HETEROCYCLIC ALKYLENE AMIDINOUREAS

Abstract: Novel class of amidinourea and amidinothiourea compounds wherein the urea nitrogen atom is substituted by a heretocyclic alkylene group, and their use in pharmaceutical preparations which are useful for producing anti-ulcerogenic, antisecretory, antispasmodic, antihypertensive, anesthetic, anti-arrhytmic, antidiarrheal and antiparasitic action.

Description: HETEROCYCLIC ALKYLENE AMIDINOUREAS FIELD OF THE INVENTION This invention relates to a novel class of heterocyclic alkylene substituted amidinoureas and amidinothioureas and their pharmaceutical use in methods for producing gastrointestinal, cardiovascular, and antiparasitic action, among others. REPORTED DEVELOPMENTS Phenylamidinoureas and their uses as antisecre- tory, antispasmodic, anti-ulcerogenic, anesthetic, and antidiarrheal agents have been reported in Arzneimit- tel Forschung, (Drug Research) , 28 (II) , 1443-1480 (1978) , and U.S. Patent Nos. 4,025,652, 4,058,557, 4,060,635, 4,088,785, 4,115,564, 4,115,647, 4,117,165, 4,147,804, 4,150,154, 4,169,155, 4,178,387, 4,204,000, and 4,220,658. OMPI J- WIPO This invention relates to a class of hetero¬ cyclic alkylene amidinourea and thiourea compounds which also possess valuable pharmaceutical properties. SUMMARY OF THE INVENTION This invention pertains to a novel class of heterocyclic alkylene substituted amidinourea and thio¬ urea compounds, according to Formula I and processes for their synthesis. This invention also relates to the treatment of humans and animals afflicted with gastrointestinal disorders, spasmolytic disorders, ulcerogenic disorders, cardiovascular disorders, diarrheal disorders, and parasitic infestations of the blood and blood-forming organs with compositions con¬ taining an effective amount of heterocyclic alkylene substituted amidinourea or thiourea according to Formula I. NR / R5 Rl - (CH 2 > n - N - C - N - C - N \ R6 R2 -*3 "BϋREA OMPI where: X is 0 or S; n is 1 to 3; R_ is a 5 to 7 atom ring or a 7 to 13 atom fused or bridged ring which may include 1 to 4 hetero atoms of N, 0 or S; and containing a total of about 3 to about 20 carbon atoms; and the N- or S- oxides thereof; R2, R3 and R4 are hydrogen or lower alkyl; R5 and Rg are hydrogen, alkyl, cycloalkyl, aralkyl, alkenyl, aryl, alkoxy or a heterocyclic group, or R5 and Rg together with the nitrogen to which they are attached form a 3 to 7 atom ring which may include 0 to 2 additional hetero atoms of N, 0 or S; and the non-toxic acid addition salts thereof. DETAILED DESCRIPTION OF THE INVENTION Exemplary embodiments of this invention comprise compounds according to Formula I in which R_ is one of the following heterocyclic groups: 1-pyrrole, 2-pyrrole, 3-pyrrole, 2-furan, 3-furan, 2- thiophene, 3-thiophene, 2-tetrahydrothiophene, 3-tetra- hydrothiophene, 1-imidizole, 2-imidizole, 4-imidizole, 5-imidizole, 2-oxazole, 4-oxazole, 5-oxazole, 2-thiazole, 4-thiazole, 5-thiazole, 1-pyrazole, 3-pyrazole, 4-pyra- zole, 5-pyrazole, 1-pyrrolidine, 2-pyrrolidine, 3-pyrro- lidine, l-(3-pyrroline) , 2-(3-pyrroline) , 3-(3-pyrro- line) , 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidine, 4-pyrimidine, 5-pyrimidine, 6-pyrimidine, 2-purine, 6-purine, 8-purine, 9-purine, 2-guinoline, 3-quinoline, 4-quinoline, 5-quinoline, 6-guinoline, 7-quinoline, 8-quinoline, 1-isoquinoline, 3-isoquinoline, -BUREA OMPI 4-isoquinoline, 5-isoquinoline, 6-isoquinoline, 7-iso- quinoline, 8-isoquinoline, or carbazole. The heterocyclic groups may be mono-, di-, tri- or tetra- substituted by ring substituents such as halo- gen, lower alkyl, lower alkenyl, aryl, lower alkynyl, aralkyl, nitro, cyano, sulfonyl, hydroxyl, carboxyl, lower alkanoyl, lower alkoxy, aryl lower alkoxy, halo lower alkoxy, amido, amino, lower alkyl acyloxy, alkyl- amino, lower alkoxyamino, and aralkoxyamino. Compounds of this invention which are preferred include those according to Formula I where: n is 1 or 2; R-^ "is a substituted or unsubstituted 5, 6 or 7 atom ring including 1 to 3 hetero atoms of N, 0 or S; and N- and S- oxides thereof: R2 is hydrogen or lower alkyl; R3 and R4 are hydrogen; R5 and Rg are hydrogen, lower alkyl, cycloalkyl, ' lower alkoxy, or aralkyl or R5 and Rg together with the nitrogen to which they are attached form a 3 to 7 atom heterocycle. A most preferred embodiment of this invention is a compound according to Formulae II-IV ( -^UREAC OMPI fi S_ where: X is 0 or S; m is zero to four; n is one or two; R represents a ring substituent as described above, and the N-oxides of the pyridyl nitrogen atom; and R 2 , R5 and Rg are as described in Formula I above. Preferred R5 and Rg groups are hydrogen, lower alkyl or lower alkoxy. Another most preferred embodiment of this invention is a compound according to Formula V or VI NH li / R _ - - C - N VI where: m is zero to three; n is one or two; R represents a ring substituent as described above; and the S-oxides of the thiophene sulfur atoms, such as, thiophenylsulfoxide and thiophenyl sulfone; R 2 , 5 and Rg are as defined above in Formula I; and the non-toxic acid addition salts thereof. In any discussion of the true structure of an amidinourea, tautomerism must be considered. It should be clear to anyone skilled in the art that the amidino¬ urea chain can be legitimately represented in any one of several tautomeric forms. When the amidinourea is in solution, one form may predominate over another depending upon the degree and location of substitution and on the nature of the solvent. The rates of conver¬ sion of one tautomer to another will depend upon the nature of the solvent, the degree of hydrogen bonding permitted, the temperature, and possibly other factors (such as pH, trace impurities and the like) . To illustrate what is meant by this, a number of likely structures are here shown for just one of the compounds of this invention: O NH ii 11 ( ) — CH 2 - NH - C - NH - C - NHCH3 -fUREAD OMPI Of course, other structures are possible, such e with hydrogen bonding. OMPI As employed above and throughout the disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings: "Alkyl" means a saturated aliphatic hydrocarbon which may be either straight- or branched- chain. Preferred alkyl groups have no more than about 12 carbon atoms and may be methyl, ethyl and structural isomers of propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl. Also included are the cycloalkyl groups such as cyclopropyl, cyclopentyl, cyclohexyl, etc., and the cycloalkylalkyl groups such as cyclopropylmethyl and the like. "Lower alkyl" means an alkyl group as above, having 1 to 6 carbon atoms. Suitable lower alkyl groups are methyl, ethyl, n-propyl, isopropyl, butyl, sec-butyl, tert-butyl, n-pentyl, isopentyl and neopentyl. "Cycloalkyl" means an aliphatic monocyclic satu- rated carbocyclic group having 3 to 6 carbon atoms. Preferred groups are cyclopropyl, cyclopentyl and cyclohexyl. "Alkenyl" means an unsaturated aliphatic hydro¬ carbon. Preferred groups have no more than about 12 carbon atoms and 1 to 3 carbon-carbon double bonds and may include straight or branched chains, and may be any structural and geometric isomers of ethenyl, propylenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, and dodecenyl or butadienyl. pentadientyl, etc. Also included are the cycloalkylene groups such as cyclopropenyl, cyclopentenyl, cyclohex- enyl, etc. and the cycloalkylalkylene groups such as cyclopropylenylmethyl, cyclohexenylmethyl and the like. "Lower alkenyl" means alkenyl of 2 to 6 carbon atoms such as ethylene, propylene, butylene, isobuty- lene, etc., including all structural and geometrical isomers thereof. "Alkynyl" means an unsaturated aliphatic hydro- carbon. Preferred groups have no more than about 12 carbon atoms and contain one or more triple bonds, including any structural or geometric isomers of acetylenyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, dodecynyl, etc. "Lower alkynyl" means alkynyl of 2 to 6 carbon atoms such as structural and geometric isomers of propargyl, butynyl, pentynyl, etc. "Aryl" means phenyl and substituted phenyl. "Substituted phenyl" means a phenyl group in which one or more of the hydrogens has been replaced by the same or different substituents including halo, lower alkyl, halo-lower alkyl, nitro, amino, acylamino, hydroxy, lower alkoxy, aryl lower alkoxy, acyloxy, cyano, halo-lower alkoxy or lower alkyl sulfonyl. The preferred substituted phenyl group is phenyl in which the 2 and 6 positions are substituted. "Aralkyl" means an alkyl (preferably a lower alkyl) in which one or more hydrogens is substituted by an aryl moiety (preferably phenyl or substituted phenyl), e.g., benzyl, phenethyl, etc. "Heterocyclic group" or "heterocycle" means a 3, 5, 6 or 7 membered ring having 1 to 3 hetero atoms which may be nitrogen, oxygen or sulfur, including I J UREAT OMPI pyridyl, pyrimidyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, thiazolyl, piperidyl, morpholinyl, oxazolidinyl, thiazolidinyl, pyrazolidinyl, i idazolidinyl, piperazinyl, thiamorpholinyl, trimethylenetriaminyl and ethyleneiminyl; where the heterocycle may be mono-, di-, tri- or tetra-substituted by lower alkyl, lower alkenyl, lower alkynyl, aryl, aralkyl, halo, nitro, cyano, sulfonyl, hydroxyl, carboxyl, lower alkanoyl, lowercarboalkoxy, lower alkoxy, aryl lower alkoxy, halo lower alkoxy, amido, a ino, lower alkylamino, aralkylamino, lower alkoxyamino, and aralkylamino. "Substituted heterocycle" means a heterocycle in which one or more of the hydrogens on the ring carbons have been replaced by substituents as given above with respect to substituted phenyl. The terms "halo" and "halogen" include all four halogens; namely, fluorine, chlorine, bromine and iodine. The halo alkyIs, halophenyl and halo- substituted pyridyl include groups having more than one halo substituent which may be the same or different such as trifluoromethyl, l-chloro-2-bromo-ethyl, chlorophenyl, 4-chloropyridyl, etc. "Acyloxy" means an organic acid radical of a lower alkanoic acid such as acetoxy, propionoxy, and the like. "Lower alkanoyl" means the acyl radical of a lower alkanoic acid such as acetyl, propionyl, butyryl, valeryl, stearoyl, and the like. "Alkoxy" is intended to include hydroxy alkyl groups, preferably lower alkyl groups such as methoxy, ethoxy, n-propoxy, i-propoxy, and the like. - B U EAU OMPI The preferred "aralkyl" groups are benzyl and phenethyl. The preferred "halo lower alkyl" group is trifluoromethyl. The preferred "halo lower alkoxy" group is tri- fluoromethox . It is well known in the pharmacological arts that non-toxic acid addition salts of pharmacologically active amine compounds do not differ in activities from their free base. The salts merely provide a convenient solubility factor. The amidinoureas of this invention may be readily converted to their non-toxic acid addition salts by customary methods in the art. The non-toxic salts of this invention are formed from the amidinourea base and an acid which is pharmacologically acceptable in the intended dosages. Such salts would include those pre¬ pared from inorganic acids, organic acids, higher fatty acids, high molecular weight acids, etc. Exemplary acids are hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methane sulfonic acid, benzene sulfonic acid, acetic acid, propionic acid, malic acid, succinic acid, glycolic acid, lactic acid, salicylic acid, benzoic acid, nicotinic acid, phthalic acid, .stearic acid, oleic acid, abietic acid, etc. Representative examples of the compounds of this invention are listed in Tables I and I-A. TABLE I l-<2* -pyridylmethyl)-3-methylamidinourea l-(2 t -pyridylmethyl)-3-ethylamidinourea l-(2*-pryidylmethyl)-3-propylamidinourea l-(2 f -pyridylmethyl)-3-i-propylamidinourea l-(2'-pyridylmethyl)-3-butylamidinourea l-(2*-pyridylmethyl)-3-i-butylamidinourea l-(2*-pyridylmethyl)-3-pentylamidinour"ea l-(2*-pyridylmethyl)—3-propargylamidinourea l-(2'-pyridylmethyl)—3-allylamidinourea l-{2'-pyridylmethyl)-3-methoxyethylamidinourea l-{2'-pyridylmethyl)-3-benzyloxyethylami inourεa l-(2*-pyridylmethyl)-3-phenethoxyethylamidinourea l-(2 « -pyridylmethyl)-3-{N,N-dime hylamidino) rea l-(2'-pyridylmethyl)-3- (N,N-diethylamidino)urea l-(2*-pyridylmethyl)-3-(N,N-tetramethyleneamidino)urea l-(2*-pyridylmethyl)-3-(N,N-pentamethyleneamidino)urea l-(2'-pyridylmethyl)-3-(N,N-hexamethyle eamidino)urea l-(3'-methyl-2'-pyridylmethyl)-3-methylamidinourea l-(3'-methyl-2'-pyridylmethyl)-3-ethylamidinourea 1-(3 T -methyl-2'-pyridylmethyl)-3-propylamidinourea l-(3'-methyl-2'-pyridylmethyl)-3-i-pχ-opylamidinourea l-(3'-methyl-2'-pyridylmethyl)-3-i-butylamidinourea l-(3'-methyl-2 * '-pyridylmethyl)-3-pentylamidinourea l-(3'-methyl-2'-pyridylmethyl)-3-allylamidinourea l-(3'-methyl-2'-pyridylmethyl)-3-ρropargylaπιidinourea " BU O l-(3'-methyl-2'-pyridylmethyl)-3-cyclopropylamidinourea 1-(3'-methyl-2'-pyridylmethyl)-3-methoxyethylamidinourea 1-(3'-methyl-2*-pyridylmethyl)-3-benzyloxyethylamidino- urea 1-(3'-methyl- '-pyridylmethyl)-3-phenethoxyethyl- amidinourea 1-(3'-methyl-2'-pyridylmethyl)-3-benzylamidinourea 1-(3'-methyl-2'-pyridylmethyl)-3-( ,N-dimethylamidino)- urea 1-(3*-methyl-2'-pyridylmethyl)-3-( ,N-diethylamidino)- urea SUBSTITUTE SHEET OMPI 1-(3'-methyl-2*-pyridylmethyl)-3- ( K,N-tetramet__hyleneamidino)urea 1-(3'-methyl-2*-pyridylmethyl)-3- ( N,N-pentaπιet_hylenea_nidino)urea 1-(3'-chloro-2*-pyridylmethyl)-3-methylamidinourea 1—(3'-chloro-2'-pyridylmethyl)—3-ethylamidinourea 1-(3'-chloro-2*-pyridylmethyl)-3-propylamidinourea 1-(3*-chloro-2.'-pyridylmethyl)-3-i-propylamidinourea 1-(3*-chloro-2*-pyridylmethyl)-3-butyl midinourea 1-(3 » -chloro-2*-pyridylmethyl)-3-i-butyla...idinourea 1-(3*-chloro-2'-pyridylmethyl)-3—fc-butylamidinourea 1-(3 τ -chloro-2 * -pyridylmethyl)-3-pentylamidinourea 1-(3'-chloro-2*-pyridylmethyl)-3-allylamidinourea 1-(3'-chloro-2'-pyridylmethyl)-3- pr0 pargylamidinourea 1-(3 * -chloro-2 » -pyridylmethyl)-3- C yclopropylamidinourea 1-(3 * -chloro-2'-pyridylmethyl)-3- C yclobutylamidinourea 1-(3'-chloro-2'-pyridylmethyl)-3-(N-[3 f -cyclopentenyl]- arr.idino)urea 1-(3'-chloro-2*-pyridylmethyl)-3- C yclopropylmethyl- amidinourea 1-{3 * -chloro-2'-pyridylmethyl)-3-methoxyethylamidinourea 1-(3'-chloro-2'-pyridylmethyl)-3-benzyloxyethylamidinourea 1-(3'-chloro-2'-pyridylmethyl)-3-phenethoxyethylamidinourea 1-(3'-chloro-2'-pyridylmethyl)—3-benzylamidinourea 1-(3'-chloro-2'-pyridylmethyl)-3-(N,N-dimethylaraidino)urea 1-(3*-chloro-2'-pyridylmethyl)-3-(N/N-diethylamidino)urea 1-(3'-chloro-2'-pyridylmethyl) ^ 3-(N,N-tetramethylene- amidino)urea 1-(2'-pyridylmethyl--3-(N,N [3'•-methyl-3 ! -azapentamethylene] amidino)urea 1-(2'-pyridylmethyl)-3-(N,NI3 • -oxapentamethylene]-amidino) • urea 1- (3*-pyridylmethyl)-3-methylamidinourea 1-(3'-pyridylmethyl)-3-ethylamidinourea 1-(3'-pyridylmethyl)--3— ropylamidinourea 1-(3'-pyridylmethyl)-3-i-propylamidinourea 1- (3'-pyridylmethyl-3-butylamidinourea 1-(3'-pyridylmethyl)-3-i'-butylamidinourea SUBSTITUTE SHEET OMPI l-(3'-pyridylmeth l)-3-t-butylamidinourea l-(3* -pyr dylmethy1) ~3-pentylamidinourea l-(3* -pyridylmethyl) -3-allylamidinourea l-(3 « -pyridylmethyl) -3-propargylamidinourea l-(3* -pyridylmethyl) -3—cyclobutylamidinourea l-(3' -pyridylmethyl) -3-cyclohexylamidinourea l-(3* -pyrid lmethy1) -3-benzylamidinourea l-(3' -pyrid lme hyl) —3-methoxyethylamidinourea l-(3' -p rid lmethy1) -3-benzyloxyethylamidinourea l-(3' -pyridylm hyl) -3-methoxyethylamidinourea l-{3' -pyridylmethy1) —3-bεnzyloxyethylamidinourea l-(3' -py idylmethyl) -3-phenethoxyethylamidinourea l-(3' -pyridylmethyl) -3—(N,N-dimethylamidino)urea l-(3* -pyridylmethyl) -3-(N,N-diethylamidino)urea. l-(3' -pyridylme hyl) -3-(N,N-pentamethyleneamidino)urea l-{4' -pyridylmethyl) —3-jnethylamidinourea l-(4' -pyridylmethyl) ~3-ethylamidinourea 1- ( ' -pyrid lme h l) -3-propylamidinourea l-(4* -pyridylmethyl) -3-i-propylamidinourea 0 l-(4' -pyridylmethyl) -3—butylamidinourea l-(4' -pyridylmethyl) -3- -butylamidinourea - l-(4* -pyridylmethyl -3-pentyla idinourea l-(4' -pyridylmethyl) -3-hexyla idinourea l-(4' -pyrid lmethyl) -3-propargylamidϊnσurea 5 l-(4' -pyridylmethyl)■ -3-all la idinourea "BU EAJ l-(4 « -pyridylmethyl) -3-ιr:ethoxyethyla idinourea OMPI IPO 1-(4'-pyridylmethyl)-3-benzyloxyethylamidinourea 1-( '-pyridylmethyl)-3-phenethαxyethylamidinourea 1-(4'•-pyridylmethyl)-3-(N,N-dimethylamidino)urea 1~-(4"-pyridylmethyl)-3- (N,N-diethylamidino)urea 1-(4'-pyridylmethyl)-3-(N-methyl-N-ethylamidino)urea 1-(4'-pyridylmethyl)-3-( ,N-tetramethyleneamidino) rea 1-(4'-pyridylmethyl)-3-(N,N-pentame hyleneamidino)urea 1-(4'-pyridylmethyl)-3-(N,N-hexamethyleneamidino)urea 1-(2'-ethyl-4 ! -pyridyl-methyl)--3-methylamidinourea 1-(2 --ethyl-4 -pyridyl ethyl)-3-ethylamidinourea 1-(2'-ethyl-4 '-pyridylmethyl)-3-propylamidinourea 1-(2'-ethyl-4 '-pyridylmethyl)-3-butylamidinourea l-(2'-ethyl-4 '-pyridylmethyl)-3-i-butylamidinourea l-(2 « -ethyl-4 '-pyridylmethyl)-3-pentylamidinourea l-(2*-ethyl-4 '-pyridylmethyl)-3-allylamidinourea l-(2'--ethyl-4 '-pyridylmethyl)-3-propargylamidinourea 1-(2'-ethyl-4 '-pyridylmethyl)-3-methoxyethylamidinourea 1-(2'-ethyl-4 '-pyrid lmethyl)-3-benzyloxyethylamidinourea 1-(2*-ethyl-4 '-pyridylmethyl ) -3- ( N.N-dimethylamidino ) urea 1-(2'-ethyl-4'-pyridylmethyl)-3-(N,N-diethylamidino)urea 1-(2'-ethyl-4 '-pyridylmethyl)-3- (N,N-tetramethylene ami- dino)urea SUESTITUTE SHEET OMPI 1-(2' ,6'-dichloro-4'-pyridylmethyl)--3-methylamidinourea 1-(2' ,6'-dimethyl-4'-pyridylmethyl)-3-methylamidinourea 1-{2'*-methyl,6'•-chloro-4*-pyridylmethyl)-3-methylamidino¬ urea 1-(2'-thiophenylmethyl)-3-methylamidinourea 1-(3'—thiophenyImeth 1)-3-methylamidinourea 1-(5'-methyl-2'-thiophenylmethyl)-3-methylamidinourea 1-(5 ! -chloro-2'-thiophenylmethyl)-3-methylamidinourea 1-(2'-pyridylme hyϊ-N-oxide)-3-(N,N-dimethylamidino)urea 1-(3'-cyano-2'—pyridylmethyl)-3-methylamidinourea 1-(3 r -carbomethoxy-2'-pyridylmethyl)-3-methylamidinourea 1-(3'-carboethoxy-2'-pyridylmethyl)-3-methylamidinourea 1-(6'-chloro-2'-pyridylmethyl)-3-methylamidinourea 1-(6'-methyl-2 τ -pyridylmethyl)-3-methylamidinourea 1-{3'-ethyl-2'-pyridylmethyl)-3-methylamidinourea ^; _ L_r _. I 3 S \_» - f— *—• ___.»— I OMP 1-(2'-methyl-3'-pyridylmethyl)-3-(methylamidmo)urea 1-(2'-ethyl-3'-pyridylmethyl)-3- (methylamidmo) rea 1-( . 2',-6'-dimethyl-3'-pyridylmethyl)-3-(methylamidmo)urea 1-(3'-cyano-2--thiophenylmethyl)-3-(methylamidmo)urea 1-(3'-carbomethoxy—2'—thiophenylraethyl)-3-(methylamidmo) urea 1-(3'-carboethoxy-2'-thiophenylmethyl)-3-(methylamidino) urea 1-(2'-methoxy-3'-pyridylmethyl)-3-(methylamidino)urea 1-(2'-ethoxy--3'-pyridylmethyl)-3-(methylamidino)urea • 1-(2'-chloro-3'-pyridylmethyl)-3-(methylamidino)urea l-furfuryl-3-amidinourea 1-(3'-methyl-furfiuryl)-3-amχdinourea l-furfuryl-3-ethylamidinourea l-furfuryl-3-propylamidinourea 1-furfuryl-3-i-propylamidinourea l-furfuryl-3-butylamidinourea l-furfuryl-3-i-bϋtylamidinourea l-furfuryl-3-sec-butylamidinourea l-furfuryl-3-t-butylamidinourea 1-furfuryl-3-pentylamidinourea 1-furfuryl-3-hexylamidinourea l-furfuryl-3-heptylamidinourea l-furfuryl-3-cyclopropylamidinourea . 1-furfuryl-3-cyclobutylamidinourea OMPI 1- (2 ' -pyridylmethyl-N-oxide) -3-methylamidinourea 1- (3 ' -pyridylmethyl-N-oxide) - -3-methylarniui.nourea 1- (.4 ' -pyridylmethyl-N-oxide). -3-methylamidϊnourea l-furfuryl-3— _:--e hylaraidinourea l-tetrahydrofurfuryl-3-methylamidinourea -BU EA OMPI 1-(1'-imidazolylmethyl)-3-methylamidinσurea 1-(2'-imidazolylme hyl -3-methylamidinourea 1-(4'-imidazolylmethyl)-3-methylamidinourea 1-(2'-oxazol lmethyl)-3-methylamidinourea 1—(4'-oxazolylmethyl)-3-methylamidinourea 1-(5'-oxazolylmethyl)-3-methylamidinourea 1-(2*-thiazolylmethyl)-3-methylamidinourea 1-(.4'-thiazolylmethyl)-3-methylamidinourea 1-(5'-thiazolylmethyl)-3-methylarnxdinourea l-d'-pyrazolylmethvD-S-methvlamidinourea 1-(3'-pyrrolidinylmethyl)-3-methylamidinourea 1-(2*-pyrrolidinylmethyl) -3-methylamidinourea 1-(4'-morpholinylmethyl) -3-methylamidinourea 1-(2'-morpholinylmethyl) -3-methylamidinourea l-(2'-pyrimidinylmethyl)-3-methylamidinourea 1-(4'-pyrimidinylmethyl)-3-methylamidinourea 1-(2'-quinolylmethyl)-3-methylamidinourea 1-( '-q inolylmethyl)-3-methylamidinourea 1-(l*-isoquinolylmethyl).-3-methylamidinourea 1-(fαrfuryl-3-cycloρenylamidinourea 1-(furfuryl-3-cyclohexylamidinourea 1-(furfuryl-3-phenylamidinourea 1-(furfuryl-3-benzylamidinourea 1-(furfuryl-3-phenethylamidinourea l-furfuryl-3-(N-methyl-N-benzylamidino)urea 1-furfury1-3-(N,N-dibenzylamidino)urea l-tetrahydrofurfuryl-3-amidinourea 1—(3*—methyl tetrahydrofurfuryl)-3-amidinourea 1-(1'-imidazolylmethyl)-3—amidinourea 1-(2'-methyl-1'—imidazolylmethyl)-3-amidinourea 1-(4'-imidazolylmethyl)-3-amidinourea 1-(1'-methyl-4'-imidazolylmethyl)-3-amidinourea 1-(2'-methyl-4'-imidazolylmethyl)-3-amidinourea ' OM l-(2'-imidazolylmethyl)-3-amidinourea l-(2'-oxazolylmethyl)-3-amidinourea l-(4*-methyl-2'-oxazolylmethyl)-3-amidinourea l-(4'-oxazolylmethyl)-3-amidinourea l-(4'-methyl-2'-oxazolylmethyl)-3-amidinourea l-(4'-oxazolylmethyl)-3-amidinourea l-(2'-methyl-4'-oxazolylmethyl)-3-amidinourea l-(5'-oxazolylmethyl)-3-amidinourea l-(2 f -methyl-5'-oxazolylmethyl)-3-amidinourea l-(4'-thiazolylmethyl)-3-amidinourea l-(5'-methyl-4'-thiazolylmethyl)-3-amidinourea l-(5 « -thiazolylmethyl)-3-amidinourea l-(4'-methyl-5*-thiazolylmethyl)-3-amidinourea 1-(1'-pyrazolylmethyl)-3-amidinourea l-(3'-pyrrolylmethyl)-3-amidinourea l-(2'-methyl-3'-pyrrolylmethyl)-3-amidinourea l-(3'-methyl-2'-pyrrolylmethyl)-3-amidχnourea 1-(1'-pyrrolidinylmethyl)-3-amidinourea 1-t2'-methyl-1'-pyrrolidinylmethyl)-3-amidinourea 1-(1' -methyl-2'-pyrrolidinylmethyl)-3-amidinourea l-(4 « '-morpholinylmethyl)-3-amidinourea l-(2?'-methyl-4'-morpholinylmethyl)-3-amidinourea l-(2'--morpholinylmethyl)-3-amidinourea l-(4'--methyl-2'-morpholinylmethyl)-3-amidinourea l-(3'--methyl-2'-morpholinylmethyl)-3-amidinourea l-(3'--morpholinylmethyl)-3-amidinourea l-(4'--methyl-3 '-morpholinylmethyl)-3-amidinourea SUBSTITUTE SHEET OMPI 1-(2'-methyl-3'-morpholin lmethyl)-3-amidinourea 1-(2'-pyrimidinylmethyl)-3-amidinourea 1-( '-methyl-2*--pyrimidinylme hyl)-3-amidinourea 1-(4'-pyrimidinylmethyl)-3-amidinourea 1-(2'-methyl-4'-pyrimidinylmethyl)-3-amidinourea 1-{2*-quinol lmethyl)—3-amidinourea 1- 3'-methyl-2'-quinolylmethyl)-r3-amidinourea (4'-quinolylme h l) . τ-3-amidinourea 1-(3'-methyl- ^ 4*-quinol lmethyl)^-3-ramidinourea 1-Cl'-isoquinolylmethyll-*r3-amidinourea - B U EAI OMPI 1- [2- (2 ' -pyridyl) ethyl] -3-methylamidinourea 1- 12- (2 '.-pyridyl) ethyl] -3-ethylamidinourea 1- 12- (2 ' - yridyl) ethy * Q-3-.propylamidinourea 1- 12- ( 2 ' -pyridyl ) ethyl] -3-i-propylamidinourea 1- 12- ( 2 ' -pyridyl ) ethyl] -3-butylamidinourea 1- 12- ( 2 ' -pyridyl ) ethyl] -3-i-butylamidinourea 1- 12- (2 '-pyridyl) ethyl] -3-pentylamidinourea 1-12- (2 '-pyridyl) ethyl] -3-propargylamidinourea 1- [2- (2 ' -pyridyl) ethyl] -3-allylamidinourea 1- 12- (2 '-pyridyl) ethyl] -3-methoxyethylamidinourea 1- 12- (2 '-pyridyl) ethyl] -3-benzyloxyethylamidinourea 1- I 2- ( 2 ' -pyridyl ) ethyl] -3-phenethoxyethylamidinourea 1- 12- (2 ' -pyridyl) ethyl] -3- (N,N-dimethylamidino) urea 1- [2- ( 2 ' -pyridyl) ethyl] - 3- (N,N-diethylamidino) urea l- [2- (2 ' -pyridyl) ethyl] -3- (N,N-tetramethyleneamidino) urea 1- 12- (2 ' -pyridyl) ethyl] -3- (N ,N-pentamethyleneamidino) urea 1- { 2- ( 2 ' -pyridyl ) ethyl] - 3- ( , N-hexamethy len ' eamidino ) urea 1-12- (3 ' -methyl-2 ' -pyridyl) ethyl] -3-methylamidinourea 1-I2-- (3 ' -methyl-2 ' -pyridyl) ethyl] -3-ethylamidinourea 1-12- (3 ' -methyl-2 '-pyridyl ) thyl] -3-propylamidinourea 1- 12- (3 ' -methyl--2 ' -pyridyl) ethyl] -3-i-propylamidinourea 1- I 2- (3 ' —methyl-2 ' -pyridyl ) ethyl] -3-i-butylamidinourea 1- 12- ( 3 ' -methyl-2 ' -pyridyl ) ethyl] -3-penty lamidinourea 1-12- (3 ' -methyl-2 '-pyridyl) ethyl] -3-allylamidinourea 1- 12- (3 '-methyl-2 ' -pyridyl) ethyl] -3-propargylamidinourea 1- 12- (3 ' -methyl-2 ' -pyridyl ) ethyl] -3-cyclopropylamidinourea 1- [2- (3 ' -methyl-2 ' -pyridyl) ethyl] -3-methoxyethylamidinourea ij _ ' E S?-?~~T 1-[2 -(3'-methyl-2'-pyridyl)ethyl]-3-benzyloxyethyl amidinourea 1-{2 -(3'-methyl-2'-pyridyl)ethyl]-3-phenethoxyethyl amidinourea 1-I2 -(3'-methyl-2'-pyridyl)ethyl]—3-benzylamidinourea 1-12 - 3'-methyl-2'-pyridyl)ethyl]-3-(N,N-dimethylamidino) urea 1-12 " -(3'-methyl-2'-pyridyl)ethyl]-3-(N N-diethylamidino) urea l-[2 -(3'-methyl-2'-pyridyl)ethyl]-3-(N,N-tetramethylene- amidino)urea 1-12 " -(3'-methyl-2'-pyridyl)ethyl]-3-(N,N-pentamethylene- amidino)urea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-methylamidinourea 1-[2-(3'-chloro-2'-pyridyl)ethyl]-3-ethylamidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-propylamidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-i-propylamidinourea 1-J2-(3'-chloro-2'-pyridyl)ethyl]-3-butylamidinourea 1-12—(3'-chloro-2'-pyridyl)ethyl]-3-i-butylamidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-t-butylamidinourea _?r_r?-rf - ϋ 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-^pentylamidinourea 1-[2- ( . 3'-chloro-2'-pyridyl)ethyl]-3-rvallylamidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl] ^ 3-propargylamidinourea 1-12-(3'-chloro-2'-pyridyl) thyl]-3-cyclopropylamidinourea 1-12-(3'--chloro-2'-pyridyl)ethyl]-3-cyclobutylamidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3- (N-£3 ! -cyclopentenyl] amidino)urea 1-12- (3'-chloro-2'-pyridyl)ethyl]-3-cyclopropylmethyl amidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-methoxyethyl amidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-benzyloxyethyl amidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-phenethoxyethyl amidinourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-benzylamidinourea 1-12-(3•-chloro-2'-pyridyl)ethyl]-3-(N,N-dimethylamidino) urea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3- (N,N-diethylamidino) urea 1-12- (3'-chloro-2'-pyridyl)ethyl]-3-( ,N-tetramethylene amidino)urea 1-12- (2'-pyridyl)ethyl]-3-( , [3'-methyl-3'-azapenta¬ methylene]amidino)urea 1-12- (2'-pyridyl)ethyl]-3- (N,N[3 '-oxapentamethylene]amidino urea w u ω * _ _ «_-■ ; __, "_ _ ______ i OMPI -£2- (2'-pyridyl)ethyl]-a-methylamidinourea -12-(2*--pyridyl)ethyl]-3-ethylamidinourea -12-(2'-pyridyl)ethyl]-3-propylamidinourea -12-(2'-pyridyl)ethyl]-3-i-propylamidinourea -12-(2'-pyridyl)ethyl]-3-butylamidinourea -12-(2*-pyridyl)ethyl]-3-i-butylamidinourea SUBSTITUT zEr c" ι~5C 1- [2- (3* -pyr idyl) ethyl! -3-t-butylamidinourea 1- [2- (3 * -pyridyD.ethyl! -3-pentylamidinourea l-[ 2- (3* -pyridyl) ethyl] -3-allylamidinourea 1- [2 - (3.' -pyridyl) ethyl] -3-propargylamidinourea 1- [2- (3* -pyridyl) ethyl] -3-cyclobutylamidinourea ' l-{2-(3'*-pyridyl).ethyl] -3-cyclohexylamidinourea 1- [2- (3 '-pyridyl). ethyl) -3-^benzylamidinourea 1- [2- (3 ' -pyridyl) ethyl] -3-methoxyethylamidinourea 1- [2.- (3 * -pyridyD.ethyl] -3-benzyloxyethylamidinourea 1- [2- (3 *» -pyridyl) .ethyl] -3-methoxyethylamidinourea l- ' [2-(3' -pyridyl) ethyl] -3-benzyloxyethylamidinourea 1- [2- {3 * -pyridyl) ethylJ * -3-phenethoxyethylamidinourea 1- 12- (3 * -pyridyl) ethyl! -3- (N,N-dimethylamidino) urea 1- [2 -(3' -pyridyl) ethyl! -3- (N,N-diethylamidino) rea ' 1- [2 -(3' -pyr idyl) ethyl! -3- (N,N-pentamethyleneamidino) re 1- [2- (4 '-pyridyl) ethyl! -3-methyla ' midinburea 1- [2- (4 '-pyridyl) ethyl! -3-ethylamidinourea 1- [2- (4 » -pyridyl) ethyl! -3-propylamidinourea 1- [ 2- (4 * -pyridyl) ethyl] -3- i-propylamidinourea 1- 12- (4 '-pyridyl) ethyl] -3-butylamidinourea 1- [2- (4 ' -pyridyl) ethyl] -3- . t-butylamidinourea l-[2- (4 ' -pyridyl) ethyl]-3-pentylamidinourea 1- [2- (4 '-pyridyl) fthyl] -3-hcxylarαidinourea l-{2- (4 * -pyridyl) ethyl]-3-proparyylamidinourea 1- [2- (4 ' --pyridyl) ethyl] -3- allylamidinourea 1- [2- (4 ' -pyridyl) ethyl! -3- me hoxyethyla-nidinourea 1- [2- (4 ' -pyridyl) ethyl! -3- enzylo yeU_yla i iriourea^-gyR 1- [2 - ( 4 ' -pyridyl) ethyl] -3-phenethoxyethylami d inourea l-£ 2 - (4 '- p yridyl) ethyl]-3- (N f N-dimethylami d ino ) urea 1-1 2 - (4 '- p yridyl) thyl] -3- (N,N— diethylamidino ) urea 1-12- ( 4 ! -pyridyl ) thyl] -3- (N-methyl- N - ethy l amidino ) urea sues Γ ΠiTUTE SHEET OMP 1- [3- ( 2 ' -pyridyl) propyl] -3-methylamidinourea l-[ 3- (2* -pyridyl) propyl] -3-ethylamidinourea 1- [3*- (2 ' -pyridyl) propyl) -3-propylamidinourea 1- [3- (2 ' -pyridyl) propyl] -3-i-propylamidinourea 1-J3- (2' -pyridyl) propyl) -3-butylamidinourea 1- [3- (2 * -pyridyl) propyl] -3-i-butylamidinourea l-[3-(2'rPyridyl)propyl)-3-pentylamidinourea l-[3- (2 ---pyridyl) propyl) -3-propargylamidinourea 1-13- (2 ' -pyridyl) propyl] -3-allylamidinourea 1-J3- (2 * -pyridyl Ipropyl) -3-mεthoxyethylamidinourea I-?- [3τ-C2 '--.pyridylXpropyl] -3-rbenzyloxyethylamϊdino * urea l-[3- [2 ' • - pyr idyl ∑propyl] -=-3-phenethoxyethylamidinourea 1 ^ -13- ( . 2 '-pyr idy 11 propyl] -=-3- ( / N--di_rαethylamidino) urea 1-13- (2 ' -pyridyl ).propyl) -3- N,N-diethylamidino) urea l-[3- (2 '-pyridyl) propyl) -3- (N,N-tetramethyleneamidino)urea l-[3- (2* -pyridyl) propyl] -3- (N,N-pentamethyleneamidino)urea 1-13- (2' -pyridyl) propyl] -3- ( , N-hexame thy leneamidino) urea 1- [3- (3 ' -methyl-2 ' -pyridyl) propyl] -3-methylamidinourea 1- 13- (3 'methyl-2 * -pyridyl) propyl] -3-ethylamidinourea 1- [3- (3 ' -methyl-2 ' -pyridyl) propyl) -3-proρylamidinourea 1- [3- (3 ' -methyl-2 * -pyridyl) propyl] -3-i-propylamidinourea 1- [3- (3 ' -methyl-2 ' -pyridyl) propyl] -3-i-buty la id inourea 1- [3- (3 ' -methyl-2 ' -pyridyl) propyl] -3-pcntylamidinourea 1- [3- (3 ' -methyl-2 ' -pyridyl) propyl] -3-allylamidinourea 1- [3- (3 * -meLhyl-2 * -pyridyl) propyl] -3-propargyla_nidinou..ea 1- [3- (3 ' -methyl-2 '- yridyl) propyl) -3-cyclopropylamidinourea 1-13- (3'--_πet_-_ l-2 '-pyr dyl) propyl] -3-methoxyethylamidinourea • BUREΛT OMPI 1-[3-(3'-methyl-2'-pyridyl)propyl]-3-benzyloxyethyl amidinourea 1-13-(3 ! -methyl-2'-pyridyl) ropyl]-3-phenethoxyethyl " amidinourea 1-I3-(3'-methyl-2'-pyridyl)propyl]-3-benzylamidinourea l-[3-(3'-methyl-2'-pyridyl)propyl]-3-(N,N-dimethylamidino) urea 1-£3-(3'-methyl-2'-pyridyl) ropyl]-3-(N,N-diethylamidino) urea l-£3-(3'-methyl-2'-pyridyl)propyl]-3-(N,N-tetramethylene amidino)urea SUBSTITUTE SHE! O 1-£3-(3'-methyl-2'-pyridyl)propyl3-3-(N,N-penta- methyleneamidino) rea 1-[3-(3*-chloro-2*-pyridyl)propyl]-3-methylamidinourea 1-[3-(3'-chloro-2'-pyridyl)propyl]-3-ethylamidinourea 1-[3-(3'-chloro-2'-pyridyl)propyl]-3-propylamidinourea 1-E3-(3'-chloro-2'-pyridyl)propyl]-3-i-propyl¬ amidinourea 1-[3-(3'-chloro-2*-pyridyl)propyl]-3-butylamidinourea 1-[3-(3'-chloro-2'-pyridyl) ropyl]-3-i-butylamidinourea l-[3-(3'-chloro-2'-pyridyl)propyl3-3-t-butylamidinourea 1-E3-(3'-chloro-2'-pyridyl)propyl]-3-pentylamidinourea 1-[3-(3'-chloro-2'-pyridyl)propyl]-3-allylamidinourea l-[3-(3'-chloro-2'-pyridyl)propyl]-3-propargylamidinourea 1-[3-(3'-chloro-2'-pyridyl)propyl]-3-cyclopropylamidino- urea 1-[3-(3'-chloro-2'-pyridyl)propyl]-3-cyclobutylamidino- urea 1-£3-(3'-chloro-2*-pyridyl)propyl]-3-(N-E3'-cyclopent- enyl]amidino)urea 1-£3-(3*-chloro-2'-pyridyl)propyl]-3-cyclopropylamidino¬ urea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-methoxyethylamidino urea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-benzyloxyethyl- amidinourea l-[3-(3'-chloro-2'-pyridyl)propyl -3-phenethoxyethyl- amidinσurea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-benzylamidinourea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-(N, -dimethyl- amidino) urea 1-[3-(3-*chloro-2 « -pyridyl)propyl -3-(N,N-diethyl- amidino) urea - U EAU OMPI " R \ 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-(N,N-tetramethylene- amidino)urea 1-13-(2 ■ --py idyl)propyl]-3-(N, £3'-methyl-3'--azapenta- methyleneamidino)urea 1-13- (2'-pyridyl) ropyl]-3-(N,N£3'-oxapentamethylene]- • amidino)urea l-£3- (2'-pyridyl)propyl]-3-methylamidinourea 1-£3-(2'-pyridyl)propyl]-3-ethylamidinourea 1-£3-(2'-pyridyl)propyl]—3-propylamidinourea l-£3-(2'-pyridyl)propyl]—3-i-propylamidinourea 1-£3-(2'-pyridyl)propyl]-3-butylamidinourea 1-£3-(2'-pyridyl)propyl]-3-i-butylamidinourea 1-13- (3'-pyridyl) ropyl]-3-t-butylamidinourea 1-£3-(3'-pyridyl)propyl]—3-pentylamidinourea l-£3-(3'-pyridyl) ropyl]-3-allylamidinourea 1-£3-(3'-pyridyl)propyl]-3-propargylamidinourea 1-£3-(3'-pyridyl)propyl]—3-cyclobutylamidinourea 1-£3-(3' • -pyridyl)propyl]-3-cyclohexylamidinourea 1-£3-(3'-pyridyl)propyl]—3-benzylamidinourea 1-£3-(3'—pyridyl)propyl]-3-methoxyethylamidinourea 1—£3-(3'-pyridyl)propyl]-3—benzyloxyethylamidinourea 1-13- (3'-pyridyl)propyl]-3-onethoxyethylamidinourea 1-13-(3'-pyridyl)propyl]-3-benzyloxyethylamidinourea 1-£3-(3'-pyridyl)propyl]-3-phenethoxyethylamidinourea l-£3- (3*-pyridyl) ropyl]-3-(N,N-dimethylamidino)urea l-£3-(3'-pyridyl)propyl]-3-(N,N-diethylamidino)urea l-£3-(3'-pyridyl)propyl]-3-(N,N-pentamethyleneaιi-idmo)urea SU IBRS TϊTϊ JTΞ SHE ET - $ ϋR O l-[3-(4'-pyridyl)propyl]-3-methylamidinourea l-£3- (4'-pyridyl)propyl]-3-ethylamidinourea l-£3-(4'---pyridyl)propyl]-3-propylamidinourea 1-13-(4'-pyridyl)propyl]-3-i-propylamidinourea 1-£3-(4'-pyridyl)propyl]-3-butylamidinourea 1-£3-(4'-pyridyl)propyl]—3-t-butylamidinourea 1-£3- (4*-pyridyl)ρropyl]-3-pentylamidinourea 1- [3-(4'-pyridyl)propyl]-3-hexylamidinourea 1-[3-(4'-pyridyl)propyl]-3-propargylamidinourea 1-[3-(4'-pyridyl)propyl]-3-allylamidinourea 1-[3-(4'-pyridyl) ropyl]-3-methoxyethylamidinourea 1-[3-(4'-pyridyl)propyl]-3-benzyloxyethylamidinourea 1- £3-(4'-pyridy1)propyl]-3-phenethoxyethylamidinourea 1-[3-(4'-pyridyl)propyl]-3-(N,N-dimethylamidino)urea l-[3-(4*-pyridyl)propyl]-3-(N,N-diethylamidino)urea 1-[3-(4'-pyridyl) ropyl]-3- (N-methyl-N-ethylamidino)urea l-£3-(3'-methyl-2'-pyridyl)propyl]-3-(N,N-tetramethylene amidino)urea l-£3-(3'-methyl-2'-pyridyl) ropyl]-3-(N,N-pentamethylene amidino)urea l-£3-(3'-chloro-2'-pyridyl)propyl]-3-methylamidinourea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-ethylamidinourea l-£3-(3'-chloro-2'-pyridyl)propyl]-3-propylamidinourea l-£3- (3'-chloro-2'-pyridyl)propyl]-3-i-propylamidinourea l-£3-(3'-chloro-2'-pyridyl)propyl]-3-butylamidinourea l-£3- (3'-chloro-2'-pyridyl)propyl]-3-i-butylamidinourea l-£3-(3'-chloro-2'-pyridyl)propyl]-3-t-butylamidinourea SUBSTITUTE SHEET OMPI 1-13-(3'-chloro-2'-pyridyl)propyl]-3-pentylamidχnourea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-allylamidinourea l-£3-(3'-chloro-2'-pyridyl)propyl]-3-propargylamidinourea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-cyclopropylamidinourea 1-13-(3'-chloro-2'-pyridyl)propyl]-3-cyclobutylamidinourea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-(N-£3'-cyclopentenyl] amidino)urea l-£3-(3'-chloro-2' -pyridyl)propyl 3-cyclopropylmethyl amidinourea l-£3- (3'-chloro-2' -pyridyl)propyl]-3-methoxyethylamidinoure l-£3- (3'-chloro-2'-pyridyl)propyl]-3-benzyloxyethylamidino-. urea 1-E3- (3'-chloro-2'-pyridyl)propyl]-3-phenethoxyethyl amidinourea l-£3- (3'-chloro-2'-pyridyl)propyl]-3-benzylamidinourea l-£3- (3'-chloro-2'-pyridyl)propyl]-3-(N / N-dimethylamidino) urea l-£3- (3'-chloro-2*-pyridyl)propyl]-3-(N,N-diet__ylamidino) urea 1 ^ £3- (3*-chloro-2'-pyridyl)propyl]-3-(N,N-tetramethylene amidino)urea l-£3- (2'-pyridyl)propyl]-3-(N,N£3'-methyl-3'-azapenta methylene]amidino)urea l-£3- (2'-pyridyl) ropyl]-3-(N,N£3'-oxapentamethylene] amidino)urea l-£3- (2'-pyridyl) ropyl]-3-methylamidinourea l-£3- (2'-pyridyl) ropyl]-3-ethylamidinourea l-£3- (2'-pyridyl) ropyl]-3-propylamidinourea 1-13- (2'-pyridyl) ropyl]-3-i-proρylamidinourea 1-13- (2*-pyridyl)propyl]-3-butylamidinourea l-£3- (2'-pyridyl)propyl]-3-i-butylamidinourea SUB S TITUTE SHEET OM l-£3-(3'-pyridyl)propyl]-3-t-butylamidinourea l-£3-(3'-pyridyl)propyl]-3-pentylamidinourea 1-£3-(3'-pyridyl)propyl]-3-all lamidinourea 1-13-(3'-pyridyl)propyl]-3-propargylamidinourea l-£3-(3'-pyridyl)propyl]-3-cyclobutylamidinourea 1-£3- (3'-pyridyl)propyl]-3-cyclohexylamidinourea 1-[3- (3'-pyridyl)propyl]-3-benzylamidinourea 1-£3- (3'-pyridyl)propyl]-3-methoxyethylamidinourea 1-[3-(3'-pyridyl)propyl]-3-benzyloxyethylamidinourea 1-[3- (3'-pyridyl)propyl]-3-methoxyethylamidinourea 1-£3- (3'-pyridyl)propyl]-3-benzyloxyethylamidinourea 1-£3-(3'-pyridyl)propyl]-3-phenethoxyethylamidinourea 1-{3-(3'-pyridyl) ropyl]-3-(N,N-dimethylaιr_idino)urea 1-£3- (3'-pyridyl)propyl]-3-(N,N-diethylamidino)urea 1-£3- (3'-pyridyl)propyl]-3-( ,N-pentamethyleneamidino)urea l-£3- (4'-pyridyl)propyl]-3-methylamidinourea l-£3- (4'-pyridyl)propyl]-3-ethylamidinourea 1-£3-(4 '-pyridyl)propyl]-3-propylamidinourea 1-13-(4'-pyridyl)propyl]-3-i-propylamidinourea l-£3- (4'-pyrxdyl)propyl]-3-butylamidinourea 1-[3-(4'-pyridyl)propyl]-3-t-butylamidinourea 1-J3- (4'-pyridyl)propyl]-3-pentylamidinourea l-£3- (4'-pyridyl)propyl)-3-hexylamidinourea l-£3- (4'-pyridyl)propyl]-3-propargylamidinourea l-£3- (4'-pyridyl)propyl]-3-allylamidinourea l-£3-(4'-pyridyl)propyl]-3-methoxyethylamidinourea l-£3- (4'pyridyl)propyl]-3-benzyloxyethylamidinourea gϋBS lT -rCE - G .K f OMPI 1- (4'-pyridyl)propyl]-3-phenethoxyethylamidinourea 1- (4'•-pyridyl)propyl]-3-(N,N~dimethylamidino)urea 1- (4'--pyridyl)propyl]-3-(N,N-diethylamidmo)urea 1- {4'-pyridyl)propyl]-3-(N-methyl-N-ethylamidino)urea 1- '-pyridylmethyl)-3-methylamidinothiourea 1- '-pyridylmethyl)-3-ethylamidinothiourea 1- '-pyridylmethyl)-3-propylamidinothiourea 1- "-pyridylmethyl)-3-i-propylamidinothiourea 1- '-pyridylmethyl)-3-butylamidinothiourea 1^ "-pyridylmethyl)-3-i-butylamidinothiourea 1- '-pyridylmethyl)-3-pentylamidinothiourea 1- 1 -pyridylmethyl)-3-propargylamidinothiourea 1- '-pyridylmethyl)-3-allylamidinothiourea 1- '-pyridylmethyl)-3-methoxyethylamidinothiourea 1- '-pyridylmethyl)-3-benzyloxyethylamidinothiourea 1- '-pyridylmethyl)-3-phenethoxyethylamidinothiourea 1- '-pyridylmethyl)-3- ( , -dimethylamidino)thiourea 1- '-pyridylmethyl)-3-(N,N-diethylamidino)thiourea 1- '-pyridylmethyl)-3-( ,N-tetramethyleneamidino) hiourea 1- '-pyridylmethyl)-3-(N,N-pentamethyleneamidino)thiourea 1- '-pyridylmethyl)-3-(N,N-hexa_r_ethyleneamidino)thiourea 1- '-methyl-2'-pyridylmethyl)-3-methylamidinothiourea 1- '-methyl-2'-pyridylmethyl)-3-ethylamidinothiourea 1- '-methyl-2'-pyridylmethyl)-3-propylamidinothiourea 1- '-methyl-2'-pyridylmethyl)-3-i-propylamidinothiourea 1- '-methyl-2'-pyridylmethyl)-3-i-butylamidinothiourea 1- '-methyl-2'-pyridylmethyl)-3-pentylamidinothiourea SUBSTITUTE SHEET ^^S J O 1- (3'-methyl-2'-pyridylmethyl)-3-allylamidinothiourea 1-(3*-methyl-2'-pyridylmethyl)-3-propargylamidinothiourea 1-(3'-methyl-2'-pyridylmethyl)-3-cyclopropylamidinothioure 1-(3'-methyl-2'-pyridylmethyl)-3-methoxyethylamidinothiour 1- (3'-methyl-2*-pyridylmethyl)-3-benzyloxyethylamidino- thiourea 1-(3'-methyl-2'-pyridylmethyl)-3-phenethoxyethylamidino- thiourea 1-(3'-methyl-2'-pyridylmethyl)-3-benzylamidinothiourea 1-(3'-methyl-2'-pyridylmethyl)-3- (N,N-dimethylamidxno) thiourea 1-(3'-methyl-2'-pyridylmethyl)-3- (N,N-diethylamidiήo).. . thiourea 1-(3'-methyl-2'-pyridylmethyl)-3-(N,N-tetramethylene amidino)thiourea 1-(3'-methyl-2'-pyridylmethyl)-3- (N,N-pentamethylene amidino)thiourea 1-(3'-chloro-2'-pyridylmethyl)-3-methylamidinothiourea 1-(3'-chloro-2'-pyridylmethyl)-3-ethylamidinothiourea 1- (.3'-chloro-2'-pyridylmethyl)-3-propylamidinothiourea 1-(.3'-chloro-2'-pyridylmethyl)-3-i-propylamidinothiourea 1-(3'-chloro-2'-pyridylmethyl)-3-butylamidinothiourea 1- (3'-chloro-2'-pyridylmethyl)-3-i-butylamidinothiourea 1-(3'-chloro-2'-pyridylmethyl)-3-t-butylamidinothiourea 1-(3'-chloro-2'-pyridylme hyl)-3-pentylamidinothiourea 1-(3'-chloro-2'-pyridylmethyl)-3-allylamidinothiourea 1- (3'-chloro-2'-pyridylmethyl)-3-propargylamidinothiourea 1- (3'-chloro-2'-pyridylmethyl)-3-cyclopropylamidinothiourea 1-(3'-chloro-2'-pyridylmethyl)-3-cyclobutylamidinothiourea %U s T vτu " "■ ""E Hc-"- * * OMP 1-(3'-chloro-2'-pyridylmethyl)-3-(N-I3'-cyclopentenyl] amidino)thiourea 1-(3'-chloro-2'-pyridylmethyl)-3-cyclopropylmethylamidino thiourea 1-(3'-chloro-2'-pyridylmethyl)-3-methoxyethylamidinothio¬ urea 1-(3'-chloro-2'-pyridylmethyl)-3-benzyloxyethylamidinothio- urea 1-(3'-chloro-2'-pyridylmethyl)-3-phenethoxyethylamidinothio- urea 1-(3'-chloro-2'-pyridylmethyl)-3-benzylamidinothiourea 1-(3'-chloro-2'-pyridylmethyl)-3-(N,N-dimethylamidino)thio¬ urea 1-(3'-chloro-2'-pyridylmethyl)-3-(N,N-diethylamidino)thio- urea 1-(3'-chloro-2'-pyridylmethyl)-3-(N,N-tetramethylene amidino)thiourea 1-(2*-pyridylmethyl)-3-(N,N£3.'-methyl-3'-azapentamethylene] amidino)thiourea 1-(2 ! -pyridylmethyl)-3-(N,N£3'-oxapentamethylene]amidino) thiourea 1- (2*-pyridylmethyl)-3-methylamidinothiourea 1-(2'-pyridylmethyl)-3-ethylamidinothiourea 1-(2'-pyridylmethyl)-3-propylamidinothiourea 1-(2'-pyridylmethyl)-3-i-propylamidinothiourea 1-(2'-pyridylmethyl)-3-butylamidinothiourea 1-(2'-pyridylmethyl)-3-i-butylamidinothiourea S Hs1ϊ« • * - *• » "- *" l"* *-—* 1-(3'-pyridylmethyl)-3-t-butylamidinothiourea 1- (3'-pyridylmethyl)-3-pehtylamidinothiourea 1-(3'-pyridylmethyl)-3-allylamidinothiourea 1-(3'-pyridylmethyl)-3-propargylamidinothiourea 1-(3'-pyridylmethyl)-3-cyclobutylamidinothiourea 1-(3'-pyridylmethyl)-3-cyclohexylamidinothiourea 1-(3'-pyridylmethyl)-3-benzylamidinothiourea 1-(3'-pyridylmethyl)-3-methoxyethylamidinothiourea 1-(3'-pyridylmethyl)-3-benzyloxyethylamidinothiourea 1-(3'-pyridylmethyl)-3-methoxyethylamidinothiourea 1-(3'-pyridylmethyl)-3-benzyloxyethylamidinothiourea 1-(3'-pyridylmethyl)-3-phenethoxyethylamidinothiourea 1-(3'-pyridylmethyl)—3-(N,N-dimethylamidino)thiourea 1-(3'-pyridylmethyl)-3-(N,N-diethylamidino)thiourea 1-(3'-pyridylmethyl)-3- (N, -pentamethyleneamidino)thiourea 1-(4'-pyridylmethyl)-3-methylamidinothiourea 1-(4'-pyridylmethyl)-3-ethylamidinothiourea 1- (4'-pyridylmethyl)-3--propylamidinothiourea 1-(4 i -pyridylmethyl)-3-i-propylamidinothiourea 1-(4'-pyridylmethyl)-3-butylamidinothiourea 1-(4'-pyridylmethyl)-3-t-butylamidinothiourea 1- (4'-pyridylmethyl)-3-pentylamidinothiourea 1-(4'-pyridylmethyl)-3-hexylamidinothiourea 1-(4'-pyridylmethyl)-3-propargylamidinothiourea 1-(4'-pyridylmethyl)-3-allylamidinothiourea 1-(4'-pyridylmethyl)-3-methoxyethylamidinothiourea 1-(4'-pyridylmethyl)-3-benzyloxyethylamidinothiourea 1-(4'-pyridylmethyl)-3-phenethoxyethylamidinothiourea «_i ^C -, \ I _ * » bM * 1-(4'-pyridylmethyl)-3-(N,N-dimethylamidino)_thiourea 1-(4'-pyridylmethyl)-3-(N,N-diethylamidino)thiourea 1- (4'-pyridylmethyl)-3- (N-methyl-N-ethylamidino)thiourea 1-12-(.2'-pyridyl)ethyl]-3-methylamidinothiourea 1-£2- (.2'-pyridyl)ethyl]-3-ethylamidinothiourea l-£2-(2'-pyridyl)ethyl]-3-propylamidinothiourea l-£2-(2'-pyridyl)ethyl]-3-i-propylamidinothiourea 1-£2-(2*-pyridyl)ethyl]-3-butylamidinothiourea 1-[2-(2'-pyridyl)ethyl]-3-i-butylamidinothiourea 1-f2-(2'-pyridyl)ethyl]-3-pentylamidinothiourea 1-£2-(2'-pyridyl)ethyl]-3-propargylamidinothiourea l-£2- (2'-pyridyl)ethyl]—3-allylamidinothiourea l-£2-(2'-pyridyl)ethyl]-3-methoxyethylamidinothiourea 1-£2-(2'-pyridyl)ethyl]-3-benzyloxyethylamidinothiourea 1-£2-(2'-pyridyl)ethyl]-3-phenethoxyethylamidinothiourea 1-£2-(2'-pyridyl)ethyl]-3-(N,N-dimethylamidino)thiourea l-£2-(.2'-pyridyl)ethyl]-3-(N,N-diethylamidino)thiourea l-£2-(2'-pyridyl)ethyl]-3-(N,N-tetramethyleneamidmo) thiourea 1-£2-(2'-pyridyl)ethyl]-3- (N,N-pentamethyleneamidino) * thiourea 1-£2-(2'-pyridyl)ethyl]-3-( ,N-hexamethyleneamidino) thiourea 1-12-(3'-methyl-2'-pyridyl)ethyl]-3-methylamidinothiourea l-£2-(3*-methyl-2'-pyridyl)ethyl]-3-ethylamidinothiourea SUBSTSTUT &n -ϊ_ i OM 1-£2- (3'-methyl-2'-pyridyl)ethyl]-3-propylamidinothiourea l-£2-(3'-methyl-2'-pyridyl)ethyl]-3-i-propylamidinothioure l-£2-(3'-methyl-2'rpyridyl)ethyl]-3-i-butylamidinothiourea 1-£2- (3'-methyl-2*-pyridyl)ethyl]-3-pentylamidinothiourea 1-£2-(3'-methyl-2'-pyridyl)ethyl]-3-allylamidinothiourea 1-12-(3'-methyl-2'-pyridyl)ethyl]-3-propargylamidinothiour l-£2-(3'-methyl-2'-pyridyl)ethyl]-3-cyclopropylamidinothio urea l-£2-(3'-methyl-2'-pyridyl)ethyl]-3-methoxy thylamidinothi urea 1-£2- (3'-methyl-2'-pyridyl)ethyl]-3-benzyloxyethylamidino¬ thiourea 1-[2-(3'-methyl-2'-pyridyl)ethyl]-3-phenethoxyethylamidino- thiourea 1-[2-(3'-methyl-2'-pyridyl)ethyl]-3-benzylamidinothiourea l-£2-(3'-methyl-2'-pyridyl)ethyl]-3-(N,N-dimethylamidino) thiourea l-£2- (3'-methyl-2'-pyridyl)ethyl]-3-(N^N-diethylamidino) thiourea l-£2- (3'-methyl-2'-pyridyl)ethyl]-3- (N,N-tetramethylene amidino)thiourea l-£2-(3'-methyl-2'-pyridyl)ethyl]-3- (N, -pentamethylene amidino)thiourea gUBSTlT _U'_J _ _ ** . 1-£2-(3*-chloro-2'-pyridyl)ethyl]-3-methylamidinothiourea 1-£2- (3'-chloro-2'-pyridyl)ethyl]-3-ethylamidinothiourea 1-£2-(3'-chloro-2'-pyridyl)ethyl]-3-propylamidinothiourea 1-I2--(3'-chloro-2*-pyridyl)ethyl]-3-i-propylamidinothiourea 1-£2-(3'-chloro-2'-pyridyl)ethyl]-3-butylamidinothiourea l-£2-(3'-chloro-2'-pyridyl)ethyl]-3-i-butylamidinothiourea 1-£2-(3'-chloro-2'-pyridyl)ethyl]-3-t-butylamidinothiourea 1-12- (3'-chloro-2'-pyridyl)ethyl]-3-pentylamidinothiourea 1-£2-(3'-chloro-2'-pyridyl)ethyl]-3-allylamidinothiourea 1-£2-(3'-chloro-2*-pyridyl)ethy]-3-propargylamidinothiourea 1-£2-(3' • -chloro-2'-pyridyl)ethyl]-3-cyclopropylamidinothio¬ urea 1-£2-(3'-chloro-2'-pyridyl)ethyl]-3-cyclobutylamidiothioure 1-£2-(3'-chloro-2*-pyridyl)ethyl]-3-(N-£3'-cyclopentenyl] amidino)thiourea 1-f2-(3'-chloro-2'-pyridyl)ethyl]-3-cyclopropylmethyl amidinothiourea 1-£2- (3'-chloro-2'-pyridyl)ethyl]-3-methoxyethylamidino¬ thiourea l-£2-(3'-chloro-2'-pyridyl)ethyl]-3-benzyloxyethylamidino- thiourea l-£2-(3'-chloro-2'-pyridyl)ethyl]-3-phenethoxyethyl. " amidinothiourea 1-12-(3'-chloro-2'-pyridyl)ethyl]-3-benzylamidinothiourea l-£2-(3*-chloro-2'-pyridyl)ethyl]-3-(N,N-dimethylamidino) thiourea 1-£2-(3'-chloro-2*-pyridyl)ethyl]-3- (N,N-diethylamidino) thiourea SUBSTITUTE SHEET ' OM l-[2- (3'-chloro-2'-pyridyl)ethyl]-3- (N,N-tetramethylene amidino)thiourea 1-£2- (2'-pyridyl)ethyl]-3- ( , £3'-methyl-3*-azapenta¬ methylene]amidino)thiourea l-£2-(2'-pyridyl)ethyl]-3-(N,N£3'-oxapentamethylene] amidino)thiourea l-£2- (2'-pyridyl)ethyl]-3-methylamidinothiourea l-£2- (2'-pyridyl)ethyl]-3-ethylamidinothiourea 1-[2- (2'-pyridyl)ethyl]-3-propylamidinothiourea i-£2-(2'-pyridyl)ethyl]-3-i-propylamidinothiourea 1-£2-(2'-pyridyl)ethyl]-3-butylamidinothiourea l-£2-(2'-pyridyl)ethyl]-3-i-butylamidinothiourea 1-£2- (3'-pyridyl)ethyl]-3-t-butylamidinothiourea 1-£2-(3'-pyridyl)ethyl]-3-pehtylamidinothiourea 1-£2- (3'-pyridyl)ethyl]-3-allylamidinothiourea l-£2- (3'-pyridyl)ethyl]-3-propargylamidinothiourea 1-12-(3'-pyridyl)ethyl]-3-cyclobutylamidinothiourea 1-12-(3'-pyridyl)ethyl]-3-cyclohexylamidinothxourea 1-£2-(3'-pyridyl)ethyl]-3-benzylamidinothiourea l-£2-(3'-pyridyl)ethyl]-3-methoxyethylamidinothiourea l-£2- (3'-pyridyl)ethyl]-3-benzyloxyethylamidinothiourea 1-£2-(3'-pyridyl)ethyl]-3-methoxyethylamidinothiourea 1-£2- (3'-pyridyl)ethyl]-3-benzyloxyethylamidinothiourea l-£2-(3 '-pyridyl)ethyl]-3-phenethoxyethylamidinothiourea l-£2- (3'-pyridyl)ethyl]-3-(N f -d__methylamidino)thiourea l-£2-(3'-pyridyl)ethyl]-3- (N,N-diethylamidino)thiourea l-£2- (3'-pyridyl)ethyl]-3- (N,N-pentamethyleneamidino) thiourea SUBSTITUTE IPO -pyridyl)ethyl]-3-methylamχdinothiourea -pyridyl)ethyl]-3-ethylamidinothiourea -pyridyl)ethyl]-3-propylamidinothiourea -pyridyl)ethy1]-3-i-propylamidinothiourea -pyridyl)ethyl]-3-butylamidinothiourea -pyridyl)ethyl]—3— -butylamidinothiourea -pyridyl)ethyl]-3-pentylamidinothiourea -pyridyl)ethyl]-3-hexylamidinothiourea -pyridyl)ethyl]-3-propargylamidinothiourea -pyridyl)ethyl]-3-allylamidinothiourea -pyridyl)ethyl]-3-methoxyethylamidinothiourea -pyridyl)ethyl]-3-benzyloxyethylamidinothiourea -pyridyl)ethyl]-3-phenethoxyethylamidinothiourea -pyridyl)ethyl]-3-(N,N-dimethylamidino)thiourea -pyridyl)ethyl]-3-(N f N-diethylamidino)thiourea -pyridyl)ethyl]-3-(N-methyl-N-ethylamidino)thiourea -pyridyl)propyl]-3-methylamidinourea -pyridyl)propyl]-3-ethylamidinothiourea . -pyridyl)propyl]-3-propylamidinothiourea -pyridyl)propyl]-3-i-propylamidinothiourea -pyridyl)propyl]-3-butylamidinothiourea -pyridyl)propyl]-3-i-butylamidinothiourea -pyridyl)propyl]-3-pentylamidinothiourea -pyridyl)propyl]-3-propargylamidinothiourea -pyridyl)propyl]-3-allylamidinothiourea -pyridyl)propyl]-3-methoxyethylamidinothiourea SUBSTITUTE SHEET l-£3- (2'-pyridyl) ropyl]-3-benzyloxyethylamidinothiourea 1-£3-(2'-pyridyl)propyl]-3-phenethoxyethylamidinothiourea 1-£3-( . 2'-pyridyl)propyl]-3-(N,N-dimethylamidino)thiourea l-£3-(2'-pyridyl)propyl]-3- (N,N-diethylamidino)thiourea l-£3-(2'-pyridyl)propyl]-3-(N,N-tetramethyleneamidino)- thiourea l-£3-(2'-pyridyl)propyl]-3-(N, -pentamethyleneamidino)- thiourea l-£3-(2'-pyridyl)propyl]-3- ( ,N-hexamethyleneamidino)- thiourea 1-£3-(3'-methyl-2*-pyridyl)propyl]-3-methylamidinothiourea 1-13-(3'-methyl-2'-pyridyl)propyl]-3-ethylamidinothiourea 1-£3-(3'-methyl-2'-pyridyl)propyl]-3-propylamidinothiourea 1-£3-(3'-methyl-2'-pyridyl)propyl]-3-i-propylamidinothiour 1-£3-(3' • -methyl-2'-pyridyl)propyl]-3-i-butylamidinothioure l-£3-(3'-methyl-2'-pyridyl)propyl]-3-pentylamidinothiourea 1-13-(3'-methyl-2'-pyridyl)propyl]-3-allylamidinothiourea 1-13- (3'-methyl-2'-pyridyl) ropyl]-3-propargylamidinothio- urea 1-£3-(3'-methyl-2'-pyridyl)propyl]-3-cyclopropylamidino¬ thiourea l-£3-(3'-methyl-2'-pyridyl)propyl]-3-methoxyethylamidino thiourea l-£3-(3'-methyl-2'-pyridyl)propyl]-3-benzyloxyethyl- amidinothiourea 1-£3-(3'-methyl-2'-pyridyl)propyl)-3-phenethoxyethy1- amidinothiourea 1-13-(3'-methyl-2'-pyridyl)propyl]-3-benzylamidinόthiourea SUBSTITUTE SHEET 1-£3-(3'-methyl-2'-pyridyl)propyl3-3-( ,N-dimethyl- amidino)thiourea 1-£3-(3'-methyl-2'-pyridyl)propyl]-3-( ,N-diethyl- amidino)thiourea 1-E3-(3'-methyl-2'-pyridyl)propyl3-3-(N,N-tetra- methyleneamidino) hiourea l-[3-(3'-methyl-2'-pyridyl)propyl]-3-(N,N-penta¬ methyleneamidino) thiourea l-E3-(3'-chloro-2'-pyridyl)propyl3-3-methylamidino- thiourea 1-E3-(3*-chloro-2'-pyridyl)propyl3-3-ethylamidino¬ thiourea 1-E3-(3'-chloro-2'-pyridyl)propyl -3-propylamidino- thiourea 1-[3-{3'-chloro-2'-pyridyl)propyl3-3-i-propylamidino¬ thiourea 1-£3-(3'-chloro-2'-pyridyl) ropyl3-3-butylamidino¬ thiourea 1-£3-(3'-chloro-2'-pyridyl) ropyl3-3-i-butylamidino- thiourea 1-E3-(3'-chloro-2'-pyridyl) ropyl3-3-t-butylamidino- * thiourea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-pentylamidino¬ thiourea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-allylamidino¬ thiourea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-propargylamidino- thiourea 1-£3-(3'-chloro-2*-pyridyl)propyl]-3-cyclopropylamidino- thiourea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-cyclobutylamidino- thiourea OMPI 1-E3-(3'-chloro-2'-pyridyl)propyl3-3-(N-3*-cyclo- pentenyl3amidino)thiourea 1-£3-(3'-chloro-2'-pyridyl)propyl]-3-cyclopropylmethyl- amidinothiourea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-methoxyethyl¬ amidinothiourea 1-[3-(3'-chloro-2'-pyridyl)propyl -3-benzyloxyethyl- amidinothiourea 1-£3-(3*-chloro-2*-pyridyl)propyl3-3-phenethoxyethyl- amidinothiourea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-benzylamidino- thiourea 1-£3-(3'-chloro-2*-pyridyl) ropyl3-3-( ,N-dimethyl- amidino)thiourea 1-[3-(3'-chloro-2'-pyridyl)propyl3-3-(N,N-diethyl- amidino)thiourea 1-[3-(3 « -chloro-2*-pyridyl)propyl3-3-(N,N-tetra- methyleneamidino)thiourea l-[3-(2*-pyridyl)propyl3-3-(N,N[3'-methyl-3'-azapenta- methylene3amidino)thiourea 1-E3-C2'-pyridyl)propyl3-3-(N,N£3'-oxapentamethylene3- amidino) thiourea 1-[3-(2'-pyridyl)propyl3-3-methylamidinothiourea 1-E3-(2'-pyridyl)propyl3-3-ethylamidinothiourea 1-[3-(2'-pyridyl)propyl3-3-propylamidinothiourea 1-[3-(2*-pyridyl)propyl3-3-i-propylamidinothiourea 1-[3-(2'-pyridyl)propyl3-3-butylamidinothiourea l-[3-(2'-pyridyl)propyl3-3-i-butylamidinothiourea 1-[3-(3*-pyridyl)propyl3-3-t-butylamidinothiourea 1-[3-(3'-pyridyl)propyl3-3-pentylamidinothiourea 1-[3-(3 • -pyridyl)propyl3-3-allylamidinothiourea 1-[3-(3'-pyridyl)propyl3-3-propargylamidinothiourea "BU EAU OMPI ^RNAΥl 1-E3- -pyridyl propyl]-3-cyclobutylamidinothiourea 1-E3- -pyridyl propyl]-3-cyclohexylamidinothiourea 1-E3- -pyridyl propyl3-3-benzylamidinothiourea 1-E3- -pyridyl propyl3-3-methoxyethylamidinothiourea l-[3- -pyridyl propyl3-3-benzyloxyethylamldinothiourea 1-E3- -pyridyl propyl -3-phenethoxyethylamidino- thiourea 1-E3- -pyridyl propyl]-3-(N,N-dimethylamidino) thiourea 1-E3- -pyridyl propyl3-3-(N,N-diethylamidino)thiourea 1-E3- -pyridyl propyl3-3-(N N-pentamethyleneamidino)- thiiourea 1-E3- -pyridyl propyl3-3-methylamidinothiourea 1-E3- -pyridyl propyl3-3-ethylamidinothiourea 1-E3- -pyridyl propyl -3-propylamidinothiourea 1-E3- -pyridyl propyl3-3-i-proρylamidinothiourea 1-E3- -pyridyl propyl3-3-butylamidinothiourea l-[3- -pyridyl propyl3-3-t-butylamidinothiourea 1-E3- -pyridyl propyl3-3-pentylamidinothiourea 1-E3- -pyridyl propyl3-3-hexylamidinothiourea l-£3- -pyridyl propyl3-3-propargylamidinothiourea l-[3- -pyridyl propyl3-3-allylamidinothiourea 1-E3- -pyridyl propyl3-3-methoxyethylamidinothiourea l-[3- -pyridyl propyl]-3-benzyloxyethylamidinothiourea 1-E3- -pyridyl propyl -3-phenethoxyethylamidino- thiourea 1-E3- -pyridyl propyl]-3-(N,N-dimethylamidino)thiourea 1-E3- -pyridyl propyl]-3-(N,N-diethylamidino) thiourea 1-E3- -pyridyl propyl -3-(N,N-methyl-N-ethylamidino)- thiourea Iξυ EAtT OMPI TABLE II X NH R 3 1! li / * Rl - N - C - NH - - C - N 1 \ H R 4 X s, o Ri *3 TABLE II X NH R 3 II II / RL - N - C - NH - C - N I \ H R x = s, o Ri R3 R 4 -BU EA OMPI $*M* TABLE II X NH R 3 11 li / *1 N - C - NH - - C - N J \ H R 4 X = S , 0 Ri R 3 R4 H H KzzzS ^ TABLE II X NH R 3 II li -*! N - C - * NH - - C - N i \ H R 4 X = s, o R l R 3 R_ CH_ I 3 OMPI TABLE ' II X NH R 3 II ii / Rl - N - C NH C - N J \ H R 4 X = S , 0 R l R_ OMPI TABLE II X NH II ii R_ - N - C - NH - - C - N A 3 1 \ H R 4 x = s, o R l R 3 CH -CH. -CH. O EAT OMPI Y WIPO TABLE II X NH II 11 / R3 R_ - N - C - NH - - C - N I \ H R 4 x =- s, o R T R 3 TAELE II X NH i! 11 3 R_ - - N - C - NH - C - N I \ H R 4 X = s r o R l R- R 4 H TABLE II X NH R 3 II II / 3 R X - N - C - NH - - C - N 1 \ H R 4 x = s, o R l R 3 R_ U E.-; OMPI IPO _^T* TABLE II X ' NH 3 U II / R ι - N - C - NH - - C - N I \ H R 4 X = S, 0 Rl 3 R 4 C_ _rJfc™L CH2' -CH. -C-H s CH_ -BUREAIT OMPI TABLE II X NH II ii N l . - C - NH - C - A 3 I \ H 4 X = S, Q R-. 4 l K CI J 2 CH 2 - H -C 2 H 5 -BUREAt OMPI _ fi- Λ, WIPO TABLE II X NH R 3 II 11 / l N - C - NH - C - N 1 \ H R 4 X = S, 0 R l 3 d N " \ H H "CHii.^CH 2 - N .,/ H K TABLE II X NH I 11 / 3 R l N - C - NH - c - N 1 \ H R 4 X = s o l R- € CH 2 CH 2 - H -C 2 H_ -B^ RE C~>- CH 2- CH 2- H -CH OMPI 3 { Λ. WIPO fei?N A Ti TABLE II X NH ii 11 R_ - N - C - NH - C - N A 3 I \ H R 4 s, o l R_ CH. TABLE II X NH 3 II II / l " N - C - NH - - C - N I \ H 4 X S, 0 l 3 R 4 The compounds of this invention may be prepared by the following general synthesis. Condensation of a heterocyclic alkylene isocya- nate (or isothiocyanate) , prepared from the heterocyclic alkylene amine and phosgene or thiophosgene in the customary manner, with an appropriate substituted guanidine results in a l-heterocyclicalkylene-3-substi- tuted amidinourea (or thiourea) . The reaction is carried out in a polar medium using solvents such as alcohol, tetrahydrofuran, etc. It is convenient to carry out the reaction by preparing the isocyanate in the reaction media and then forming a guanidine _iιι situ by hydrolyzing a guanidine carbonate with base. Condensation of the isocyanate takes place when the guanidine forms and the amidinourea compounds result. When R2 substitution is desired the starting material can be a heterocyclic alkylene N-alkyl-amine. Reaction with phosgene (or thiophosgene) results in the heterocyclic acid chloride (or thioacid chloride) which is then reacted with the appropriate substituted guanidine to prepare the amidinourea or amidinothiourea. (Scheme I) Scheme I NR 4 R_ it */ ** - NHR3-C-N COC1-? 0 0 Rg rι Rl-(CH 2 n -NH -*> R_-(CH 2 ) n -N-C-Cl 2 R 2 O NR4 _.R5 11 11 4 D Rl~(CH 2 n -N-C-NR 3 -C-N R 2 "R. - O EAtT OMPI _ Another method of preparing R 2 substituted amidinothioureas is one in which the heterocyclic alkylene N-alkylamine is reacted with ammonium or sodium thiocyanate to form a thiourea. Subsequent reaction with an appropriate substituted cyanamide forms the heterocyclic alkylene R 2 substituted amidinourea. (Scheme ID Scheme II N ..R5 ill / D C-N DNaNCS S R6 II ° R* ) _-(CH 2 ) n -NH R 1 -(CH 2 ) n -N-C-NH 2 -> R 2 2)HX R 2 S NH il II / 5 R l " (CH 2 ) n - N - - C - - NH - - C - N 1 \ R 6 Another method for preparing heterocyclic alkylene amidinoureas is by reacting a phenyl carbamate with an appropriately substituted guanidine. The reaction may be conducted in a polar aprotic solvent. It is preferred to hydrolyze the guanidine sulfate iji situ and react it with the carbamate. (Scheme III) Scheme III The starting heterocyclic alkylene amines are known, or may be prepared by known techniques. Reactions may also be carried out at other stages of synthesis depending on the substituents present and the substituents desired. Various combinations of the foregoing reactions will be determined by one skilled in the art in order that the desired product results. Thus a pyridylmethylene amidinourea may be halogenated or nitrated, etc. -BUR E tT OMPI The following are detailed examples which show the synthetic preparation of the compounds of this invention. EXAMPLE I Preparation of l-propylamidino-3-(2-pyridyl- methyDurea 75.10 g (0.25 moles) of propylguanidine sulfate are added to a stirred mixture of 40 g of a 50% aqueous NaOH and 500 ml of THF. After stirring at RT for two hours, 75 g of anhydrous Na 2 S0 are added. Stirring is continued for one hour. A solution of 57.06 g (0.25 mol) of 0-phenyl-N-(2-pyridylmethyl) carbamate in 100 ml of CH C1 is added rapidly in small portions to the stirred mixture. The reaction is warmed to near boiling for one hour. The mixture is allowed to stand at room temperature overnight. The product is extracted with CH C1 2 , dried (sat'd NaCl), concentrated and recrystallized from boiling CH3CN to give 18.89 g (28%) of l-n-propylamidino-3-(2-pyridyl-methyl) urea, M.P. 195-197°C. EXAMPLE 2 Preparation of l-methylamidino-3-[2-(2'-pyridyl) ethyl]thiourea 9.6 g (0.12 moles) of 50% w/w aqueous NaOH are added dropwise to a stirred suspension of 17.7 g (60.0 mmol) of methylguanidine sulfate in 200 ml of THF. The mixture is stirred for one hour after which 10.0 g of anhydrous NaS0 are added and stirring continued for an additional half hour. Over a period of one to two OMPI hours, a solution of 10.0 g of 2-(2-pyridyl) ethyliso- thiocyanate in 100 ml of a 9 to 1 THF/MeOH mixture is added dropwise and the reaction stirred overnight. The THF is evaporated and the residue partitioned between H 2 0 and CHCI3. The aqueous layer is extracted with CHCI3, dried and concentrated to give a dark oil. The oil is dissolved in EtOAc and placed on a silica gel column to give a yellow-orange solid which is twice recrystallized from CH3CN to give 2.0 g (14%) of l-methylamidino-3-[2-(2'-pyridyl)ethyl]thiourea as an orange solid. This invention further describes a novel method for the treatment of human and veterinary spasmolytic disorders, arrhythmic conditions, hypertensive condi- tions, gastrointestinal disorders and protozσal infes¬ tations by the administration of a compound of the Formula I. The compounds of this invention have a useful degree of gastric antisecretory activity and are effec- tive in reducing the volume and the acidity of the gas¬ tric fluid in humans and mammals. Further, these compounds produce a considerable spasmolytic action on the gastrointestinal musculature, i.e., they reduce the peristaltic action of the gastrointestinal musculature which is manifested by a delay in gastric emptying time. It should further be noted that these compounds are also characterized by their low acute oral toxicity. In particular, the heterocyclic alkylene amidino- ureas as herein described are useful in the treatment of such gastrointestinal disorders and diseases as duodenal ulcer and peptic ulcer. The compounds of this invention are also useful as antidiarrheal agents. The instant compounds may be used alone or in combination with other known antacids such as aluminum hydroxide, magnesium hydroxide, magnesium trisilicate, aluminum glycinate, calcium carbonate and the like. IPO The compounds of this invention possess blood- pressure-lowering activities and are also useful as anti-hypertensive agents. The compounds described herein also possess useful anti-arrhythmic properties as well as useful local anesthetic properties. For all these purposes, the heterocyclic alkylene amidinoureas of this invention can be normally administered orally, parenterally or rectally. Orally, they may be administered as tablets, aqueous or oily suspension, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Paren¬ terally, they may be administered as a salt in solution which pH is adjusted to physiologically accepted values. Aqueous solutions are preferred. Compositions intended for oral use may be prepared according to any method known to 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 pharmaceuti¬ cally elegant and palatable preparation. The dosage regimen in carrying out the methods of this invention is that which ensures maximum thera¬ peutic 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 treatment of gastrointestinal disease conditions or symptoms, such as duodenal ulcer, peptic ulcer or diarrhea, and in the alleviation of hypertensive and arrhythmic disorders. The therapeutically effective doses correspond to those dosage amounts found effective in tests using animal models which are known to correlate to human activity - U EAU OMPI for each particular disorder. In general, it is expected that daily doses between about 0.25 mg/kg and about 50 mg/kg (preferably in the range of about 0.5 to about 10 mg/kg/day) will be sufficient to produce the desired therapeutic effect, bearing in mind, of course, that in selecting the appropriate dosage in any specific case, consideration must be given to the patient's weight, general health, age, the severity of the disorder, and other factors which may influence response to the drug. 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. These tests involve such factors as the effect of the heterocyclic alkylene amidinoureas on gastric secretion, their spasmolytic effect, their blood-pressure-lowering effect, and determination of their toxicity. It has been found that the compounds of this invention, when tested in the above variety of situations, show a marked activity. One such test is the gastric secretion test. This test is carried out as follows: Shay rats are fasted for 4-8 hours and water is given ad lib. The rats are selected at random and separated into groups of ten. The animals are treated intraduodenally (I.D.) with the test compound or the vehicle immediately subsequent to the ligation of the stomach at the pyloric sphincter. The animals are sacrificed with chloroform at four hours post-drug-administration, the stomach removed and its contents assayed for volume, pH and total acids. A second gastric secretion test is carried out on the dog. This is outlined in the Handbook of Physiology, Section 6: Alimentary Canal, Volume II: Secretion; American Physiology Society, Washington, D.C., 1967. " • UREAZ OMPI _ It has been found that the compounds of this invention, when subjected to the above gastric secretion tests, display marked ability to decrease gastric volume and gastric acidity. These tests are known to correlate well with gastric activity in humans and are standard tests used to determine antisecretory properties. Determination of antispas olytic properties can be carried out by the procedure outlined by D.A. Brodie and S.K. Kundrats in their article entitled "Effect of Drugs on Gastric Emptying in Rats," Fed. Proc. 24:714 (1965). Acute toxicity is calculated according to the standard Litchfield-Wilcoxon procedure. Various tests can be carried out in animal models to show the ability of the amidinoureas of this invention to exhibit reactions that can be correlated with antidiarrheal activity in humans. The following tests show the ability of the compounds of this invention to inhibit diarrhea in animals and are known to correlate well with antidiarrheal activity in humans. These are considered to be standard tests used to determine antidiarrheal properties. This correlation can be shown by the activities of compounds known to be clinically active. 1. Fecal output in rat: The oral ED50 (that dose which would be expected to reduce fecal output by 50%) is determined by a method described by Bass et al., 1972. Briefly, the method involves dosing the rats and collecting the fecal output over an 8-hour period (4 P.M.-midnight) with the room darkened starting at 4:30 P.M. Ref: Bass, P., Kennedy, J.A. and Willy, J.N. : Measurement of fecal output in rats. Am. J. Dig. Pis. 10:925-928, 1972. - URE _ . OMPI 2. Castor oil test in mice: Groups of mice are orally dosed with test compound and a half hour later all mice are given 0.3 ml of castor oil. Three hours after castor oil administration, all mice are checked for diarrhea and the dose of testing compound which protected 50% of the mice from diarrhea is the ED50 dose, p 3. Castor oil test in rats: The test is conducted according to Neimegeers et al. , 1972. The rat is orally dosed with graded doses of test compound. One hour after dosing, each animal is challenged with 1 ml of castor oil orally. Fecal output is examined 1, 2, 3, 4, 6 and 8 hours after castor oil. - Absence of diarrhea is the criterion of drug effectiveness. Ref: Neimegeers, C.J.E., Lenaerts, F.M. , and Janssen, P.A.J. Difenoxine, a potent, orally active and safe antidiarrheal agent in rats. Arzneim- Forschunq (Drug. Res.) 22, 516-518, 1972. Tests in animals have also been carried out to show the ability of compounds of this invention to inhibit reactions that can be correlated with antihyper- tensive effects in humans. One such test is outlined by Jacques de Champlain, Lawrence R. Krahoff and Julius Axelrod in Circulation Research XXIII:479 (1968). This testing method is known to correlate well with antihyper- tensive activity in humans and is a standard test used to determine antihypertensive properties. In view of the results of this test, the heterocyclic alkylene amidinoureas of this invention can be considered to be active antihypertensive agents. Novel heterocyclic amidinoureas of this invention are useful in the treatment of parasitic infestations of a human host, particularly parasitic protozoal infestations in the genus Plasmodium. -BU RE T OMPI Novel heterocyclic alkylene amidinoureas are also useful in the veterinary treatment of blood-residing diseases afflicting cattle, horses, sheep and dogs. These compounds are useful in the treatment of veterinary diseases caused by parasitic helminths, parti¬ cularly Filaria, and by parasitic protozoa, particularly Plasmodiu and Babesia. Microbiological tests can be carried out in model systems to show the ability of the heterocyclic alkylene amidinoureas of this invention to exhibit activity that can be correlated with antiprotozoal acitvity in humans and animals. The following microbiological test can show the ability of the compounds of this invention to inhibit parasitic protozoal growth and reproduction. Antimalarial Blood Smear Test Mice are injected intraperitoneally with 5,000,000 parasitized blood cells from a donor. Groups of ten mice receive inoculations administered subcutane- ously in doses ranging from 0.15 to 100 mg/kg, suspended in 0.5% methecel solution (doses expressed as base) . The compound of interest is repeatedly injected on the day of inoculation (Day 1) , Day 2 and Day 3. Blood smears are performed on Days 4, 5, 6 and 10 and the number of parasitic protozoa noted. The compounds of this invention are also useful chelating agents for treating patients suffering from metal poisoning, for example, poisoning by magnesium, arsenic, chromium, manganese, cobalt, nickel, copper, zinc, cadmium, silver, lead, antimony and mercury, by administering to a patient suffering from metal poi¬ soning a therapeutically effective amount between 0.5 mg and 500 mg per dosage unit of at least one of said compounds. BU E AT OMPI

Claims: WE CLAIM: 1. A compound of the formula X NR 4 II H ^R5 Rl - (CH 2 ) n - N - C - N - C - N I I ^R R 2 R 3 wherein: X is oxygen or sulfur; n is 1 to 3; Rl is a 5 to 7 atom ring or a 7 to 13 atom fused or bridged ring which may include 1 to 4 hetero atoms of N, 0 or S; and containing a total of about 3 to about 20 carbon atoms; and the N- or S- oxides thereof; R 2 , R3 and R 4 are hydrogen or lower alkyl; R5 and Rg are hydrogen, alkyl, cycloalkyl, alkenyl, alkoxy, aryl, aralkyl, or a heterocyclic group, or R5 and Rg together with the nitrogen to which they are attached form a 3 to 7 atom ring which may include 0 to 2 additional hetero atoms of N, 0 or S; and the non-toxic pharmaceutically acceptable salts thereof. 2. A compound according to Claim 1, wherein R_ is a heterocycle selected from a group consisting of 1-pyrrole, 2-pyrrole, 3-pyrrole, 2-furan, 3-furan, 2- thiophene, 3-thiophene, 2-tetrahydrothiophene, 3-tetra- hydrothiophene, 1-imidizole, 2-imidizole, 4-imidizole, 5-imidizole, 2-oxazole, 4-oxazole, 5-oxazole, 2-thia- zole, 4-thiazole, 5-thiazole, 1-pyrazole, 3-pyrazole, 4-pyrazole, 5-pyrazole, 1-pyrrolidine, 2-pyrrolidine, 3-pyrrolidine, l-(3-pyrroline) , 2-(3-pyrroline) , 3-(3- pyrroline) , 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidine, 4-pyrimidine, 5-pyrimidine, 6-pyrimidine, 2-purine, 6-purine, 8-purine, 9-purine, 2-quinoline, 3-quinoline, 4-quinoline, 5-quinoline, 6-quinoline, 7-quinoline, 8-quinoline, 1-isoquinoline, 3-isoquinoline, 4-isoquino- line, 5-isoquinoline, 6-isoquinoline, 7-isoquinoline, 8-isoquinoline, or carbazole; where the heterocyclic groups may be mono-, di-, tri- or tetra- substituted by ring substituents, such as hydrogen, lower alkyl, lower alkenyl, aryl, lower alkynyl, aralkyl, halo, nitro, cyano, sulfonyl, hydroxyl, carboxyl, lower alkanoyl, lower alkoxy, aryl lower alkoxy, halo lower alkoxy, amido, amino, lower alkylacyloxy, alkylamino, lower alkoxyamino, and aralkoxyamino. 3. A compound of the formula X NH I I II /- 5 l - ( CH 2 ) n - N - C - - NH - - C - N 1 • * " R 6 2 wherein: n is 1 or 2; X is oxygen or sulfur; R_ is a substituted or unsubstituted 5, 6 or 7 atom ring including 1 to 3 hetero atoms of N, 0 or S; and N- and S-oxides thereof. R 2 is hydrogen or lower alkyl; R5 and Rg are hydrogen, lower alkyl, cycloalkyl, lower alkoxy, or aralkyl, or R5 and Rg together with the nitrogen to which they are attached form a 3 to 7 atom heterocycle. 4. A compound according to Claim 3 wherein: R]_ is one of the following heterocyclic groups - IS E ZT OMPI and, m is zero to four; R is a ring substituent selected from the group consisting of halogen, lower alkyl, lower alkenyl, aryl, lower alkynyl, aralkyl, nitro, cyano, sulfonyl, hydroxyl, carboxyl, lower alkanoyl, lower alkoxy, aryl lower alkoxy, halo lower alkoxy, amido, amino, lower alkyl acyloxy, alkylamino, lower alkoxyamino, and aralkoxyamino; and the non-toxic pharmaceutically acceptable salts thereof. 5. A compound according to Claim 3, wherein: τ_ is one of -the following heterocyclic groups and, m is zero to four; R is a ring substituent selected from the group consisting of halogen, lower alkyl, lower alkenyl, aryl, lower alkynyl, aralkyl, nitro, cyano, sulfonyl, hydroxyl, carboxyl, lower alkanoyl, lower alkoxy, aryl lower alkoxy, halo lower alkoxy, amido, amino, lower alkyl acyloxy, alkylamino, lower alkoxyamino, and aralkoxyamino; and the non-toxic pharmaceutically acceptable salts thereof. - ΪJREALT OMPI ^SNATIO 6. A compound according to Claims 1, 2, 3, or 4 wherein X is oxygen. 7. A method for the treatment of gastrointes¬ tinal hyperacidity and ulcerogenic symptoms or disor- ders in mammals comprising administering thereto an effective amount of a compound according to Claim 1. 8. A method for treating gastrointestinal spasms comprising administering to a patient suffering from said gastrointestinal spasms a therapeutically effective amount of a compound according to Claim 1. 9. A method for the treatment of diarrhea in humans and mammals which comprises the administering thereto of an effective amount of a compound according to Claim 1. 10. A method for the treatment of arrhythmia in a patient suffering from arrhythmia which comprises administering to said patient an effective amount of a compound according to Claim 1. 11. A method for the treatment of humans and mammals afflicted with parasitic infections of the blood and blood-forming organs, comprising adminis¬ tering to the afflicted host a composition containing an effective amount of a compound according to Claim 1. 12. A method for lowering blood pressure in humans and mammals which comprises administering a compound according to Claim 1. 13. A compound of the formula X NRc i l II D R l - { CH 2 } n - N - C - NH - C - NHRg H wherein : X may be oxygen or sulfur; n is 1 or 2; Rl is selected from the group consisting of 2- pyridyl, 3-pyridyl and 4-pyridyl; R5 and Rg are hydrogen, lower alkyl or lower alkoxy. 14. A compound of the formula X NH II II l - <CH 2 ) n - N C - NH - C - NHRg 1 H wherein: X may be oxygen or sulfur; n is 1 or 2; Ri is selected from the group consisting of 2-pyridyl, 3-pyridyl and 4-pyridyl; Rg is hydrogen, lower alkyl, or lower alkoxy. 15. A compound according to Claim 12 where X is oxygen. 16. A compound according to Claim 13 where X is oxygen. 17. l-propylamidino-3-(2-pyridylmethyl)urea; and the pharmaceutically acceptable acid addition salts thereof. - UREIT OMPI 18. l-methylamidino-3-[2-(2'-pyridyl)ethyl]thio¬ urea; and the pharmaceutically acceptable acid addition salts thereof. *gυ EAir OMPI

Inventors: DODSON STUART ALAN, DOUGLAS GEORGE HENRY, STUDT WILLIAM LYON, ZIMMERMAN HARRY KARL
Applicants: RORER INT OVERSEAS, RORER INT OVERSEAS INC
Application year: 1982
Main classification: C07D213
IPC codes: C07D207, C07D213, C07D215, C07D217, C07D233, C07D239, C07D261, C07D263, C07D265, C07D275, C07D277, C07D295, C07D307, C07D333, C07D521