United States Patent Office 3,271,393

Patented Sept. 6, 1966

2
and pyrrollidino
3,271,393
2,4-DAMENO-6-NON-OXO-CARBONYLC
TRAZINES
Takeo Ueda, 1066 Ezumi, Konnae-cho, Kitatama-ge, ( -) /
N

In a preferred embodiment of this invention, Y in

Tokyo, Japan; Shigeshi Toyoshima, 355 Fu nabashi-cho, 5
Sedagaya-ku, Tokyo, Japan; and Mitsuru Furukawa, Formula I is
897 Yukigaya-cho, (Ota-ku, Tokyo, Japan
No Drawing. Filed Mar. 28, 1963, Ser. No. 268,551
Claims priority, application Japan, July 3, 1962,
-NH-C-NH,
NH
37/27,69 O and the group
4 (Claims. (C. 260-247.2) R1
This invention relates to new chemical compounds N
which are useful in therapeutic compositions. More par R2
/
ticularly, this invention relates to 2,4-diamino- and 2
amino-4-(substituted)-amino-6-(N-carbonyl)-2-triazine. taken together is morpholino, i.e.,
Viral infections, such as poliomyelitis and measles,
are notoriously resistant to treatment with known thera O
Y-?
N
peutic agents.
It is an object of this invention to provide a new The compounds of the present invention (except those
class of chemical compounds which possess antiviral ac wherein Y is -OH) may be prepared by the reaction of
tivity, and, more particularly, compounds which inhibit an cy-substituted biguanide having the formula
and/or inactivate viruses which cause measles and polio (II) R1 NH NI
myelitis. N
N-C-NE-C-NE
There are provided, according to the present inven /
R2
tion, compounds having the formula
(I) wherein R1 and R2 are the same as defined above, with
a di(lower) alkyl oxalate, such as diethyl oxalate. The
2-y reaction may be conducted in an inert reaction media
e's Such as methanol. The reaction may be hastened by
heating. This reaction results in the formation of a com
R. N. Y.
N-C C-NEH
pound having the formula
/ N / (III) R NH NH-6-0
R2 N
wherein R1 and R2 are members selected from the group
consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl and R2
N-C-N=c, NH-C=O
cycloalkyl, and wherein the group This product is then reacted with ammonia or an amine
R1
selected from the group consisting of
N
40
and
taken together may be a heterocyclic group containing R3
from 4 to 5 carbon atoms; and Y is a member selected NH
N
from the group consisting of morpholino, piperidino, pyr R4
rolidino, in which R3 and R4 are the same as defined above, pref
erably in an inert reaction medium such as ethanol. The
-OH, -N1-(-NH,
NH
reaction is preferably conducted at elevated tempera
tures. The product, represented by Formula I above,
and may be recovered by filtration. Alternatively, these com
pounds may be prepared in one step by reacting in the
absence of any additional solvent an ox-substituted bi
guanide having the Formula II above, a di (lower) alkyl
oxalate and ammonia or an amine selected from the
55 group consisting of
in which R3 and R4 are members selected from the group NII--NH.
consisting of hydrogen, alkyl, alkenyl, aralkyl and aryl. NH
The group and
R1 60 R3
Y
/
EIN
N
2 R4
taken together may be, for example, morpholino in which R3 and R4 are the same as defined above.
/ Y
65 The compounds represented by Formula II are known
O N in the art. For example, when R1 and R2 are both hy
N-1 drogen, the compound is biguanide which is commer
piperidino cially available. When the group
R
70 N
(O-) R2
/
N
 3,271,393
3 4.
taken together is morpholino, i.e., talc, stearic acid, magnesium stearate, gums or the like.
Any of the encapsulating or tabletting materials used in
6Y-1Y pharmaceutical practice may be employed where there is
no incompartibility with the compounds. The materials
which is the preferred embodiment of this invention, may be tabletted with or without adjuvants. Alterna
the compound is 4-morpholinecarboximidoylguanidine tively, the compounds may be placed in the usual capsule
which is described in Chemical Abstracts, 54, 10131 and or resorbable material such as the usual gelatin capsule
21510. and administered in that form. In yet another embodi
Another method for making the novel compounds of ment, the compounds may be put up as a powder and so
this invention (except those wherein Y is -OH) in O employed, as by nasal inhalation, or the compounds may
Volves the reaction of a compound having the formula be prepared in the form of a palatable suspension in
(IV) g which the compounds are not soluble. Suspensions may
be given orally as made or may be encapsulated. Oint
g-x ments and lotions are useful topically; use for topical
5 therapy is made of nose drops, troches and suppositories.
R1 N. 2 eY. The compounds of the present invention are particular
Y-d
/ SS /
(-NH, ly useful when given by the oral, intramuscular, or in
travenous routes.
R2 N
The following examples will illustrate the preparation
in which R1 and R2 are the same as defined above and 20 of the compounds of the present invention.
X is a member selected from the group consisting of EXAMPLE 1.
chloro, bromo, fluoro, iodo, and --OR (R5 being alkyl),
With ammonia or an amine selected from the group con A solution of sodium methoxide (0.1 mole) in absolute
sisting of methanol is added, with heating and stirring, to a suspen
NII-C-NH 25 Sion of 0.1 mole of powdered 4-morpholinecarboximidoyl
NH guanidine hydrochloride in absolute methanol. NaCl
and which is formed as a precipitate is removed by filtration.
R3 Diethyl oxalate (0.1 mole) is then added and the solu
tion is refluxed for 30 minutes on a steam bath. The
IN 30 reaction which occurs may be represented by the fol
Y. lowing equation:
in which R3 and R4 are the same as defined above. Com N NH
pounds of Formula IV in which X is OR5 may be ob 4. N COC2H5
N-C-NH-C-NH2 -
tained by the reaction of a compound of Formula III 35
N-1 CO2Cs
With an alcohol; or by the reaction of a compound of
Formula II, a di(lower) alkyl oxalate and an alcohol.
Compounds represented by Formula I wherein Y is NE
–2C-H.OH
NH-C=O
hydroxyl may be synthesized by the hydrolysis of a com ? \--N-r?
-C-N=C
pound of Formula IV in which X is -OR5; or by the 40 N-1 YH-d=0
hydrolysis of a compound of Formula III, or by react
ing a compound of Formula II with an oxalic acid mono The reaction mixture is allowed to stand overnight and the
ester. The product from any of these reactions may be precipitated product is collected by filtration. The prod
further reacted with a halogenation reagent to obtain a uct is found to have a melting point of 268 C., a yield
compound of Formula IV in which X is halogen. of 79%. Elemental analysis.-Calculated for CHONs:
The compounds of this invention possess useful anti N, 31.10%. Found: 31.02%.
viral activity, particularly virucidal activity. Some of the A suspension of 0.01 mole of the product obtained
compounds, particularly 2-amino-4-morpholino - 6-(N- above is refluxed in 150 cc. of absolute ethanol until all
amidinocarbamoyl)-s-triazine are useful in inhibiting the of the material has been dissolved. To the solution there
multiplication of and inactivating of such strains of virus is added 0.01 mole of guanidine and the mixture is re
as the Mahoney and MEF strain of poliomyelitis virus 50
fluxed for 5 hours. A white precipitate is formed during
and in the suspension of the production of the toxin-like the refluxing. The reaction which occurs may be repre
substance (the C.P.E. factor) produced by poliomyelitis Sented by the following equation:
virus. The compounds of the present invention also are
effective in inhibiting the multiplication of the measles -ow. NH NEI-C-cO NH
virus (Edmonstan strain). They have also been found 6N - NN-C-NicO
|| / -- H2N-C-NII
to have a significant chemotherapeutic and chemoprophy NH-Cat O
lactic effect on influenza virus and to be effective against
echo and coxsackie viruses. The compounds of this in |-Ho
vention are also useful in the study of viruses, particularly J.
as a tool to facilitate study of their basic biological char 60
acteristics, including their intracellular multiplication. NII
The compounds of the present invention may be asso (-NH- C-NET
ciated with a significant amount of a pharmaceutically ac /'s
N
ceptable carrier which may be either a solid material or
a liquid. The compositions may take the form of tablets, 65 N-C C-NI
effervescent tablets, powder, granules, capsules (both Y-1 Y1
hard and soft shell capsules), of suspensions in edible
oils, or other dosage forms which are particularly useful The reaction mixture is concentrated, the precipitate re
for oral ingestion. Liquid diluents are employed in sterile covered and recrystallized from water. The product, 2
conditions for parenteral use, that is by intramuscular, 70 amino-4-morpholino-6-(N-amidinocarbamoyl)-s-triazine,
intravenous and intraperitoneal injection. Such a me consists of prisms having a melting point of 271° C. Ele.
dium may be a sterile solvent or suspending agent such mental analysis.-Calculated for CHION: N, 42.08%.
as Water or an injectable oil. The compositions may take Found: N, 41.50%.
the form of active material admixed with solid diluents The inhibitory effect of 2-amino-4-morpholino-6-(N-
and/or tabletting adjuvants such as cornstarch, lactose, 75 amidinocarbamoyl)-s-triazine on the multiplication of
 3,271,893
5 6
polio virus (type 1-Mahoney and type 2-MEF) and EXAMPLE 3
measles (Edmonstan strain) is determined using the Preparation of 1,1-(2,2-oxydiethyl)-3-(4,5-dioxo-2-
standard tissue culture method. KB cells were used for inidazolidinylidene)-guanidine
polio and Hep. No. 2 cells for measles. Table I sets
forth the tissue culture inhibitory dose (TCID)osom.
for the compound tested as well as for the control.
TABLE I
To a Solution of 21 g. of 1,1-(2,2-oxydiethyl)-biguanide
TCID50/0.1 ml. hydrochloride in 1 I. of dehydrated methanol is added
Viral Material
Control Tteated
0. Sodium methoxide prepared from 2.5 g. of metal sodium
and a suitable volume of dehydrated methanol. The pre
Polio: cipitated NaCl is removed by filtration. After addition
Type i-Mahoney------- 1 Oc 10C8 of 15 g. of diethyl oxalate to the filtrate and allowing to
Type 2-MEF-------
Measles:
10C8.5 OC3,5 stand for 2 hours, the resulting precipitate is collected by
Edmonstan----------- 107 10C3 Suction; yield 19.8 g. (79%), M.P. 268° C. (with decom
position). Analysis.-Calcd. for CaH11ONs: N, 31.10.
In another test procedure, the minimum inhibitory con Found: N, 31.02.
EXAMPLE 4
centration of 2-amino-4-morpholino-6-(N-amidinocarbam Preparation of 1-(p-methoxyphenyl)-3-(4,5-dioxo-2-
oyl)-S-triazine on measles virus in Hep. No. 2 cells is 20 imidazolidinylidene)-guanidine
determined. The results are set forth in Table II.
NH NEI-C-O
TABLE I
Concentration of
compound (in moles): Results NH-CeO
10------------------------------------ 4/4 To a solution of 2.07 g. of 1-(p-methoxyphenyl)-bi
X10"--------------------------------- 4/4
2X10"--------------------------------- 0/4 guanide in 5 cc. of dehydrated methanol is added 1.46 g.
None ----------------------------------- 0/4 of diethyl oxalate. After allowing to stand for 2 hours,
the yellow precipitate immediately deposited from the re
(In the results column, the denominator denotes the total 30 action mixture is collected by filtration; yield 2.40 g.
number of assay tubes used in the experiment and the nu (92%), M.P. 208 C. (with decomposition). Analysis.-
merator denotes the number of tubes in which no cyto Calcd. for CHONs: N, 26.81. Found: N, 27.05.
pathogenic effect was observed.) Other examples of intermediates of the type represented
The minimum inhibitory concentration of 2-amino-4- by Formula III which are prepared by the general method
morpholino-6-(N-amidinocarbamoyl)-s-triazine on the described above are set forth in Table III.
TABLE III

R1 Analysis N Percent
Melting Yield Molecular
Example Group N of formula III Point (Percent) Formula
(6 C.) Calc. Exper.
R2

5-------------- NH- >300 ---------- C4H5ON5------- 45.5 45.50

6-------------- iso-C3H7NH- 218 77 CH11ON5------ 35, 52 35.90

7-------------- {O-NH- 249 83. C10H15O2N5. --. 29, 52 29.80

8.------------- C II-& S-NIH- 214 95 C11EIONs----- 28.56 28.86

Mahoney strain of virus (10-6) is found to be 4x10-4 The following examples are illustrative of the prepara
mole. tion of various compounds represented by Formula I,
The following examples are illustrative of the prepara above:
tion of various intermediates of the type represented for 55 EXAMPLE 9
Formula III, above: Preparation of 4-amino-6-isopropylamino-S-
EXAMPLE 2 triazine-2-carbanlide
Preparation of 1,1-dimethyl-3-(4,5-dioxo-2-
imidazolidinylidene)-guanidine 60 o
CEE3 NH NH--0 -NH-( >
cá,N-(-N=c(NH-C-O
2
CH N N
65 CH-N-C C-NE
Sodium ethoxide prepared from 0.23 g. of metallic so CH3
N /
N
dium and a small amount of dehydrated ethanol is added,
with warming, to a suspension of 1.65 g. of 1,1-dimethyl
biguanide hydrochloride in 5 cc. of dehydrated ethanol. A suspension of 1.97 g. of 1-isopropyl-3-(4,5-dioxo-2-
After the precipitated NaCl is filter off, 1.46 g. of diethyl 70
imidazolidinylidene)-guanidine in 5 cc. of aniline is heated
oxalate is added into the filtrate and allowed to stand on a water bath until completely dissolved. After a com
overnight. The resulting precipitate is collected by Suc pletion of the reaction, an excess of aniline is distilled off
tion. Yield 1.13 g. (62%), M.P. 266-267° C. (with under reduced pressure. The resulting residue is recrystal
decomposition). Analysis.-Calcd. for C6HgONs: C, lized from ethanol to colorless plates which melt at 218
39.34; H, 4.95; N, 38.28. Found: C, 39.61; H, 4.90; N, 219 C.; yield 1.14 g. (42%). Analysis.-Calcd. for
38.32. CHONs: N, 30.80. Found: N, 30.80.
 3,271,393
7 3.
EXAMPLE 10 is heated for 2 hours on a water bath. After a comple
Preparation of 4-amino-6-cyclohexylamino-s-triazine tion of the reaction, the resulting residue is recrystallized
2-carboxypiperidide from a small amount of ethanol to give colorless prisms
O
which melt at 258 C.; yield 1.24 g. (50%). Analysis.-
5 Calcd. for CHONs: N, 28.17. Found: N, 28.34.
g gr)
C
EXAMPLE 1.4
N2 N
Preparation of 4-amino-6-(p-toluidino)-5-triazine
2-carboxylic acid
-NIE O
N /
N
A mixture of 2.37 g. of 1-cyclohexyl-3-(4,5-dioxo-2-
imidazolidinylidene)-guanidine and 1 cc. of piperidine is N
heated for 1 hour on a water bath. The resulting precipi C-NI
tate is collected by suction on cooling and recrystallized
from ethanol to colorless prisms which melt at 266 C.;
yield 1.64 g. (54%). Analysis.-Calcd. for C15H24ONG: Procedure 1-2.45 g. of 1-(p-tolyl)-3-(4,5-dioxo-2-
N, 27.61. Found: N, 27.89. imidazolidinylidene)-guanidine is dissolved in a dilute
EXAMPLE 1. 20 alkaline aqueous solution and the Solution is neutralized
Preparation of 4-amino-6-(p-methoxyphenylamino)- with hydrochloric acid. The resulting precipitate is col
s-triazine-2-carboxypyrrollidide lected by suction, washed with hot water and dried at
105 C. under pressure; M.P. 234-235 C. (with decom
O
/ position). Analysis.-Calcd. for C11H11O2N5: C, 53.87;
C-N H. 25 H, 4.52; N, 28.56. Found: C, 53.21; H, 4.29; N, 28.48.
C
Y Procedure 2-2.7 g. of ethyl 4-amino-6-(p-toluidino)-
2 NN s-triazine-2-carboxylate is refluxed with ethanolic Sodium
N hydroxide solution for 5 hours. After cooling, the pre
CIO-( )-NH-6S/C-NE 30
cipitate is collected and dissolved in a small amount of
water, followed by neutralization with hydrochloric acid,
A mixture of 2.61 g. of 1-(p-methoxyphenyl)-3-(4,5- and the colorless crystals precipitated are collected by
dioxo-2-imidazolidinylidene)-guanidine and 1 cc. of pyr suction, M.P. 234-235 C. .
rolidine is refluxed for 1 hour on a water bath. After
Procedure 3.-A mixture of 1.91 g. of 1-(p-tolyl)-
cooling, the deposited precipitate is collected by filtration biguanide and 1.51 g. of potassium salt of monethyl oxa
and recrystallized from ethanol to colorless needles which late in dehydrated ethanol is refluxed for 10 hours. When
melt at 215-216 C.; yield 1.82 g. (58%). Analysis cool, the precipitate is filtered and dissolved in a small
amount of water. The solution is neutralized with hy
Calcd. for C5H8ONs: N, 26.74. Found: N, 26.73. drochloric acid and the colorless crystals precipitated are
EXAMPLE 12
40
collected by suction, M.P. 234-235 C.
Preparation of 4-amino-6-(N-morpholinyl)-s-triazine EXAMPLE 1.5
2-carboxyguanidide hydrate Procedure 1.-Preparation of ethyl-4-amino-6-
(N-morpholinyl)-s-triazine-2-carboxylate
C-NII-C-NII O

a N
NH 45
(-oc.H.
N N
6 FI N-6 (-NH. -\
N - N
Y-1 S/ 6 in N- 8–NII,
50 Y-1 SN/
A suspension of 2.25 g. of 1,1-(2,2-oxydiethyl)3-(4,5-
dioxo-2-imidazolidinylidene)-guanidine in 150 cc. of de 2.25 g. of 1,1-(2,2-oxydiethyl)-3-(4,5-dioxo-2-imid
hydrated ethanol is refluxed for about 10 hours. After azolidinylidene)-guanidine in 150 cc. of dehydrated eth
completely dissolving, 0.6 g. of guanidine is added into anol is refluxed for 10 hours. The mixture is concen
the reaction mixture to reflux for 5 hours. The deposited 55 trated, followed by chilling. The precipitate is filtered
precipitate which forms on concentration of the solution and recrystallized from ethanol to obtain colorless prisms;
is collected by filtration upon cooling and recrystallized yield 1.62 g., M.P. 172 C. Analysis.--Calcd. for
from water to give colorless prisms which melt at 271 C.; CH5ONs: N, 27.66. Found: N, 28.13.
yield 1.3 g. (36%). Analysis.-Calcd. for C9H16ONs:
C, 38.02; H, 5.67; N, 39.42. Found: C, 38.19; H, 5.23; 60 Procedure 2.-Preparation of 4-amino-6-(N-mor
N, 39.33. pholinyl)-s-triazine-2-carboxyguanidide
EXAMPLE 13 To a solution of 2.53 g, of ethyl 4-amino-6-(N-mor
Preparation of 4-amino-6-(p-toluidino)-s-triazine pholinyl)-s-triazine-2-carboxylate in 100 cc. of dehydrated
2-carboxypyrrollidide ethanol, 0.6 g. of guanidine was added. After refluxing
O
65 on a water bath for 5 hours, the mixture was concen
/ trated and chilled. The precipitate was collected by suc
C-N tion, recrystallized from water to colorless prisms; M.P.
| Y
C 2.71° C.
a N EXAMPLE 16
N N 70 Preparation of 4-amino-6-(p-toluidino)-
CH-(D-NH-6NN /C-NI S-triazine-2-carboxypyrrollidide
To 2.45 g. of 4-amino-6-(p-toluidino)-s-triazine-2-
A mixture of 2.45 g. of 1-(p-tolyl)-3-(4,5-dioxo-2- carboxylic acid prepared by the above method is added
imidazolidinylidene)-guanidine and 0.71 g of pyrrolidine 75 an excess amount of thionyl chloride. After removal of
 3,271,393
O
excess thionyl chloride in vacuo, 1.5 cc. of pyrrolidine EXAMPLE 38
is added to the residue, and warmed on a water bath for In the process of Example 1, when the 4-morpholine
2 hours. After cooling, a diluted solution of alkali is carboximidoylguanidine hydrochloride is replaced with
added to the mixture, the resulting precipitate is recrys 0.1 mole of the hydrochlorides of biguanide, ox-methyl
tallized from ethanol to colorless prisms; yield 1.8 g., 5 biguanide, c-ethylbiguanide, c-methyl-o-isopropylbigua
M.P. 258 C. nide, a-n-butylbiguanide, ox-isobutylbiguanide, {3-pentyl-o-
Further examples of compounds of this invention rep- t-butylbiguanide, ox-hexylbiguanide, ox-2-ethylhexylbigua
resented by Formula I and which are prepared by the nide, 4-piperidinecarboximidoylguanidine, 4-pyrrolidine
general methods described above are set forth in Table IV. carboximidoylguanidine, and 2-cyclohexylbiguanide, re

TABLE IW

R Analysis NPercent
Group Y of Melting | Yield Molecular
Example Group N of Formula Formula I Appearance Point (Percent) Formula
R2 ( C.) Calc. Exper,

17----------- is0-C3HNH- -NH-CEIg-n Needles-------- ... 172-173 51 C11H20ON---- 33.31 33,08

18----------- iso-CHNF- -N H Plates.------------ 244 64 CuPIs ON---- 33.58 33.11

/
19----------- iso-CHNI- -N H X -- do------------- 266 59 C12H2OONs---- 31.80 31.78

20----------- iso-CHNI- -N E O -----do------------- 273 38 CH18ON--- 31.56 31,72

Y-1
21----------- ( )-Nit- -NH-C3H7-iso Rhombic Prisms. 175-176 48 C13EI2ONs---. 30.20 30, 55
/
22- ---------- H NH- -N H -----do------------- 246 57 C14H2ON6---- 28.95 28.73
-- (hy
23----------- H NH- -N E Plates------------- 214-215 36 C14H22ONs--- 27.43 27.49
Y-1
24----------- { i )-Nit- -NH-( ) -----do------------- 239 38 C1H20ON---- 26.91 26.80
25----------- O. H. N- --- H Rhombic Prisms. 205-206 53 C1F1s ONs--- 30, 20 30.20
Y-/
/ N /
26----------- O. H. N- -N H X ----- do------------- 274 52 C130ON6--- 28.75 28.95
N-1 N
27----------- O E. N- -N H Ö Plates------------- 84 57 C12H18O3.N.--- 28.56 28,86
Y-1 Y-1
/ N
28----------- O H N- -NH- Needles----------- 253-254 31 C14H16O2N6- - - 27.99 28, 02
Y--/
29----------- CH-( )-NH- -NH- C3H-iso ----- do------------- 22-222 56 C14H18ON6---- 29.35 29.83

30----------- CH,-( )-NH- -NH-CHg-n -----do------------- 193 63 C15H26ONs 27.98 28, 16

/
31----------- CH- -NH- -N H Rhombic Prisms. 245 5 C18H20ONs---. 26.91 27. 12

/
32----------- CH- -NE- -N H O Plates------------- 251 62 C15H18ON--. 26.74 26.84
N-/
33----------- CH-( >-NH- -NH-( ) - - - - -do------------- 239 39 C17H16ON6---. 26, 24 26, 11

34----------- CH,0-( )-NH- -NH-C3H7-iso Rhombic Prisms. 183-185 62 C14H8ON--- 27.80 27, 94
/
85----------- CH3O- -NE- -N H X -- do------------- 254-255 54 C10H10ONs--- 25.60 25.68

36----------- CHO-K >-Nit- -NN-1

E O Plates.------------- 236 41 C15H18O3Ns--- 25. 44 25, 68

37----------- CH,0-( )-NH- -NH-( ) - - Mrdo------------- 256 37 C17H16ON. 24.99 25.28

 3,271,393
11 2
3. A compound selected from the group consisting of
spectively, there are obtained, instead of 2-amino-4-mor compounds
pholino-6-(N-amidinocarbamoyl)-s-triazine as the final of the formula
product, the corresponding O
2,4-diamino-6-(N-amidinocarbamoyl)-s-triazine,
2-amino-4-N-methylamino-6-(N-amidinocarbamoyl)-s- {-y
triazine, e'sN
2-amino-4-N-ethylamino-6-(N-amidinocarbamoyl)-s- R1 N

triazine,
2-amino-4-(N-methyl-N-isopropylamino)-6-(N-amidino
carbamoyl)-s-triazine, IO
DN- 8-NH,
R2 N

2-amino-4-N-n-butylamino-6-(N-amidinocarbamoyl)-s- Ri and R2 taken together with >N- constitute a hetero

cyclic group selected from the group consisting of mor
triazine, pholino, piperidino and pyrrolidino, and Y is a member
2-amino-4-isobutylamino-6-(N-amidinocarbamoyl)-s- selected from the group consisting of morpholino, piperi
triazine, dino, pyrrolidino, hydroxy, amino, (lower)-alkylamino,
2-amino-4-(N-pentyl-N-t-butylamino)-6-(N-amidinocar phenylamino, and a radical of the formula
bamoyl)-s-triazine,
2-amino-4-hexylamino-6-(N-amidinocarbamoyl)-s-
triazine,
2-amino-4-(2-ethylhexylamino)-6-(N-amidinocar 20 4. A compound selected from the group consisting
bamoyl)-s-triazine, of compounds of the formula
2-amino-4-piperidino-6-(N-amidinocarbamoyl)-s- O
triazine, -x
2-amino-4-pyrrollidino-6-(N-amidinocarbamoyl)-s-
triazine, and
2-amino-4-cyclohexylamino-6-(N-amidinocarbamoyl)-s-
d
2 N
R N N
triazine.
We claim:
1.
DN- (-NH.
R S/
O NH
30 wherein the group R and R taken together with >N-
constitute a heterocyclic group selected from the group
(-NH-i-Nil,
-\ N
consisting of morpholino, piperidino and pyrrollidino,
and X is a member selected from the group consisting of
N chloro, bromo, fluor, iodo, and (lower) alkoxy.
6 N-d (-NH, References Cited by the Examiner
Y-1 SN UNITED STATES PATENTS
2.
40
2,881,170 4/1959 Bellet ----------- 260-247.2
3,060,181 10/1962 Strassberger et al. -- 260-249.9
O OTHER REFERENCES
'-ocii,
e'sN 45
Sokolovskara et al.: Chemical Abstracts, vol. 51, page
16, 493 (1957).
N
ALEX MAZEL, Primary Examiner.
6 II Y-d 8-NII, NICHOLAS RIZZO, HENRY R. JILES, JOSE TOVAR,
Yu-/ S/ Assistant Examiners.