azide 16 Cyclohexylsulfamoyl azide O 17 2-blcyc1o[2.2.2]octy1su1iamoyl azlde 18 l-(Myclopentylpropyl)sulfamoyl amide 19 (CyclohexylmethylJsuliamoyl azide Z0 (2-bicyc1o[2.2.2]octy1methyl)sulfamoyl azide 21 (l-adamantylmethyl)sulfamoyl azide 22 l-indansultamoyl azide 23 2-indansu1famoy1 azide 24 Phenethylsulfamoyl azide CHaCHr- 25 2-(4-phenylbutyl)sulfamoylazide CHzCHzCH- 41H: 26 Diphenylmethylsulfamoylazide @011 2" (1,1-dimeth l-2 henethyl) sullamo \azlde y p @cmcmnm- 28 l-naphthylsfiliamoyl azide l 29 2-naphthy1sulfamoy1 azide TABLE 1-Contlnued I 7 7 7 R I| I-SO2N H Mono-substituted sultamoyl azides Compound number Name R 30 4-t0lylsu1famoy1 azlde i if 7 31 2-to1y1su1famoy1azide 32 4-tert-butylphenylsulfmnoyl azide 33 2-chlorophenylsullamoyl azide 34 4-bromophenylsulfamoyl azide B Q 35 4-fluorophenylsulfamoyl'azide 3-i0dophenylsu1famoylazide. I

37 3-trifluoromethylphenylsultamoyl azide F c 38 3-hydroxypheny1su1famoyl azide HO 39 4-hydroxyphenylsu1famoy1 azide 40 3-ethoxyphenylsulfamoyl azide 41 4-tert-butoxyphenylsulfamoyl azide 0 z) aC- 42 1-(4-chloronaphthyDsulfamoyl azlde I 43 1-(6-chloronaphthyl)suliamoyl azlde 44 1-(6-methoxynaphthyl)sulfamoylazide l 45 Z-(Q'rmethylnaphthyDsulfamoyl azlde TABLE 2 R I]IS ON [Di-substituted sulfamoyl azldes] Compound number Name R R 1 Methylphenylsulfamoylazide G OH;

2 Banzylmethylsulfamoyl azide CH;

3 Methyl-4-t0lylsulfamoyl azide 011:

4 tart-Butyl-z-tolylsuuamoylazlde (CHmC 5 Butyl-4-tolylsulfamoy1azide C I Q n- 4 l 6 Isopropyl-l-naphthylsulfamoyl azide (CHah H 7 MathyI-I-(G-methoxynaphthyl) sulfamoyl azide I C CHzO 8 Diphenylsulfamoyl azide Q 9 (1,l-dimethyl-2-phenethyl)-phenylsulfamoy1azide Q 10 Phenethyl-4-methoxybhehlsulfarficl a'zide .Q H 7 V V CHaO- 11 Ethyl--hydroxyphenylsulfamoylazide HO G 12 Methyl-4chlorophenylsultamoylazide Cl Q 13 Methyl-3-trifluoromethylphenylsulfamoyl azide n 14 Benzyl-4-bromophenylsultamoyl azide 15 Phenethy1-2-fluorophenylsulfamoyl azlde l0 Benzylphenylsuliamoyl azide 17 Dlbenzylsullamoy azlde 18 Benzylisopropylsulfamoyl azide 19 Benzyl-l,1dimethylphenethylsulfamoylazide @CH 20 Dimethylsulfamoylazide CH @cmcm TABLE 2 Continued R -NS OIN;

[Di-substituted sulfamoyl azides] Compound number Name R R Methylcyclohexylsulfamoyl azide 3 CH; 26 Dicyclohexylsullamoylazide Q Q 27 4-methylpiperazine-l-sulfonyl azide hydrochloride CHQN N- 28 Morpholylsulfonylazide 6 29 Piperldylsulfonylazide N v 30 Pyrrolldylsulfonyl azide 31 +ethy1piperazine-l-sulfonyl azide CzH5N N- 32 4-isopropylpiperazIne-l-sulfonyl azide (CHa)2CHN N- 33 4-n-butylplperazine-l-sulfonvl azide Example 1. Intravenous Hypotensive Effects. The process of the present invention for lowering blood pressure by the administration of sulfamoyl azides of Formula I is illustrated by the following test for hypotensive activity in the dog.

According to this test a pentobarbital-sodium anesthetized normotensive dog of either sex is arranged for recording carotid arterial blood pressure. The test agent is given in graduated doses by intravenousadministration into the jugular vein. Representative values of the blood pressure lowering effects obtained with the sulfamoyl azides are indicated below in Table 3.

Example 2. Hypotensive Effects Produced by Intraduodenal Administration. In this test an anesthetized normotensive dog of either sex is arranged for recording carotid arterial blood pressure. The sulfamoyl azide is dissolved in 1:1 dimethylformamide-water by volume which is adjusted to a pH of 2 to 3 with dilute hydrochloric acid before the addition of the azide. The sulfamoyl azide in the aqueous-dimethylformamide pharmaceutical carrier is administered through an incision in the wall of the stomach through the pyloric sphincter .hypotensive effect into the duodenum. The results of administering two representative sulfamoyl azides of Formula I to the dog at a dose of 1.0 mg./kg. body weight are:

4-Chlorophenylsulfamoyl azide [-2 minutes 7-22 minutes 7-27 minutes 49 minutes 49 minutes Example 3. Pharmaceutical Compositions. The sulfamoyl azides of Formula I employed in Example 1 are compounded with pharmacologically acceptable carriers to provide the pharmaceutical compositions useful in the present invention. Typical of the pharmaceutical compositions are the following.

A. Suspensions. A small amount of U.S.'P. methylcellulose .is intimately mixed with the sulfamoyl azides of Formula I and the mixture is suspended in distilled water which is adjusted to a pH of about 5 with dilute hydrochloric acid to provide a mixture comprised of the sulfamoyl azide and 0.25 percent methylcellulose by weight per volume. This mixture is suitable for either oral or parenteral administration. An example of a unit dose prepared in this manner consists of 500 mg. of 4-chlorophenylsulfamoyl azide, 0.25 g. of methylcellulose suspended in I00 ml. of distilled water adjusted to a pH of 5. i

B. Tablets. The sulfamoyl azides of Formula I are compounded into tablets according to the following example.

Lactose 185.0 g.

l-2 minutes 13 The foregoing materials are blended in a twin-shell blender and then granulated and pressed into tablets weighing 250 mg. each. Each tablet contains 50 milligrams of active ingredient. The tablet may be scored in quarters so that a dose of 12.5 mg. of active ingredient is provided.

PREPARATION OF SULFAMOYL AZIDES Methods of preparation of the sulfamoyl azides of Formula I are disclosed in R. J. Shozda and J. A. Vernon, J. Org. Chem., 32, 2,876 (1967) and in W. B. Hardy and F. H. Adams, U.S. Pat. No. 2,863,866. In order to assure that the sulfamoyl azides which are employed in the present invention are readily available, descriptions of preparations of selected new sulfamoyl azides are given below.

Procedure A. Condensation of Amine with Chlorosulfonyl Azide.

l-Methoxyphenylsulfamoyl Azide. chlorosulfonyl azide is prepared in situ by stirring a suspension of sodium azide (7.0 g., 0.108 mole) in 100 ml. of acetonitrile with sulfuryl chloride (13.5 g., 0.1 mole) for 48 hr. at room temperature and then removing the solids by filtration. The filtrate consists of approximately 0.1 mole of chlorosulfonyl azide dissolved in 100 ml. of acetonitrile. Caution should be exercised in handling this reagent since, in an undiluted state, the chlorosulfonyl azide has a tendency to be shock sensitive. When diluted with an inert solvent, however, chlorosulfonyl azide can be safely manipulated in chemical processes.

An acetonitrile solution (100 ml.) of 4- methoxyaniline (24.6 g., 0.2 mole) is added dropwise at 25C. to a stirred solution of 0.1 mole of chlorosulfonyl azide in 100 ml. of acetonitrile prepared as described above. After stirring the mixture for 16 hr., the by-product 4-methoxyaniline hydrochloride (14.3 g.) is collected and the filtrate is concentrated in vacuo. Unreacted 4-methoxyaniline is recovered by dissolving residual material in 200 ml. of anhydrous ether, acidifying with ethereal hydrogen chloride and filtering. The residue remaining after evaporation of the ether filtrate is extracted several times with 1:9 isopropyl etherpetroleum ether (b.p. 6080C.). Concentration of the combined extracts provides 12.6 g. of a red oil. The product is isolated from this oil by chromatography employing a silica gel column (4 cm. diameter) and using 30 parts of absorbent to 1 part oil. The column is first eluted with a 5 percent ether-petroleum ether (b.p. 60-80C.) fraction and then with a second fraction consisting of a gradually increasing proportion to 25 percent) of ether to petroleum ether. Concentration v methoxyaniline in Procedure A provides rnethylphenylsulfamoyl azide. The purification step involving chromatographic separation is omitted and analytical material obtained by crystallization from isopropyl ether, m.p. 6263C. (corr.).

Analysis. Calcd. for C-,H N O S: C, 39.62; H, 3.80; N, 26.40. Found: C, 39.36; H, 4.06; N, 26.48.

Procedure B. Condensation of Sulfamoyl Chlorides With Amines.

Methylsulfamoyl Azide. Methylsulfamoyl chloride is prepared by refluxing a stirred mixture of methylamine hydrochloride (20.3 g., 0.3 mole) and sulfuryl chloride 5 (80 ml., 1 mole) in 150 ml. of acetonitrile for a 24 hr.

period. Excess sulfuryl chloride and acetonitrile solvent are removed in vacuo and the residual oil is taken up in about 300 ml. of anhydrous ether, filtered, and the filtrate concentrated to provide a residue which on dis- 10 tillation yields 31 g. (80 percent) of methylsulfamoyl chloride, b.p. 54C. at 0.2 mm Hg., n 1.4630.

A mixture of methylsulfamoyl chloride (9.7 g., 0.075 mole) and sodium azide (5.2 g-., 0.08 mole) in 150 ml. of acetone is stirred for 24 hr. at 25C. The mixture is filtered to remove insoluble inorganics and the filtrate concentrated in vacuo. Distillation of the residual oil provides 5.2 g. (50 percent) of analytically pure methylsulfamoyl azide, b.p. 8788C. at 0.25 mm Hg., n,, 1.4680.

Analysis. Calcd. for CH N O S: C, 8.82; H, 2.96; N, 41.17; S, 23.56. Found: C, 8.86; H, 3.23; N, 40.62; S, 23.32.

By substituting various amines for methylamine, additional sulfamoyl azides useful in the present invention are obtained according to Procedure B. Table 4 lists sulfamoyl chloride intermediates and sulfamoyl azides prepared therefrom.

TABLE 4 ADDITIONAL SULFAMOYL AZIDES Sulfamoyl Azide 2. lsopropylsulfamoyl chloride b.p. lsopropylsult'amoyl Azide b.p.

596lC. at 0.03 mm Hg. n 55$7C. at 0.05 mm Hg. n 1.5340 1.4580. Analysis calcd. for

C,H,N O,S: C, 21.95; H, 4.91; N, 34.12. Found: C, 22.25; H, 4.72; N, 34.04.

3. lsobutylsulfamoyl Chloride: b.p. lsobutylsulfamoyl Azide b.p.

74-75C. at 0.03 mm Hg. 120-130C. at 0.1-3.0 mm.

Hg. Analysis Calcd. for C,H,,,N.O,S: C, 26.96; H, 5.66; N, 31.44. Found: C, 26.92; H, 5.58; N, 31.12.

terL-Butylsulfamoyl Azide b.p.

6263C. at 0.04 mm Hg. n 1.4600. Analysis Calcd. for C,H ,N,0,S: C, 26.96; H, 5.66; N, 31.45. Found: C, 27.12; H, 5.93; N, 31.55.

. l-Adamantylsull'amoyl Chloride:

m.p. l04-l06C. Analysis Calcd. for C,.,H,,C|N0,s= C, 48.07; H, 6.46; N, 5.61. Found: C, 48.12; H, 6.44; N, 5.56.

While several specific embodiments are described in the foregoing, it will be appreciated that other modifications may be made without departing from the spirit and scope of the appended claims.

What is claimed is:

1. A process for eliciting a hypotensive effect in a mammalian host which comprises administering thereto a dose of from about 0.003 to about 10 mg./kg. of body weight of said host ofa compound selected from a group consisting of compounds having the formula RR NSO N wherein R and R taken together with nitrogen is a member of the group consisting of N-(lower alkyl of from one to four carbon atoms inclusive)-piperazinyl and a non-toxic pharmaceutically acceptable acid addition salt thereof.

2. The process of claim 1 in which the compound is 4-methylpiperazine-l-sulfonyl azide hydrochloride.

3. A pharmaceutical composition in unit dosage form suitable for systemic administration to a mammalian host comprising a pharmaceutical carrier and an effective dose between 0.003 to 10 milligrams per kilogram of body weight of a sulfamoyl azide selected from the group consisting of compounds having the formula R'R NSO N wherein R and R taken together with nitrogen is a member of the group consisting of N-(lower alkyl of from one to four carbon atoms inclusive )piperazinyl and a non-toxic pharmaceutically acceptable acid addition salt thereof.

4. The composition of claim 3 containing 4-methylpiperazinel -sulfonyl azide hydrochloride.

Claims (3)

1. 2. The process of claim 1 in which the compound is 4-methylpiperazine-1-sulfonyl azide hydrochloride.
2. 3. A pharmaceutical composition in unit dosage form suitable for systemic administration to a mammalian host comprising a pharmaceutical carrier and an effective dose between 0.003 to 10 milligrams per kilogram of body weight of a sulfamoyl azide selected from the group consisting of compounds having the formula R1R2NSO2N3 wherein R1 and R2 taken together with nitrogen is a member of the group consisting of N-(lower alkyl of from one to four carbon atoms inclusive)piperazinyl and a non-toxic pharmaceutically acceptable acid addition salt thereof.
3. 4. The composition of claim 3 containing 4-methylpiperazine-1-sulfonyl azide hydrochloride.