IL43280A - Preparation of(substituted phenylamidino)urea derivatives pharmaceutical compositions containing them and some new such derivatives - Google Patents

Abstract

Novel phenylguanidines of the formula <IMAGE> in which X is a hydrogen or halogen atom, Y is a hydrogen or halogen atom or a halogen-lower alkyl, nitro, lower alkyl or lower alkoxy group and Z is a halogen-lower alkyl, halogen-lower alkoxy or lower alkylsulphonyl group or, if X and Y are not both hydrogen atoms, Z is a halogen atom, or a lower alkoxy, lower alkyl, nitro or cyano group, and their non-toxic acid addition salts are obtained by reacting an acid addition salt of a corresponding aniline with cyanamide. The salts obtained can be converted to the free bases. Both are therapeutically useful as blood pressure-lowering (anti-hypertensive) and cardiovascular agents. They are also useful intermediates for the preparation of corresponding phenylamidine-urea compounds, possessing the same therapeutic properties. [GB1451477A]

Description

(Substituted phenylamid1no)urea derivatives This Invention provides new (substituted phenyl aml^no) urea compounds and processes for their preparation. This Invention further provides valuable pharmaceutical preparations which contain (substituted phenyl -ami dino)urea compounds which possess an effective degree of antihypertensive properties and exert activities on the cardiovascular system. A method for the treatment of hypertensive disorders by the administration substituted of a (.s-ibs-t-i-tut-ed phenyl ami d1 no ) urea compound is also described.

BACKGROUND OF THE INVENTION .

The pharmaceutical compositions which have been used as antihypertensive agents have included such as the thiazides, reserplne, hydralazine, a-methyl dopa, guanethidine and the like, These. compounds , however, while being effective produce undesirable side effects such as electrolyte imbalance, orthostatic hypertension, and gastric secretory and spasmolytic properties.

We have unexpectedly found that amidinourea compounds exhibit valuable pharmacologic properties.

We have unexpectedly found that the amidinoureas of this invention are useful antihypertensive agents.

We have further found that the amidinoureas compounds of this invention are novel and can easily be prepared.

We have also found that the compounds of this invention have a minimum of the side effects which accompany other antihypertensive agents.

We have still further found a simple and effective method for the treatment of cardiovascular disorders such as hypertensive disorders.

DESCRIPTION AND PREFERRED EMBODIMENT This Invention describes a class of novel chemical compound^^ which comprises a substituted phenyl radical which is attached to an amidinourea chain. This results in. urea type compounds having a substi nitrogen atoms. ceutically acce stituted phenyl The novel c structural form where: X is hydrogen or halo; Y is hydrogen, halo; hal ol oweral kyl , nitro, loweralkyl or loweralkoxy; Z is hal ol oweral kyl , Z is also halo, loweralkoxy, loweralkyl , or nitro, provided X and Y are not both hydrogen at the same time; and the non-tox1c acid addition salts thereof.

In Chem. Abstracts subject index referring to the abstract appearing in Chem. Abstracts 62, 404b there 1s mentioned a compound which appears to fall within the scope of the compounds, of the present invention, id compound is 1n fact N-(3,5 formula which diffe he present invention h - A-03.17 Compounds of this invention which are preferred are described by general formula I where: X is hydrogen or halo; Y is hydrogen, halo, loweralkyl or haloloweral kyl ; and Z is halo or loweralkyl (provided X and Y are not both hydrogen) or haloloweral kyl .

The more preferred compounds of this invention include those compounds where: X is hydrogen, chloro, bromo or fluoro; Y is hydrogen, chloro, bromo, fluoro, methyl or trifl uoromethyl and Z is chloro provided X and Y are not both hydrogen, bromo provided X and Y are not both hydrogen, fluoro provided X and Y are not both hydrogen, methyl provided X and Y are not both hydrogen or trifl uoromethyl .

A-0317 specification This -flveflt «*i further describes a new method for the treatment of cardiovascular disorders by the administration of a therapeutically effective amount of an amidinourea compound of formula II where: R2' ^3' *¼» R5 anc* ^6 may ^e *ne same or different and are hydrogen (provided at least one of R2, R3, R4, 5 and Rs is other than hydrogen), halo, haloloweral kyl , nitro, eyane-, ϊ 0 were -ky-4 *y J f e*iyJ , loweralkoxy or loweral kyl ; and the non-toxic acid addition salts thereof.

The preferred compounds which are useful in the treatment of cardio-vascular disorders are exemplified by those compounds of formula III where: X', Y' and V may be the same or different and are hydrogen (provided at least one of X', Y1 and V is other than hydrogen) , halo, nitro, -ey-antr, lowcralkyloulfonyl , loweralkoxy or loweral kyl .

The more preferred compounds which are useful in the treatment of cardiovascular disorders are shown in formula III where: X' , Y' and V are hydrogen (provided at least one of X', Y' and V is other than hydrogen) , halo, haloloweral kyl or loweral kyl .

The most preferred compounds are described by formula III where: X' is hydrogen, chl oro bromo or fluoro; Y' is hydrogen, chloro, methyl or trifl uoromethyl ; V is chloro, bromo, fluoro, methyl or 1 It is well known in the pharmacological arts that non-toxic acid 2 addition salts of pharmacologically active amine compounds do not differ 3 in activities from their free base. The salts merely provide a convenient 4 solubility factor. 5 The amines of this invention may be readily converted to their non- 6 toxic acid addition salts by customary methods in the art. The non-toxic 7 salts of this invention are those salts the acid component of which is 8 pharmacologically acceptable in the intended dosages; such salts would 9 include those prepared from inorganic acids, organic acids, higher fatty 10 acids, high molecular weight acids, etc., and include such as: 11 hydrochloric acid, succinic acid, 12 hydrobromic acid, glycolic acid, 13 sulfuric acid, lactic acid, 14 nitric acid, salicylic acid, 15 phosphoric acid, benzoic acid, 16 methanelsul fonic acid, nicotinic acid, 17 benzene sul fonic acid, phthalic acid, 18 acetic acid, stearic acid, 19 propionic acid, oleic acid, 20 malic acid, abietic acid, etc. 21 Representative compounds of this invention which are particularly 22 useful are as follows: 23 o-chlorophenylamidinourea 24 m-chlorophenylamidinourea 5 p-chlorophenylamidinourea 6 (2,3-dichlorophenylamidino)urea 27 (2,4-dichlorophenylamidino)urea 28 2 5-dichloro hen lamidino urea (3,4-dich1orophenylamidino)urea (3, 5-di chl orophenyl amidi no) urea (2 ,3, 4-tri chl orophenyl amidi no) urea (2, 3, 5- tri chl orophenyl amidi no) urea ( 2 , 3 ,6- tri chl orophenyl ami di no ) urea (2, 4, 5- tri chl orophenyl amidi no) urea ( 2, 4, 6- trichi orophenyl amidi no) urea ( 3 ,4 ,5- tri chl orophenyl ami di no) urea o-bromophenyl ami di nourea m-bromophenylamidi ourea p-bromophenyl amidi nourea ( 2 ,3-di bromophenyl amidi no) urea ( 2 ,4-di bromophenyl amidi no) urea ( 2, 5-di bromophenyl amidi no) urea ( 2, 6-di bromophenyl amidi no) urea ( 3, 4-di bromophenyl amidi no) urea (3, 5-di bromophenyl amidi no) urea (2-chloro-3-bromophenyl amidi no) urea (2-chloro-4-bromophenyl amidi no) urea (2-chloro-5-bromophenyl amidi no) urea ( 2-chl oro-6-bromophenyl ami di no) urea (3-chloro-2-bromophenyl amidi no) urea (3-chloro-4-bromophenyl amid no) urea (3-chloro-5-bromophenyl amidi no) urea (3-chloro-6-bromophenyl amidi no) urea ( 4-chl oro-2-bromophenyl amidi no) urea ( 4-chl oro-3-bromophenyl amidi no) urea - - - hl r h n i di no ure A-0317 (2-chloro-4-fl uorophenylamidino)urea ( 2-f 1 uoro-6-bromophenyl ami di no) urea (2-bromo-4-fl uorophenylamidino)urea (2-iodo-4-chlorophenyl ami di no) urea (2-iodo-6-chlorophenylamidino)urea ( 2-chl oro-4-i odophenyl ami di no) urea (2- odo-4-bromophenylamidino)urea o.-f 1 uorophenyl ami di nourea m-fl uorophenyl ami di nourea p-fl uorophenyl ami di nourea p-i odophenyl ami di ourea (2,4-difl uorophenyl ami di no) urea ( 2 , 5-di f 1 uorophenyl ami di no ) urea (2,6-difl uorophenyl ami di no) urea ( 2, 4-di i odophenyl ami di no) urea (2-iodo-6-bromophenyl ami di no) urea (2-bromo-4-i odophenyl ami di no) urea ( 2-f 1 uoro-4-i odophenyl ami di no) urea ( 2-i odo-4-f 1 uorophenyl ami di no ) urea (2 ,4-dichloro-6-bromophenyl ami di no) urea ( 2 ,6-di chl oro-4-bromophenyl amidi no) urea (2, 4-di bromo-6-chlorophenyl amidi no) urea (2 ,6-di bromo-4-chlorophenyl amidi no) urea (2, 4-d chl oro-6-fl uorophenyl amidi no) urea ( 2 ,6-d chl oro-4-fl uorophenyl ami di no) urea ( 2, 5-di chl oro-4-fl uorophenyl amidi no) urea (2, 4-di chl oro-6-iodophenyl amidi no) urea ( 2, 6-d chl oro-4-i odophenyl amidi no) urea A-0317 1 ( 2 ,4-di bromo-6-f 1 uorophenyl ami di no) urea 2 (2,6-dibromo-4-fl uorophenyl ami di no) urea 3 ( 2-chl oro-4-bromo-6-f 1 uorophenyl ami di no) urea 4 ( 2-bromo-4-f 1 uoro-6-chl orophenyl ami di no) urea 5 (2-bromo-4-chloro-6-fl uorophenylamidino)urea 6 ( 2-chl oro-4-iodo-6-bromophenyl ami di no) urea 7 (2 ,4, 6- tri f 1 uorophenyl ami di no) urea 8 o- tri f 1 uoromethyl phenyl ami di nourea 9 m- tri f 1 uoromethyl henyl ami di nourea 10 p-trifl uoromethyl henyl ami di nourea U p- tri f 1 uoromothoxyphonyl ami di nouroa •1-2 pnmethylsul fonylphenyl amidinourea'- 13 ( 2-chl oro-4-ni trophenylamidino)urea 1 (2-bromo-4-nitrophenylamidino)urea 15 (2-iodo-4-ni trophenyl ami di no) urea 16 (2-fl uoro-4-nitrophenylamidino)urea 17 ( 2- nitro-4-chl orophenyl ami di no) urea 18 (2-nitro-4-bromophenylamidino)urea 19 (2-nitro-4-fl uorophenylamidino)urea 20 (2-nitro-4-trifl uoromethyl phenyl ami di no) urea 21 ( 2-ni tro-4-methoxyphenyl ami di no ) urea 2 f ?-rvann-4-chlnroph >nvlamidi no hi es 2-3— ( -chl oro-4-cyanophonyl ami di no) urea — 24 ( 2-methyl -4-chl orophenyl ami di no ) urea 25 ( 2-methyl -4-bromophenyl ami di no ) urea 26 (2-methyl -4- fl uorophenyl ami di no) urea 27 (2-methyl -4-nitrophenylamidino)urea ¾ (2 methyl cyonophonyl ami di no) urea A-,0317 2 ,4-dimethyl phenyl ami di no ) urea 2, 6-dimethyl phenyl ami di no) urea 2, 6- di methyl -4-chl orophenyl ami di no) urea 2, 6-dimethyl -4-fl uorophenyl amidino)urea ,6- dimethyl -4-bromophenyl ami di no) urea 2, 6-dimethyl -4-nitrophenylamidino)urea 2,6-dimethyl-4-trifTuoromethylphenylamidino)urea 2-chl oro-4-methyl henyl ami di no) urea 2-bromo-4-methyl phenyl ami di no) urea 2-fl uoro-4-methyl phenyl ami di no) urea 2-ni tro-4-methyl phenyl ami di no ) urea 2,6-dichloro-4-methylphenylamidino)urea 2,4-dichloro-6-nitrophenylam dino)urea 2,6-dichloro-4-ni trophenyl ami di no) urea 2-ethyl-4-n trophenyl ami di no) urea 2-ethyl -4-chl orophenyl ami di no) urea 2-ethyl -4-bromophenyl ami di no ) urea 2-ethyl -4-fl uorophenyl ami di no) urea 2-ethyl -4-tri fl uorophenyl ami di no ) urea 2=cyaoQ=.l=methylpheH affl4^ fle-)y-Fea-2-tri fl uoromethyl -4-methyl phenyl ami di no) urea 2-trifl uo rome thy 1 -6- chl orophenyl ami di no) urea 4-trifl uoromethyl -2-chl orophenyl ami di no) urea 4-trifl uoromethyl -2-bromophenyl ami di no) urea 4-tri fl uoromethyl -2-fl uorophenyl ami di no) urea 2.4- di chl oro-6-methyl phenyl ami di no) urea 2,6-dichloro-6-methyl phenyl ami di no) urea A-Q317 The compounds of this invention may be prepared by the following general synthesis: Condensation of cyanamide and a substituted aniline results in the corresponding substituted phenyl guanidine .

The reaction is preferably carried out on the aniline salt either in a polar medium or neat and using increased temperatures. The salt used may be any acid addition amine salt but preferably the salt of a mineral acid. The polar medium may be aqueous, partially aqueous or a non-aqueous solution. It is convenient to. choose a solvent that will reflux at the desired reaction temperature. The more preferred solvents are water or alcohol but other solvents may be used such as DMSO, diethyl enejglycol , ethyleneglycol, tetrahydrofuran, dimethyl formamide , etc. The most preferred solvent is a mildly acidic solvent which is non-nucleophi 1 i c such as phenol, cresol , xylenol, etc. The reaction should also be carried out at a temperature which is high enough so that condensation takes place readily, but not sufficient to decompose the guanidine formed. The reaction temperature can very from room "temperature to about 250°C although it is preferable to run the reaction at temperatures from about 50°C to 150°C. The guanidine salt which is formed can be converted to the free base with a metal hydroxide or alkoxide solution. The isolation of the desired guanidine can be carried · out by any method known in the art.

When the substituted phenylguanidine is reacted with t-butyl*socyanate then the product formed is a 1-substituted phenyl amidino-3-t-butyl urea .

This reaction is preferably carried out in a non-polar medium using solvents such as benzene, toluene, xylene, etc. The reaction is also carried out as above at raised temperatures.

Treatment of the 1-substituted phenyl ami di no- 3- t-butyl urea with acid A-Q317 The following reaction equations illustrate this synthesis: CO where: HX1 is a mineral acid.

Appropriately desired end products having various X, Y and Z substit-uents may be prepared at various steps of synthesis using suitable reactions in order to convert one group to another.

The starting anilines are either known, may be prepared by known techniques or reference to the preparation is shown. Thus, chlorination or bromi nation of an acetanilide or aniline may be carried out in acetic acid, or in the presence of a small amount of iodine dissolved in an inert 43 280/2 Alkylatlon may be carried out on an acetan111de using an alkyl hallde and aluminum chloride under Frledel -Crafts conditions to obtain desired alkyl substitution.

Nitration may be carried out using fuming nitric add at about 0°C.

A nltro compound may be hydrogenated to the corresponding amine which may then be diazotlzed and heated In an alcohol medium to form the alkoxy compound.

An amino compound may also be diazotlzed to the dlazonlum fluoroborate which Is then thermally decomposed to the fluoro compound. D1azot1zat1on followed by a Sandmeyer type reaction may yield the bromo, chloro or lodo compound.

A chloro, bromo or 1odo compound may also be reacted with trlf luoromethyl Iodide and copper powder at about 150°C 1n dimethyl formamlde to obtain a trlf luoromethyl compound [Tetrahedron Letters: 47, 4095 (1959)].

Of course the above reactions may also be carried out on acetophenone in order to direct substitution.

Formation of an oxlme followed by Beckmann Rearrangement results n the acetamlde which 1s then deacylated to the anil 1ne.

A-0317 Reactions may also be carried out on the substituted anilines which would result in di- and tri- substituted anilines.

Reactions may also be carried out at other stages of synthesis depending on the substituents present and the substituents desired and various combina-tions of the foregoing reactions will be determined by one skilled in the art in order that the desired product results. Thus, a phenyl guanidi ne may be halogenated or nitrated as above, etc.

The compounds of this invention exert activity on the cardiovascular system. They possess blood-pressure lowering effects and are useful as antihypertensive agents.

For these purposes, the amidinoureas of this invention can be normally administered orally or parenteral ly. Orally they may be administered as tablets, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs.

Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents, preserving agents and the like, in order to provide a pharmaceutically elegant and palatable preparation.

The dosage regimen in carrying out the methods of this invention is that which insures maximum therapeutic response until improvement is obtained and thereafter the minimum effective level which gives relief.

Thus, in general, the dosages are those that are therapeutically effective in the alleviation of hypertensive disorders. In general ,· the daily dose can be between about 0.05 mg/kg/day and 70 mg/kg/day (preferably in the range of 1-25 mg/kg/day), bearing in mind, of course, that in selecting the appropriate dosage in any specific case, consideration must be given Various tests, in animals have been carried out to show the ability of the compounds of this invention to exhibit reactions that can be correlated with activity in humans.

One such test is the ability of the compound to lower blood pressure in the spontaneous hypertensive rat (Ryo Tabei , e_t , Clin. Pharm. & Therap. TJ_: 269-274, 1970). Blood pressure measurements are recorded by both the tail cuff method and by direct cannulation of a common carotid artery. Compounds that are effective antihypertensives in man have been shown to be active in lowering blood pressure in this animal model. In view of the results of this test, the amidinoureas of this invention can be considered to be active antihypertensive agents.

The following are detailed examples which show the preparation of the compounds of this invention. They are to be construed as illustrations of said compounds and not as limitations thereof. r Example 1 2,6-Dichlorophenylquanidine To 51 g. (0.315 mole) of 2,6-dichloroanil ine is added 0.4 moles of -e Jn&rr&l HC1 and 200 ml of m-cresol . The mixture is then stirred and heated on a steam bath to drive off the ether and excess hydrogen chloride. To the resultant mixture is then added 13.3 g. (0.315 mole) of cyanamide then heated for 2 hours on a steam bath. The reaction mixture is then cooled, added to 150 ml of cone, sodium hydroxide solution, cooled and extracted with 2 liters of ether. The ether layer is washed with 2 x 1 liter of water, dried over sodium sulfate, charcoaled and evaporated. The residue is triturated with hexane and the precipitate is filtered off and washed with ether and dried to obtain 2,6-dichlorophenylguanidine.

The free base is prepared by dissolving 2,6-dichlorophenylguanidine hydrochloride in 10% sodium hydroxide solution and extracting with ether. The ether is dried and evaporated to dryness to obtain 2,6-dichloro- phenyl guanidine.

When the above procedures are followed using the amines of Table I, below, then the corresponding product of Table II, below, is prepared.

TABLE I TABLE II o-chloroanil ine o-chlorophenylguanidine m-chloroanil ine m-chlorophenylguanidine p-chloroanil ine p-chlorophenylguanidine 2 3-dichloroanil ine 2 3-dichloro hen l uanidine 2,5-dichloroanil ine 2, 5-di chl orophenyl guani dine 3 ,4-di chl oroanil i ne 3, 4-di chl orophenyl guani dine 3,5-dichloroanil ine 3, 5-di chl orophenyl guani dine 2, 3, 4-tri chl oroanil ine 2,3,4-trichlorophenylguanidine 2, 3, 5- tri chl oroanil ine 2 ,3, 5- tri chl orophenyl guani dine 2, 3, 7- tri chl oroanil ine 2, 3, 6- tri chl orophenyl guani dine 2, 4, 5- tri chl oroanil ine 2, 4, 5- tri chl orophenyl guani dine 2, 4, 6- tri chl oroanil ine 2, 4, 6- tri chl orophenyl guani dine 3, 4 ,5- tri chl oroanil ine 3,4,5-trichlorophenylguanidine o-bromoanil ine o-bromophenyl guanidi ne m-bromoanil ine m-bromophenyl guani dine p-bromoanil ine p-bromophenylguanidine 2,3-dibromoanil ine 2, 3-dibromophenyl guani dine 2,4-dibromoanil ine 2 ,4-di bromophenyl guani dine 2,5-dibromoanil ine 2, 5-dibromophenyl guani d ne 2,6-dibromoanil ine 2 ,6-di bromophenyl guani dine 3 ,4-dibromoanil ine 3, 4-di bromophenyl guani dine 3,5-dibromoanil ine 3,5-di bromophenyl guani di e 2-chloro-3-bromoanil ine 2-chl oro-3- bromophenyl guani dine 2-chl oro-4-bromoani 1 i ne 2-chl oro-4-bromophenyl guani dine 2-chl oro-5-bromoani 1 i ne 2-chl oro-5-bromophenyl guani dine 2-chl oro-6-bromoani 1 i ne 2-chl oro-6-bromophenyl guani dine 3-chl oro-2-bromoani 1 i ne 3-chl oro-2-bromophenyl guani dine 3-chloro-4-bromoanil ine 3-chl oro-4-bromophenyl guani dine 3-chl oro-5-bromoani 1 i ne 3-chl oro-5-bromophenyl guanidi ne 3-chl oro-6-bromoani 1 i ne 3-chl oro-6-bromophenyl guani dine 4-chloro-2-bromoanil ine 4-chl oro-2-bromophenyl guanidi ne 4-chloro-3-bromoanil ine 4-chl oro-3-bromo hen l uani dine 1 2-fl uoro-4-chloroanil ine 2-fl uoro-4-chl orophenyl guani di ne 2 2-fl uoro-6-chloroanil ine 2-fl uoro-6-chl orophenyl guan dine 3 2-chloro-4-fluoroanil ine 2-chloro-4-fl uorophenyl guani dine 4 2-fl uoro-6-bromoanil ine 2-fl uoro-6-bromophenyl guanidine 5 2-bromo-4-fl uoroanil ine 2-bromo-4-fl uorophenyl guani dine 6 2-iodo-4-chloroanil ne 2- iodo-4-chl orophenyl guani dine 7 2-iodo-6-chloroanil ine 2- iodo-6-chl orophenyl guani dine 8 2-chloro-4-iodoan l ine 2-chloro-4-iodophenyl guani dine 9 2-iodo-4-bromoanil ine 2- iodo-4-bromophenyl guani dine 10 o-fl uoroanil ine o-fl uorophenylguanidine 11 m-fl uoroanil ine m-fl uorophenyl guani dine 12 p-fl uoroanil ine p-fl uorophenyl guani dine 13 p-iodoanil ine p-iodophenylguanidi ne 14 2, -difl uoroanil ine 2.4- difl uorophenylguanidine 15 2, 5-d fl uoroanil ine 2.5- difl uorophenylguanidine 16 2, 6-difl uoroanil ine 2.6- difl uorophenyl guani dine 17 2,4-diiodoanil ine 2, 4-diiodophenyl guani dine 18 2-iodo-6-bromoanil ine 2- iodo-6-bromophenyl guanidine 19 2-bromo-4-iodoanil ine .2-bromo-4-iodophenyl guani dine 20 2-fl uoro-4-iodoanil ine 2-fl uoro-4-iodophenyl guani dine 21 2-iodo-4-fl uoroanil ine 2-iodo-4-f 1 uorophenyl guani di ne 22 o-trifl uoromethyl anil ine 2-tri f 1 uoromethyl phenyl guani di ne 23 m-trifl uoromethyl anil ine m-tri f 1 uoromethyl phenyl guani di ne 24 p-trifl uoromethyl anil ine p- tri f 1 uoromethyl phenyl guani di ne £5 — p-* »= p tri fl uoromethoxyphenyl guani drnt; ■p-methyl sul f onyl phenyl guani di ne 27 o-nitroaniline o-ni trophenyl guani di ne A--0317 1 2-chloro-4-nitroanil ine 2-chl oro-4-ni trophenyl guani dine 2 2-bromo-4-nitroanil ine 2-bromo-4-ni trophenyl guani dine 3 2-iodo-4-nitroanil ine 2- iodo-4-ni trophenyl guani dine 4 2-fl uoro-4-nitroani line 2-fl uoro-4-ni trophenyl guani dine 5 2-nitro-4-chloroanil ine 2-ni tro-4-chl orophenyl guani di ne 6 2-nitro-4-bromoanil ine 2-ni tro-4-bromophenyl guani dine 7 2-nitro-4-fluoroanil ine 2-nitro-4- fluorophenyl guani dine 8 2-ni tro-4-tri f 1 uoromethyl ani 1 i ne 2-ni tro-4-trifl uoromethyl phenyl guanidine 9 2-ni tro-4-methoxyanil ine 2-ni tro-4-methoxyphenyl guani dine 10 2-cyano-4-chloroanil ine 2-cyano-4-chl orophenyl guanidine *W — 2-chl oro-4-cyanoanil ine 2-chl oro Ί cyanophcnylgudiiidiiie 12 2-methyl -4-chloroani line 2-methyl -4-chl orophenyl guani di ne 13 2-methyl -4-bromoanil ine 2-methyl -4-bromophenyl guani di ne 14 2-methyl -4-fluoroani line 2-methyl.-4-f 1 uorophenyl guani di ne 15 2-chloro-4-methyl ani line 2-chl oro-4-methyl henyl guanidi ne 16 2-bromo-4-methyl anil ine 2-bromo-4-methyl phenyl guani di ne 17 2-fl uoro-4-methyl ani line 2-fl uoro-4-methyl phenyl guani dine 2-cyano- -methyl phenyl guani dine 19 2- trifl uoromethyl -4-methyl anil ine 2-tri fl uoromethyl -4-methyl phenyl guanidi ne 20 2-methyl-4-nitroanil ine 2-methyl -4-ni trophenyl guani di ne —— methyl - 4-cyanoanil ino -2"methyl ^cyanophenyl guani di ne 22 2-methyl -4-tri f 1 uoromethyl ani 1 i ne- 2-methyl -4-tri fl uoromethyl phenyl guani dine 23 2-chloro-6-nitroanil ine 2-chl oro-6-ni trophenyl guani dine 24 2-bromo-6-nitroanil ine 2-bromo-6-ni trophenyl guani dine 25 2-iodo-6-nitroanil ine 2- iodo-6-ni trophenyl guani dine 26 2-fl uoro-6-nitroanil ine 2-fl uoro-6-ni trophenyl guani dine 27 2-ni tro-6-trifl uoromethyl anil ine 2-ni tro-6- trifl uoromethyl phenyl guani dine -[ 2-cyano-6"Ch1oroani1 ine 2"CyanO"6-chlorophenyl guanidine 2 2-methyl -6-chl oroani 1 ine 2-methyl -6-chl orophenylguanidine 3 2-methyl-6-brornoaniline 2-methyl -6-bromophenyl guanidine 4 2-methyl-6-fl uoroanil ine 2-methyl-6-fl uorophenylguanidine 5 2-methyl -6-nitroanil ine 2-methyl -6-nitrophenyl guanidine 6 2-methyl -6-trifl uoromethyl anil ine 2-methyl -6-tri fl uoromethyl phenyl guanidine 2*mQthy1- 6 cyanoaniH-ne -Θ 2- methyl 6 methyl sulfonylani lino 2-mothyl 6 methyl GUI fonyl phenyl ffl^a-n d 10 2 ,6-dimethyl anil ine . • 2 ,6-dimethyl henyl guanidine 11 2-trifl uoromethyl -6-chl oroani 1 ine 2-tri fl uoromethyl -6- chlorophenyl guanidine 12 2-trifl uoromethyl -6-bromoanil ine 2-tri fl uoromethyl -6-bromophenyl guanidine 13. 2-trifl uoromethyl -6-fl uoroanil ine 2-trifl uoromethyl -6-fl uorophenylguanidine 14 2-trifl uoromethyl-6-nitroanil ine 2-trifl uoromethyl -6-nitrophenyl guanidine 15 2- tri f 1 uoromethyl -4-chl oroani 1 i ne 2-trifl uoromethyl -4- chlorophenyl guanidin 16 2-trifl uoromethyl -4-bromoani line : 2-tri fl uoromethyl -4-bromophenyl guanidine 17 1 2-trifl uoromethyl -4-fl uoroanil ine 2-trifl uoromethyl -4-fl uorophenyl guanidine 18' 4-trifl uoromethyl -2-chloroanil ine 4-trifl uoromethyl -2-chlo ophenyl guanidine 19 4-trifl uoromethyl -2-bromoanil ine 4- tri fl uoromethyl -2-bromophenyl guanidi ne 20 4-trifl uoromethyl -2-fl uoroanil ine 4-trifl uoromethyl -2-bromophenyl guanidi ra 21 2,4-dichloro-6-methylanil ine 2.4- dichloro-6-me.thyl phenyl guanidine 22 2,6-dichloro-4-methylanil ine 2 ,6-dichloro-4-methyl phenyl guanidine ■ i s 23 3,5-dtftrifl uoromethyl)anil ine 3.5- €l trifl uoromethyl)phenyl guanid ne 24 2-methoxy-4-nitroanil ine 2-methoxy-4-nitrophenyl guanidine 25 :. 2-trifl uoromethyl -4-nitroanil ine 2-trifl uoromethyl -4-ni trophenyl guanidine 26 2,4-dichloro-6-methoxyanil ine ,4-di chl oro-6-methoxyphenyl guanidi ne .27 2,6-dimethyl-4-chloroanil ine 2.6- dimethyl -4-chl orophenyl guan dine A-p317 2,6-dimethyl -4-bronioanil ine 2,6-dimethyl -4-bromophenylguanidine 2,6-dimethyl -4-ni troanil ine 2,6-dimethyl -4-ni tro phenyl guanidine 2 ,6-dimethyl -4- tri f 1 uoromethyl ani 1 i ne 2 ,6-diinethyl -4- tri f 1 uoromethyl phenyl guani 2-ethyl -4-ni troanil ine 2-ethyl -4-n trophenyl guanidine 2-ethyl -4-chloroanil ine 2-ethyl-4-chlorophenylguanidine 2-ethyl -4-bromoanil ine 2-ethyl -4-bromophenylguanidine 2-ethyl -4-fl uoroanil ine 2-ethyl-4-fluorophenylguanidine 2-ethyl -4-trifl uoromethyl anil ine 2-ethyl -4-trifl uoromethyl phenyl guani dine 2-othyl-4 cyanoanilino 2 othyl Ί cyanophonyl guani dine 2-ethyl -4 -methyl sul fonyl ani 1 i ne 2 othyl ■ 1 mothyl oul fonyl phenyl guani dine-2,4-dichloro-6-bromoanil ine 2, 4-dichloro-6-bromophenyl guani dine 2,6-dichloro-4-bromoanil ne 2, 6-dichloro-4-bromophenyl guani dine 2,4-dibromo-6-chloroanil ine 2 ,4-dibromo-6-chlorophenylguanidine 2,6-dibromo-4-chloroanil ine 2 ,6-dibromo-4-chlorophenyl guani dine 2,4-dichloro-6-fl uoroanil ine 2,4-dichloro-6-fl uorophenyl guani dine 2,6-dichloro-4-fl uoroanil ine 2,6-dichloro-4-fl uorophenyl guani dine 2, 5-dichloro-4-fl uoroanil ine 2,5-dichloro-4-fl uorophenyl guani dine 2,4-dichloro-6-iodoanil ine 2, 4-dichloro-6-iodophenyl guani dine 2,6-dichloro-4-iodoanil ine 2, 6-dichloro-4-iodophenyl guani dine 2,4-dibromo-6-iodoanil ine 2 ,4-dibromo-6-iodophenylguanidine 2, 4-dibromo-6-fl uoroanil ine 2 ,4-dibromo-6-fluorophenylguanidine 2,6-dibromo-4-fl uoroanil ine 2 ,6-dibromo-4-fl uorophenyl guani dine 2-chl oro-4-bromo-6-f 1 uoroani 1 i ne 2-chl oro-4-bromo-6-f 1 uorophenyl guani di ne 2-bromo-4-f 1 uoro-6-chl oroani 1 i ne 2-bromo-4-f 1 uoro-6-chl orophenyl guani di ne 2-bromo-4-chloro-6-fl uoroanil ine 2-bromo-4-chloro-6-fl uorophenylguanidine 2-chloro-4-iodo-6-bromoanil ine 2-chloro-4-iodo-6-bromophenylguanidine 2,4,6-tribromoanil ine 2,4 ,6-tribromophenylguanidine 2 4 6-trifl uoroanil ne 2 4 - A-0317 Example 2 1 -(2,6-Dich1oropheny1amidino)-3-(t-buty1 )urea me To a mixture of 10 g. (0.05 mole) of 2,6-dichlorophenylguanide and 10 ml xylene is added 5 g. of 5-butyl isocyanate (0.05 mole) and the mixture is refluxed for 2 hours. The reaction product is cooled, triturated with heptane and filtered. Recrystall ization from 1:1 isopropyl /water results in l-(2,6-dichlorophenylamidino)-3-(t-butyl )urea.

When the above procedure is followed using the guanidines of Table II, Example 1, then the products prepared are shown in Table I below.

TABLE I o-chl orophenyl ami di no) -3- (t-butyl )urea m-chlorophenylamidino)-3-(t-butyl )urea p-chlorophenylamidino)-3-( t-butyl )urea 2.3- dichVorophenylamidino) -3-(t-butyl )urea 2.4- dichlorophenylamidino)-3-(t-butyl )urea 2.5- dichlorophenylamidino)-3-( t-butyl )urea 3.4- dichlorophenylamidino)-3-(t-butyl )urea 3.5- di chl orophenyl ami di no) -3- (t-butyl )urea 2.3.4- tri chl orophenyl ami di no) -3- t-butyl )urea 2.3.5- tri chl orophenyl ami di no) -3- t-butyl )urea 2.3.6- tri chl orophenyl ami di o) -3- t-butyl )urea 2.4.5- trichlorophenylamidino)-3- t-butyl )urea 2.4.6- tri chl orophenyl ami di no) -3- t-butyl )urea 3, 4, 5- tri chl orophenyl ami di no) -3- t-butyl )urea o-bromophenyl ami di no) -3- (t-butyl urea m-bromophenyl ami di no) -3- ( t-butyl urea -bromo hen l ami d o -3- t-but l urea 2.3- dibromophenyl amidino) -3- (t-butyl )urea 2. - dibromophenyl amidino) -3- (t-butyl )urea 2.5- dibromop enyl amidino) -3- (t-butyl )urea 2.6- dibromophenyl amidi no) -3- (t-butyl )urea 3. - dibromophenyl amidino) -3- (t-butyl )urea 3.5- dibromophenyl amidino) -3- (t-butyl )urea 2-chloro-3-bromoplienyl amidi no) -3- (t-butyl )urea 2-chloro-4-bromophenyl am d no) -3- (t-butyl )urea 2-chloro-5-bromophenyl amidino )- 3- ( t-butyl )urea 2- chloro-6-bromophenyl am di no) -3- (t-butyl )urea 3- chloro-2-bromophenyl amidi no) -3- (t-butyl )urea 3-chloro-4-bromophenyl amidi no) -3- (t-butyl )urea 3-chloro-5-bromophenyl amidi no) -3- (t-butyl )urea 3- chloro-6-bromophenyl ami di o) -3- ( t-butyl )urea 4- chloro-2-bromophenyl amidi no) -3- (t-butyl )urea 4-chloro-3-bromophenyl amidi no) -3- (t-butyl )urea 2-fl uoro-4-chlorophenyl amid no) -3- (t-butyl )urea 2-fl uoro-6-chlorophenyl amidino) -3- (t-butyl )urea 2-chloro-4-fl uorophenyl amidi no) -3- (t-butyl )urea 2- fluoro-6-bromophenyl amidi no) -3- (t-butyl )urea 2-bromo-4- fluorophenyl amidi no) -3- (t-butyl )urea 2-iodo-4-chl orophenyl amidi no) -3- ( t-butyl ) urea 2- iodo-6-chlorophenyl amidi no) -3- (t-butyl )urea 2-chloro-4-iodophenyl amidi no) -3- (t-butyl )urea 2-iodo-4-bromophenyl amidi no) -3- (t-butyl )urea o-fl uorophenylamidino)-3-(t-butyl )urea m-fl uorophenylamidino)-3-(t-butyl )urea - id n - - -b 1 1 -(2,4-difl uorophenyl amidi no) -3- (t-butyl )urea 2 l-(2,5-difluorophenylamidino)-3-(t-butyl )urea 3 1 -(2,6-difl uorophenyl amidi no) -3- (t-butyl )urea 4 l-(2,4-diiodophenylamidino)-3-(t-butyl )urea 5 1 - ( 2-iodo-6-bromophenyl amidi no) -3- ( t-butyl )urea 6 l-(2-bromo-4-iodophenylamidino)-3-( t-butyl )urea 7 1 -(2-fl uoro-4-iodophenyl amidi no) -3- (t-butyl )urea 8 1 -<(2-iodo-4-fl uorophenyl ami di no) -3- ( t-butyl )urea 9 l-(2-trifluoromethylphenylamidino)-3-(t-butyl )urea 10 l-(m-trifl uoromethyl phenyl amidi no) -3- (t-butyl )urea 11 1 -(p-trifl uoromethyl phenyl amidi o) -3- ( t-butyl )urea -**2— l-(p-trifluoromcthoxyphGnylann'dino) 3 ( t- -butyl ) urea 14 l-(o-nitrophenylamidino)-3-(t-butyl )urea 15 l-(m-nitrophenylamidino)-3-(t-butyl )urea ' 16 1 -(p-nitrophenylamidino)-3-(t-butyl )urea 17 l -( 2-chl oro-4-ni trophenyl amidi no) -3- (t-butyl )urea 18 1 -(2-bromo-4-ni trophenyl amidi o)- 3-( t-butyl )urea 19 1 -(2-iodo-4-ni trophenyl amidi no) -3- (t-butyl )urea 20 1 -(2-fl uoro-4-ni trophenyl amidi no) -3- (t-butyl )urea 21 1 -(2-ni tro-4-chlorophenyl amidi no) -3- (t-butyl )urea 22 1 -(2-ni tro-4-bromophenyl amidi no) -3-( t-butyl )urea 23 1 -(2-nitro-4-fl uorophenylamidino)-3-(t-butyl )urea 2^ 1 -( 2-ni tro-4-tri f 1 uoromethyl phenyl ami di no) -3- ( t-butyl ) ^ 1 - ( 2-ni tro-4-methoxyphenyl am di no) -3- ( t-butyl ) urea \ (2 cyano 4 chlorophenyl ami dino-)-~3 The free base is prepared according to Example 1. 1 TABLE I 2 (o-chlorophenyl ami di no) urea 3 (m-chlorophenylamidino)urea 4 (p-chl orophenyl amidino)urea 5 (2,3-dich1orophenylamidino)urea 6 ( 2 ,4-di chl orophenyl ami di no ) urea 7 ( 2, 5- di chl orophenyl ami di no) urea 8 ( 3, 4-di chl orophenyl ami di no) urea 9 (3,5-dichlorophenylamidino)urea 10 ( 2, 3, - tri chl orophenyl ami di no) urea 11 (2, 3, 5- tri chl orophenyl ami di no) urea 12 (2,3,6-trichlorophenyl amidino)urea 13 (2,4,5-trichlorophenylamidino)urea 1 ( 2, 4, 6- tri chl orophenyl ami di no) urea 15 (3, , 5-tri chl orophenyl ami di no) urea 16 (o-bromophenyl amidino)urea 17 (m-broniophenylamidino)urea 18 (p-bromophenyl amidino)urea 9 (2,3-dibromophenylamidi o)urea 20 (2,4-dibromophenylamidino)urea 21 (2,5-di romophenylamidi o)urea 22 (2,6-dibromophenylam dino)urea 23 (3,4-dibromophenyl am di no) urea 24 (3,5-dibromophenyl amidino)urea 25 (2-chloro-3-bromophenyl amidino)urea 26 (2-chloro-4-bromophenylamidino)urea 27 (2-ch1oro-5-bromophenylamidino)urea 28 2-chl oro-6-bromo henyl ami di no ) urea 1 (3-chloro-4-bromophenylamidino)urea 2 (3-chloro-5-bromophenylamidino)urea 3 ( 3-chl oro-6-bromophenyl ami di no) urea 4 (4-chloro-2-bromophenylamidino)urea 5 (4-chloro-3-bromophenyl ami di no) urea 6 (2-fluoro-4-chlorophenylamidino)urea 7 (2-fluoro-6-chlorophenylamidino)urea 8 (2-chloro-4-fl uorophenylam dino)urea 9 (2-fl uoro-6-bromophenylamidino)urea 10 (2-bromo-4-fl uorophenyl amidino)urea 11 (2-iodo-4-ch1orophenyl ami di no) urea 12 (2-iodo-6-chlorophenylamidino)urea 13 ( -chloro-4-iodophenyl amidino)urea 14 ( 2-iodo-4-bromophenyl amidino)urea 15 (o-fluorop.henylamidino)urea 16 (m-fl uorophenylamidino)urea 17 (p-fluorophenylamidino)urea 18 (p-iodophenyl amidino)urea 19 (2,4-difl uorophenylamidino)urea 20 (2,5-difl uorophenylamidino)urea 21 (2,,6-difl uorophenyl ami di no) urea 22 (2 ,4-di iodophenylamidino)urea 23 (2-iodo-6-bromophenylamidino)urea 24 ( 2-bromo-4-iodophenyl ami di no) urea 25 (2-fl uoro-4-iodophenylamidino)urea 26 (2-iodo-4-fl uorophenylamidino)urea 27 (2-trifluoromethylphenylamidino)urea 28 (m- tri f 1 uoromethyl phenyl ami di no ) urea p-tri Π uorometho yphcnyl ami di no) urea p-methy sul fonyl henyl amidi no )uroa < o-ni trophenyl amidi no)urea m-ni trophenyl amidi no) urea p-ni trophenyl amidi no) urea 2-chloro-4-n trophenyl amidi no) urea 2-bromo- 4- ni trophenyl amidi no) urea 2- odo-4-ni trophenyl amid no) urea 2-fl uoro-4-ni trophenyl amidi no) urea 2-nitro-4-chlorophenylamidino)urea 2-ni tro-4-bromophenyl amidi no) urea 2- ni tro-4-fl uorophenyl amidi no) urea 2-ni tro-4- tri fl uoromethyl phenyl ami di no ) urea 2-ni tro-4-methoxyphenyl ami di no ) urea 2-cyano-4"Chl orophenyl am4 di no ) urea 2"Chloro-4-cyanophonyl amidi no) urea 2-methyl -4-chlorophenylamidino)urea 2-methyl -4-bromophenyl amidi no) urea 2-methyl -4-fl uorophenyl amidi no) urea 2-chloro-4-methyl phenyl amidi no) urea 2-bromo-4-methyl phenyl ami di no ) urea 2-fl uoro-4-methyl phenyl amidi no) urea 2-Lydiiu-4unie'tliyl phenyl ami di no ) urea 2-trifl uoromethyl -4-methyl phenyl amidi no) urea 2HTietnyl -4-ni trophenyl ami di no ) urea -g-rnethyl -4-cyanophenyl amidi no) urea 2 -methyl -4-tri f 1 uoromethyl phenyl ami di no ) urea 2-chloro-6-ni trophenyl amidi no) urea 1 (2-fl uoro-6-ni trophenyl ami di no) urea 2 (2-nitro-6-trifl uoromethyl henyl ami di no) urea 3 (2-ni tro-6-methoxyphenylamidino)urea 4 (2-cyano-6-chlorophenyl amidino)urea 5 ( 2-methyl -6-chl orophenyl ami di no) urea 6 ( 2-methyl -6-bromophenyl ami di no) urea 7 (2-methyl -6-fl uorophenyl ami di no) urea 8 (2-methyl -6-ni trophenyl ami di no) urea 9 ( 2-methyl -6- tri f 1 uoromethyl phenyl ami di no) urea 12 (2,4-dimethyl phenyl ami di no) urea 13 (2,6-dimethylphenylamidino)urea 14 ( 2- tri f 1 uorome thy 1 -6-chl orophenyl ami di no) urea 15 (2-trifluoromethyl-6-bromophenylamidino)urea 16 (2-trifl uoromethyl -6-fl uorophenyl ami d no) urea Ϊ7 (2- tri fl uoromethyl -6-ni trophenyl ami di no) urea 18 (2-trifluoromethyl-4-chlorophenylamidino)urea 1.9 ( 2- tri f 1 uoromethyl -4-bromophenyl ami di no ) urea 20 ( 2- tri f 1 uoromethyl -4-f 1 uorophenyl ami di no ) urea 21 (4-trifl uoromethyl-2-chlorophenylamidino)urea 22 (4-trifl uoromethyl -2-bromophenyl ami di no) urea 23 (4- tri f 1 uoromethyl -2-bromophenyl ami di no) urea 24 ( 2 ,4-di chloro-6-methyl henyl ami di no ) urea 25 ( 2 ,6-di chl oro-4-methyl phenyl ami di no) urea 26 (3,5-ditrifl uoromethyl henyl ami di no) urea 27 (2-methoxy'-4-ni trophenyl ami di no) urea 28 ( 2-tri f 1 uoromethyl -4-ni trophenyl ami di no) urea A-0317 1 (2,6-dimethyl -4- l uorophenyl ami di no) urea 2 ( ,6- dimethyl -4-bromophenyl ami di no ) urea 3 (2,6-dimethyl -4- nitrophenyl ami di no) urea 4 ( 2 ,6-dimethyl -4-tri f 1 uoromethyl phenyl ami di no) 5 (2-ethyl -4-nitrophenylam dino)urea 6 (2-ethyl -4-chlorophenyl amidino)urea 7 (2-ethyl -4-bromophenyl ami di no) urea 8 (2-ethyl -4-fl uorophenyl ami di no) urea 9 (2-ethyl -4-trifl uoromethyl phenyl ami di no) urea >θ 2-e%h 4- -6 aH9pheH 4affl d «e-)tni'ea » f2-eth †- -ffle%h ^eH4feH 4phen 4am4^ «e-)w€« 12 (2 ,4-dichloro-6-bromophenylamidino)urea 13 (2,6-dichloro-4-bromophenylamidino)urea 14 (2,4-dibromo-6-chlprophenyl ami di no) urea 15 ( 2 ,6-dibromo-4-chlorophenyl ami di no) urea 16 (2 ,4-dichloro-6-fl uorophenyl ami di no) urea 17 (2,6-dichlord-4-fl uorophenyl ami di no) urea 18 ( 2 ,5-di chl oro-4-fl uorophenyl ami di no ) urea 19 (2,4-dichloro-6-iodophenyl ami di no) urea 20 (2,6-dichloro-4riodophenylamidino)urea 21 (2,4-d brorno-6-iodophenyl ami di no) urea 22 (2,4-dibromo-6-fl uorophenyl ami di no) urea 23 (2,6-dibromo-4-fl uorophenyl ami d no) urea 24 (2-chloro-4-bromo-6-fl uorophenyl amidino)urea 25 (2-bromo-4-fl uoro-6-chlorophenyl ami di no) urea 26 (2-bromo-4-chloro-6-fl uorophenyl amidino)urea 27 (2-chloro-4-iodo-6-bromophenyl ami di no) urea 28 (2,4,6-tribromophenylamidino)urea Similarly the following salts may be prepared using the appropriate add: Melting Po< ami di no) urea ^ - (4-bromo-2-methyl phenyl am4-d+ieti-re»)n1 trate 178-80°C -(2,4-dichlorophenylam1d1no)urea nitrate 184-5°C 2 ^ eHK>-Fep4e* i^1-d >o-UFe*-Rit -a-te- 7≥€- -(4-bromo-2-chlorophenylam1d1no)urea nitrate 188.5-189°C -(2-bromo-4-methylphenylam1d1no)urea nitrate 205-6°C -(4-chloro-2-methylphenylam1di no)urea nitrate 190-190.5°C -(4-1odo-2-methylphenylam1dino)urea nitrate 189.5-190.5°C l-(4-bromo-2-ethylphenylam1dino)urea nitrate 152-3°C -(3,5-d1chlorophenylamid1no)urea nitrate 198. -9°C - (2 ,5-d1 chlorophenyl ami d1 no)urea hydrochloride 187°C -(2,3-d1chlorophenylam1d1no)urea nitrate .194.5°C ^(2,5-d1chlorophenylam1dino)urea nitrate 182-182.5°C -(3,4-d1chlorophenylam1d1no)urea nitrate 197-198°C -(3,4-d1chlorophenylam1d1no)urea hydrochloride 203-4°C -(o-chlorophenylamldlno)urea nitrate 159=160°C (m-chl orophenylaml d1 no)urea nitrate 171-173°C p-chlorophenyl ami di noXirea nitrate 182-3°C (2-tr1 f 1 uoromethyl -4-f 1 uorophenyl ami d1 no) urea nitrate 164-165°C -(m-trifluoromethylphenylamidlno)urea nitrate 173-174°C -(2>6-d1chlorophenylam1d1ho)urea nitrate 181-183°C -(2,6-d1chlorophenylam1d1no)urea hydrochloride 212-213°C -(p-fluorophenylamidlno)urea nitrate 188-189°C -(p-fluorophenylam1d1no)urea hydrochloride 198-0°C -(p-bromophenylamidlno)urea nitrate 177-179°C -(2,6-dimethylphenylam1d1no)urea hydrochloride 203-204°C -(2-chloro-6-methylphenylamidino)urea hydrochloride 205.-206°C -(2-ethyl-6-methylphenylam1d1no)urea nitrate 192-5°C -(4-methoxy-2-methylphenylam1dino)urea hydrochloride 160°C Melting Point (2,4-d1f1uorophenylam1d1no)urea hydrochloride 205°C l-(4-chloro-2-methoxy-phenylam1dino)urea hydrochloride 197°C l-(2-methoxy-6-methylphenylam1d1no)urea hydrochloride 167°C l-(2,5-d1fluorophenylam1d1no)urea hydrochloride 200°C l-(3-chloro-4-fluorophenylam1d1no)urea hydrochloride 208°C l-(pentafluorophenylam1d1no)urea hydrochloride 206-7°C 1 - (2-chloro-6-f 1 uorophenyl amidi no)urea hydrochloride 199-200°C l-(2,6-d1fluorophenylam1d1no)urea hydrochloride 212°C l-(p-n1 trophenylam1d1no)urea hydrochloride 215°C l-(p-trifluoromethylphenylam1d1no)urea hydrochloride 194°C l-(2,4,6-tr1methylphenylam1d1no)urea hydrochloride 118°C

Claims (1)

1. WE A conpound of where X hydrogen or helot Y 1a 1 or Z halolowtralkyl Z 1a 1 or nltro provided X and Y are not both hydrogen at the tame and tht addition A conpound of claim 1 X hydrogen or Y 1s loweralkyl or haloloweral kyl and halo or loweralkyl X and Y are not both hydrog at the same or haloloweral kyl A compound of Claim 2 X is bromo or Y is bromo methyl or trifluoromethyl and Z is chloro provided X and Y are not both bromo provided X and Y are not both fluoro provided X and Y are not both methyl provided X and Y are not both hydrogen or trifl uoromethyl A compound of Claim 3 X is chloro or bromo Y is chloro or Z 1s fluoro or tr1 1 uoromethyl A compound of cl aim 4 which 1s chl orophenyl A compound of claim 4 which 1s am1d1 A compound of claim 4 which 1s A compound of claim 4 which 1s chlorophenyl A compound of claim 4 which 1s chlorophenyl A compound of claim 4 which 1s A compound of claim 3 which 1s 3 A compound of Claim which 1s 2 A compound of claim A which 2 A compound of which is A pharmaceutical composition for the treatoent of cardiovascular disorders which comprises a therapeutically effective amount of at least one of the compounds of the same hydrogen at least one of R5 and 1s other than 36 or and the addition thtraof A composition according to 15 of fornuiat and V nay be sane or different and are hydrogen at least one of and 1s other than ha haloloweralkyl or A according to Claim 16 and are hydrogen at least one of and other than haloloweralkyl or 37 composition 1 A according to Claim 2 3 1s 5 bromo or 6 7 Y 8 9 methyl or 10 11 is 13 methyl or 15 composition 18 1 A according to Claim where the compound is 2 selected from the group consisting of 3 4 amidinourea 5 amidinourea 6 7 8 10 11 composition 19 Process for the preparation of a compound of the X s hydrogen or Y 1s haloloweralkyl n loweralkyl or Z 1s Z 1s also loweralky o nltro provided X and Y are not both hydrogen at tha sane and the addition salts thereof which reacting a compound of the formula which eyananldo to a guanldino of the reacting said with ψ socyanate to form the corresponding of the formula and treating compound with a pharmaceutically acceptable mineral or organic to form the corresponding salt of the desired compound and when desired treating the add salt a base to form the corresponding free Process for the preparation of a compound of the and Rg may be the same or different and are hydrogen at least one of and is other than haloloweralkyl or loweralkyl and add addition salts thereof al n a Bfldly acidic w th to forn a guanld ne of the reacting said guanldlne with Isocyanate to form the corresponding of the and treating said compound with a pharmaceutically acceptable mineral or organic to the corresponding of the desired compound and when desired treating the add with a base to form the corresponding free The process of claim 22 wherein and are chloro and and are hydrogen and the compound obtained is the The process of claim wherein and R are chloro and and are hydrogen and the product obtained 1s the The process of claim 22 wherein and are chloro and and are hydrogen and the product obtained Is the The process of claim wherein Rg 1s 4 bromo and and are hydrogen and the product obtained 1s the process of claim wherein R3 1s fluoro and and are hydrogen and the product obtained Is the The process of claim 22 wherein and are chloro and and are hydrogen and the product obtained Is the The process of claim 22 wherein Rg 1s bromo and and Rg are hydrogen and the compound obtained 1s the The process of claim wherein 1s Is methyl and and are hydrogen and the product obtained 1s the The process of claim 22 wherein g chloro and Rg and Rgare hydrogen and the product obtained 1s the The process of claim wherein Is bromo Rg and Rg are hydrogen and the product obtained 1s the The process of claim wherein 1s ethyl Is and are hydrogen and the product obtained Is the The process of claim wherein and Rg are and Rg are hydrogen and the product obtained 1s the ami The process of claim wherein Rg and are and are hydrogen and the product obtained Is the The process of claim wherein and are and and Rg are hydrogen and the product obtained Is the The process of claim wherein Is fluoro and Rg and Rg are hydrogen and the product obtained 1s the For the Applicants ragman and Goller 43 insufficientOCRQuality