The invention relates to compounds of the formula (I) ##STR1## and physiologically acceptable salts, hydrates and bioprecursors thereof, in which PA1 R.sub.1 and R.sub.2 represent hydrogen, an aliphatic or cycloaliphatic group, or R.sub.1 and R.sub.2 together with the nitrogen atom form a 5 to 10 membered heterocyclic ring: PA1 Alk represents a straight or branched alkylene chain; PA1 Q represents furan, thiophen or benzene ring which is incorporated into the rest of the molecule; PA1 X represents --CH.sub.2 --, ##STR2## --O-- or --S-- where PA1 R.sub.6 represents hydrogen or methyl; PA1 n represents zero, 1 or 2; PA1 m represents 2, 3 or 4; PA1 R.sub.3 represents hydrogen, a substituted or unsubstituted aliphatic or aryl group and; PA1 R.sub.4 and R.sub.5, which may be the same or different, each represent hydrogen, a substituted or unsubstituted aliphatic, aryl, or together with the nitrogen atom form a heterocyclic group.

This invention relates to novel heterocyclic derivatives having action on 
histamine receptors, to processes for the preparation thereof, to 
pharmaceutical compositions containing them and to their use in 
therapeutics. 
Certain novel heterocyclic derivatives have now been found which have 
potent activity as H.sub.2 -antagonists. These compounds, which are more 
particularly described below, for example show inhibition of the secretion 
of gastric acid when this is stimulated via histamine receptors (Ash and 
Schild, Brit. J. Pharmacol, Chemother, 1966, 27, 427). Their ability to do 
so can be demonstrated in the perfused rat stomach using the method 
described in German Offenlegungsschrift No. 2,734,070, modified by the use 
of sodium pentobarbitone (50 mg/kg) as anaesthetic instead of urethane, 
and in conscious dogs equipped with Heidenhain pouches using the method 
described by Black et al, Nature 1972 236, 385. Furthermore the compounds 
antagonise the effect of histamine on the contraction frequency of 
isolated guinea pig right atrium but do not modify histamine induced 
contractions of isolated gastro-intestinal smooth muscle which are 
mediated via H.sub.1 -receptors. Certain compounds according to the 
invention have the advantage of an extended duration of action. 
Compounds with histamine H.sub.2 -blocking activity may be used in the 
treatment of conditions where there is a hypersecretion of gastric acid, 
particularly in gastric and peptic ulceration, as a prophylactic measure 
in surgical procedures, and in the treatment of allergic and inflammatory 
conditions where histamine is a known mediator. Thus they may be used for 
example, either alone, or in combination with other active ingredients in 
the treatment of allergic and inflammatory conditions of the skin. 
The present invention provides compounds of the general formula (I) 
##STR3## 
and physiologically acceptable salts, hydrates and bioprecursors thereof, 
in which 
R.sub.1 and R.sub.2, which may be the same or different, each represent 
hydrogen, C.sub.1-10 alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, 
trifluoroalkyl or alkyl substituted by hydroxy, alkoxy, amino, alkylamino, 
dialkylamino or cycloalkyl, or R.sub.1 and R.sub.2 may together with the 
nitrogen atom to which they are attached form a 5 to 10 membered alicyclic 
heterocyclic ring which may be saturated or may contain at least one 
double bond, may be unsubstituted or may be substituted by one or more 
C.sub.1-3 alkyl groups, e.g. methyl, or a hydroxy group and/or may 
contain another heteroatom, e.g. oxygen or sulphur, 
Alk represents a straight or branched alkylene chain of 1 to 6 carbon 
atoms, preferably 1 to 4 carbon atoms; 
Q represents a furan or thiophen ring in which incorporation into the rest 
of the molecule is through bonds at the 2- and 5-positions, the furan ring 
optionally bearing a further substituent R.sub.7 adjacent to the group 
##STR4## 
or Q represents a benzene ring in which incorporation into the rest of 
the molecule is through bonds at the 1- and 3- or 1- and 4-positions; 
R.sub.7 represents halogen or C.sub.1-4 alkyl which may be substituted by 
hydroxy or C.sub.1-4 alkoxy; 
X represents --CH.sub.2 --, 
##STR5## 
--O-- or --S-- where 
R.sub.6 represents hydrogen or methyl; 
n represents zero, 1 or 2; 
m represents 2, 3 or 4; 
R.sub.3 represents hydrogen, alkyl, alkenyl, aralkyl, hydroxyalkyl having 
at least two carbon atoms, alkoxyalkyl or aryl; and 
R.sub.4 and R.sub.5, which may be the same or different, each represent 
hydrogen, alkyl, alkyl substituted by hydroxy or C.sub.1-3 alkoxy, 
alkenyl, aralkyl or heteroaralkyl or R.sub.4 and R.sub.5 may together with 
the nitrogen atom to which they are attached form a 5 to 7-membered 
saturated heterocyclic ring which may contain another heteroatom, e.g. 
oxygen, or the group 
##STR6## 
or R.sub.4 and R.sub.5 taken together may represent the group 
.dbd.CR.sub.8 R.sub.9 where R.sub.8 represents aryl or heteroaryl and 
R.sub.9 represents hydrogen or alkyl. 
Preferably when X represents an oxygen atom or 
##STR7## 
and n is zero, then Q only represents a benzene ring. 
The term `alkyl` as a group or part of a group means that the group is 
straight or branched and has unless otherwise stated preferably 1 to 6 
carbon atoms, and in particular 1 to 4 carbon atoms e.g. methyl or ethyl 
and the terms `alkenyl` and `alkynyl` mean that the group has preferably 3 
to 6 carbon atoms. The term `cycloalkyl` means that the group has 3 to 8 
carbon atoms. The term `aryl` as a group or part of a group preferably 
means phenyl or substituted phenyl, for example phenyl substituted with 
one or more C.sub.1-3 alkyl or C.sub.1-3 alkoxy groups or halogen atoms. 
The term `heteroaryl` as a group or part of a group preferably means 
pyridyl or substituted pyridyl, e.g. pyridyl substituted with one or more 
C.sub.1-3 alkyl groups. 
According to one aspect the invention provides compounds of the formula (I) 
and physiologically acceptable salts, hydrates and bioprecursors thereof, 
in which 
R.sub.1 and R.sub.2, which may be the same or different, each represent 
hydrogen, C.sub.1-6 alkyl, cycloalkyl, C.sub.3-6 alkenyl, aralkyl or 
C.sub.1-6 alkyl substituted by alkoxy, alkylamino or dialkylamino, or 
R.sub.1 and R.sub.2 may together with the nitrogen atom to which they are 
attached form a 5 to 10 membered alicyclic heterocyclic ring which may 
contain oxygen; 
Alk represents a straight or branched alkylene chain of 1 to 6 carbon 
atoms; 
Q represents a furan or thiophen ring in which incorporation into the rest 
of the molecule is through bonds at the 2- and 5-positions, the furan ring 
optionally bearing a further substituent R.sub.7 adjacent to the group 
R.sub.1 R.sub.2 N-Alk-, or Q represents a benzene ring in which 
incorporation into the rest of the molecule is through bonds at the 1- and 
3- positions; 
R.sub.7 represents C.sub.1-4, alkyl which may be substituted by hydroxy or 
C.sub.1-4 alkoxy; 
X represents --CH.sub.2 --, --O-- or --S--; 
n represents zero, 1 or 2; 
m represents 2, 3 or 4; 
R.sub.3 represents hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl, 
hydroxyalkyl having at least two carbon atoms, alkoxyalkyl, aryl or 
aralkyl; and 
R.sub.4 and R.sub.5, which may be the same or different, each represent 
hydrogen or C.sub.1-6 alkyl; 
with the proviso that when Q represents a furan, substituted furan or 
thiophen ring system and X represents oxygen, n cannot be zero. 
The invention includes the compounds of formula (I) in the form of 
physiologically acceptable salts with inorganic and organic acids. 
Particularly useful salts include hydrochlorides, hydrobromides and 
sulphates; acetates, maleates, succinates, citrates and fumarates. The 
compounds of formula (I) and their salts may also form hydrates, which 
hydrates are also to be considered as part of the invention. The compounds 
of formula (I) can exhibit tautomerism and the formula is intended to 
cover all tautomers. Where optical isomers may exist the formula is 
intended to cover all diastereoisomers and optical enantiomers. 
The compounds according to the invention, preferably in the form of a salt, 
may be formulated for administration in any convenient way and the 
invention includes within its scope pharmaceutical compositions containing 
at least one compound according to the invention adapted for use in human 
or veterinary medicine. Such compositions may be formulated in a 
conventional manner using one or more pharmaceutically acceptable carriers 
or excipients. Such compositions may also contain if required other active 
ingredients, e.g. H.sub.1 -antagonists. 
Thus the compounds according to the invention may be formulated for oral, 
buccal, topical, parenteral or rectal administration. Oral administration 
is preferred. 
For oral administration, the pharmaceutical composition may take the form 
of for example, tablets, capsules, powders, solutions, syrups or 
suspensions prepared by conventional means with acceptable excipients. For 
buccal administration the composition may take the form of tablets or 
lozenges formulated in conventional manner. 
The compounds of the invention may be formulated for parenteral 
administration by bolus injection or continuous infusion. Formulations for 
injection may be presented in unit dosage form in ampoules, or in 
multi-dose containers, with an added preservative. The compositions may 
take such forms as suspensions, solutions or emulsions in oily or aqueous 
vehicles, and may contain formulatory agents such as suspending, 
stabilising and/or dispersing agents. Alternatively, the active ingredient 
may be in powder form for reconstitution with a suitable vehicle, e.g. 
sterile pyrogen-free water before use. 
The compounds of the invention may also be formulated in rectal 
compositions such as suppositories or retention enemas, e.g. containing 
conventional suppository bases such as cocoa butter or othe glyceride. 
For topical application, the compounds of the invention may be formulated 
as ointments, creams, gels, lotions, powders or sprays. Ointments and 
creams may, for example, be formulated with an aqueous or oily base with 
the addition of suitable pharmaceutical excipients. Lotions may be 
formulated with an aqueous or oily base and will include the necessary 
adjustments to ensure pharmaceutically acceptable products. Spray 
compositions may, for example, be formulated as aerosols which may be 
pressurised by means of a suitable agent such as dichlorofluoromethane or 
trichlorofluoromethane or may be delivered by means of a hand-operated 
atomizer. 
For internal administration a convenient daily dosage regime of the 
compounds according to the invention would be 1 to 6 doses to the total of 
some 5 mg to 2 g per day, preferably 5 to 500 mg per day. 
In the compounds according to the invention, preferably the total of m+n is 
3 or 4, more preferably 3. 
When X is sulphur, n is preferably 1 and m is preferably 2. When X is 
oxygen or 
##STR8## 
n is preferably zero and m is preferably 3 or 4, more preferably 3. 
Preferably Q is a furan ring optionally substituted by the group R.sub.7, 
where R.sub.7 represents C.sub.1-3 alkyl optionally substituted by alkoxy 
or is a benzene ring in which incorporation into the rest of the molecule 
is through bonds at the 1- and 3- or 1- and 4-positions. 
Preferably Alk represents a methylene, ethylene or propylene group. 
Preferably R.sub.1 represents hydrogen or C.sub.1-4 alkyl and R.sub.2 
represents C.sub.3-5 alkenyl or alkynyl, C.sub.5-7 cycloalkyl, benzyl, 
C.sub.1-8 alkyl, or C.sub.1-4 alkyl substituted by C.sub.1-3 alkoxy, 
hydroxy, diC.sub.1-3 alkylamino or trifluoromethyl or R.sub.1 and R.sub.2 
together with the nitrogen atom to which they are attached form an 
alicyclic heterocyclic ring with 5 to 8 members and optionally containing 
one double bond and/or substituted by hydroxy or one or two C.sub.1-3 
alkyl group(s). 
Preferably R.sub.3 represents hydrogen or C.sub.1-4 alkyl or hydroxyalkyl. 
Preferably R.sub.4 represents hydrogen or C.sub.1-5 alkyl optionally 
substituted by a phenyl, pyridyl, hydroxy or C.sub.1-3 alkoxy group and 
R.sub.5 represents hydrogen or C.sub.1-3 alkyl or R.sub.4 and R.sub.5 
together with the nitrogen atom to which they are attached represent a 
C.sub.5-7 saturated heterocyclic ring or R.sub.4 and R.sub.5 together 
represent the group .dbd.CHR.sub.8 where R.sub.8 represents a phenyl or 
pyridyl group. 
Where R.sub.1 and R.sub.2 together with the nitrogen atom to which they are 
attached form a heterocyclic ring this ring may be pyrrolidine, piperidine 
optionally substituted in the 4-position by C.sub.1-3 alkyl or hydroxy, 
tetrahydropyridine, morpholine, 2,6-dialkylmorpholine, hexamethyleneimine 
or heptamethyleneimine. 
When Q represents a furan or substituted furan ring, preferably Alk 
represents a methylene group, R.sub.1 and R.sub.2 both represent C.sub.1-3 
alkyl groups and when present R.sub.7 preferably represents a C.sub.1-3 
alkyl group optionally substituted with a C.sub.1-3 alkoxy group n is 1, X 
is sulphur and m is 2. More preferably Q represents a substituted furan 
group in which R.sub.7 represents a C.sub.1-3 alkyl group, in particular 
methyl, which may be optionally be substituted with a C.sub.1-3 alkoxy 
group, in particular a methoxy group. 
When Q represents a benzene ring preferably Alk represents a methylene, 
ethylene or propylene group; n is zero; X is oxygen or NH; m is 3 or 4; l 
R.sub.1 represents hydrogen or C.sub.1-4 alkyl; R.sub.2 represents a 
straight chain C.sub.1-7 alkyl group which may be branched by a methyl 
group, or a C.sub.1-4 alkyl group substituted by a di(C.sub.1-3) 
alkylamino, C.sub.1-3 alkoxy, trifluoromethyl or phenyl group or R.sub.2 
represents a C.sub.5-7 cycloalkyl group or a C.sub.3-5 alkenyl group or 
R.sub.1 and R.sub.2 together with the nitrogen atom to which they are 
attached form a 5 to 8 membered alicyclic heterocyclic ring which may be 
saturated or contain at least one double bond, or be saturated and 
substituted by one or more C.sub.1-3 alkyl e.g. methyl groups and may 
contain an additional heteroatom e.g. oxygen; R.sub.3 is H or C.sub.1-2 
alkyl or hydroxyethyl; R.sub.4 represents hydrogen or C.sub.1-3 alkyl 
optionally substituted by a phenyl or pyridyl group and R.sub.5 represents 
hydrogen or C.sub.1-3 alkyl or R.sub.4 and R.sub.5 together represent the 
group .dbd.CHR.sub.8 where R.sub.8 is phenyl or pyridyl. 
More preferably when Q represents benzene, R.sub.1 and R.sub.2 represent 
C.sub.1-3 alkyl, e.g. methyl, or R.sub.1 represents hydrogen and R.sub.2 
represents C.sub.1-7 alkyl, e.g. methyl, propyl, butyl, secondary butyl 
and n-heptyl, or C.sub.3-5 alkenyl, e.g. allyl or C.sub.5-7 cycloalkyl, 
e.g. cyclohexyl, or R.sub.1 and R.sub.2 together with the nitrogen atom to 
which they are attached represent a 5 to 7 membered alicyclic heterocyclic 
ring which may be saturated, or contain a double bond, or be saturated and 
substituted by one C.sub.1-3 alkyl group e.g. methyl, in particular 
pyrrolidine, piperidine optionally substituted in the 4-position by a 
methyl group; or tetrahydropyridine or hexamethyleneimine; R.sub.3 
represents hydrogen, methyl, ethyl or hydroxyethyl; R.sub.4 and R.sub.5 
both represent hydrogen or ethyl or R.sub.4 and R.sub.5 together represent 
the group .dbd.CHR.sub.8 where R.sub.8 represents phenyl or 4-pyridyl. 
Particularly, preferred compounds in which Q is benzene are those in which 
it is incorporated into the rest of the molecule through bonds at the 1 
and 3 positions and in which Alk represents methylene, n is zero, X is 
oxygen and m is 3. 
Particularly preferred compounds of the invention are those in which 
R.sub.3 represents methyl and R.sub.4 and R.sub.5 represent hydrogen. 
Particularly preferred compounds are: 
(1) 1-methyl-N.sup.5 
-[3-[3-[1-piperidinylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(2) 1-methyl-N.sup.5 
-[3-[3-[1-pyrrolidinylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(3) 1-methyl-N.sup.5 
-[3-[3-[1-hexamethyleneiminylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5- 
diamine 
(4) N.sup.3 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(5) 1-methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
(6) 1-methyl-N.sup.3 -phenylmethylene-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
(7) 1-methyl-N.sup.3 -(4-pyridinylmethylene)-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
(8) 1-methyl-N.sup.5 
-[2-[[[5-(dimethylamino)methyl-4-methyl-2-furanyl]methyl]thio]ethyl]-1H-1, 
2,4-triazole-3,5-diamine 
(9) 1-methyl-N.sup.5 
-[3-[3-[(dimethylamino)ethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(10) 1-methyl-N.sup.5 
-[3-[3-[(1-propylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
(11) 1-merthyl-N.sup.5 -[3-[3-[1-(1,2,3,6-tetrahydropyridinyl) 
methyl]phenoxy]propyl]-1H-1,2,4-triazole-B 3,5-diamine 
(12) 1-methyl-N.sup.5 -[2-[[4-methoxymethyl-5-[(diamethylamino) 
methyl]-2-furanylmethyl]thio]ethyl]-1H-1,2,4-triazole-3,5-diamine 
(13) 1-methyl-N.sup.5 
-[3-[4-[3-(dimethylamino)propyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diam 
ine 
(14) 1-ethyl-N.sup.5 -[3-[3-(1-piperidinylmethyl) 
phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(15) 1-methyl-N.sup.3 -diethyl-N.sup.5 -[3-[3-[(dimethylamino) 
methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(16) 1-methyl-N.sup.5 
-[4-[3-(1-piperidinylmethyl)phenoxy]butyl]-1H-1,2,4-triazole-3,5-diamine 
(17) 1-methyl-N.sup.5 -[3-[3-[1-(4-methylpiperidinyl)methyl] 
phenoxy]propyl]-1H-1,2,4,-triazole-3,5-diamine 
(18) 1-methyl-N.sup.5 
-[3-[3-[(cyclohexylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diam 
ine 
(19) 1-methyl-N.sup.5 
-[3-[3-[(2-propen-1-amino)methyl]phenoxy]proyl]-1H-1,2,4-triazole-3,5-diam 
ine 
(20) 1-methyl-N.sup.5 
-[3-[3-[(heptylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(21) 1-methyl-N.sup.5 
-[3-[3-[(2-methylpropylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5- 
diamine 
(22) 1-methyl-N.sup.5 -[3-[3-[(2,2,2-trifluoroethylamino) 
methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(23) 1-methyl-N.sup.5 
-[3-[3-[(butylmethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-dia 
mine 
(24) 1-(2-hydroxyethyl)-N.sup.5 -[3-[3-[(dimethylamino) 
methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(25) 1-(2-hydroxyethyl)-N.sup.5 
-[3-[3-[(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
and their physiologically acceptable salts. 
Of the above mentioned compounds, compound Nos. (1), (2), (3) and (4) and 
their salts are particularly preferred. 
It will be appreciated in the methods for the preparation of compounds of 
formula (I) given below, that for certain reaction steps it may be 
necessary to protect various reactive substituents in the starting 
materials for a particular reaction and subsequently to remove the 
protecting group. Such protection and subsequent deprotection may be 
particularly pertinent where R.sub.1 and/or R.sub.2 in intermediates used 
to prepare compounds of formula (I) are hydrogen atoms and/or when R.sub.3 
in intermediates is an alkyl group bearing a hydroxy substituent and/or 
when R.sub.4 and/or R.sub.5 in certain intermediates are hydrogen atoms. 
Standard protection can deprotection procedures can be employed: 
for example formation of phthalimide (in the case of primary amines), 
benzyl, benzyloxycarbonyl, or trichloroethoxycarbonyl derivatives. 
Subsequent cleavage of the protecting group is achieved by conventional 
procedures. Thus a phthalimide group may be cleaved by treatment with a 
hydrazine e.g. hydrazine hydrate or a primary amine for example 
methylamine; benzyl or benzyloxycarbonyl derivatives may be cleaved by 
hydrogenolysis in the presence of a catalyst, e.g. palladium, and 
trichloroethoxycarbonyl derivatives may be cleaved by treatment with zinc 
dust. 
Compounds according to the invention in which R.sub.4 and R.sub.5 are 
hydrogen can be prepared by cyclising a compound of formula (II) 
##STR9## 
in which R.sub.1, R.sub.2, Alk, Q, n, X, m and R.sub.3 are as defined in 
formula (I) or are groups convertible thereto and Z represents two 
hydrogen atoms. 
In carrying out the above reaction it is convenient to prepare compounds of 
formula (I) in which R.sub.4 and R.sub.5 are both hydrogen by reacting a 
compound of formula (III) 
##STR10## 
in which R.sub.1, R.sub.2, Alk, Q, n, X, and m are as defined in formula 
(II) and L represents a leaving group, for example a lower alkoxy or lower 
alkyl thio group with a hydrazine (IV) 
EQU R.sub.3 NHN.dbd.Z (IV) 
in which R.sub.3 is as defined in formula (I) and Z represents two hydrogen 
atoms. The reaction may be carried out in the presence of a suitable 
solvent such as an aromatic hydrocarbon, e.g. toluene, an alkanol, e.g. 
ethanol or isopropanol, water or dimethylformamide at a temperature of 
from room temperature to reflux. The compund of formula (II) is thus 
formed and cylises in situ to give the compound of the invention. 
In a further embodiment of the process, compounds of formula (I) in which 
R.sub.4 and R.sub.5 are both hydrogen may also be prepared via the 
intermediate (II) from a diamine of formula (V) 
EQU R.sub.1 R.sub.2 N-Alk-Q-(CH.sub.2).sub.n X(CH.sub.2).sub.m NH.sub.2 (V) 
in which R.sub.1, R.sub.2, Alk, Q, n, X and m are as defined in formula 
(II) by reaction with a compound of formula (VI) 
##STR11## 
in which R.sub.3 is as defined in formula (I), L is as defined in formula 
(III) and Z represents two hydrogen atoms or a protecting grup which can 
readily be removed to yield two hydrogen atoms, e.g. a benzylidene group. 
The reaction may be carried out in the absence of presence of a suitable 
solvent, for example toluene, ethanol, methanol, isopropanol, acetonitrile 
or water, at a temperature from room temperature to reflux. When the 
reaction is carried out with a compound (VI) in which Z is a protecting 
group, it is necessary to remove the protecting group before cyclisation 
can take place. Where Z represents a benzylidene group it may be removed 
with aqueous acid, e.g. hydrochloric acid, and under these conditions the 
intermediate (II) where Z represents two hydrogen atoms cyclises to give 
the compound of formula (I). When Z represents a benzylidene group it may 
also be removed by heating with an amine e.g. piperidine, to give the 
compound of formula (I). 
The compound of formula (VI) may be prepared from a compound of formula 
(VII) 
##STR12## 
in which L is as defined in formula (III) and L ' may have one of the 
meanings of L or may represent a lower alkyl sulphoxide group. The 
compound (VII) is reacted with the hydrazine. (IV) to give the compound of 
formula (VI) the reaction preferably being carried out in a solvent for 
example toluene, an alkanol or acetonitrile, and preferably with heating. 
Compounds of formula (I) in which R.sub.4 and R.sub.5 are other than the 
group .dbd.CR.sub.8 .sub.9 may be prepared by cyclisation of a compound of 
formula (VIII) 
##STR13## 
where V is NH and Y is sulphur, oxygen or NH or V is sulphur or oxygen and 
Y is NH, and in which R.sub.1, R.sub.2, Alk, Q, n, X, m, R.sub.3, R.sub.4 
and R.sub.5 are as defined in formula (I) except that R.sub.4 and R.sub.5 
are other than the group .dbd.CR.sub.8 R.sub.9. The reaction is preferably 
carried out by heating the compound (VIII) in a suitable solvent such as 
acetonitrile or dimethylformamide. 
A compound (VIII) in which V is NH and Y is sulphur, oxygen or NH may be 
prepared by reacting an alkylisothiourea (IX) 
##STR14## 
in which R.sub.10 represents a C.sub.1-4 alkyl group, with a semicarbazide 
thiosemicarbazide or aminoguanidine (X) 
##STR15## 
in which Y is oxygen, sulphur or NH, in a suitable solvent, e.g. 
dimethylformamide. 
Compounds of formula (VIII) in which V is sulphur or oxygen Y is NH and 
R.sub.4 and R.sub.5 are both hydrogen or alkyl may be prepared by the 
reaction of the compound (XI) 
EQU R.sub.1 R.sub.2 N--Alk--Q--(CH.sub.2).sub.n X(CH.sub.2).sub.m --NCY (XI) 
in which Y is sulphur or oxygen and in which R.sub.1, R.sub.2, Alk, Q, n, X 
and m are as defined in formula (I), with an aminoguanidine (X) in which Y 
is NH and R.sub.3 is as defined in formula (I) and R.sub.4 and R.sub.5 
both represent hydrogen or alkyl. The reaction may be carried out 
preferably with heating, optionally in the presence of a suitable solvent 
such as a lower alkanol, e.g. ethanol, or acetonitrile. 
Compounds of formula (I) in which R.sub.4 and R.sub.5 are other than 
hydrogen or the group .dbd.CR.sub.8 R.sub.9 may be prepared from an 
aminoguanidine (XII) 
##STR16## 
in which R.sub.1, R.sub.2, Alk, Q, n, X, m and R.sub.3 are as defined in 
formula (I) by reaction with a carbamoyl halide (XIII) 
EQU R.sub.4 R.sub.5 NCOHal (XIII) 
in which R.sub.4 and R.sub.5 are as defined in formula (I) and are other 
than hydrogen or the group .dbd.CR.sub.8 R.sub.9 and Hal is a halogen 
atom. The reaction is preferably carried out in a suitable solvent such as 
acetonitrile or an aromatic hydrocarbon, e.g. benzene or toluene. 
The aminoguanidine (XII) may be prepared by the reaction of a thiourea 
(XIV) 
##STR17## 
with an alkyl halide or a dialkyl sulphate in the presence of an acid to 
produce the alkylisothiourea (IX). Reaction of this alkylisothiourea (IX) 
with the hydrazine (IV) in a suitable solvent such as dimethylformamide, 
followed by removal of the protecting group Z where appropriate gives the 
aminoguanidine (XII). 
Compounds of formula (I) in which R.sub.4 and R.sub.5 are other than the 
group .dbd.CR.sub.8 R.sub.9 can be prepared by reducing a compound of 
formula (XV) 
##STR18## 
in which Q, n, X, m and R.sub.3 are as defined in formula (I) and in which 
at least one of D, D' and D" represents a reducible group and the other(s) 
take the appropriate meaning corresponding to formula (I); 
where D represents R.sub.1 R.sub.2 Nalk--or a group convertible thereto 
under reducing conditions where R.sub.1, R.sub.2 and Alk are as defined in 
formula (I); 
where D' represents --CH.sub.2 NH--or a group --CONH--or --CH.dbd.N--; and 
where D" represents NR.sub.4 R.sub.5 where R.sub.4 and R.sub.5 are as 
defined in formula (I) or a group --NR.sub.4 COR.sub.11 in which R.sub.4 
is as defined in formula (I) and R.sub.11 represents hydrogen, alkyl, 
optionally substituted by a hydroxy group or a group convertible thereto 
under the reducing conditions aryl, aralkyl, or alkoxy. 
Thus for example compounds of formula (I) in which R.sub.4 and R.sub.5 are 
other than the group .dbd.CR.sub.8 R.sub.9 may be prepared by reducing 
compounds of formula (XVI) 
##STR19## 
in which W represents the group --CHO or --(CH.sub.2).sub.p CONR.sub.1 
R.sub.2, Q, n, X, m, R.sub.3, R.sub.4, R.sub.5, R.sub.1 and R.sub.2 are as 
defined in formula (I) and p is zero, 1, 2, 3, 4 or 5. Compounds of 
formula (I) in which Alk represents CH.sub.2 may be prepared from the 
compound (XVI) in which W represents the group --CHO by reaction with 
ammonia or an amine R.sub.1 R.sub.2 NH in a solvent e.g. tetrahydrofuran 
or an alkanol such as ethanol or methanol, followed by reduction e.g. with 
a hydride reducing agent such as an alkali or alkaline earth metal 
borohydride, e.g. sodium borohydride, or aluminium hydride or lithium 
aluminium hydride or with hydrogen and a metal catalyst e.g. palladium or 
platinum. 
Similarly compounds of formula (I) in which Alk is a C.sub.1-6 alkylene 
group may be prepared by reduction of a compound of formula (XVI) in which 
W represents the group R.sub.1 R.sub.2 NCO(CH.sub.2).sub.p. The reduction 
may be carried out with aluminium hydride or lithium aluminium hydride in 
a suitable solvent such as dioxan or tetrahydrofuran. The compounds of 
formula (XVI) may be prepared from an amine of formula (XVII) 
EQU W--Q--(CH.sub.2).sub.n X(CH.sub.2).sub.m --NH.sub.2 (XVII) 
in which W represents the group R.sub.1 R.sub.2 NCO(CH.sub.2).sub.p or a 
protected aldehyde group e.g. an acetal or cyclic ketal, by methods 
analagous to those described herein for preparing the corresponding 
compounds of formula (I). 
In a further aspect of the reduction of compounds of formula (XV) compounds 
of formula (I) in which R.sub.4 and R.sub.5 are other than the group 
.dbd.CR.sub.8 R.sub.9 may be prepared by the reduction of an amide (XVIII) 
##STR20## 
in which R.sub.1, R.sub.2, Alk, Q, n, X, m, R.sub.3, R.sub.4 and R.sub.5 
are as defined in formula (I), with a suitable reducing agent such as 
lithium aluminium hydride or an aluminium hydride in a solvent such as 
tetrahydrofuran or dioxan, at temperatures from ambient to reflux. 
Compounds of formula (XVIII) in which R.sub.3 is hydrogen and R.sub.4 and 
R.sub.5 are both hydrogen or alkyl or in which R.sub.3 is other than 
hydrogen and R.sub.4 and R.sub.5 are both alkyl may be prepared from an 
activated derivative of a carboxylic acid (XIX) 
EQU R.sub.1 R.sub.2 N--Alk--Q--(CH.sub.2).sub.n X(CH.sub.2).sub.m-1 CO.sub.2 H 
(XIX) 
and the appropriate diaminotriazole (XX) 
##STR21## 
in which R.sub.3 is hydrogen and R.sub.4 and R.sub.5 are both hydrogen or 
alkyl or in which R.sub.3 is other than hydrogen and R.sub.4 and R.sub.5 
are both alkyl. Suitable activated acid derivatives include acyl halides, 
mixed acid anhydrides, esters, for example alkyl esters or (1-alkyl 
2-pyridinyl) esters and products formed by reaction of the carboxylic acid 
with a coupling agent such as carbonyldiimidazole or a carbodiimide such 
as dicyclohexylcarbodiimide. 
The intermediate diaminotriazole (XX) in which R.sub.4 and R.sub.5 are both 
other than hydrogen may be prepared by reaction of the carbamoyl halide 
(XIII) with the aminoguanidine (XXI) 
##STR22## 
in a solvent such as benzene or acetonitrile. 
In a further asepct of the reduction of compounds of formula (XV), 
compounds of formula (I) in which R.sub.4 and R.sub.5 are other than the 
group .dbd.CR.sub.8 R.sub.9 may also be prepared by reduction of an imine 
(XXII) 
##STR23## 
in which R.sub.1, R.sub.2, Alk, Q, n, X, m, R.sub.3, R.sub.4 and R.sub.5 
are as defined in formula (I). Suitable reducing agents include metal 
hydrides such as alkali or alkaline earth metal borohydrides, e.g. sodium 
borohydride, in a solvent such as an alkanol, e.g. methanol or ethanol, or 
aluminum hydride or lithium aluminium hydride in a solvent such as 
tetrahydrofuran or dioxan. The imine (XXII) may also be reduced with 
hydrogen and a suitable metal catalyst such as platinum, in a solvent such 
as an alkanol, e.g. methanol or ethanol. 
The imine (XXII) may be formed by reaction of an aldehyde (XXIII) 
EQU R.sub.1 R.sub.2 N--Alk--Q--(CH.sub.2).sub.n X(CH.sub.2).sub.m-1 CHO (XXIII) 
with the diaminotriazole (XX) in a suitable solvent such as benzene, 
toluene, ethanol or methanol, preferably with heating optionally in the 
presence of an acid catalyst, e.g. hydrochloric acid or p-toluene 
sulphonic acid. 
In the above process it is sometimes unnecessary to isolate the imine 
(XXII). Thus, for example, treatment of a mixture of an aldehyde (XXIII) 
and a triazole (XX) in an appropriate solvent e.g. ethanol or methanol, 
with a suitable reducing agent, e.g. sodium borohydride, gives the 
compound of formula (I) directly. 
In another aspect of the reduction process described above compounds, of 
formula (I) in which R.sub.4 is --CHR.sub.8 R.sub.9 and R.sub.5 represents 
hydrogen can be prepared by the reduction of a compound of formula (XV) as 
defined above in which D" represents --N.dbd.CR.sub.8 R.sub.9. The 
reduction may conveniently be carried out with an alkali or alkaline earth 
metal borohydride such as sodium borohydride or with hydrogen and a metal 
catalyst such as platinum or palladium. Similarly compounds of formula (I) 
in which R.sub.4 and R.sub.5 are both alkenyl or alkyl optionally 
substituted by hydroxyl may be prepared by reacting a compound of formula 
(I) in which at least one of R.sub.4 and R.sub.5 are hydrogen with the 
appropriate aldehyde or ketone, followed by reduction by the procedure 
described above. 
In a further embodiment of the reduction process described above compounds 
of formula (I) in which R.sub.1 and/or R.sub.5 are other than hydrogen may 
be prepared by reduction of a compound of formula (XV) in which D 
represents the group R.sub.1.sup.a CONR.sub.2 Alk and/or the group D" 
represents the group --NR.sub.4 COR.sub.5.sup.1, where R.sub.1.sup.a and 
R.sub.5.sup.a have meanings such that under the conditions of the 
reduction the groups R.sub.1.sup.a CO and R.sub.5.sup.a CO are converted 
into the required groups R.sub.1 and R.sub.5. 
The reduction is preferably carried out with aluminium hydride or lithium 
aluminium hydride in a solvent such as dioxan or tetrahydrofuran. 
The compounds of formula (XV) in which D and/or D" have the meanings 
R.sub.1.sup.a CONR.sub.2 Alk or --NR.sub.4 COR.sub.5.sup.a may be prepared 
by treating a compound of formula (I) in which R.sub.1 and/or R.sub.5 
represent hydrogen with an activated derivative of the appropriate acid 
R.sub.1.sup.a CO.sub.2 H or R.sub.5.sup.a CO.sub.2 H. 
Compounds of formula (I) can be produced by reacting a compound of the 
formula (XXIV) 
EQU R.sub.1 R.sub.2 NAlKQE (XXIV) 
in which E represents (CH.sub.2).sub.n X(CH.sub.2).sub.m P or CH.sub.2 P', 
where P and P' are leaving groups, with a compound of the formula (XXV). 
##STR24## 
in which U represents hydrogen, HS(CH.sub.2).sub.m or HO(CH.sub.2)m 
Thus for example compounds of formula (I) may be prepared by reacting a 
compound of formula (XXVI) 
EQU R.sub.1 R.sub.2 N--Alk--Q--(CH.sub.2).sub.n X(CH.sub.2).sub.m P (XXVI) 
in which R.sub.1, R.sub.2, Alk, Q, n, X and m are as defined in formula (I) 
and P represents a leaving group such as mesyloxy or tosyloxy group, with 
the diaminotriazole (XXV) in which U represents hydrogen. The reaction is 
carried out in a suitable solvent such as dimethylformamide or 
acetonitrile. 
Compounds of formula (XXVI) in which P represents a mesyloxy or tosyloxy 
group may be prepared from the corresponding alcohol (i.e. the compound of 
formula (XXVI) in which P represents a hydroxyl group) by reaction with 
the appropriate sulphonyl chloride. Compounds of formula (XXVI) in which P 
represents a hydroxyl group may for example be prepared by reduction of 
the corresponding acid (XIX) or an ester thereof. 
As a further example of this reaction, compounds of formula (I) in which n 
is 1 and X is sulphur may be prepared by reacting a thiol (XXVII) 
##STR25## 
in which m, R.sub.3, R.sub.4 and R.sub.5 are as defined in formula (I), 
with a compound (XXVIII) 
EQU R.sub.1 R.sub.2 N--Alk--Q--CH.sub.2 P' (XXVIII) 
in which R.sub.1, R.sub.2, Alk and Q are as defined in formula (I) and P' 
represents a leaving group such as halogen a hydroxyl group or an acyloxy 
group, e.g. acetoxy. 
When P' is other than a hydroxyl group the reaction is carried out in an 
organic solvent such as dimethylformamide in the presence of a strong 
base, e.g. sodium hydride. When P' is a hydroxyl the reaction is 
preferably carried out in the presence of a mineral acid such as 
hydrochloric acid and preferably at a temperature of 0.degree. to 
80.degree. C. 
Compounds of formula (I) in which n is 1 and X is oxygen may similarly be 
prepared by reacting the compound (XXVIII) in which P' is a hydroxyl group 
with an aminoalcohol (XXIX) 
##STR26## 
The reaction is carried out in a solvent such as tetrahydrofuran in the 
presence of a strong acid such as methane sulphonic acid or hydrochloric 
acid. In the above process the reaction with (XXVIII) in which P' is 
hydroxyl is preferably carried out when Q represents a furan or 
substituted furan group. 
Compounds of formula (I) in which Q is other than benzene and Alk is 
methylene may be prepared by introducing a group R.sub.1 R.sub.2 NCH.sub.2 
into a compound of formula (XXX) 
##STR27## 
in which n, X, m, R.sub.3, R.sub.4 and R.sub.5 are as defined in formula 
(I). Thus a compound of formula (I) in which Q is a furan or substituted 
furan ring may be prepared by reacting a compound of formula (XXX) with 
formaldehyde and an amine R.sub.1 R.sub.2 NH or a salt thereof in which 
R.sub.1 and R.sub.2 are as defined in formula (I). The reaction may be 
carried out by reacting the amine salt with aqueous formaldehyde and the 
compound (XXX) or by refluxing the amine salt with paraformaldehyde and 
compound (XXX) in a solvent such as ethanol. 
Compounds of formula (I) in which Q is other than benzene, Alk is CH.sub.2 
and R.sub.1 and R.sub.2 and methyl may be prepared by reacting compounds 
of formula (XXX) with the compound of formula (XXXl) 
EQU (CH.sub.3).sub.2 N.sup..sym. =CH.sub.2 Cl.sup..crclbar. (XXXI) 
The reaction is carried out in a solvent such as acetonitrile at an 
elevated temperature e.g. reflux. The compounds of formula (XXX) may be 
prepared by methods analogous to those already described for the compounds 
of formula (I). 
Compounds of formula (I) in which the groups R.sub.4 and R.sub.5 together 
represent the group .dbd.CR.sub.8 R.sub.9 may be prepared from compounds 
of formula (I) in which R.sub.4 and R.sub.5 are both hydrogen by reaction 
with an aldehyde or ketone R.sub.8 R.sub.9 CO in a solvent such as 
benzene, ethanol, or methanol. The reaction is preferably carried out with 
heating, e.g. at reflux. 
Compounds of formula (I) in which R.sub.4 and R.sub.5 are both hydrogen can 
be converted into compounds of formula (I) in which R.sub.4 and R.sub.5 
are both methyl by reaction with formic acid and formaldehyde using the 
Eschweiler-Clarke procedure. 
Compounds of formula (I) can be prepared by reacting a compound of formula 
(XXXIII) or a compound of formula (XXXII; in which L" is a leaving group 
and can represent halogen e.g. bromine, acyloxy, e.g. acetoxy, or a 
quaternary ammonium group) with an amine R.sub.1 R.sub.2 NH or R.sub.4 
R.sub.5 NH in which R.sub.1, R.sub.2, R.sub.4 and R.sub.5 are as defined 
in formula (I). 
##STR28## 
The reaction of the compounds (XXXII) in which Alk, Q, n, X, m, R.sub.3, 
R.sub.4 and R.sub.5 are as defined in formula (I) and L" is halogen, with 
the amine R.sub.1 R.sub.2 NH can be carried out in an inert solvent such 
as acetonitrile, in the presence of a base e.g. potassium carbonate. 
Displacement of the chlorine atom in the compound of formula (XXXIII) may 
be carried out by heating with the appropriate amine at elevated 
temperatures. 
In a compound of formula (XXXII) where L" is a quaternary ammonium group 
the reaction with the amine R.sub.1 R.sub.2 NH may be carried out in a 
suitable solvent such as acetonitrile or an alkanol, e.g. ethanol, at a 
temperature of ambient to reflux; this reaction is particularly useful for 
preparing compounds in which Alk is CH.sub.2. 
The compounds of formula (XXXII) may be prepared by conventional methods 
for example from the corresponding alcohol (compound of formula (XXXII) 
where L" is hydroxy) or the corresponding tertiary amino compound 
(compound of formula (I) where R.sub.1 and R.sub.2 are other than 
hydrogen). 
The chloro-compound (XXXIII) can be prepared by treating the compound of 
formula (I) in which R.sub.4 and R.sub.5 are both hydrogen, with sodium 
nitrite in the presence of a mineral acid such as hydrochloric acid or 
sulphuric acid to give the diazonium salt (XXXIV) 
##STR29## 
in which A.sup..crclbar. is the anion of the acid used in the 
diazotisation. Reaction of the diazonium salt (XXXIV) with hydrochloric 
acid in the presence of an aqueous cuprous chloride solution, gives the 
required chloro-derivative (XXXIII). 
In some reactions in which a leaving group e.g. a quaternary ammonium group 
is displaced by an amine R.sub.1 R.sub.2 NH in order to insert the group 
R.sub.1 R.sub.2 N than cyclisation to form the triazole ring may occur. 
Thus compounds of formula (I) in which R.sub.4 and R.sub.5 are both 
hydrogen and Alk is CH.sub.2 can be prepared by reacting a compound of 
formula (XXXV) 
##STR30## 
where R.sup.a, R.sup.b, and R.sup.c are alkyl or aralkyl, Q, n, X, m, and 
R.sub.3 are as defined in formula (I) A is anion, e.g. halide and Z is a 
protecting group, e.g. benzylidene, with an amine of formula R.sub.1 
R.sub.2 NH in which R.sub.1 and R.sub.2 are as defined in formula (I) but 
are other than hydrogen. The compound of formula (XXXV) may be prepared by 
reacting a compound of formula (XXXVI) 
##STR31## 
with an alkyl or aralkyl halide, e.g. methyl iodide or benzyl iodide. 
In a process for the production of compounds of formula (I) where R.sub.1 
and R.sub.2 are hydrogen a compound of formula (XXXII) where L" is a 
quaternary ammonium group e.g. trimethylammonium, Alk is CH.sub.2 and Q, 
n, X, m, R.sub.3, R.sub.4 and R.sub.5 are as defined in formula (I) is 
heated with a phthalimide salt e.g. potassium phthalimide, in a solvent 
e.g. dimethylformamide at an elevated temperature e.g. 150.degree. C. to 
give the compounds of formula (XXXII) where L" is the group 
##STR32## 
The phthalimide group is cleaned by standard procedure described earlier 
e.g. with hydrazine. 
The compounds of formulae (III), (V) (XIV) (XI) (XVII) (XIX) and (XXVIII) 
may be prepared as described in German Offenlegungsschrifts Nos. 
2,734,070, 2,821,410 and 2,821,409 or by methods analogous to those 
described in these documents. The aldehydes of formula (XXIII) can be made 
by partial reduction of acids of formula (XIX). 
Where the product of any of the above processes is a free base and a salt 
is required, the salt may be formed in a conventional manner. Thus, for 
example, a generally convenient method of forming the salts is to mix 
appropriate quantities of the free base and the acid in an appropriate 
solvent(s), e.g. an alcohol such as ethanol or an ester such as ethyl 
acetate.

The invention is illustrated but not limited by the following Examples. 
PREATION 1 
N-Cyano-1-methyl-2-(phenylmethylene)hydrazinecarboximidothioic acid, methyl 
ester 
A mixture of cyanocarbonimidodithioic acid dimethyl ester (1.46 g) and 
benzaldehyde N-methyl hydrazone (1.34 g) in acetonitrile was heated under 
reflux for 50 hr. The reaction mixture was cooled to 25.degree. to give 
the title compound as colourless crystals, m.p. 132.degree.-133.degree. 
(0.73 g). 
T.l.c. silica gel, 0.25 mm thickness/ethyl acetate: light petroleum (b.p. 
60.degree.-80.degree.) 1:4, single spot Rf 0.35. 
Similarly prepared from benzaldehyde N-ethyl hydrazone (3 g) and 
cyanocarbonimidodithioic acid dimethyl ester (1.46 g) was 
N-cyano-1-ethyl-2-phthylmethylene)hydrazine carboximidothioic acid methyl 
ester (2.1 g) m.p. 138.degree.-9.degree.. 
PREATION 2 
3-[3-(1,3-Dioxolan-2-yl)phenoxy]propanamine 
A solution of 2-[3-(3-formylphenoxy)propyl]-1H-isoindole-1,3-(2H)-dione (90 
g) and p-toluenesulphonic acid, monohydrate (200 mg) in benzene (900 ml) 
and ethane-1,2-diol (25 g) was heated under reflux using a Dean-Stark 
separator for 8 h. The cooled solution was washed successively with sodium 
carbonate solution, water, sodium chloride solution, and evaporated in 
vacuo. The resulting oil was dissolved in tetrahydrofuran (1 liter) and 
stirred with hydrazine hydrate (50 ml) at room temperature for 24 hr. The 
mixture was diluted with ether and filtered. The filtrate was distilled to 
give the title compound as a colourless oil (55.2 g) b.p. 
134.degree.-6.degree. (0.7 mm). TLC silica; methanol:ammonia 80:1; Rf 0.4. 
N'-Cyano-N-[3-[3-(1,3-dioxolan-2-yl)phenoxy]propyl]-1-methyl-2-(phenylmethy 
lene)hydrazinecarboximidamide 
3-[3-(1,3,-Dioxolan-2-yl)phenoxy]propanamine (8.92 g) and 
N-cyano-1-methyl-2-(phenylmethylene) hydrazinecarboximidothioic acid 
methyl ester (9.28 g) were heated under water-pump vacuum at 80.degree. 
for 4 h to yield the title compound, a pale yellow glass (16.03 g). TLC 
silica; ethyl acetate:cyclohexane 1:1; Rf 0.2 NMR (CDCl.sub.3) 2.3-2.2 m 
(10H); 4.36 s (1H), 5.8-6.1 m (8H); 6.55 s (3H); 7.83 m (2H). 
PREATION 3 
3-(1-Piperidinylmethyl)benzoic acid, methyl ester 
A mixture of piperidine (25 ml) and 3-(bromomethyl)benzoic acid, methyl 
ester (20 g) in toluene (600 ml) was stirred at room temperature for 4 h. 
The white precipitate was removed by filtration and the filtrate was 
distilled to give the title compound as a colourless oil (17.56 g) b.p. 
110.degree. (10.sup.-1 mm). TLC silica; ether; Rf 0.7. 
3-(1-Piperidinylmethyl)benzenemethanol 
A mixture of 3-(1-piperidinylmethyl)benzoic acid, methyl ester (17.56 g) 
and lithium aluminium hydride (2.68 g) in tetrahydrofuran (500 ml) was 
stirred at room temperature for 30 h and quenched with water. The solid 
was removed by filtration and the filtrate distilled to give the title 
compound as a colourless oil (11.1 g) b.p. 135.degree. (10.sup.-1 mm). TLC 
silica; ether; Rf 0.2. 
2-[[[3-(1-Piperidinylmethyl)phenyl]methyl]thio]ethanamine 
A mixture of 3-(1-piperidinylmethyl)benzenemethanol (10.8 g) and cysteamine 
hydrochloride (6.48 g) in concentrated hydrochloric acid (25 ml) was 
heated at 100.degree. for 3 h. The cooled mixture was added to ether (500 
ml) and treated with an excess of sodium carbonate. The organic solution 
was filtered and distilled to give the title compound as an oil (9.51 g) 
b.p. 175.degree. (6.times.10.sup.-2 mm). TLC silica; ethyl 
acetate:water:isopropanol:0.88 ammonia 25:8:15:2; Rf 0.7. 
PREATION 4 
2-[3-[4-[2-(Dimethylamino)ethyl]phenoxy]propyl]-1H-isoindole-1,3-(2H)-dione 
A mixture of 4-[2-(dimethylamino)ethyl]phenol (4.13 g) and sodium hydride 
(0.67 g) in dimethylformamide was stirred at room temperature for 24 h. 
N-(3-Bromopropyl) phthalimide (6.7 g) was added at 0.degree. and stirring 
was continued for 24 h. The solution was treated with water and extracted 
with ether. Evaporation of the solvent gave the title compound as a white 
solid which was recrystallised from light petroleum (b.p. 
60.degree.-80.degree.) 2.3 g) m.p. 81.degree.-82.degree.. TLC silica; 
ethyl acetate:water:isopropanol:0.88 ammonia 25:8:15:2; Rf 0.45. 
Similarly prepared from 4-[3-(dimethylamino)propyl]phenol (7.2 g) sodium 
hydride (1.06 g) and N-(3-bromopropyl)phthalimide (10.7 g) was 
2-[3-[4-[3-(dimethylamino)propyl]phenoxy]propyl]-1H-isoindole-1,3-(2H)-dio 
ne (5.2 g) m.p. 67.degree.-67.5.degree.. TLC Silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.5. 
4-[3-Aminopropoxy]-N,N-dimethylbenzeneethanamine 
2-[3-[4-[2-(Dimethylamino)ethyl]phenoxy]propyl]-1H-isoindole-1,3-(2H)-dione 
(2.1 g) and hydrazine hydrate (1.2 ml) were heated at reflux in ethanol 
for 4 h. The solvent was evaporated and the residue was distilled to give 
the title compound as a clear yellow oil b.p. 170.degree. (0.1 mm). TLC 
silica; ethyl acetate:water:isopropanol:0.88 ammonia 25:8:15:2; Rf 0.35. 
Similarly prepared from 
2-[3-[4-[3-(dimethylamino)propyl]phenoxy]propyl]-1H-isoindole-1,3-(2H)-dio 
ne (4.4 g) and hydrazine hydrate (3 ml) was 
4-(3-aminopropoxy)-N,N-dimethylbenzenepropanamine (2 g) b.p. 
150.degree./0.06 mm. TLC silica, ethyl acetate/water/isopropanol/0.88 
ammonia 25:8:15:2, Rf 0.2. 
PREATION 5 
3-[3-[1-Piperidinylmethyl]phenoxy]propanamine 
2-[3-[3-Formylphenoxy]propyl]-1H-isoindole-1,3-dione (50 g) and piperidine 
(20.7 g) in ethyl acetate (750 ml) were hydrogenated over 10% 
palladium/carbon catalyst. The catalyst was removed by filtration and the 
solvent evaporated and hydrazine hydrate (40 ml) was added to an ethanolic 
solution of the residue at 25.degree.. After 67 hr the reaction mixture 
was diluted with ether, filtered and the filtrate was distilled to give 
the title compound as a colourless oil (31.05 g) b.p. 
154.degree.-8.degree./0.15 mm. TLC silica, methanol/0.88 ammonia 80:1, Rf 
0.2. 
The following compounds were similarly prepared from the appropriate 
phthalimide (A) and the corresponding amine. 
(ii) A (50 g) and hexamethyleneimine (25 g) gave 
3-[3-[1-hexamethyleneiminylmethyl]phenoxy]propanamine (19.4 g) b.p. 
170.degree.-4.degree./0.25 mm. TLC silica, methanol/0.88 ammonia 80:1, Rf 
0.2. 
(iii) A (5 g) and 2,2,2-trifluoroethylamine (3.21 g) gave 
3-[3-aminopropoxy]-N-(2,2,2-trifluoroethyl)benzenemethanamine (1.5 g) b.p. 
130.degree./0.1 mm. TLC silica, ethyl acetate/water/isopropanol/0.88 
ammonia 25:8:15:2, Rf 0.57. 
(iv) A (25 g) and N-methylbutylamine (20 ml) gave 
3-[3-aminopropoxy]-N-butyl-N-methylbenzenemethanamine (1.84 g) b.p. 
135.degree./0.1 mm. TLC silica, ethyl acetate/water/isopropanol/0.88 
ammonia 25:8:15:2, Rf 0.36. 
(v) A (15.5 g) and piperidine (15 ml) gave 
3-[4-(1-piperidinylmethyl)phenoxy]propanamine (4.92 g) b.p. 
200.degree./0.1 mm. TLC silica, methanol/0.88 ammonia 80:1, Rf 0.2. 
PREATION 6 
3-(1-Piperidinylmethyl)phenol 
3-Hydroxybenzaldehyde (15 g) and piperidine (15 ml) in ethanol (500 ml) 
were hydrogenated over 10% palladium/carbon catalyst. The catalyst was 
removed by filtration and the solvent was evaporated off. The residue was 
triturated with light petroleum (b.p. 60.degree.-80.degree.) and the 
resulting solid was recrystallised from acetonitrile to give the title 
compound as a buff coloured solid (8.7 g) m.p. 134.degree.-7.degree.. TLC 
silica, methanol, Rf 0.56. 
4-[3-(1-Piperidinylmethyl)phenoxy]butanamine 
A mixture of 3-(1-piperidinylmethyl)phenol (8.7 g) and sodium hydride (1.2 
g) in dimethylformamide (60 ml) was stirred at 25.degree. during 3 h. 
N-(4-Bromobutyl) phthalimide (12.8 g) was added and the mixture was 
stirred at 25.degree. during 20 h then at 65.degree. for 3 h. The reaction 
mixture was poured onto water and extracted with ethyl acetate. The 
solvent was concentrated and the crystalline impurity was removed by 
filtration. The filtrate was evaporated in vacuo and the residue was 
dissolved in ethanol and heated at reflux with hydrazine hydrate (2.5 ml) 
for 3 h. The mixture was filtered and the filtrate distilled to give the 
title compound as a colourless oil (4.1 g) b.p. 140.degree./0.1 mm TLC 
silica, ethyl acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.32. 
PREATION 7 
5-[(4-Aminobutoxy)methyl]-N,N-dimethyl-2-furanmethanamine 
A mixture of methanesulphonic acid (86 g), 
5-[(dimethylamino)methyl]-2-furanmethanol (15.5 g) and 4-aminobutanol 
(17.8 g) in dry tetrahydrofuran was heated at 100.degree. for 11/2 h. 
Excess sodium carbonate was added to the cooled solution, the suspension 
was filtered and the filtrate was evaporated to give a red oil which was 
dissolved in water and extracted with ether. The extract was distilled to 
give the title compound as an oil (6.6 g) b.p. 100.degree.-110.degree., 
0.08 mm. TLC silica, methanol/ammonia 0.88 80:1, Rf 0.3. 
PREATION 8 
2-[3-[4-Formylphenoxy]propyl]-1H-isoindole-1,3-dione 
4-Hydroxybenzaldehyde (24.4 g) and sodium hydride (4.8 g) in dry 
dimethylformamide (400 ml) were stirred at room temperature for 3 h. 
N-(3-Bromopropyl)phthalimide (55.0 g) was added and the reaction was 
stirred for a further 5 h. The mixture was poured onto ice and the 
resulting white solid was recrystallised from a mixture of dichloromethane 
and cyclohexane to yield the title compound (42.2 g) m.p. 
120.degree.-1.degree.. TLC silica, ethyl acetate, Rf 0.7. 
PREATION 9 
3-[3-[[[(Cyanimino)[1-methyl-2-(phenylmethylene) 
hydrazino]]methyl]amino]propoxy]-N,N,N-trimethylbenzenemethanium iodide 
3-(3-Aminopropoxy)-N,N-dimethylbenzenemethanamine (2.2 g) and 
N-cyano-1-methyl-2-(phenylmethylene) hydrazine carboximidothioic acid 
methyl ester (2.52 g) were heated together at 100.degree. for 2 h to give 
a red oil which was dissolved in acetone and treated with methyl iodide 
(1.7 g) at room temperature. After 2 h solvent was removed to give the 
title compound as a white solid which was washed with ether (5.58 g). TLC 
alumina, aqueous ammonia (1.4%) Rf 0.45. NMR (DMSO d.sub.6) 1.7 t (1H); 
1.9 s (1H); 1.9-2.2 s (2H); 2.5-2.65 m (4H); 2.7-2.9 m (3H); 5.37 s (2H); 
5.8 t (2H); 6.15 q (2H); 6.45 s (3H); 6.83 s (9H); 7.80 m (2H). 
PREATION 10 
3-[3-[[3-Amino-1-methyl- 
1H-1,2,4-triazol-5-yl]amino]propoxy]-N,N,N-trimethylbenzenemethanium 
iodide 
Methyl iodide (1.9 g) and 1-methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (3.9 g) in acetonitrile were stirred at room temperature for 45 min. The 
suspension was heated at 100.degree. for 15 min to give the title compound 
as a yellow solid which was collected and washed with acetonitrile (4.6 g) 
m.p. 178.degree.-179.degree.. 
PREATION 11 
Following the method of Preparation 5: 
(i) A (10 g) and 4-hydroxypiperidine (6.54 g) gave 
3-[3-[1-(4-hydroxypiperidinyl)methyl]phenoxy] propanamine (3.6 g) b.p. 
180.degree./0.1 mm. TLC silica, ethyl acetate/water/isopropanol/0.88 
ammonia 25:8:15:2, Rf 0.2. 
(ii) A (16.34 g) and diethylamine (15 ml) gave 
3-[3-aminopropoxy]-N,N-diethylbenzene methanamine (2.63 g) b.p. 
130.degree./0.1 mm. TLC silica, ethyl acetate/water/isopropanol/0.88 
ammonia 25:8:15:2, Rf. 0.4. 
PREATION 12 
1-Methyl-N.sup.5 -(3-hydroxypropyl)-1H-1,2,4-triazole-3,5-diamine 
N'-Cyano-N-[1-(3-hydroxypropyl)]-N"-[(phenylmethylene) 
amino]-N"-methyl-guanidine 
A solution of 3-aminopropanol (3 g) and N-cyano-1- 
methyl-2-(phenylmethylene)hydrazine carboximidothioic acid, methyl ester 
(9.8 g) in acetone (50 ml) was heated under reflux for 6 h. The reaction 
was cooled and the precipitate that formed was filtered off and 
recrystallised from ethyl acetate to give the title compound as a white 
solid (3.9 g) m.p. 126.degree.-7.degree.. TLC silica, ethyl acetate, Rf 
0.35. 
1-Methyl-N.sup.5 -(3-hydroxypropyl)-1H-1,2,4-triazole-3,5-diamine 
A solution of 
N'-cyano-N-[1-(3-hydroxypropyl)]-N"-[(phenylmethylene)amino]-N"-methyl-gua 
nidine (3.9 g) and 2 N hydrochloric acid (20 ml) in acetone (100 ml) was 
stirred at 25.degree. for 18 h. Sodium carbonate was added and the solvent 
removed in vacuo. The residue was crystallised from acetonitrile to give 
the title compound as a white solid (2.2 g) m.p. 139.degree.-140.degree.. 
TLC silica, ethyl acetate/isopropanol/water/0.88 ammonia 25:8:15:2, Rf 
0.5. 
EXAMPLE 1 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
N'-Cyano-N-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]carbamimidothioic 
acid, methyl ester 
A mixture of 3-(3-aminopropoxy)-N,N-dimethylbenzenemethanamine (5 g) and 
cyanocarbonimidodithioic acid, dimethyl ester (3.5 g) in ether was stirred 
at 25.degree. for 3 hours. The product (6.7 g) was filtered off and washed 
with ether, m.p. 118.degree.-9.degree.. 
Similarly prepared from 3-[3-(1-piperidinylmethyl) phenoxy]propanamine] (10 
g) and cyanocarbonimidodithioic acid, dimethyl ester (5.84 g) was 
N'-cyano-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]carbamimidothioic 
acid methyl ester (11.5 g) m.p. 89.degree.-90.degree.. 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
N-Cyano-N-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]carbamimidothioic 
acid methyl ester (1.5 g) and N-methylhydrazine (1.2 g) in 
dimethylformamide (15 ml) were heated at 40.degree. for 24 hours. The 
solvent was removed, and the residue was triturated with ether to yield 
the title compound as a white solid (1.0 g) m.p. 95.degree.-96.5.degree.. 
T.l.c. silica gel, 0.25 mm thickness, methanol: 0.880 ammonia 80:1, single 
spot Rf 0.4. 
EXAMPLE 2 
1-Methyl-N.sup.5 
-[3-[3[(dimethylamino)methyl]phenoxy]-propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
A mixture of 
N-cyano-1-methyl-2-(phenylmethylene)-hydrazine-carboximidothioic acid 
methyl ester (166 mg) and 
3-(3-aminopropoxy)-N,N-dimethylbenzenemethanamine (104 mg) was heated at 
45.degree. under a reduced pressure of 20 mm of mercury for 3 hr. Acetone 
was added, and the resulting solution treated with dilute hydrochloric 
acid for 1 hour at room temperature. The mixture was diluted with water, 
washed with ether, basified with excess sodium carbonate and extracted 
with ethyl acetate. Evaporation of the ethyl acetate extracts gave an oil 
which crystallised from ethyl acetate/light petroleum b.p. 
60.degree.-80.degree. to give the title compound as colourless crystals 
m.p. 95.degree.-96.5.degree. (87 mg). 
T.l.c. silica gel, 0.25 mm thickness, methanol: 0.88 ammonia 80:1, single 
spot Rf 0.4. 
The following compounds were similarly prepared from the appropriate 
diamine and the corresponding N-cyano-1-alkyl-2-(phenylmethylene)hydrazine 
carboximidothioic acid methyl ester (A). 
(ii) Diamine (1 g) and A (1.05 g) gave 1-methyl-N.sup.5 
-[3-[4-[2-(dimethylamino)ethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diami 
ne (0.47 g) m.p. 125.degree.-126.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.56. 
(ii) Diamine (0.5 g) and A (0.5 g) gave 1-ethyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(0.48 g) m.p. 116.5.degree.-118.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.6. 
EXAMPLE 3 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-2,5-diamin 
e 
N-Cyano-1-methylhydrazinecarboximidothioic acid, methyl ester 
A mixture of methyl hydrazine (0.48 ml) and cyanocarbonimidodithioic acid 
methyl ester (1.3 g) in acetonitrile was stirred at 25.degree. for 16 
hours. The resulting solution was evaporated to a gum which was 
crystallised from acetonitrile/ether to give the title compound as 
colourless granules (210 mg) m.p. 69.degree.-71.degree.. 
T.l.c. silica gel 0.25 mm thickness, methanol; single spot Rf 0.7. 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
A mixture of N-cyano-1-methylhydrazinecarboximidothioic acid methyl ester 
(200 mg) and 3-(3-aminopropoxy)-N,N-dimethylbenzenemethanamine (289 mg) 
was heated at 40.degree. under a reduced pressure of 20 mm of mercury for 
4 hours. The reaction mixture was cooled, triturated with ether and the 
resulting solid recrystallised from ethyl acetate to give the title 
compound as colourless crystals (246 mg) m.p. 95.degree.-96.5.degree.. 
T.l.c. silica gel 0.25 mm thickness, methanol: 0.880 ammonia 80:1, single 
spot Rf 0.4. 
EXAMPLE 4 
1-Methyl-N.sup.5 
-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-1H-1,2,4-triaz 
ole-3,5-diamine oxalate 
N'-Cyano-N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-N"-[( 
phenylmethylene)amino]-N"-methylguanidine 
A mixture of N-cyano-1-methyl-2-(phenylmethylene)-hydrazine 
carboximidothioic acid methyl ester (4.64 g) and 
2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethanamine (4.28 g) was 
heated at 40.degree. under a reduced pressure of 20 mm of mercury for 3 
hr. The resulting solid was crystallised from ethyl acetate/light 
petroleum (b.p. 60.degree.-80.degree. ) to give the title compound (7.96 
g) as white fibrous crystals, m.p. 94.degree.-97.degree.. TLC silica gel, 
0.25 mm thickness, methanol: 0.88 ammonia 80:1, single spot Rf 0.7. 
1-Methyl-N.sup.5 
-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-1H-1,2,4-triaz 
ole-3,5-diamine, oxalate 
A solution of N'-cyano-N-[2-[[[5-(dimethylamino) 
methyl-2-furanyl]methyl]thio]ethyl]-N"-[(phenylmethylene)amino]-N"-methyl- 
guanidine (3.98 g) in acetone was treated with dilute hydrochloric acid for 
1 hour at room temperature. The resulting mixture was diluted with water, 
evaporated free of acetone, and washed with ether. The aqueous mixture was 
basified with excess sodium carbonate and extracted with ethyl acetate. 
Evaporation of the ethyl acetate extracts gave a gum which was dissolved 
in ethanol and treated with an excess of a solution of oxalic acid in 
ethanol to give the title compound (3.69 g) as small white prisms m.p. 
163.degree.-164.degree. (dec). TLC silic gel, 0.25 mm thickness, 
methanol:0.88 ammonia 80:1, single spot Rf 0.4. 
EXAMPLE 5 
N.sup.5 
-[2-[[[5-(Dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-1H-1,2,4-triaz 
ole-3,5-diamine 
N-Cyano-N'-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]carbam 
imidothioic acid, methyl ester 
2-[[[5-(Dimethylamino)methyl-2-furanyl]methyl]thio]ethanamine (1.07 g) was 
added to a solution of cyanocarbonimidodithioic acid, dimethyl ester (0.73 
g) in ether, and stirred overnight. The crystalline solid which formed was 
filtered off, washed with ether and dried to give 
N-cyano-N'-[2-[[[5-(dimethylamino)-methyl-2-furanyl]methyl]thio]ethyl]carb 
amimidothioic acid, methyl ester (1.14 g) m.p. 78.degree.-79.degree.. 
N.sup.5 
-[2-[[[5-(Dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-1H-1,2,4-triaz 
ole-3,5-diamine 
Hydrazine hydrate (3.5 ml) was added to a solution of 
N-cyano-N'-[2-[[[5-(dimethylamino) 
methyl-2-furanyl]methyl]thio]ethyl]carbamimidothioic acid, methyl ester 
(5.47 g) in ethanol (40 ml). After stirring for 3 days at room temperature 
the solvent was removed and the residual oil crystallised from water to 
give the title compound as white needles (2.95 g) m.p. 
76.degree.-78.5.degree.. 
EXAMPLE 6 
N.sup.5 
-[3-[3-[(Dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
N'-Cyano-N-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-carbamimidothioic 
acid, methyl ester (1.0 g) and hydrazine hydrate (825 mg) were stirred at 
25.degree. for 3 days in ethanol. The solvent was removed and the residue 
crystallised from water to give a white solid (870 mg) m.p. 
92.degree.-3.degree.. 
(ii) Similarly prepared from 
N'-cyano-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-carbamimidothioic 
acid, methyl ester (14.1 g) and hydrazine hydrate (10 ml) was N.sup.3 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(10.4 g) m.p. 100.degree.-101.5.degree.. TLC silica; ethyl 
acetate:water:isopropanol:0.088 ammonia 25:8:15:2; Rf 0.4. 
EXAMPLE 7 
1-Methyl-N.sup.5 
-[3-[3-[1-pyrrolidinylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A mixture of 3-[3-[1-pyrrolidinylmethyl]phenoxy]propanamine (0.97 g) and 
N-cyano-1-methyl-2-(phenylmethylene)hydrazine carboximidothioic acid 
methyl ester (0.97 g) was heated at 70.degree. for 8 hr under a reduced 
pressure of 20 mm of mercury. Acetone was added and the solution was 
treated with hydrochloric acid at room temperature for one hour, washed 
with ether, basified with sodium carbonate and extracted with ethyl 
acetate. Evaporation of the ethyl acetate extracts gave a thick oil which 
crystallised from ethyl acetate/light petroleum (b.p. 
60.degree.-80.degree. ) to give the title compound as a white solid (0.2 
g). TLC; silica/methanol/0.88 ammonia 80:1) Rf 0.5, m.p. 
95.degree.-95.5.degree.. 
The following compounds were similarly prepared from the corresponding 
diamine and the corresponding N-cyano-1-alkyl-2-(phenylmethylene)hydrazine 
carboximidothioic acid methyl ester (A). 
(ii) Diamine (1.7 g) and A (2 g) gave N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1-ethyl-1H-1,2,4-triazole-3, 
5-diamine (0.22 g) m.p. 104.degree.-105.degree.. TLC Silica, methanol:0.88 
ammonia 80:1, Rf 0.53. 
(iii) Diamine (0.25 g) and A (0.23 g) gave 1-methyl-N.sup.5 
-[2-[[[5-[1-pyrrolidinylmethyl]-2-thienyl]methyl]thio]ethyl]-1H-1,2,4-tria 
zole-3,5-diamine (0.13 g), m.p. 99.5.degree.-104.5.degree.. TLC silica, 
ethyl acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.6. 
(iv) Diamine (4.9 g) and A (4.33 g) gave 1-methyl-N.sup.5 
-[3-[3-[1-hexamethylene 
iminylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine (6.82 g) m.p. 
106.degree.-7.degree.. TLC silica, methanol/0.88 ammonia 80:1, Rf 0.5. 
(v) Diamine (0.42 g) and A (0.46 g) gave 1-methyl-N.sup.5 
-[4-[2-(dimethylamino)methyl-5-thienyl]butyl]-1H-1,2,4-triazole-3,5-diamin 
e (0.18 g) b.p. 190.degree. (0.05 mm). TLC silica; ethyl 
acetate:water:isopropanol:0.88 ammonia 25:8:15:2; Rf 0.5. 
(vi) Diamine (0.8 g) and A (0.8 g) gave 1-methyl-N.sup.5 
-[2-[[[5-(dimethylamino)methyl-4-methyl-2-furanyl]methyl]thio]ethyl]-1H-1, 
2,4-triazole-3,5-diamine (0.65 g). TLC silica; methanol:0.88 ammonia 79:1; 
Rf 0.4. NMR (CDCl.sub.3) 4.01 s (1H); 5.40 t (1H); 5.06 brs (2H); 6.32 s 
(2H); 6.56 q; 6.60 s and 6.65 s (7H); 7.20 m (2H); 7.76 s (6H); 8.02 s 
(3H). 
(vii) Diamine (1.54 g) and A (1.16 g) gave 1-methyl-N.sup.5 
-[[[5-(dimethylamino)methyl-2-furanyl]methoxy]propyl]-1H-1,2,4-triazole-3, 
5-diamine (0.52 g). TLC silica; methanol:0.88 ammonia 79:1, Rf 0.5. NMR 
(CDCl.sub.3) 3.75 d (1H); 3.86 d (1H); 5.20 t (1H); 5.58 s (2H); 6.00 brs 
(2H); 6.40 t (2H); 6.60 s; 6.62 q and 6.73 s (7H); 7.76 s (6H); 8.12 m 
(2H). 
(viii) Diamine (0.9 g) and A (0.8 g) gave 1-methyl-N.sup.5 
-[2-[[[5-(dimethylamino)methyl-4-(1-methyl)ethyl-2-furanyl]methyl]thio]eth 
yl]-1H-1,2,4-triazole-3,5-diamine (0.54 g) m.p. 76.degree.-8.degree.. TLC 
silica; methanol; 0.88 ammonia 79:1; Rf 0.3. 
(ix) Diamine (3 g) and A (2.63 g) gave 1-methyl-N.sup.5 
-[2-[[[3-(1-piperidinylmethyl)phenyl]methyl]thio]ethyl]-1H-1,2,4-triazole- 
3,5-diamine (0.78 g) m.p. 92.degree.-93.degree.. TLC silica; ethyl 
acetate:water:isopropanol:0.88 ammonia 25:8:15:2; Rf 0.7. 
(x) 2-[[[2-[1-Piperidinylmethyl]-5-furanyl]methyl]thio]ethanamine (2.54 g) 
and A (2.32 g) gave 1-methyl-N.sup.5 
-[2-[[[2-[1-piperidinylmethyl]-5-furanyl]methyl]thio]ethyl]-1H-1,2,4-triaz 
ole-3,5-diamine (3.1 g) b.p. 250.degree. (0.08 mm). TLC silica; ethyl 
acetate: water:isopropanol:0.88 ammonia 25:8:15:2; Rf 0.6. 
(xi) Diamine (0.47 g) and A (0.46 g) gave 1-methyl-N.sup.5 -[3-[4-[3- 
dimethylamino)propyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine (0.36 
g) m.p. 111.5.degree.-113.5.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.3. 
(xii) Diamine (2.3 g) and A (2.04 g) gave 1-methyl-N.sup.5 
-[3-[3-[(2,2,2-trifluoroethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazol 
e-3,5-diamine (1.58 g) m.p. 62.degree.-64.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.55. 
(xiii) Diamine (1.8 g) and A (1.67 g) gave 1-methyl-N.sup.5 
-[3-[3-[(butylmethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-dia 
mine (1.25 g). TLC silica, ethyl acetate/water/isopropanol/0.88 ammonia 
25:8:15:2, Rf 0.47. NMR (CDCl.sub.3) 2.77 t, 1H; 3.0-3.33, m, 3H; 5.52 t 
(1H); 5.6-6.2 brs, (2H); 5.9, t (2H); 6.47 q (2H); 6.52 s (3H); 6.61, s 
(2H); 7.63 m (2H); 7.83 s (3H); 7.93 m (2H); 8.3-8.9, m (4H); 9.10, m 
(3H). 
(xiv) Diamine (2.0 g) and A (1.8 g) gave 1-methyl-N.sup.5 
-[4-[3-(1-piperidinylmethyl)phenoxy]butyl]-1H-1,2,4-triazole-3,5-diamine 
(0.67 g) m.p. 82.degree.-82.5.degree.. TLC silica; ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.42. 
(xv) Diamine (0.46 g) and A (0.37 g) gave 1-methyl-N.sup.5 
-[2-[[4-bromo-5-(dimethylamino)methyl-2-furanylmethyl]thio]ethyl]-1H-1,2,4 
-triazole-3,5-diamine (0.6 g) NMR (CDCl.sub.3) 3.75 s (1H)l; 5.6 t (1H); 
6.15 brs (2H); 6.3 s (2H); 6.53 s (2H); 6.6 s (3H); ca. 6.6 t (2H); 7.2 t 
(2H); 7.73 s (6H); IR (CHBr.sub.3) 3480, 3380, 3430, 1548, 1010, 840 
cm.sup.-1. 
(xvi) Diamine (0.5 g) and A (0.46 g) gave 1-methyl-N.sup.5 
-[2-[[4-methoxymethyl-5-[(dimethylamino)methyl]-2-furanylmethyl]thio]ethyl 
]-1H-1,2,4-triazole-3,5-diamine (0.45 g). NMR (CDCl.sub.3) 3.78 s (1H); 
5.73 s (2H); 5.55 t (1H); 6.15 brs (2H); 6.15 s (2H); 6.4-6.7 3s t (10H); 
7.22 t (2H); 7.77 s (6H); IR (CHBr.sub.3) 3460, 3380, 2770, 2815, 1582, 
1548, 1075, 840 cm.sup.-1. 
(xvii) Diamine (1.8 g) and A (1.74 g) gave 1-methyl-N.sup.5 
-[2-[[5-[(dimethylamino)methyl]-2-furanyl]methoxy]ethyl]-1H-1,2,4-triazole 
-3,5-diamine (1.55 g) m.p. (oxalate salt) 131.degree.-133.degree.. TLC 
silica, methanol/0.88 ammonia Rf 0.5. 
(xviii) Diamine (1.24 g) and A (1.16 g) gave 1-methyl-N.sup.5 
-[3-[4-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(1.26 g) m.p. 104.degree.-105.degree.. TLC silica, methanol/0.88 ammonia 
80:1, Rf 0.5. 
EXAMPLE 8 
1-Methyl-N.sup.5 
-[3-[3-[1-pyrrolidinylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
N'-Cyano-N-[3-[3-(1-pyrrolidinylmethyl)phenoxy]propyl]carbamimidothioic 
acid, methyl ester 
A solution of N-cyano-carbonimidodithioic acid dimethyl ester (5 g) in 
ethyl acetate (50 ml) was added to a solution of 
3-[3-(1-pyrrolidinylmethyl)phenoxy]propanamine in ethyl acetate (60 ml). 
The reaction mixture was stirred at room temperature for 1 hr to give the 
title compound as an off-white solid m.p. 107.degree.-108.5.degree. (7.45 
g). TLC silica; ethyl acetate: isopropanol:water:0.88 ammonia (25:15:8:2) 
single spot Rf 0.7. 
1-Methyl-N.sup.5 
-[3-[3-(1-pyrrolidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
Methyl hydrazine (6.9 g) and dry dimethylformamide (10.95 g) were heated at 
reflux in toluene for 1 hr. 
N'-Cyano-N-[3-[3-(1-pyrrolidinylmethyl)phenoxy]propyl]carbamimidothioic 
acid, methyl ester (10 g) was then added and the mixture heated at reflux 
for 5 hr. Evaporation of the solvent gave the title compound as a yellow 
oil which was converted to the fumarate salt in ethanol. The title 
compound was regenerated as the free base with aqueous sodium carbonate, 
and extracted into ethyl acetate. Evaporation of the solvent and 
trituration of the residue with light petroleum (b.p. 
60.degree.-80.degree.) gave the title compound as a white solid (3.4 g) 
m.p. 95.degree.-95.5.degree.. TLC silica; methanol:0.88 ammonia (80:1) 
single spot Rf 0.5. 
EXAMPLE 9 
1-Methyl-N.sup.3 -dimethyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (1.1 g) was added portionwise to 98% formic acid (0.85 ml) at 5.degree.. 
Formaldehyde solution (37%) was then added and the reaction mixture heated 
to 100.degree.. After 12 hr the reaction was cooled, basified with 
potassium carbonate, and extracted with ethyl acetate. Distillation of the 
organic extract gave the title compound as a colourless oil (1.03 g) b.p. 
180.degree. (0.03 mm). TLC silica; ethyl acetate:isopropanol:water:0.88 
ammonia (25:15:8:2) Rf 0.54. 
Similarly prepared from 1-methyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(1.0 g) was 1-methyl-N.sup.3 -dimethyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(0.99 g) b.p. 223.degree./0.04 mm. TLC silica, methanol/0.88 ammonia 80:1, 
Rf 0.55. 
EXAMPLE 10 
(i) 1-Methyl-N.sup.3 -phenylmethylene-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
A mixture of 1-methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (6.08 g) and benzaldehyde (2.4 g) in dry benzene was heated under reflux 
during 12 hr in a Dean & Stark apparatus. The solvent was removed and the 
residue purified by column chromatography on silica using methanol to give 
the title compound as a yellow oil (7.4 g). TLC silica; methanol: ammonia 
(80:1) Rf 0.43. NMR (CDCl.sub.3) 0.85 s (1H); 2.05 m (2H); 2.5-3.0 m (4H); 
3.0-3.3 m (3H); 5.35 t (1H); 5.88 t (2H); 6.39 q (2H); 6.42 s (3H); 6.62 s 
(2H); 7.77 s (6H); 7.83 m (2H). 
The following compounds were similarly prepared from the corresponding 
aldehyde and 1-methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e, (A). 
(ii) 3-Pyridinecarboxaldehyde (0.4 g) and (A) (1.0 g) gave 1-methyl-N.sup.3 
-(3-pyridinylmethylene)-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (1.23 g) m.p. 92.degree.-3.degree.. TLC Silica: methanol:ammonia (80:1) 
Rf 0.4. 
(iii) 4-Pyridinecarboxaldehyde (0.4 g) and (A) (1.0 g) gave 
1-methyl-N.sup.3 -(4-pyridinylmethylene)-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (1.12 g) m.p. 127.degree.-8.degree.. TLC silica; methanol:ammonia (80:1) 
Rf 0.4. 
EXAMPLE 11 
(i) 1-Methyl-N.sup.3 -phenylmethyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
A mixture of 1-methyl-N.sup.3 -phenylmethylene-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (2.0 g) and sodium borohydride (0.95 g) in methanol was stirred at 
25.degree. for 12 hr. The mixture was poured onto water and extracted with 
ethyl acetate. The organic extract was washed with ethyl acetate. The 
organic extract was washed with brine and distilled to give the title 
compound as a pale yellow oil (1.4 g) b.p. 180.degree. (0.04 mm). TLC 
silica; methanol:ammonia (80:1) Rf 0.7. 
The following compounds were similarly prepared from the corresponding 
imine and sodium borohydride. (ii) The 3-Pyridinylimine of Example 10(ii) 
(0.56 g) and sodium borohydride (0.075 g) gave 1-methyl-N.sup.3 
-(3-pyridinylmethyl)-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (0.43 g). TLC silica; methanol:ammonia (80:1) Rf 0.4. NMR (CDCl.sub.3) 
1.41 d (1H); 1.58 dd (1H); 2.30 dd (1H); 2.8 m (2H); 3-3.4 m (3H); 5.55 m 
(1H); 5.61 s (2H); 5.92 t (2H); 6.49 m (2H); 6.6 s (5H); 7.33 m (1H); 7.76 
s (6H); 7.6-8.2 m (2H). 
(iii) The 4-Pyridinylimine of Example 10 (iii) (0.5 g) and sodium 
borohydride (0.075 g) gave 1-methyl-N.sup.3 -(4-pyridinylmethyl)-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (0.4 g) m.p. 110.degree.-111.degree.. TLC silica; methanol:ammonia (80:1) 
Rf 0.4. 
EXAMPLE 12 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenylamino]propyl]-1H-1,2,4-triazole-3,5-di 
amine 
3-[(3-Aminopropyl)amino]-N,N-dimethylbenzamide 
A mixture of 3-amino-N,N-dimethylbenzamide (15.4 g) and 
N-(3-bromopropyl)phthalimide (12 g) in dry xylene was heated under reflux 
during 12 hr. The precipitate that formed was dissolved in methanol and 
ethyl acetate added. The mixture was washed with water and the organic 
phase was evaporated to leave a crude oil (15 g) which was used without 
further purification. 
The oil and hydrazine hydrate (5.55 g) were heated under reflux in ethanol 
for 2 hr and then cooled to 25.degree.. A solid precipitate that formed 
was removed by filtration and the filtrate concentrated in vacuo to give 
the title compound (2.2 g) b.p. 170.degree.-5.degree., (0.01 mm). TLC 
silica; methanol:ammonia (80:1) Rf 0.2. 
3-[[3-[(3-Amino-1-methyl-1H-1,2,4-triazol-5-yl)amino]propyl]-amino]-N,N-dim 
ethylbenzamide 
3-[(3-Aminopropyl)amino]-N,N-dimethylbenzamide (0.8 g) and 
N-cyano-1-methyl-2-(phenylmethylene)hydrazine carboximidothioic acid, 
methyl ester (0.84 g) were heated together under reduced pressure of 14 mm 
Hg during 4 hr at 100.degree.. The cooled reaction mixture was dissolved 
in acetone, treated with 1N hydrochloric acid (2 ml) and heated at 
60.degree. for 0.5 hr. The mixture was cooled, basified with potassium 
carbonate and extracted with ethyl acetate. Evaporation of the organic 
extracts gave a viscous oil which was triturated with ether to give the 
title compound (0.49 g). TLC silica; methanol:ammonia (80:1) Rf 0.63. NMR 
(CDCl.sub.3) 2.9 m (1H); 3.2-3.7 m (3H); 5.28 t (1H); 6.12 s (2H); 6.7 s 
(3H); 7.0 s (6H); 6.4-7.4 m (5H); 8.23 t (2H). 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenylamino]propyl]-1H-1,2,4-triazole-3,5-di 
amine 
A mixture of 
3-[[3-[(amino-1-methyl-1H-1,2,4-triazol-5-yl)amino]propyl]amino]-dimethylb 
enzamide (0.47 g) and lithium aluminium hydride (0.15 g) in dry 
tetrahydrofuran was stirred at 25.degree. for 12 hr. Water was added and 
the reaction mixture was filtered. The filtrate was evaporated and the 
residue purified by column chromatography on silica using methanol to give 
the title compound as a buff coloured solid (0.07 g) m.p. 
101.degree.-2.degree.. TLC silica; methanol:ammonia (80:1) Rf 0.53. 
EXAMPLE 13 
1-Methyl-N.sup.5 
-[3-[3-[1-piperidinylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
3-[3-[1-Piperidinylmethyl]phenoxy]propanamine (2.48 g) and 
N-cyano-1-methyl-2-(phenylmethylene)hydrazine carboximidothioic acid, 
methyl ester (2.32 g) were heated at 70.degree. under water-pump vacuum 
for 4 hr. Acetone was added and the solution was treated with dilute 
hydrochloric acid for 1 hr, washed with ether, basified and extracted with 
ethyl acetate. Evaporation of the ethyl acetate extracts gave an oil which 
crystallised from toluene/ether to give the title compound as a white 
solid (0.98 g) m.p. 94.degree.-5.degree.. TLC silica, methanol/0.88 
ammonia 80:1, Rf 0.5. 
EXAMPLE 14 
1-Methyl-N.sup.5 
-[3-[3-[1-(1,2,3,6-tetrahydropyridinyl)methyl]phenoxy]propyl]-1H-1,2,4-tri 
azole-3,5-diamine 
A solution of 
N'-cyano-N-[3-[3-(1,3-dioxolan-2-yl)phenoxy]propyl]-1-methyl-2-(phenylmeth 
ylene)hydrazinecarboximidamide (2.62 g) in tetrahydrofuran (40 ml) was 
stirred at room temperature for 0.5 h with 2 N hydrochloric acid (5 ml). 
The mixture was treated with 1,2,3,6-tetrahydropyridine (9 ml) and stirred 
at room temperature for a further 1 h. The mixture was treated with sodium 
borohydride (1.5 g), stirred at room temperature for 18 h, diluted with 
ethyl acetate, filtered and the filtrate evaporated in vacuo. The 
resulting oil was partitioned between ethyl acetate and water. The organic 
phase was evaporated in vacuo and the residue was purified by column 
chromatography on silica, using methanol. Evaporation of the eluates gave 
the title compound which was recrystallised from a mixture of benzene and 
cyclohexane (1.26 g) m.p. 102.degree.-3.degree.. TLC silica; 
methanol-ammonia 80:1; Rf 0.6. 
The following compounds were similarly prepared from 
N'-cyano-N-[3-[3-(1,3-dioxolan-2-yl)phenoxy]propyl]-1-methyl-2-(phenylmeth 
ylene) hydrazine carboximidamide (A) and the corresponding amine. 
(ii) (A) (3.00 g) and 4-methylpiperidine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-[1-(4-methylpiperidinyl)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3, 
5-diamine (1.67 g) m.p. 133.degree.-4.degree.. TLC silica; methanol:ammonia 
80:1; Rf 0.7. 
(iii) (A) (2.70 g) and cyclohexylamine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-[(cyclohexylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diam 
ine (1.03 g) m.p. 102.degree.-3.degree.. TLC silica, methanol:ammonia 80:1; 
Rf 0.7. 
(iv) (A) (3.12 g) and heptamethyleneimine (10 g) gave 1-methyl-N.sup.5 
-[3-[3-[(1-heptamethyleneiminyl)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3 
,5-diamine (0.63 g) m.p. 71.degree.-3.degree.. TLC silica; methanol:ammonia 
80:1; Rf 0.6. 
(v) (A) (1.74 g) and allylamine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-[(2-propen-1-amino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-dia 
mine (0.47 g) m.p. 71.degree.-2.degree.. TLC silica; methanol:ammonia 80:1; 
Rf 0.6. 
(iv) (A) (2.42 g) and benzylamine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-[[(phenylmethyl)amino]methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5- 
diamine (1.44 g) m.p. 90.degree.-1.degree.. TLC silica; methanol:ammonia 
80:1; Rf 0.8. 
(vii) (A) (3.43 g) and n-propylamine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-[(1-propylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (0.2 g) m.p. 79.degree.-81.degree.. TLC silica; ethyl 
acetate:isopropanol: water: ammonia 25:15:8:2; Rf 0.7. 
(viii) (A) (3.2 g) and morpholine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-(4-morpholinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(0.74 g) m.p. (hydrochloride salt) 55.degree. (softens). TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.48. 
(ix) (A) (2.2 g) and 2,6-dimethylmorpholine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-[4-(2,6-dimethylmorpholinyl)methyl]phenoxy]propyl]-1H-1,2,4-triazol 
e-3,5-diamine (0.3 g) m.p. (hydrochloride salt) 60.degree. (softens). TLC 
silica, ethyl acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.5. 
(x) (A) (3.2 g) and N,N-dimethylethylenediamine (5.5 ml) gave 
1-methyl-N.sup.5 
-[3-[3-[(4,4-dimethylaminoethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triaz 
ole-3,5-diamine (1.1 g) b.p. 250.degree./0.04 mm. TLC silica ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.3. 
(xi) (A) (1.98 g) and heptylamine (15 ml) gave 1-methyl-N.sup.5 
-[3-[3-[(heptylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(0.21 g) m.p. 64.degree.-65.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf. 0.5. 
(xii) (A) (2.47 g) and isobutylamine (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-[(2-methylpropylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5- 
diamine (1.23 g) m.p. 89.degree.-90.degree.. TLC silica, methanol/0.88 
ammonia 80:1, Rf 0.6. 
(xiii) (A) (2.0 g) and 2-methoxyethanamine (20 ml) gave 1-methyl-N.sup.5 
-[3-[3-[[(2-methoxyethyl)amino]methyl]phenoxy]propyl]-1H-1,2,4-triazole-3, 
5-diamine (0.5 g) m.p. 61.degree.-62.5.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.58. 
(xiv) (A) (4.4 g) and n-butylamine (20 ml) gave 1-methyl-N.sup.5 
-[3-[3-[(butylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(0.3 g) m.p. 99.5.degree.-101.degree.. TLC silica; ethyl acetate, water, 
isopropanol, 0.88 ammonia 25:8:15:2, Rf 0.45. 
EXAMPLE 15 
1-Methyl-3-(1-pyrrolidinyl)-N.sup.5 
-[3-[3-[(dimethyl-amino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-5-amine 
1-Methyl-3-chloro-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-5-amine 
A solution of sodium nitrite (0.46 g) in water (1.5 ml) was added dropwise 
to a solution of 1-methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (2.0 g) in concentrated hydrochloric acid at 5.degree.. This solution of 
the diazonium salt was added to a solution of cuprous chloride at 
75.degree. [prepared by adding a solution of sodium metabisulphite (0.41 
g) and sodium hydroxide (0.27 g) in water (3 ml) to a hot solution of 
copper sulphate (1.89 g) and sodium chloride (1.61 g) in water (6 ml)]. 
Concentrated hydrochloric acid (84 ml) was added to the reaction mixture 
which was allowed to stand at 25.degree. for 12 h, cooled, basified with 
sodium bicarbonate and extracted with ethyl acetate. Distillation of the 
organic extract gave the title compound as a pale yellow oil (1.23 g) b.p. 
225.degree. (0.04 mm). TLC silica; methanol: 0.88 ammonia 80:1; Rf 0.64. 
1-Methyl-3-(1-pyrrolidinyl)-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-5-amine 
A mixture of 1-methyl-3-chloro-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-5-amine 
(0.4 g), pyrrolidine (0.71 g) and sodium iodide (0.3 g) was heated at 
180.degree. in an autoclave for 16 hr. The reaction mixture was dissolved 
in dilute hydrochloric acid, washed with ethyl acetate, basified with 
sodium hydroxide and extracted with toluene. The toluene extracts were 
fractionally distilled to give the title compound as a pale yellow oil 
(0.27 g) b.p. 210.degree. (0.04 mm). TLC silica; ethyl 
acetate:isopropanol: water:0.88 ammonia 25:15:8:2; Rf 0.6. 
EXAMPLE 16 
(i) 1-Methyl-N.sup.3 -diethyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (1.0 g) and acetaldehyde (10 ml) were hydrogenated at room temperature 
and atmospheric pressure in ethanol over 10% palladium on charcoal. The 
catalyst was removed by filtration and the filtrate distilled to give the 
product as a pale yellow oil (0.95 g) b.p. 190.degree. (6.times.10.sup.-2 
mm). TLC silica; methanol:0.88 ammonia 80:1; Rf 0.58. 
Similarly prepared from 1-methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (0.5 g) and propionaldehyde (3 ml) was 1-methyl-N.sup.3 -dipropyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (0.5 g) b.p. 200.degree./0.06 mm. TLC silica, methanol/0.88 ammonia 80:1, 
Rf 0.53. 
EXAMPLE 17 
(i) 1-Methyl-N.sup.5 
-[3-[3-[2-(dimethylamino)ethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diami 
ne 
3-[3-(Aminopropoxy)]-N,N-dimethylbenzeneethanamine (0.36 g) and 
N-cyano-1-methyl-2-(phenylmethylene) hydrazinecarboximidothioic acid 
methyl ester (0.37 g) were heated at reflux in toluene for 4 h. The cooled 
solution was treated with dilute hydrochloric acid (5 ml) for 1 h, washed 
with ethyl acetate, basified and extracted with ethyl acetate. The organic 
extract was evaporated to give the title compound as a white solid (0.11 
g) after recrystallisation from toluene, m.p. 81.degree.-2.degree.. TLC 
silica; ethyl acetate:isopropanol: water:0.88 ammonia; 25:15:8:2; Rf 0.35. 
The following compounds were similarly prepared from the corresponding 
diamine and the appropriate N-cyano-1-alkyl-2-(phenylmethylene)hydrazine 
carboximidothioic acid methyl ester (A). 
(ii) Diamine (0.6 g) and A (0.55 g) gave 1-methyl-N.sup.5 
-[2-[[[4-methyl-5-(1-pyrrolidinylmethyl)-2-furanyl]methyl]thio]ethyl]-1H-1 
,2,4-triazole-3,5-diamine (0.45 g). NMR (CDCl.sub.3) 4.03, s (1H); 6.38 s 
(2H); 6.52 s (2H); 6.6, s+t (5H); 7.30 t (2H); 7.52 m (4H); 8.10 s (3H); 
8.31 m (4H); C.sub.16 H.sub.26 N.sub.6 OS requires C, 54.83; H, 7.48; N, 
23.98%. 
Assay found C, 54.95; H, 7.85; N, 23.89%. 
(iii) Diamine (0.82 g) and A (0.81 g) gave 1-methyl-N.sup.5 
-[2-[3-[2-(dimethylamino)ethyl]phenoxy]ethyl]-1H-1,2,4-triazole-3,5-diamin 
e (0.22 g) m.p. 72.degree.. TLC silica, methanol/0.88 ammonia 80:1, Rf 0.3. 
EXAMPLE 18 
1-Methyl-N.sup.3 -ethyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
N-[5-[[3-[3-[(Dimethylamino)methyl]phenoxy]propyl]amino]-1-methyl-1H-1,2,4- 
triazol-3-yl]acetamide 
A mixture of 1-methyl-N.sup.5 -[3-[3-[(dimethylamino) 
methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine (1.0 g), acetic 
anhydride (0.35 g) and pyridine (50 ml) was stirred at 25.degree. for 12 
h. The pyridine was removed and the residue was dissolved in ethyl 
acetate. The organic solution was washed with aqueous sodium carbonate and 
evaporated to give the title compound as a pale yellow oil (1.1 g). TLC 
silica, methanol/0.88 ammonia 80:1, Rf 0.49. NMR (CDCl.sub.3) 1.42 brs 
(1H); 2.81 m (1H); 3-3.4 m (3H); 5.34 t (1H); 5.98 t (2H); 6.52 s (3H); 
6.65 s (2H); 6.5 m (2H); 7.8 s (6H); 7.5-8.1 m (2H); 7.9 s (3H). 
1-Methyl-N.sup.3 -ethyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
A mixture of 
N-[5-[[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-amino]-1-methyl-1H-1,2, 
4-triazol-3-yl]acetamide (1.1 g), lithium aluminium hydride (0.15 g) and 
tetrahydrofuran (20 ml) was heated at reflux for 12 h under a nitrogen 
atmosphere. The mixture was quenched with water (5 ml), filtered and the 
filtrate distilled to give the title compound as a pale yellow oil (0.6 g) 
b.p. 220.degree./0.06 mm. TLC silica, methanol/0.88 ammonia 80:1, Rf 0.54. 
EXAMPLE 19 
1-Methyl-N.sup.3 -methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
5-[[3-[3-[(Dimethylamino)methyl]phenoxy]propyl]amino]-1-methyl-1H-1,2,4-tri 
azole-3-carbamic acid, ethyl ester 
A mixture of 1-methyl-N.sup.5 -[3-[3-[(dimethylamino) 
methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine (2.0 g), ethyl 
chloroformate (0.72 g) and dimethylformamide (30 ml) was stirred at 
25.degree. for 12 h. The suspension was diluted with water (100 ml) and 
extracted with ethyl acetate. The organic extracts were evaporated to 
leave the title compound as a pale yellow oil (2.1 g). TLC silica, 
methanol/0.88 amonia 80:1, Rf 0.61. NMR (D.sub.2 O 2.52 t (1H); 2.8-3 m 
(3H); 5.42 s (2H); 5.6-6 m (6H); 6.48 t (2H); 6.5 s (3H); 7.09 s (6H); 
7.88 m (2H); 8.67 t (3H). 
1-Methyl-N.sup.3 -methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e 
A mixture of 
5-[[3-[3-[(dimethylamino)methyl]phenoxy]propyl]amino]-1-methyl-1H-1,2,4-tr 
iazole-3-carbamic acid, ethyl ester (0.35 g) lithium aluminum hydride (0.13 
g) and tetrahydrofuran (10 ml) was heated under reflux for 48 h. The 
mixture was quenched with water (0.5 ml), filtered and the filtrate was 
evaporated. The residue was purified by column chromatography on silica 
with methanol as the eluant to give the title compound as a pale yellow 
oil (0.1 g). TLC silica; methanol/0.88 ammonia 80:1, Rf 0.43. NMR 
(CDCl.sub.3) 2.78 t (1H); 3.0-3.3 m (3H); 5.47 t (1H); 5.95 t+brs (3H); 
6.50 q (2H); 6.6 s (5H); 7.17 t (3H); 7.78 s (6H); 7.93 m (2H). 
EXAMPLE 20 
(i) 1-(2-Hydroxyethyl)-N.sup.5 -[3-[3 
-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A mixture of N-cyanocarbonimidodithioic acid, dimethyl ester (2.92 g) and 
2-hydroxyethyl hydrazine (1.52 g) in acetonitrile (50 ml) was stirred at 
25.degree. for 12 h. The solvent was removed at 25.degree. to give a pale 
yellow oil (3.4 g) which was used without further purification. 
The oil (3.4 g) and benzaldehyde (2.12 g) were stirred at 30.degree. for 2 
h and the resulting mixture triturated with ether to leave a solid (4.15 
g), which was used without further purification. 
The solid (2.0 g) was heated with 
3-(3-aminopropoxy)-N,N-dimethylbenzenemethanamine (1.59 g) at 60.degree. 
under water pump vacuum during 3 h to give a tarry residue which was 
washed with ether and extracted with ethyl acetate. The ethyl acetate 
extract was evaporated and the residue was dissolved in acetone (50 ml). 
2N Hydrochloric acid was added and the solution stirred at 25.degree. for 
1 h. The solvent was removed and the residue partitioned between water (25 
ml) and ethyl acetate (25 ml). The aqueous phase was separated, treated 
with 2N sodium hydroxide and extracted with ethyl acetate. The organic 
extracts were evaporated and the residue purified by column chromatography 
using methanol as eluant to give the title compound as a white crystalline 
solid (0.14 g) m.p. 105.degree.-6.degree.. TLC silica, methanol/0.88 
ammonia 80:1 Rf 0.36. 
(ii) Similarly prepared from 3-[3-(1-piperidinylmethyl) phenoxy]propylamine 
(1.7 g) was 1-(2-hydroxyethyl)-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(0.1 g) m.p. 90.degree.-1.degree.. TLC silica, methanol:0.88 ammonia 80:1, 
Rf 0.37. 
EXAMPLE 21 
1-Methyl-N.sup.5 
-[3-[3-[1-piperidinylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine, 
salt with succinic acid (2:1), hydrate 
A solution of 1-methyl-N.sup.5 
-[3-[3-[1-piperidinylmethyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(34 g) in ethyl acetate (85 ml) was added to a solution of succinic acid 
(5.9 g) in boiling ethanol (80 ml). The mixture was cooled, stirred at 
room temperature for 1 hr and filtered to give the title compound as a 
white crystalline solid (33.1 g) m.p. 118.degree.-121.degree.. UV data: 
E.sup.1 in water at 267 nm=46.2. 
EXAMPLE 22 
1-Methyl-N.sup.3 -[5-hydroxypentyl]-N.sup.5 -[3-[3-[(dimethylamino) 
methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
1-Methyl-N.sup.5 
-[3-[3-[(dimethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamin 
e (1.0 g) and 5-hydroxypentanal (1.9 ml) were heated at reflux in ethanol 
(30 ml) for 5 h. The solution was cooled at 5.degree. and treated with 
sodium borohydride (0.76 g). The resulting suspension was stirred at room 
temperature for 16 h, treated with water and reduced in volume in vacuo. 
The aqueous solution was extracted with ethyl acetate, and the organic 
extracts were distilled to give the title compound as a pale yellow oil 
(0.47 g) b.p. 250.degree./0.5 mm. TLC silica; ethyl 
acetate:isopropanol:water: 0.88 ammonia 25:15:8:2, Rf 0.6. 
EXAMPLE 23 
1-Methyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A solution of 
3-[3-[(3-amino-1-methyl-1H-1,2,4-triazol-5-yl)amino]propoxy]-N,N,N-trimeth 
ylbenzene-methanium iodide (1 g) and piperidine (2.14 ml) in water (1 ml) 
was heated under reflux for 8 h. The solution was evaporated to give an 
oil which was purified by column chromatography using methanol as eluant 
to give the title compound as a white solid (0.36 g) m.p. 
93.degree.-94.degree.. TLC silica, methanol/0.88 ammonia 80:1, Rf 0.6. 
EXAMPLE 24 
Following the method of Example 7: 
(i) Diamine (2.0 g) and A (1.96 g) gave 1-methyl-N.sup.5 
-[3-[3-[(diethylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(0.25 g) m.p. 68.degree.-9.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.7. 
(ii) Diamine (0.23 g) and A (0.23 g) gave 1-methyl-N.sup.5 
-[3-[3-[3-(dimethylamino)propyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diam 
ine (0.12 g) m.p. 64.degree.-65.5.degree.. TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.3. 
EXAMPLE 25 
Following the method of Example 14: 
(i) A (1.92 g) and 0.88 ammonia (10 ml) gave 1-methyl-N.sup.5 
-[3-[3-(aminomethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine (0.15 
g). TLC silica, methanol/0.88 ammonia 80:1, Rf 0.5. NMR (d.sub.4 MeOH) 
2.77 t (1H); 3.0-3.3 m (3H); 5.95 t (2H); 6.30 s (2H); 6.57 q (2H); 6.65 s 
(3H); 7.95 m (2H). 
(ii) A (2.5 g) and propargylamine (5 ml) gave 1-methyl-N.sup.5 
-[3-[3-[(2-propynylamino)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3,5-diam 
ine (0.43 g). NMR (CDCl.sub.3) 2.72 t (1H); 3.0-3.3 m (3H); 5.41 t (1H); 
5.90 t (2H); 5.97 brs (2H); 6.15 s (2H); 6.48 q (2H); 6.58 d (2H); 6.60 s 
(3H); 7.72 t (1H); 7.92 m (2H). TLC silica, ethyl 
acetate/water/isopropanol/0.88 ammonia 25:8:15:2, Rf 0.67. 
EXAMPLE 26 
1-Methyl-N.sup.5 
-[3-[3-[1-(4-hydroxypiperidinyl)methyl]phenoxy]propyl]-1H-1,2,4-triazole-3 
,5-diamine 
Following the method of Example 17, the appropriate diamine (1.0 g) and A 
(0.23 g) gave the title compound (0.3 g) m.p. hydrochloride salt 
148.degree. (dec). TLC ethyl acetate/water/isopropanol/0.88 ammonia 
25:8:15:2, Rf 0.6. 
EXAMPLE 27 
1-Methyl-N.sup.5 
-[3-3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A solution of 
3-[3-[[[(cyanimino)[1-methyl-2-(phenylmethylene)hydrazino]]methyl]amino]pr 
opoxy]-N,N,N-trimethylbenzenemethanium iodide (1.07 g) and piperidine (1.7 
g) in water (1 ml) was heated under reflux for 24 hr. The water was 
removed to give an oil which was purified by column chromatography using 
methanol/0.88 ammonia 80:1 as eluent to give the title compound as a white 
solid (0.2 g), m.p. 94.degree.-95.degree.. TLC silica, methanol/0.88 
ammonia 80:1, Rf 0.6. 
EXAMPLE 28 
1-Methyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
3-[3-[(1-Methyl-3-amino-1H-1,2,4-triazol-5-yl)amino]propoxy]benzenemethanol 
, hydrochloride 
N'-Cyano-N-[3-[3-(1,3-dioxolan-2-yl)phenoxy]propyl]-1-methyl-2-(phenylmethy 
lene)hydrazinecarboximidamide (18.2 g) in tetrahydrofuran (150 ml) was 
treated with 5N hydrochloric acid (30 ml) at 30.degree. C. for 30 mins. 
Triethylamine (20 ml) was added followed by sodium borohydride (8.0 g). 
The resulting mixture was stirred at room temperature for 14 hrs, diluted 
with ethyl acetate (150 ml) and evaporated to a red oil which was 
dissolved in ethyl acetate, washed with sodium bicarbonate solution and 
evaporated to leave an oil. This oil was treated with etheral hydrogen 
chloride to give the title compound as a white solid (8 g). m.p. 
148.degree.-9.degree.. TLC silica, ethyl acetate, water, isopropanol 0.88 
ammonia (25:8:15:2) Rf 0.56. 
1-Methyl-N.sup.5 
-[3-[3-(bromomethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine, 
hydrobromide 
A solution of 
3-[3-[(1-methyl-3-amino-1H-1,2,4-triazol-5-yl)amino]propoxy]benzene 
methanol (1.9 g) in methylene chloride (25 ml) was treated with phosphorus 
tribromide (3.27 g) at room temperature for 76 hrs. The resulting oil was 
purified by column chromatography using ethyl acetate/methanol, 8:1 as 
eluant to yeild the title compound as a white solid) 1.7 g). TLC silica 
ethyl acetate, water, isopropanol 0.88 ammonia (25:8:15:2) Rf 0.72. m.p. 
129.degree.-130.degree.. 
1-Methyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
1-Methyl-N.sup.5 
-[3-[3-(bromomethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine, 
hydrobromide (0.3 g) was dissolved in ethanol (5 ml) and treated with 
piperidine (0.3 g) at room temperature. The solvent was evaporated in 
vacuo and the residue triturated with ethyl acetate to afford the title 
compound as a white crystalline solid (0.22 g). 
TLC silica, ethyl acetate, water, isopropanol 0.88 ammonia (25:8:15:2) Rf 
0.5, m.p. 93.degree.-94.degree. C. 
EXAMPLE 29 
N.sup.3 
-[3-[3-(1-Piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
[3-[3-(1-Piperidinylmethyl)phenoxy]propyl]isothiocyanate 
A solution of carbon disulphide (3.3 ml) in acetone (8 ml) was added 
dropwise to a solution of 3-[3-(1-piperidinylmethyl)phenoxy]propanamine 
(12.4 g) in acetone (30 ml) over a 15 minute period, between -5.degree. 
and -10.degree. C. The solution was cooled to -14.degree. C. and mercury 
(II) chloride (13.6 g) in acetone (30 ml) was added, during 45 minutes. 
Triethylamine (16 ml) was added at 0.degree. C. during 15 minutes, and the 
mixture was heated at reflux for 45 minutes. The resulting suspension was 
purified by filtration and the filtrate evaporated in vacuo. The residue 
was purified by column chromatography using methanol as eluant to give the 
title compound (6 g) as an amber oil. TLC silica/cmethanol Rf 0.4. 
Assay: Found C, 65.9; H, 7.7; N, 9.6; S, 11.1; C.sub.16 H.sub.22 N.sub.2 OS 
requires; C, 66.2; H, 7.6; N, 9.6; S, 11.0%. 
N.sup.3 
-[3-[3-(piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A mixture of [3-[3-(1-Piperidinylmethyl)phenoxy]propyl]-isothiocyanate (0.9 
g) and aminoguanidine (0.45 g) was heated at 140.degree.-160.degree. for 3 
hours. The resulting mixture was purified by column chromatography using 
ethyl acetate: ethanol:0.88 ammonia (100-10:1) as eluant to afford the 
title compound (0.1 g) m.p. 100-101.5. TCL 
silica/ethylacetate/ethanol/0.88 ammonia 10:1:1 Rf 0.3. 
EXAMPLE 30 
1-Methyl-N.sup.5 -[3-[[5-(dimethylamino)methyl]-2-furanyl] 
methoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A mixture of 5-[(dimethylamino)methyl]-2-furanmethanol (0.31 g), 
1-methyl-N.sup.5 -(3-hydroxypropyl)-1H-1,2,4-triazole-3,5-diamine (0.72 g) 
and methanesulphonic acid (1.2 ml) in dry tetrahydrofuran (20 ml) was 
stirred at 25.degree. for 3 h and then at reflux for 8 h. The cooled 
mixture was diluted with water (10 ml), treated with anhydrous potassium 
carbonate and extracted with ethyl acetate. The combined extracts were 
evaporated and the residue was purified by column chromatography with 
methanol as eluant to give the title compound as a yellow oil (0.1 g). NMR 
(CDCl.sub.3) 3.75 d (1H); 3.86 d (1H); 5.20 t (1H); 5.58 s (2H); 6.00 br.s 
(2H); 6.40 t (2H); 6.60 s (2H); 6.62 q (2H); 6.73 s(3H); 7.76 s (6H); 8.12 
m (2H). TLC silica, methanol/0.88 ammonia 79:1, Rf 0.5. 
EXAMPLE 31 
1-Methyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
1-Methyl-N.sup.5 
-[3-[3-(1,3-dioxolan-2-yl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A solution of N'-cyano-N-[3-(1,3-dioxolan-2-yl) 
phenoxy]propyl]-1-methyl-2-phenylmethylene hydrazine carboximidamide (2.50 
g) in piperidine (6 ml) was heated under reflux for 70 h. The mixture was 
evaporated in vacuo, and the resulting oil was chromatographed on silica. 
Elution with a mixture of methanol and ethyl acetate (1:1) gave an oil 
which was crystallised from a mixture of benzene and cyclohexane, to give 
the title compound (0.29 g) m.p. 117.degree.-8.degree.. TLC silica 
(methanol) Rf 0.7. 
1-Methyl-N.sup.5 
-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A solution of 1-methyl-N.sup.5 -[3-[3-(1,3-dioxolan-2-yl) 
phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine (106 mg) in tetrahydrofuran 
(2 ml) was stirred with 2N hydrochloric acid (0.2 ml) for 1/2 h at room 
temperature. The mixture was treated with piperidine (0.5 ml), stirred at 
room temperature for 1 h, and then treated with sodium borohydride (75 
mg). After a further 1 h, the mixture was diluted with water, and 
extracted with ethyl acetate. The combined extracts were dried and 
evaporated in vacuo. The resulting oil was crystallised from a mixture of 
benzene and cyclohexane to yield the title compound (60 mg) m.p. 
93.degree.-4.degree. . TLC silica (methanol:ammonia 80:1) Rf 0.5. 
EXAMPLE 32 
N.sup.5 
-[4-[3-(1-Piperidinylmethyl)phenoxy]butyl]1H-1,2,4-triazole-3,5-diamine 
4-[3-(1-piperidinylmethyl)phenoxy]butanitrile 
3-[1-Piperidinylmethyl]phenol (11.2 g) was added to a stirred suspension of 
sodium hydride (1.5 g) in dry dimethylformamide (60 ml) at room 
temperature. The mixture was stirred at room temperature for 5 h, and 
treated with 4-bromobutanitrile (9 g). After a further 24 h at room 
temperature, the mixture was poured onto ice and extracted with ethyl 
acetate. The combined extracts were washed with water and evaporated in 
vacuo. The residual oil was distilled under reduced pressure to yield the 
title compound (14.8 g) b.p. 200.degree./0.06 mm. TLC silica 
(methanol:ammonia 80:1) Rf 0.8. 
4-[3-(1-Piperidinylmethyl)phenoxy]butanal, semicarbazone 
A solution of 4-[3-(1-piperidinylmethyl)phenoxy]butanitrile (5.16 g), 
sodium acetate (7.38 g) and semicarbazide hydrochloride (7.76 g) in 
ethanol (60 ml) and water (60 ml) was hydrogenated over Raney nickel (12 
g) at room temperature and one atmosphere. The mixture was filtered, and 
reduced to a volume of 50 ml in vacuo. The resulting solution was diluted 
with water, basified with potassium carbonate and extracted with ethyl 
acetate. The organic extracts were evaporated to give an oil which was 
chromatographed on silica with methanol as the eluant to give the title 
compound as a colourless oil. (4.4 g) TLC silica (methanol:ammonia 80:1) 
Rf 0.7. NMR (CDCl.sub.3) 0.28 bs, (1H); 2.6-2.9 m, (2H); 3.0-3.4 m (3H); 
4.4 bs (2H); 6.02 t (2H); 6.57 s (2H); 7.4-8.9 m (14H). 
4-[3-(1-Piperidinylmethyl)phenoxy]butanal 
A solution of 4-[3-(1-piperidinylmethyl)phenoxy]butanal, semicarbazone 
(4.34 g) in 2N hydrochloric acid (40 ml) was stirred with 37% aqueous 
formaldehyde solution (40 ml) for 1 h at room temperature. The mixture was 
diluted with water, treated with potassium carbonate and extracted with 
ethyl acetate. The combined organic extracts were evaporated in vacuo and 
the residual oil was chromatographed on silica with methanol as eluant to 
give the title compound (1.93 g) as a colourless oil. TLC silica 
(methanol) Rf 0.5, NMR (CDCl.sub.3) 0.1 t (1H); 2.75 t (1H); 3.0-3.3 m 
(3H); 6.02 t (2H); 6.55 s (2H); 7.35 m (2H); 7.5-7.7 m (4H); 7.88 m (2H); 
8.2-8.6 m (6H). 
N.sup.5 
-[4-[3-(1-Piperidinylmethyl)phenoxy]butyl]-1H-1,2,4-triazole-3,5-diamine 
A solution of 4-[3-(1-piperidinylmethyl)phenoxy]butanal (522 mg) and 
3,5-diamino-1,2,4-triazole (200 mg) in absolute ethanol (20 ml) was heated 
under reflux for 2 h. The cooled solution was treated with sodium 
borohydride (200 mg) and stirred at room temperature for 18 hr. The 
mixture was evaporated in vacuo and the residue partitioned between ethyl 
acetate and water. The combined organic extracts were evaporated in vacuo 
and the residue was chromatographed on silica with methanol as eluant to 
give the title compound as an oil (250 mg), TLC silica (ethyl 
acetate:isopropanol:water:ammonia 25:15:8:2) 0.4, NMR (CDCl.sub.3) 2.8 t 
(1H); 3.0-3.3 m (3H); 5.3 m (2H); 6.2 m (2H); 6.6-6.8 m (4H); 7.7 m (4H); 
8.0-8.8 m (10H). 
EXAMPLE 33 
1-Methyl-N.sup.3 -[2-methoxyethyl]-N.sup.5 -[3-[3-(1 
-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
1-Methyl-N.sup.5 
[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
(2.39 g) and methoxyacetaldehyde diethylacetal (2.96 g) were heated at 
reflux in ethanol (50 ml) and 2N hydrochloric acid (10 ml) for 24 hr. 
The cooled reaction mixture treated with sodium borohydride (7.6 g) and 
stirred at room temperature for 24 hr. The suspension was treated with 
water, filtered, and the filtrate was extracted with ethyl acetate. The 
organic extracts were distilled to give the title compound as a yellow oil 
(0.2 g). b.p. 250.degree./0.06 mm. TLC silica, ethyl 
acetate:isopropanol:water:0.88 ammonia (25:15:8:2) Rf 0.65. 
EXAMPLE 34 
1-Methyl-N.sup.5 
-[3-[3-(aminomethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
2-[[3-[3-[(3-Amino-1-methyl-1H-1,2,4-triazol-5-yl)amino]propoxy]phenyl]meth 
yl]-1H-isoindole-1,3-(2H)-dione 
A mixture of potassium phthalinide (5.58 g) and 
3-[3-[[3-amino-1-methyl-1H-1,2,4-triazol-5-yl]amino]propoxy]N,N,N-trimethy 
lenzenemethanium iodide (6.69 g) in dimethylformamide was heated at 
140.degree.-160.degree. for 6 h. The solvent was evaporated and the 
residue was dissolved in water and extracted with ethyl acetate. 
Evaporation of the organic extract gave an oil which was purified by 
column chromatography using methanol/acetone 1:9 as eluant to give the 
title compound as a white solid (2.3 g) m.p. 55.degree.-57.degree. TLC 
silica methanol/acetone; 1:9, Rf 0.42. 
1-Methyl-N.sup.5 
-[3-[3-(aminomethyl)phenoxy]propyl]-1H-1,2,4-triazole-3,5-diamine 
A solution of 
2-[[3-[3-[(3-amino-1-methyl-1H-1,2,4-triazol-5-yl)amino]propoxy]phenyl]met 
hyl]-1H-isoindole-1,3-(2H)-dione (1.62 g) and hydrazine hydrate (0.22 g) in 
ethanol (10 mol) was heated at reflux for 1.5 h. The solvent was 
evaporated and the residue was dissolved in dilute hydrochloric acid and 
filtered. The filtrate was basified with sodium carbonate, evaporated to 
dryness and extracted with hot isopropanol to give an oil which was 
purified by column chromatography using methanol/0.88 ammonia 79:1 an 
eluant to give the title compound as a crystalline solid (0.79 g) TLC 
silica, methanol/0.88 ammonia 79:1 Rf 0.5 NMR (d.sub.4 MeOH) 2.77 t (1H); 
3.0-3.3 m (3H); 5.95 t (2H); 6.30 s (2H); 6.57 q (2H); 6.65 s (3H); 7.95 m 
(2H). 
EXAMPLE 35 
Pharmaceutical Compositions 
______________________________________ 
(a) TABLETS mg/tablet mg/tablet 
______________________________________ 
Active ingredient 
20.0 40.0 
Microcrystalline 
cellulose BPC 99.5 199.0 
Magnesium stearate 
B.P. 0.5 1.0 
Compression weight 
120.0 240.0 
______________________________________ 
The drug is sieved through a 250 .mu.m sieve, blended with the excipients 
and compressed using 6.5 mm and 8.0 mm diameter punches for the 20 and 40 
mg strengths respectively. Tablets of other strengths may be prepared by 
increasing the compression weight and using punches to suit. 
The tablets may be film coated with suitable film forming materials, e.g. 
methyl cellulose, ethyl cellulose or hydroxypropylmethyl cellulose, using 
standard techniques. Alternatively the tablets may be sugar coated. 
______________________________________ 
(b) CAPSULES mg/capsule 
______________________________________ 
Active ingredient 20.0 
**Sta-Rx 1500 Starch 
79.5 
Magnesium Stearate B.P. 
0.5 
Fill Weight 100.0 
______________________________________ 
**A form of directly compressible starch supplied by Colorcon Ltd., 
Orpington, Kent. 
The active ingredient is sieved through a 250 .mu.m sieve and blended with 
the other materials. The mix is filled into No. 3 hard gelatin capsules 
using a suitable filling machine. Other doses may be prepared by 
increasing the fill weight and if necessary changing the capsule size to 
accommodate the increase. 
______________________________________ 
(c) SUSTAINED RELEASE TABLETS 
mg/tablet 
______________________________________ 
Active ingredient 80 
*Cutina HR 25 
Lactose B.P. 142.5 
Magnesium Stearate B.P. 2.5 
Compression weight 250.0 
______________________________________ 
*Cutina HR is a grade of microfine hydrogenated castor oil supplied by 
Sipon Products Ltd. London. 
The drug is sieved through a 250 .mu.m sieve and blended with the Cutina HR 
and lactose. The mixed powders are moistened with Industrial Methylated 
Spirits 74 O.P., granules are made, dried, screened and blended with the 
magnesium stearate. The lubricated granules are compressed using 8.5 mm 
punches to produce tablets with a hardness of not less than 10 Kp 
(Schleuniger tester). 
______________________________________ 
(d) INJECTION FOR 
INTRAVEVOUS ADMINISTRATION 
% w/v 
______________________________________ 
Active ingredient 0.25 
Water for Injections BP to 
100.00 
______________________________________ 
Sodium chloride may be added to adjust the tonicity of the solution and the 
pH may be adjusted to that of maximum stability using either dilute acid 
or alkali. 
The solution is prepared, clarified and filled under nitrogen into 
appropriate sized ampoules sealed by fusion of the glass. The injection is 
sterilised by heating in an autoclave using one of the acceptable cycles. 
Alternatively the solution may be sterilised by filtration and filled into 
sterile ampoules under aseptic conditions. 
______________________________________ 
(e) SYRUP mg/5ml dose 
______________________________________ 
Active ingredient 20.0 mg 
Sucrose 2750.0 mg 
Glycerine 500.0 mg 
Buffer 
Flavour as necessary 
Colour 
Preservative 
Distilled water to 5.0 ml 
______________________________________ 
The active ingredient, buffer, flavour, preservative and colour are 
dissolved in some of the water. The remainder of the water is heated to 
approximately 80.degree. C. and the sucrose is dissolved in this and 
cooled. The two solutions are mixed, adjusted to volume and clarified by 
filtration. 
(f) Cream 
A 1% cream may be prepared by dispersing the finely divided active 
ingredient in either of the two formulae for Cetamacrogol Cream B.P.C. 
______________________________________ 
(g) OINTMENT % w/w 
______________________________________ 
Active ingredient 1.0 
Propylene glycol 5.0 
White soft paraffin 
to 100.0 
______________________________________ 
The finely divided active ingredient is suspended in the propylene glycol 
and this is dispersed in the molten soft paraffin. The mixture is stirred 
until cool.