IL30782A - Amino guanidines - Google Patents

Description

Amino 29009 We have now surprisingly found that some of compounds of the above general formula have pharmacological as is mentioned in more detail below0 The present invention provides a pharmaceutical composition comprising a compound of the general formula or an acid addition salt thereof X is a direct bond or a ethylene vinylene R R2 and Y are the same or different and each represent a halogen atom or a lower lower substituted or unsubstituted hydroxy or trifluoromethyl and n is 2 2 or or n is 1 and Y and R together form a methylenedioxy is cyclo alkyl of 3 to carbon lower allyl or and each is a hydrogen atom a lower alkyl or and when taken together with the nitrogen atoms to which they are attached form an imidazoline and is a hydrogen atom or a lower alkyl radical with the proviso that when and are taken together to form an imidazoline ring is the terms and meaning the radicals contain up to 6 carbon and a pharmaceutically acceptable said composition being in a standard acceptable form for mammalian For the compositions should be capable of being administered to human beings orally or parenterallyo The invention therefore does not include herbicidal compositions containing the compounds of general formula When there are more than two substituents in the benzene ring n is 2 or then Y preferably is a halogen a very preferred group of compounds of the above general formula are those where n is 0 and is in the This preferred group of compounds comprise those of the general formula and the salts wherein and are the same and are halogen nitro radicalss lower alkyl radicals or lower alkoxy and have the meanings defined 1 2 Examples of radicals R and R are unsubstituted lower alkyl preferably containing 1 to carbon atoms methyl or lower alkoxy preferably containing 1 to alogen carbon atoms methpxy or or unsubstituted benzyloxy benzyloxy or and trifluoromethylo In Y can have any of the above meanings R1 2 for and R but preferably Y is alkoxy or methoxy or methylo 2 Alternatively Y and R can complete a methylenedioxy across the of the benzene Examples of are and benzylo R R and preferably are all though they can for example 5 propyl or butylo Alternatively R and R can 6 complete an imidazoline ring while R is In the compounds of the present when is a direct bond between the substituted benzene ring and the carbon the compounds are designated as substituted when is the compounds are named and when is the compounds are described as substituted Typical examples thereof are and The compounds of formula I generally show one or more of the following pharmacological namely hypotensive antibacterial activity on the depressant or mydriatic analgesic diuretic hyperglycemic activity and anorectic activityc the and hypotensive activities are very particularly the hypotensive activity compounds having substituents in the and of the benzene and some compounds having substituents in the and Compounds with substantial antibacterial activity but little or no hypotensive activity include in general and benzylideneso Other compounds provided by the invention include potential stimulants or psychic tranquilisers and For preparing pharmaceutical compositions from the cologically active compounds of general formula ceutically acceptable carriers can be either solid or Solid form preparations include unit dosage cachets and A solid carrier can be one or more substances which complete one of the above forms and which may also act as flavouring suspending binders or agents5 it can also be an encapsulating materialo In powders the carrier is a finely divided solid which is in admixture with the finely divided compound and then made into unit dosage form0 In the tablet the compound is mixed with a carrier having the necessary binding properties in suitable proportions and compacted in the shape and size The powders and tablets preferably contain from 5 to 99 percent of the active ingrediento Suitable solid carriers are magnesium magnesium methyl sodium carboxymethyl a low melting wax and cocoa Capsules can be prepared by surrounding the active compound or without other by a Liquid form preparations include sterile suspensions and emulsions0 As an example may be mentioned glycol solutions for parenteral Liquid preparations can also be formulated in solution in aqueous polyethylene glycol solutions0 Aqueous suspensions suitable for oral use can be made by dispensing the finely divided compound in sterile water with viscous natural or synthetic for methyl sodium carboxymethyl cellulose and other well known suspending the pharmaceutical preparation is in unit dosage In such the preparation is in unit doses containing appropriate quantities of the the unit dosage form can be a packaged the package containing discrete quantities of for packeted powders of vials or ampoules0 The unit dosage form can be a cachet or tablet itself or it can be the appropriate number of any of these in packaged form0 The quantity of compound in a unit dose of preparation may be varied or adjusted from a 1 to 100 mgo according to the particular application and the potency of the active In the pharmacological evaluation of the compounds of this the following tests inter alia were To test for hypotensive and activity the following procedures were carried Female rats were rendered hypertensive by the application of a ligature to the left kidney and contralateral nephrectomy as described by in Proco Exptlo Biol0 and and in Am0 1020 Systolic blood pressure was recorded indirectly from the tail using an and a sensing such the Decker Caudal smo raph made by the Decker which detects changes in the volume in the tail which occurs with each heart Test compounds were administered orally at various concentrations with a stomach tube and pressures recorded prior to dosing and k sometimes 2k hours The compounds of this ivention in the above test when administered orally at a dosage range of about 1 to about of body weight generally reduced the blood pressure an average of 20 to 60 mm In this particularly effective results are afforded by 2 acetate and as in hereinafter Table A which lists the maximum changes in pressure in rats that are encountered at any of the three observation periods regardless of the time of although these peaks are usually observed at hours Table A Blood Pressure Rats Control 1 12 aminolguanidine 2 11 183 acetate 3 11 185 8 183 o k amino3guanidine 10 k 178 nitrate Hypertension was produced in dogs by a each performed under pentobarbital anesthesia carotid artery bifurcations were exposed by two incisions and the sinuses denervated by stripping the adventitia in the regionD The right renal artery was exposed by a flank incision and constricted by a silver Goldblatt clamp0 the left kidney was removedo The blood pressure was recorded indirectly from the tail with a condenser phone by the method described by Prioli9 and in Jo Physicolo acetate was administered to four groups of intraperitoneally at doses of and and orally at and the blood pressure was recorded at two and four hours0 The results are in the following table TABLE B Blood Pr Control 20V131 acetate 5 orally 5 In the above all doses of acetate significantly lowered blood pressure and decreased heart rate whether administered intraperitoneally or orallyo To test for the following procedures were carried outo The compounds were screened initially as the compound was administered orally to three mice at each of the following and The animals were watched for a minimum of two hours during which time signs of general stimulation increased spontaneous motor hyperactivity on tactile general depression decreased spontaneous motor decreased and autonomic activity were The animals were tested for changes in reflexes and were rated by use of a pole climb and inclined screen for the presence of The Eddy and Dorothy Jo was used to test for analgesiao The experiment was terminated by subjecting each animal to a maximal electroshock to test for activity was measured as Compounds at a number of dose levels were administered to groups of six One hour later hour later if the compound was administered the animals were challenged with metrazol 125 The incidence of clonic and tonic convulsions and deaths was observed for Protection against convulsions and death was determined comparison with controls run simultaneousl An against convulsions deaths was calculated from dose curveso Antagonism to reserpine ptosis was measured by the process of Rubin et Vol 120 page 125 activity was measured by the process of Everett Science Colo 12k page 29 Ataxia was measured by the method of Dunham and Heya in Pharmo Scientific edo 6 page 206 is usedo activity was measured by the test of Acta Pharmacol et Toxicol Vol 13 page 113 Protection against maximal electroshock was measured by the procedure of Swinyard et J 106 page 319 o Hypoglycemic activity was measured as Male rats weighing grams are fasted a control blood sample was taken from the and a test dose of 60 is administered by stomach tubeQ Subsequent blood samples were taken at hourly intervals for five hours0 In a compound was considered active if a depression in blood sugar approximating was observed for at least three of the five hour test periodo activity was measured by the procedures of Buttle et Nature Volo 159 page 629 and Winter et ProCo Medo Volo 111 page Diuretic activity was measured by the procedure of Lipschitz et o Pharmacol 97 activity was measured as Stock solutions at 10 000 prepared in suitable vehicleso dilutions were made with sterile 1 quantities of each dilution were incorporated in Seed agar in sterile petri dishes0 The hardened surface was inoculated with test organisms and incubated for 18 hours at against various standard and the minimal inhibitory concentration was In therapeutic use as medicinal the compounds of this invention usually are administered at the initial dosage of Ool mgo to 10 mgo per kilogram daily0 The may be varied depending upon the requirements of the In which has been found to possess outstanding hypotensive activity may be employed in animals at a range from Ool to 10 per kilo per although variations will occur0 a dosage level that is in the range of from 0o05 to per kilo per day is most desirably employed in order to achieve effective results0 In a related novel and useful compositions are provided by admixing the active compound of this invention with an animal feedo Suitable feeds are described in the book and by published by Morrison Publishing New York When R is cycloalkyl of 3 to carbon lower 1 2 5 6 alkyl or benzyl and the remaining variables E fi and have the meanings defined above9 or R is 1 2 hydrogen and R R and Y are lower substituted or unsubstituted benzyloxy or n being 2 or 3 R and Y together form a methylenedioxy n being the compounds of general formula are novel compounds and the invention also provides such compounds and their acid addition The compounds of general formula can be prepared by reacting an aldehyde or ketone of the general formula with an aminoguanidine of the general formula 1 2 6 or a salt thereof in which formulae R R R R R n X have the meanings defined in connection with general formula the compound of general formula 2 has n equal to zero and R in the it is a compound of the general formula where R R R and X have the meanings defined in connection with general formula The reaction usually is carried out by heating the aldehyde or in solution in an organic with an acidic aqueous solution of a soluble acid addition salt of the the nitrate or acetateo Heating is generally effected on a steam bath for reaction times of from a few minutes 10 up to several hours l6 depending on the particular compound being preparedo The presence of an inorganic or organic acid acetic formic or gluconic is recommended during the in which case the product is obtained the acid addition salto The free base can be obtained if by neutralisation with a suitable Many of the substituted phenyl carbonyl starting materials of general formula are commercially available and these and others may also be prepared by any conventional method such as described in 62 and The alkyl substituted aminoguanidines employed as reactants herein may be prepared by the process described in Medo Chem0 6 while may be prepared by the process described in Chem0 18 790 The compounds of general formula may also be prepared 5 by other methods known in the for example when R R and R are hydrogen they may be prepared by heating a corresponding thiosemicarbazide of the aldehyde or ketone of formula with ammonia or by reacting a corresponding hydrazone of the aldehyde or ketone of general formula with cyanamideo The acid addition salts may be prepared by treating the free base with an acido Among the suitable salts of the compounds of the present invention are inter inorganic such as the hydrohalio acids hydrochloric and hydrobromic sulphuric nitric and phosphoric and organic acids such as glutaric and maleic The following Examples illustrate the preparation of compounds of general formula and 5 ceutical compositions containing such EXAMPLE 1 A A A sssooollluuutttiiiooonnn ooofff ooofff 222 iiinnn 222000 ooofff eeettthhhaaannnooolll iiisss aaaddddddeeeddd tttooo aaa sssooollluuutttiiiooonnn ooofff ooofff aaammmiiinnnoooggguuuaaannniiidddiiinnneee 111000 bbbiiicccaaarrrbbbooonnnaaattteee iiinnn 444000 ooofff wwwaaattteeerrr aaannnddd ooofff aaaccceeetttiiiccc AAAnnn oooiiilll ssseeepppaaarrraaattteeesss wwwhhhiiiccchhh dddiiissssssooolllvvveeesss wwwhhheeennn ttthhheee sssooollluuutttiiiooonnn iiisss hhheeeaaattteeeddd ooonnn aaa sssttteeeaaammm AAAfffttteeerrr aaannn ttthhheee sssooollluuutttiiiooonnn iiisss fffiiilllttteeerrreeeddd aaannnddd cccooonnnccceeennntttrrraaattteeeddd tttooo hhhaaalllfff vvvooollluuummmeee iiinnn aaa ooofff sssooollliiiddd hhhaaavvviiinnnggg aaa mmmeeellltttiiinnnggg pppoooiiinnnttt ooofff wwwiiittthhh dddeeecccooommmpppooosssiiitttiiiooonnn iiisss fffooorrr FFFooouuunnndddsss S S bbbyyy ttthhheee ppprrroooccceeeddduuurrreee ooofff EEExxxaaammmpppllleee bbbuuuttt 222000 sssuuubbbssstttiiitttuuutttiiinnnggg aaannnooottthhheeerrr ooorrrgggaaannniiiccc aaaccciiiddd ooorrr iiinnnooorrrgggaaannniiiccc aaaccciiiddd fffooorrr aaaccceeetttiiiccc aaaccciiiddd ttthhheeerrreee iiisss ooobbbtttaaaiiinnneeeddd ttthhheee cccooorrrrrreeessspppooonnndddiiinnnggg EXAMPLE 2 amino3guanidine nitrate Following the procedure of Example but substituting for and nitric acid for acetic acid there is obtained having a melting point of for the procedure of Example but substituting dibromoacetophenone for there is obtained acetate EXAMPLE acetate Following the procedure of Example but substituting for there is obtained acetateo acetate Following the procedure of Example but substituting for there is obtained guanidine acetate after a long heating tirae0 EXAMPLE 6 acetate Following the procedure of Example but substituting for there is obtained guanidine EXAMPLE 7 Following the procedure of Example but substituting for there is aGetateo EXAMPLE 8 aminojguanidine acetate Following the procedure of Example but substituting dichlorobutyrophenone for there is obtained acetatec EXAMPLE 9 acetate Following the procedure of Example but substituting for there is obtained guanidine acetate0 EXAMPLE 10 aminoguanidine chloride Following the procedure of Example but substituting for and hydrochloric acid for acetic acid there is obtained EXAMPLE 11 sulphate Following the procedure of Example but for and sulphuric acid for acetic acid there is obtained uanidine EXAMPLE 12 Repeating the procedure for the prior Examples with appropriate acid salts of the compounds designated by the following structural formula were wherein in each compound the substxtuents are defined as F F H H H H H H CI Cl H H H H CI Cl H H H H Br Br H N02 H H H Cl H H H H H H Br Br H H H H H H H Cl Cl H H H H Cl Br H H H H Br F H H H H EXAMPLE 13 Following the procedure of Example but substituting hydrochloride for aminoguanidine and hydrochloric acid for acetic acid there is obtained Similarly9 the following compounds are and EXAMPLE Ik Repeating the procedure of Example the following compounds are uanidine5 2 and uanidine salts A solution of 9 of in 25 of ethanol was added to a solution of 7 of aminoguanidine bicarbonate dissolved in 60 mlo of water and of concentrated nitric to which were added 60 of ethanolo The solution was warmed on a steam and after 10 minutes a which precipitate began to gradually increasing for 1 The solid was collected on a filter and washed with water and ethanolo It weighed and melted at with Anal0 for Founds By substituting 5 5 of lactic acid nitric acid in Example the lactate was Yield 11 Analo Calcdo for By of glycollic acid for acetic acid in Example l the glycollate was obtainedo Yield 10 Calcdo for Founds By adding of in 10 of Addition of mlo of formic acid to a suspension of of aminoguanidine bicarbonate in of water gave a solution of which go of in mlo of ethanol was addedo An oil separated which gradually dissolved as the mixture was heated on a steam batho After an the oil had and the solution was filtered into an evaporating dish and concentrated to half when small white rosettes began to form0 White platelets of the formate soon filled the liquid and were collected on a filter to give with decomposition Analo Calcdo for A solution of of in of ethanol was added to 7 of amino uanidine bicarbonate dissolved in mlo of water with 9 g of gluconic anhydride and the mixture was heated overnight on a steam The sirupy solution was concentrated to dryness on a steam leaving the gluconate as a glassy solid which when powdered took on an electric charge and very readily dispersed as an aerosolo The powder melted at Analo Calcdo for Founds 13o06o A solution of 9 of 2 in mlo of ethanol mixed with a solution of 7 of aminoguanidine becarbonate in 80 of water with mlo of acetic acid was warmed on a steam bath for 2 hours and filteredo On it deposited 15 go of white platelets of the acetate melting at with decomposition Analo Calcd0 for 2 1 Founds 2 EXAMPLE 16 acetate A solution of 10 of in mlo of ethanol was added to a solution of 7 of aminoguanidine bicarbonate in mlo of water and ml0 of acetic acido This gave a mixture of oil and supernatant aqueous solution which was heated three days on a steam when a little oil was still presento On 2 go of white solid melting at slowly Analo Calcdo for Founds EXAMPLE 17 A solution of 10 of in 25 of ethanol was added to a solution of 7 of antinoguanidine bicarbonate in of water and ml0 of acetic heating the resulting solution on a steam bath for 2 11 of bright yellow powder separated on Analo Calcdo for EXAMPLE 18 nitrate To 220 of and l80 of anhydrous aluminium chloride there was added 80 of propionic anhydride with stirring and heating at The mixture was then poured on ice and the lower oily layer taken up in washed with and distilledo The faintly yellow product boiled at at 15 and weighed 130 for A solution of 15 of in of ethanol was added to a solution of 10 of aminoguanidine bicarbonate in of water and of nitric acid and the mixture was heated overnight on a steam On 9 of white crystals of the title compound melting at with for 1 EXAMPLE 19 ormate A solution of 7 in 30 mlo of ethanol was added to a solution of of guanidine bicarbonate in of water and mlo of formic acid and the mixture was heated overnight on a steam On 7 of white crystals melting at were collectedo Analo Calcdo for 360885 Founds EXAMPLE 20 formate A solution of 12 of l in mlo alcohol was added to a solution of 7 of aminoguanidine bicarbonate in mlo and of formic and the mixture was heated for minutes on a steam batho On cooling a layer of yellow solid separated and was slowly overlaid by a thick mass of white when collected on a melted above becoming yellow at Analo Calcdo for 2o77i Clo 17ol0o EXAMPLE 21 formate To a solution of go of in of there were added 8 g0 of aminoguanidine bicarbonate dissolved in mlo of water and of formic acid The resulting mixture was digested overnight on a steam bath to 2 give a clear solution which on cooling of white platelets separatedo for l EXAMPLE 22 acetate By heating a mixture of a solution of 10 of propiophenone in ethanol and a solution of 7 of aminoguanidine bicarbonate in 80 mlo of and 5 of acetic acid for three days on a steam crystals of the title compound are obtained on cooling0 EXAMPLE 23 acetate By heating a solution of 3 of benzaldehyde in 15 ethanol with one of 3 of guanidine bicarbonate in 15 of water and 3 of acetic acid overnight on a steam of crystals of the title compound were obtained on cooling with Analo Calcdo for EXAMPLE ormate By heating a solution of 15 of in mlo of ethanol with a solution of 7 of aminoguanidine bicarbonate in 30 of water and 5 of acetic acid for 2 hours on a steam crystals of the title compound are obtained on cooling0 By heating a solution of of benzaldehyde in mlo of ethanol with a solution of 7 of aminoguanidine bicarbonate in mlo of water and 5 of formic acid on a steam bath for an crystals of the title compound are obtained on coolingo EXAMPLE 26 formate By heating a mlo ethanolic solution of 10 of by the treatment of hydroxybenzaldehyde stirred in a solution of excess potassium carbonate with diethyl with a solution of 7 of aminoguanidine bicarbonate in mlo of water and of formic acid overnight on a steam crystals of the title compound are obtained on EXAMPLE 27 formate By heating a ethanolic solution of 15 of by the treatment of stirred in a solution of potassium carbonate in excess with diethyl with a solution of 7 of aminoguanidine bicarbonate in mlo of water and 5 of formic acid for an hour on a steam crystals of the title compound are obtained on coolingo EXAMPLE 28 ormate By heating a mlo ethanolic solution of 10 go of by treating a stirred solution of in excess aqueous potassium carbonate with diethyl with a solution of 7 of bicarbonate in of water and of formic acid on a steam bath for 2 crystals of the title compound are obtained on coolingo EXAMPLE 29 acetate A solution of 10 of by treating a mixture of and butyric anhydride with excess aluminium in ralo of ethanol and of mixed with a solution of 7 g of aminoguanidine bicarbonate in mlo of water with of acetic and heated on a steam bath for three days gives on cooling crystals of the title compoundo EXAMPLE acetate A solution of 10 go of in of ethanol added to a solution of 7 g of aminoguanidine bicarbonate in of water and 5 of acetic acid gives the title compound after heating overnight on a steam bath and coolingo This compound was prepared from aminoguanidine bicarbonate and acetic following the procedure given in Example lo Yield 6 go mp This compound was prepared from aminoguanidine bicarbonate and acetic acid following the procedure of Example Yield o EXAMPLE 33 This compound was prepared from aminoguanidine bicarbonate and acetic acid following the procedure of Example 10 Yield 13 m0p0 EXAMPLE This compound was prepared from aminoguanidine bicarbonate and acetic acid following the procedure of Example Yield 10 This compound was prepared from i go aminoguanidine bicarbonate g and acetic acid following the procedure of Example lo Yield llo5 go EXAMPLE e 2 This compound was prepared from aminoguanidine bicarbonate and acetic acid following the procedure of Example lo Yield 3 This compound was prepared from aminoguanidine bicarbonate 7 and acetic acid following the procedure of Example Yield EXAMPLE This compound was prepared from aminoguanidine bicarbonate 7 and acetic acid following the procedure of Example Yield This compound was prepared from go aminoguanidine bicarbonate 7 g o and nitric acid following the procedure of Example 10 Yield 7 EXAMPLE This compound was prepared from aminoguanidine bicarbonate and acetic acid following the procedure of Example Yield 7 EXAMPLE This compound was prepared from g o aminoguanidine bicarbonate 7 and acetic acid following the procedure of Example Yield 7 EXAMPLE This compound was prepared from aminoguanidine bicarbonate and nitric acid following the procedure of Example Yield 7 T T Thhhiiisss cccooommmpppooouuunnnddd wwwaaasss ppprrreeepppaaarrreeeddd fffrrrooommm aaammmiiinnnoooggguuuaaannniiidddiiinnneee bbbiiicccaaarrrbbbooonnnaaattteee aaannnddd nnniiitttrrriiiccc aaaccciiiddd ttthhheee ppprrroooccceeeddduuurrreee ooofff EEExxxaaammmpppllleee YYYiiieeelllddd ttt E E EXXXAAAMMMPPPLLLEEE This prepared from aminoguanidine bicarbonate and acetic acid following the procedure of Example gave fibrous crystals difficult to purify0 These were converted to the nitrate by addition of of nitric acido Yield 7 This compound was prepared from aminoguanidine bicarbonate and nitric acid o following the procedure of Example lo Yield 9 EXAMPLE 6 C This compound was prepared from benzaldehyde aminoguanidine bicarbonate go and acetic acid following the procedure of Example Yield EXAMPLE This compound was prepared from benzaldehyde aminoguanidine bicarbonate and acetic acid following the procedure of Example Yield 11 o EXAMPLE 8 e This compound was prepared from aminoguanidine bicarbonate go and nitric acid following the procedure of Example Yield 12 go o This compound was prepared from benzaldehyde aminoguanidine bicarbonate go and nitric acid following the procedure of Example Yield 102 go EXAMPLE This compound was prepared from go aminoguanidine bicarbonate and nitric acid following the procedure of Example 1 with the addition of butanol and 8 hours heatingo Yield 12 po 17 EXAMPLE This compound was prepared from 2 propiophenone 10 aminoguanidine bicarbonate and nitric acid following the procedure of Example lo Yield 12 EXAMPLE 52 This compound was prepared from 10 aminoguanidine bicarbonate 8 and acetic acid following the procedure of Example adding nitric Yield Ik EXAMPLE e This compound was prepared from benzaldehyde 10 aminoguanidine bicarbonate go and acetic acid following the procedure of Example Yield 11 g 2 EXAMPLE This compound was prepared from dichlorostyryl methyl ketone 10 aminoguanidine bicarbonate 7 and acetic acid followed by nitric acid following the procedure of Example Yield l EXAMPLE 55 A unit liquid dosage composition suitable for oral or parenteral administration is prepared by admixing one gram of acetate in sufficient sterile distilled water containing weight of methylcellulose to make 100 This admixture may then be flavoured for oral use or filled aseptically into sterile ampules which are then flame and stored under refrigeration until oral and parenteral liquid compositions of the following hypotensive agents are amino amino and EXAMPLE Tablets and capsules for oral use are prepared with the following Ingredients Milligrams 1 10 15 25 50 100 aminolguanidine acetate lactose 296 287 282 272 197 magnesium stearate 3 3 3 3 3 3 300 300 300 300 300 300 tablets and capsules of the following hypotensive agents are amino uanidine and EXAMPLE Repeating the procedures of Examples 55 and tablets and liquid compositions of the hypotensive agents described in Examples to be insufficientOCRQuality

Claims (2)

1. AHP-4220-fl^ WHAT WE CLAIM IS: lo A pharmaceutical composition comprising a compound of the general formula or an acid-addition salt thereof (wherein X is a direct bond 1 2 or a methylene, ethylene or vinylene radical^ R , R and Y are the same or different and each represent a halogen atom halogen or a nitro, amino, lower alkyl, lower alkoxy,/substituted or unsubstituted benzyloxy, hydroxy or trifluoromethyl radical, 2 and n is 0, 1, 2 or 3» or n is 1 and Y and R together form a me hylenedioxy radical; R^ is a hydrogen atom or a cyclo (lower)alkyl of 3 to 5 carbon atoms, lower alkyl, ethynyl, allyl or benzyl? R* and R5 each is a hydrogen atom or a lower alkyl radical, or R * and R5 when taken together with the nitrogen atoms to which they are attached form an imidazoline ring; and R^ is a hydrogen atom or is lower alkyl with the i 5 proviso that when R and are taken together to form an imidazoline ring R^ is hydrogen; the terms "lower alkyl" and "lower alkoxy" meaning the radicals contain up to 6 carbon atoms) and a pharmaceutically acceptable carrier, said composition being in a form which is adopted for administration to mammals orally or parenterally and not being a standard form for herbicidal application of a compound,.

2. A pharmaceutical composition as claimed in Claim 1 and which is in medicinal unit dosage forn ΑΗΡ-*+220-ίΊ α 3« A pharmaceutical composition as claimed in Claim 19 said composition being in the form of a tablet0 o A pharmaceutical composition as claimed in Claim 1, said composition being in the form of a capsule» 5· A pharmaceutical composition as claimed in Claim 1, said composition being in the form of a sterile solutione 6. A pharmaceutical composition as claimed in any of Claims 1 to 5s wherein n is 1, 2 or 3 and Y is a halogen atome 7o A pharmaceutical composition as claimed in any of Claims 1 to 5s wherein n is zero, 8 is in the 6-position and R and 2 R are the same and are halogen atoms, nitro radicals, lower alkyl radicals or lower alkoxy radicals,, 8. A pharmaceutical composition as claimed in Claim 7S wherein ^ is a hydrogen atom or a lower alkyl radicalβ 9o A pharmaceutical composition as claimed in any of Claims 1 to 5i said composition containing [(2,6-dichlorobenzylidene) amino]guanidine or an acid addition salt thereof. 10» A pharmaceutical composition as claimed in any of Claims 1 to 5» said composition containing [(2-chloro-6-fluorobenzylidene) amino^guanidine, or an acid addition salt thereof» 11. A compound of the general formula given in Claim 1, or an acid 5 6 addition salt thereof wherein X, R , R and R have the meanings 3 1 2 defined in Claim 1 and either (a) R is hydrogen and R , R and Y are the same or different and each represent a nitro, amino, halogen lower alkyl,/substituted or unsubstituted benzyloxy or trifluoro- AHP-*t220-f: methyl radical, n being 0, 1, 2 or 55 or Y and R together form a methylenedioxy radical, n being 1 or (b) R is cycloalkyl of 3 to 5 carbon atoms, lower alkyl, ethynyl, allyl or benzyl and 1 2 R , R , Y and n have the meanings defined in Claim 1<> 2 12o A compound as claimed in Claim 11, wherein n is zero, R is in 1 2 the 6-position, R and R are the same and are nitro or lower 3 alkyl radicals and R is hydrogen» 13o A compound as claimed in Claim 11, wherein R^ is a lower alkyl radical„ 1* C(2,1f-Dichloro-a-=methylbenzylidene)amino]guanidine, or an acid addition salt thereofo 15« C(2,5-Dibromo-a=ethylbenzylidene)amino]guanidine, or an acid addition salt thereofa l6o C(2,5-Dibromo-a-methylbenzylidene)amino]guanidine, or an acid addition salt thereof» 17 C(2,5-Dicbloro-a-ethylbenzylidene)amino3guanidine, or an acid addition salt thereofo l8o [ (2,5-Dichloro-a-n-propylbenzylidene) amino]guanidine, or an acid addition salt thereofo 19o C(2,1-Diethoxy-a»methylbenzylidene)amino3guanidine, or an acid addition salt thereofo 20. [(2,5-Dichloro-a-methylbenzylidene)amino3guanidine, or an acid addition salt thereofo AHP-l+220-fld 21 o C( 2 , -Dinitrobenzylidene)amino]guanidine, or an acid addition salt thereofo 22o C( 2 , 5-Din>ethoxy-a-methylbenzylid4.ne)amino]guanidine, or an acid addition salt thereof0 23 o C( 2 , 6-Dihyiiroxy^-methylbenzylid.ne)amino]guanidine, or an acid addition salt thereof., 2k, C(a, 2,5-Trimethylbenzylidine)amino3guanid ne, or an acid addition salt thereof„ e 2.5° [(a^j^-TrimethylbenzylidineJaminoDguanidjfoe, or an acid addition salt thereofo e 26» [ ( 2 , 5-Diethoxy-a-methylbenzylidine)amino]guanidine, or an acid addition salt thereofo e 27o [(a, 29 , 5-Tetramethylbenzylidine)aminoiguanidj!ne, or an acid addition salt thereofo addition salt thereofo e 29o [ (2,1-Dichloro-a-methylcinnamylidine)amino]guanidjAie, or an acid addition salt thereofo 30 e A compound as claimed in any of Claims Ik to 29$ said compound being in the form of a nitrate, acetate, formate, lactate, glycollate, trifluoroacetate or gluconate0 31. A process for the preparation of a compound as claimed in Claim 11 , which comprises reacting an aldehyde or ketone of the general formula AHP- 220-fl, with an aminoguanidine of the general formula acid addition salt thereof, in which formulae R 1, R , R 3 R^, Y, n and X have the meanings defined in Claim 11» 32 o A process as claimed in Claim 31» wherein the aldehyde or ketone is a compound of the general formula in which R and R are the same and are nitro groups or lower alkyl radicals. 33· A process as claimed in Claim 31 or 32 wherein the reaction is carried out by heating a solution of the aldehyde or ketone in an organic solvent with a solution of an aminoguanidine salt in water0 3^· A process as claimed in Claim 33» wherein an acid is added to the reaction mixture0 35. A process as claimed in Claim 31» substantially as described with reference to any of Examples 16, 18, 21» 22, 29» 30» 31» 36, 38, 39, ½3, ^ , 50, 51 or ½. ΑΗΡ-^Ο-ίΙ^ accoding to Claim 11, Aminoguanidines/when prepared by the process claimed in any of Claims 31 to 35» A pharmaceutical composition as claimed in Claim 1, substantially as described with reference to any of Examples 55 to 57 - i+0 -