Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen; alkyl of 1 to 7 carbon atoms; cycloalkyl of 3 to 7 carbon atoms; monosubstituted alkyl of 1 to 3 carbon atoms, where the substituent is pyridyl, methylpyridyl, phenyl, mono-, di- or trisubstituted phenyl, where the substituents on the phenyl ring, which may be identical to or different from each other, are selected from the group consisting of one amino, one dimethylamino, one to two hydroxyls, one to three methoxys and one to three halogens; .omega.-monosubstituted alkyl of 2 to 4 carbon atoms, where the substituent is hydroxyl or di(alkyl of 1 to 3 carbon atoms)amino; phenyl; monohalo-phenyl; unsubstituted or monosubstituted straight or branched alkanoyl of 1 to 6 carbon atoms, where the substituent is phenyl, methoxyphenyl or cycloalkyl of 3 to 7 carbon atoms; or unsubstituted or monosubstituted phenylsulfonyl, where the substituent is methyl or methoxy; and, PA1 R.sub.2 is hydrogen or alkyl of 1 to 3 carbon atoms; and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as cardiotonics, hypotensives and antithrombotics.

This invention relates to novel benzotriazolyldihydropyridazinones and 
salts thereof, to methods of preparing these compounds, to pharmaceutical 
compositions containing them as active ingredients, and to methods of 
using them as cardiotonics, hypotensives and antithrombotics. 
More particularly, the present invention relates to a novel class of 
compounds represented by the formula 
##STR2## 
wherein R.sub.1 is hydrogen; alkyl of 1 to 7 carbon atoms; cycloalkyl of 3 
to 7 carbon atoms; mono-substituted alkyl of 1 to 3 carbon atoms, where 
the substituent is pyridyl, methylpyridyl, phenyl, or mono-, di- or 
trisubstituted phenyl, where the substituents on the phenyl ring, which 
may be identical to or different from each other, are selected from the 
group consisting of one amino, one dimethylamino, one to two hydroxyls, 
one to three methoxys and one to three halogens; .omega.-monosubstituted 
alkyl of 2 to 4 carbon atoms, where the substituent is hydroxyl or 
di(alkyl of 1 to 3 carbon atoms)amino; phenyl; monohalo-phenyl; 
unsubstituted or monosubstituted straight or branched alkanoyl of 1 to 6 
carbon atoms, where the substituent is phenyl, methoxyphenyl or cycloalkyl 
of 3 to 7 carbon atoms; or unsubstituted or monosubstituted 
phenylsulfonyl, where the substituent is methyl or methoxy; and 
R.sub.2 is hydrogen or alkyl of 1 to 3 carbon atoms; and non-toxic, 
pharmacologically acceptable addition salts thereof formed with inorganic 
or organic acids. 
Specific examples of substituents R.sub.1 and R.sub.2 in formula I are the 
following: 
R.sub.1 --Hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 
tert.butyl, pentyl, isopentyl, neopentyl, tert. pentyl, hexyl, heptyl, 
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzyl, 
1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 
3-phenylpropyl, pyridylmethyl, methylpyridylmethyl, 
2-pyridylethyl-3-(methylpyridyl)-propyl, aminobenzyl, dimethylaminobenzyl, 
methoxybenzyl, dimethoxybenzyl, trimethoxybenzyl, hydroxybenzyl, 
dihydroxybenzyl, fluorobenzyl, difluorobenzyl, chlorobenzyl, 
dichlorobenzyl, trichlorobenzyl, bromobenzyl, dibromobenzyl, 
aminodichlorobenzyl, aminodibromobenzyl, dimethylamino-dichlorobenzyl, 
dimethylamino-dibromobenzyl, hydroxydichlorobenzyl, hydrocydibromobenzyl, 
methoxychlorobenzyl, methoxydichlorobenzyl, methoxybromobenzyl, 
methoxydibromobenzyl, 2-(methoxyphenyl)-ethyl, 2-(dimethoxyphenyl)-ethyl, 
2-(chlorophenyl)-ethyl, 3-(methoxyphenyl)-propyl, 3-(fluorophenyl)-propyl, 
3-(bromophenyl)-propyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 
2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 2-dimethylaminoethyl, 
2-dipropylaminoethyl, 3-dipropylaminopropyl, 4-dimethylaminobutyl, 
4-diethylaminobutyl, 4-dipropylaminobutyl, phenyl, fluorophenyl, 
chlorophenyl, bromophenyl, formyl, acetyl, propionyl, butanoyl, pentanoyl, 
hexanoyl, dimethylacetyl, benzoyl, methoxybenzoyl, phenyldimethylacetyl, 
cyclopropanoyl, cyclopentanoyl, cyclohexanoyl, cycloheptanoyl, 
phenylacetyl, 3-phenylpropionyl, 4-phenylbutanoyl, phenylsulfonyl, 
methylphenylsulfonyl or methoxyphenylsulfonyl group; and 
R.sub.2 --hydrogen, methyl, ethyl, propyl or isopropyl. 
A preferred subgenus is constituted by those compounds of the formula I 
wherein 
R.sub.1 is hydrogen; alkyl of 1 to 6 carbon atoms; cycloalkyl of 3 to 6 
carbon atoms; benzyl; hydroxybenzyl; dimethylamino-benzyl; mono- or 
dimethoxy-benzyl; amino-dichloro-benzyl; amino-dibromo-benzyl; 
.omega.-monostubstituted alkyl of 2 to 4 carbon atoms, where the 
substituent is hydroxyl, methoxy-phenyl of di(alkyl of 1 to 3 carbon 
atoms)amino; alkanoyl of 1 to 6 carbon atoms; phenyl-(alkanoyl of 1 to 6 
carbon atoms); methoxyphenyl-(alkanoyl of 1 to 6 carbon atoms); 
pyridylmethyl; methylpyridylmethyl; phenyl; fluorophenyl; chlorophenyl; 
bromophenyl; cyclohexanoyl; or methoxyphenylsulfonyl; and 
R.sub.2 is hydrogen or methyl; and non-toxic, pharmacologically acceptable 
acid addition salts thereof, especially those where the pyridazinone ring 
is attached to the 5-position of the benzotriazole moiety. 
An especially preferred subgenus is constituted by compounds of the formula 
##STR3## 
wherein R.sub.1 is alkyl of 1 to 4 carbon atoms, dimethylaminoethyl, 
cyclohexanoyl, p-methoxy-benzoyl or p-methoxy-benzyl, 
and non-toxic, pharmacologically acceptable addition salts thereof. 
The compounds embraced by formula I may be prepared by the following 
methods: 
Method A 
By reacting a compound of the formula 
##STR4## 
wherein R.sub.1 and R.sub.2 have the meanings previously defined, with an 
inorganic or organic nitrite. 
The reaction is advantageously performed in a suitable solvent, for 
instance with an inorganic nitrite such as sodium nitrite in water, 
water/methanol or water/dioxane, and in the presence of an acid such as 
hydrochloric, sulfuric or glacial acetic acid, but preferably in 
semi-concentrated hydrochloric acid as the solvent, or with an organic 
nitrite such as an ester of nitrous acid, for example ethyl nitrite or 
tert. butyl nitrite, in methanol, ethanol or dioxane, at low temperatures, 
for instance at temperatures between -10.degree. and 40.degree. C., but 
preferably at temperatures between 0.degree. and 25.degree. C. 
Method B 
By reacting a carboxylic acid of the formula 
##STR5## 
wherein R.sub.1 and R.sub.2 have the meanings previously defined, or an 
anhydride, ester, thioester, amide, imidazolide or halide thereof, with 
hydrazine. 
The reaction is advantageous carried out in a solvent such as methanol, 
ethanol, isopropanol, glacial acetic acid or propionic acid and/or in an 
excess of hydrazine or hydrazine hydrate at temperatures between 0.degree. 
and 200.degree. C., for instance at temperatures between 20.degree. and 
150.degree. C., but preferably at the boiling point of the reaction 
mixture, and optionally in the presence of an acid such as sulfuric acid 
or p-toluenesulfonic acid as a condensation agent. However, the reaction 
may also be carried out without a solvent. 
The compounds of the formula I wherein R.sub.2 is other than hydrogen 
comprise an optically active carbon atom in the 5-position of the 
pyridazinone ring and can be separated into their optically active 
enantiomers by cleavage of the racemates. 
Cleavage of the racemates is advantageously effected by fractional 
crystallization of the corresponding salts with optionally active acids, 
such as tartaric, dibenzoyltartaric, malic, camphoric or camphorsulfuric 
acid, or by chromatography on optically active adsorbents. 
The compounds embraced by formula I are basic and therefore from addition 
salts with inorganic or organic acids. Examples of non-toxic, 
pharmacologically acceptable acid addition salts are those formed with 
hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, 
fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid, 
maleic acid or the like. 
The starting compounds of the formuls II and III may be prepared by methods 
described in the literature. For example, a compound of the formula II is 
obtained by reacting a corresponding substituted 
3-(nitroaminobenzoyl)-propionic acid ester with hydrazine and subsequently 
reducing the nitro group. 
A compound of the formula III is obtained by reacting a compound of the 
formula 
##STR6## 
with a malonic acid ester. The compound thus obtained is then hydrolyzed, 
decarboxylated and nitrated, the chlorine atom is replaced by a 
corresponding amino group, the resulting amino compound is optionally 
alkylated or acylated, the nitro group is reduced, and the resulting 
intermediate is cyclized with a nitrite to form the desired triazole.

The following examples illustrate the present invention and will enable 
others skilled in the art to understand it more completely. It should be 
understood, however, that the invention is not limited solely to the 
particular examples given below. 
PREATION OF STARTING COMPOUNDS 
Example I 
5-Methyl-6-[3'-nitro-4'-benzylamino-phenyl]-4,5-dihydro-3(2H)-pyridazinone 
10.9 gm (40.0 mmols) of 
3-methyl-4-oxo-4-(3'-nitro-4'-chloro-phenyl)-butyric acid and 21.4 gm 
(200.0 mmols) of benzylamine were dissolved in 100 ml of ethanol, and the 
solution was refluxed for 5 hours. Then, the solvent was evaporated in 
vacuo, and the residue was added to a mixture of 500 ml of ice-cold water 
and 50 ml of concentrated hydrochloric acid, whereupon an oily product 
precipitated. After being separated from the aqueous phase and without 
prior purification, this oil was heated for one hour at 110.degree. C. in 
a solution of 20 ml of 99% hydrazine hydrate and 100 ml of glacial acetic 
acid. The reaction mixture was then stirred into 200 ml of water, and the 
precipitated product was suction-filtered off, washed with water and dried 
at 80.degree. C. 
Yield: 13.4 gm (99% of theory). 
Melting point: 187.degree.-191.degree. C. 
C.sub.18 H.sub.18 N.sub.4 O.sub.3 (338.37). 
Calc.: C--63.89%; H--5.36%; N--16.56%; Found: C--64.58%; H--5.48%; 
N--16.22%. 
Example II 
5-Methyl-6-[3'-amino-4'-benzylamino-phenyl]-4,5-dihydro-3(2H)-pyridazinone 
12.5 gm (36.9 mmols) of 
5-methyl-6-[3'-nitro-4'-benzylamino-phenyl]-4,5-dihydro-3(2H)-pyridazinone 
were added to a mixture of 20 ml of 99% hydrazine hydrate and 350 ml of 
ethanol, and then 10 gm of Raney nickel were added. After 24 hours' 
stirring at room temperature, the solid components were suction-filtered 
off, dissolved in dimethyl formamide, the catalyst was filtered off, and 
the filtrate was evaporated. The crystalline residue thus obtained was 
digested with ethanol, washed with ether and dried. 
Yield: 9.5 gm (82.5% of theory). 
Melting point: 186.degree.-188.degree. C. 
Example III 
3-Methyl-4-oxo-4-[3'-nitro-4'-(4-dimethylamino-butylamino)-phenyl]-butyric 
acid 
4 gm (14.75 mmols) of 3-methyl-4-oxo-4-(3'-nitro-4'-chlorophenyl)-butyric 
acid and 5.8 gm (50.0 mmols) of 4-dimethylaminobutyl-amine were refluxed 
in 50 ml of ethanol for 2 hours, and then the volatile components were 
evaporated in vacuo. A viscous oil was obtained, which was reacted further 
without being purified. 
Yield: 5.18 gm (100% of theory). 
Thin-layer chromatogram: R.sub.f =0.12 (silicagel, eluant: methylene 
chloride/ethanol=19:1). 
Example IV 
3-Methyl-4-oxo-4-[3'-amino-4'-(4-dimethylamino-butylamino)-phenyl]-butyric 
acid 
5.18 gm (about 14.75 mmols) of crude 
3-methyl-4-oxo-4-[3'-nitro-4'-(4-dimethylaminobutyl-amino)-phenyl]-butyric 
acid were dissolved in 50 ml of methanol and, after the addition of 1 gm 
of Raney nickel, treated in a Parr apparatus at room temperature with 
hydrogen (5 bars). After the calculated amount of hydrogen had been taken 
up, the reaction was stopped, the catalyst was removed from the reaction 
mixture, and the filtrate was evaporated in vacuo. The reaction product 
thus obtained was reacted further without being purified. 
Yield: 4.8 gm (100% of theory). 
Thin-layer chromatogram: R.sub.f =0.19 (silicagel, eluant: ethanol). 
Example V 
3-Methyl-4-oxo-4-[1'-(4-dimethylamino-butyl)-benzotriazol-5'-yl]-butyric 
acid 
4.8 gm (about 14.7 mmols) of cryde 
3-methyl-4-oxo-4-[3'-amino-4'-(4-dimethylamino-butylamino)-phenyl]-butyric 
acid were dissolved in 100 ml of 2N hydrochloric acid, and at 0.degree. to 
5.degree. C. a solution of 1.38 gm (20 mmols) of sodium nitrite in 10 ml 
of water was added dropwise thereto. After being stirred for two hours at 
room temperature the reaction mixture was evaporated to dryness in vacuo. 
The crude product thus obtained was reacted further without being 
purified. 
Yield: 5.3 gm of crude product. 
Thin-layer chromatogram: R.sub.f =0.38 (silicagel, eluant: ethanol). 
Example VI 
Methyl 
3-methyl-4-oxo-4-[3'-nitro-4'-(.alpha.-methyl-.alpha.-phenyl-propionylamin 
o)]-butyrate 
6 gm (22.5 mmols) of methyl 
3-methyl-4-oxo-4-(3'-nitro-4'-amino-phenyl)-butyrate were refluxed with 9 
ml of .alpha.-methyl-.alpha.-phenyl-propionic acid chloride in 50 ml of 
chlorobenzene for 8 hours. Then, the solvent was evaporated in vacuo, and 
the reaction product was obtained from the residue as a yellow oil by 
column chromatography (800 gm of silica gel, methylene chloride). 
Yield: 9.25 gm (100% of theory). 
Thin-layer chromatogram: R.sub.f =0.73 (silica gel, eluant: methylene 
chloride/ethanol=19:1). 
Example VII 
5-Methyl-6-[3'-nitro-4'-(.alpha.-methyl-.alpha.-phenyl-propionylamino)-phen 
yl]-4,5-dihydro-3(2H)-pyridazinone 
9 gm (21.8 mmols) of methyl 
3-methyl-4-oxo-4-[3'-nitro-4'-(.alpha.-methyl-.alpha.-phenyl-propionylamin 
o)]-butyrate were heated at 110.degree. C. for 11/2 hours in a solution of 
20 ml of 99% hydrazine hydrate in 100 ml of glacial acetic acid. The 
mixture was then poured into 200 ml of ice-cold water. The reaction 
product which precipitated was suction-filtered off, dried and purified by 
column chromatography (500 gm of silica gel, methylene chloride with 0.5% 
of ethanol). 
Yield: 7.0 gm (79% of theory). 
Melting point: 160.degree.-162.degree. C. 
C.sub.21 H.sub.22 N.sub.4 O.sub.4 (394.4). 
Calc.: C--63.95%; H--5.62%; N--14.20%; Found: C--64.05%; H--5.65%; 
N--14.51%. 
Example VIII 
5-Methyl-6-[3'-amino-4'-(.alpha.-methyl-.alpha.-phenyl-propionylamine)-phen 
yl]-4,5-dihydro-3(2H)-pyridazinone 
6.78 gm (17.2 mmols) of 
5-methyl-6-[3'-nitro-4'-(.alpha.-methyl-.alpha.-phenyl-propionlyamino)-phe 
nyl]-4,5-dihydro-3(2H)-pyridazinone were dissolved in 80 ml of 
dimethylformamide and, after the addition of 1 gm of 10% 
palladium-on-charcoal, the mixture was treated with hydrogen (5 bars) in a 
Parr apparatus at room temperature. After the uptake of hydrogen was 
complete, the catalyst was filtered off, and the filtrate was concentrated 
by evaporation in vacuo. The crude product thus obtained as an oily 
residue was reacted further without being purified. 
Yield: 6.3 gm (about 100% of theory). 
Thin-layer chromatogram: R.sub.f =0.55 (silica gel, eluant: methylene 
chloride/ethanol=9:1). 
PREATION OF THE END PRODUCTS OF THE FORMULA 1 
Example 1 
5-methyl-6-(1'-benzyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
9 gm (29.2 mmols) of 
5-methyl-6-(3'-amine-4'-benzyl-amino-phenyl)-4,5-dihydro-3(2H)-pyridazinon 
e were dissolved in 200 ml of semi-concentrated hydrochloric acid, and at 
0.degree. to 5.degree. C. a solution of 4.13 gm (60 mmols) of sodium 
nitrite in 40 ml of water was slowly added dropwise, while stirring. After 
the reaction mixture had been stirred for another 5 hours at room 
temperature, the reaction product was suction-filtered off and 
recrystallized from acetone. 
Yield: 6.5 gm (69.6% of theory). 
Melting point: 160.degree.-162.degree. C. 
C.sub.18 H.sub.17 N.sub.5 O (319.4). 
Calc.: C--67.70%; H--5.37%; N--21.93%; Found: C--67.52%; H--5.45%; 
N--21.56%. 
Example 2 
5-Methyl-6-[1'-(4-dimethylamino-butyl)-benzotriazol-5-yl]-4,5-dihydro-3(2H) 
-pyridazinone 
5.3 gm (about 14 mmols) of crude 
3-methyl-4-oxo-4-[1'-(4-dimethylamino-butyl)-benzotriazol-5'-yl]-butyric 
acid were added to a solution of 15 ml of 99% hydrazine hydrate in 50 ml 
of glacial acetic acid, and the mixture was heated at 110.degree. C. for 2 
hours and then poured into 150 ml of water. The aqueous solution was made 
slightly alkaline with 2N ammonia and was extracted several times with 
methylene chloride. After drying over sodium sulfate, the combined organic 
extracts were evaporated to dryness in vacuo. The crude product thus 
obtained was purified by column chromatography (300 gm of silica gel, 
methylene chloride +10% ethanol). 
Yield: 1.4 gm (28.8% of theory). 
Melting point: 134.degree.-136.degree. C. 
C.sub.17 H.sub.24 N.sub.6 O (328.43). 
Calculated: C--62.17%; H--7.37%; N--25.59%; Found: C--61.23%; H--7.35%; 
N--25.38%. 
Example 3 
5-Methyl-6benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3',4'-diamino-phenyl)-4,5-dihydro-3(2H)-pyridazinone. 
Yield: 39.5% of theory. 
Melting point: 247.degree.-249.degree. C. 
C.sub.11 H.sub.11 N.sub.5 O (229.2) 
Calculated: C--57.63%; H--4.84%; N--30.55%. Found: C--57.40%; H--4.90%; 
N--30.31%. 
Example 4 
5-Methyl-6-(1'-methylbenzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-methylamino-phenyl)-4,5-dihydro-3(2H)-pyridazinone 
. 
Yield: 29.4% of theory. 
Melting point: 223.degree.-224.degree. C. 
C.sub.12 H.sub.13 N.sub.5 O (243.3). 
Calculated: C--59.25%; H--5.39%; N--28.79%; Found: C--59.13%; H--5.60%; 
N--29.28%. 
Example 5 
5-Methyl-6-(1'-ethyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'ethylamino-phenyl)-4,5-dihydro-3(2H)-pyridazinone. 
Yield: 29.5% of theory. 
Melting point: 189.degree.-192.degree. C. 
C.sub.13 H.sub.15 N.sub.5 O (257.3). 
Calculated: C--60.69%; H--5.88%; N--27.22%; Found: C--60.60%; H--5.86%; 
N--27.41%. 
Example 6 
5-Methyl-6-(1' 
-isopropyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-isopropylamino-phenyl)-4,5-dihydro-3(2H)-pyridazin 
one. 
Yield: 51.3% of theory. 
Melting point: 185.degree.-187.degree. C. 
C.sub.14 H.sub.17 N.sub.5 O (271.3). 
Calculated: C--61.98%; H--6.32%; N--25.81%; Found: C--62.03%; H--6.26%; 
N--25.69. 
Example 7 
5-Methyl-6-(1'-cyclopropyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazino 
ne 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-cyclopropylamino-phenyl)-4,5-dihydro-3(2H)-pyridaz 
inone. 
Yield: 39.5% of theory. 
Melting point: 219.degree.-221.degree. C. 
C.sub.14 H.sub.15 N.sub.5 O (269.3). 
Calculated: C--62.44%; H--5.61%; N--26.00%; Found: C--62.91%; H--5.61%; 
N--26.44%. 
Example 8 
5- Methyl-6-(1'-n-hexyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'n-hexylamino-phenyl)-4,5-dihydro-3(2H)-pyridazinone 
. 
Yield: 38.2% of theory. 
Melting point: 162.degree.-164.degree. C. 
C.sub.17 H.sub.23 N.sub.5 O (313.4). 
Calculated: C--65.15%; H--7.40%; N--22.35%; Found: C--65.30%; H--7.16%; 
N--22.48%. 
Example 9 
5-Methyl-6-[1'(2-hydroxy-ethyl)-benzotriazol-5'-yl]-4,5-dihydro-3(2H)-pyrid 
azinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-[3'-amino-4'-(2-hydroxyethyl)amino-phenyl]-4,5-dihydro-3(2H)-py 
ridazinone. 
Yield: 26% of theory. 
Melting point: 182.degree.-183.degree. C. 
C.sub.13 H.sub.15 N.sub.5 O (273.3). 
Calculated: C--57.13%; H--5.53%; N--25.63%; Found: C--57.00%; H--5.50%; 
N--25.60%. 
Example 10 
5-Methyl-6-[1'-(2-dimethylamino-ethyl)-benzotriazol-5'-yl)-4,5-dihydro-3(2H 
)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-dimethylaminoethylamino-phenyl)-4,5-dihydro-3(2H)- 
pyridazinone. 
Yield: 32% of theory. 
Melting point: 146.degree.-148.degree. C. 
C.sub.15 H.sub.20 N.sub.6 O (300.37). 
Calculated: C--59.98%; H--6.71%; N--27.98%; Found: C--60.07%; H--6.70%; 
N--28.09%. 
Example 11 
5-Methyl-6-[1'-(3-di-n-propylamino-propyl)-benzotriazol-5'-yl]-4,5-dihydro- 
3(2H)-pyridazinone 
This compound is prepared analogous to Example 1 from 
5-methyl-6-[3'amino-4'-(3-di-n-propylaminopropyl-amino)-phenyl]-4,5-dihydr 
o-3(2H)-pyridazinone. 
Yield: 11% of theory. 
Melting point: 142.degree.-144.degree. C. 
C.sub.20 H.sub.30 N.sub.6 O (370.51). 
Calculated: C--64.84%; H--8.16%; N--22.68%; Found: C--65.28%; H--7.96%; 
N--22.63%. 
Example 12 
5-Methyl-6-(1'-cyclohexyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinon 
e 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-cyclohexylamino-phenyl)-4,5-dihydro-3(2H)-pyridazi 
none. 
Yield: 64% of theory. 
Melting point: 212.degree.-213.degree. C. 
C.sub.17 H.sub.21 N.sub.5 O (309.4). 
Calculated: C--65.57%; H--6.80%; N--22.49%; Found: C--65.12%; H--6.70%; 
N--22.47%. 
Example 13 
5-Methyl-6-(1'-phenyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-phenylamino-phenyl)-4,5-dihydro-3(2H)-pyridazinone 
. 
Yield: 38.4% of theory. 
Melting point: 218.degree.-219.degree. C. 
C.sub.17 H.sub.15 N.sub.5 O (305.3). 
Calculated: C--66.87%; H--4.95%; N--22.94%; Found: C--66.51%; H--4.94%; 
N--22.77%. 
Example 14 
5-Methyl-6-(1'-fluorophenyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazin 
one 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-p-fluorophenylamino-phenyl)-4,5-dihydro-3(2H)-pyri 
dazinone. 
Yield: 58% of theory. 
Melting point: &gt;250.degree. C. 
C.sub.17 H.sub.14 N.sub.5 OF (323.34). 
Calculated: C--63.14%; H--4.36%; N--21.66%; Found: C--63.20%; H--4.51%; 
N--21.59%. 
Example 15 
5-Methyl-6-(1'-p-methoxybenzyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyrida 
zinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-p-methoxybenzylamino-phenyl)-4,5-dihydro-3(2H)-pyr 
idazinone. 
Yield: 14.3% of theory. 
Melting point: 157.degree.-159.degree. C. 
C.sub.19 H.sub.19 N.sub.5 O.sub.2 (349.4). 
Calculated: C--65.32%; H--5.48%; N--20.04%; Found: C--65.40%; H--5.55%; 
N--20.01%. 
Example 16 
5-Methyl-6-(1'-p-hydroxybenzyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyrida 
zinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-p-hydroxybenzylamino-phenyl)-4,5-dihydro-3(2H)-pyr 
idazinone. 
Yield: 26.9% of theory. 
Melting point: 193.degree.-195.degree. C. 
C.sub.18 H.sub.17 N.sub.5 O.sub.2 (335.4). 
Calculated: C--64.47%; H--5.11%; N--20.88%; Found: C--64.48%; H--5.22%; 
N--21.16%. 
Example 17 
5-Methyl-6-{1'-[2-(p-methoxy-phenyl)-ethyl]-benzotriazol-5'yl{-4,5-dihydro- 
3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-{3'-amino-4'-[2-(p-methoxy-phenyl)-ethyl-amino]phenyl{-4,5-dihy 
dro-3(2H)-pyridazinone. 
Yield: 20.8% of theory. 
Melting point: 218.degree.-220.degree. C. 
C.sub.20 H.sub.21 N.sub.5 O.sub.2 (363.4). 
Calculated: C--66.10%; H--5.82%; N--19.27%; Found: C--66.24%; H--5.71%; 
N--19.27%. 
Example 18 
5-Methyl-6-[1'-(3,4-dimethoxy-benzyl)-benzotriazol-5'-yl]-4,5-dihydro-3(2H) 
-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-[3'-amino-4'-(3,4-dimethoxybenzyl-amino)-phenyl]-4,5-dihydro-3( 
2H)-pyridazinone. 
Yield: 52% of theory. 
Melting point: 197.degree.-200.degree. C. 
C.sub.20 H.sub.21 N.sub.5 O.sub.3 (379.4). 
Calculated: C--63.31%; H--5.58%; N--18.40%; Found: C--63.37%; H--5.46%; 
N--18.29%. 
Example 19 
5-Methyl-6-(1'-p-dimethylaminobenzyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)- 
pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-p-dimethylaminobenzylaminophenyl)-4,5-dihydro-3(2H 
)-pyridazinone. 
Yield: 35% of theory. 
Melting point: 196.degree.-198.degree. C. 
C.sub.20 H.sub.22 N.sub.6 O (362.44). 
Calculated: C--66.27%; H--6.12%; N--23.18%; Found: C--65.52%; H--6.29%; 
N--23.64%. 
Example 20 
5-Methyl-6-(1'-p-methoxyphenylsulfonyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H 
)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-p-methoxyphenylsulfonylamino-phenyl)-4,5-dihydro-3 
(2H)-pyridazinone. 
Yield: 33% of theory. 
Melting point: 170.degree.-173.degree. C. 
C.sub.18 H.sub.17 N.sub.5 O.sub.4 S (399.44). 
Calculated: C--54.12%; H--4.29%; N--17.53%; S--8.03%; Found: C--54.20%; 
H--4.38%; N--17.85%; S--8.13%. 
Example 21 
5-Methyl-6-[1'-(2-picolyl)-benzotriazol-5'-yl]-4,5-dihydro-3(2H)-pyridazino 
ne 
This compound was prepared analogous to Example 1 from 
5-methyl-6-[3'-amino-4'-(2-picolylamino)-phenyl]-4,5-dihydro-3(2H)-pyridaz 
inone. 
Yield: 39.7% of theory. 
Melting point: 95.degree.-97.degree. C. 
C.sub.17 H.sub.16 N.sub.6 O (320.36). 
Calculated: C--63.74%; H--5.03%; N--26.24%; Found: C--63.04%; H--5.43%; 
N--26.93%. 
Example 22 
5-Methyl-6-[1'-(3-picolyl)-benzotriazol-5'-yl]-4,5-dihydro-3(2H)-pyridazino 
ne 
This compound was prepared analogous to Example 1 from 
5-methyl-6-[3'-amino-4'-(2-picolylamino)-phenyl]-4,5-dihydro-3(2H)-pyridaz 
inone. 
Yield: 39.8% of theory. 
Melting point: 202.degree.-204.degree. C. 
C.sub.17 H.sub.16 N.sub.6 O (320.36). 
Calculated: C--63.74%; H--5.03%; N--26.24%; Found: C--63.95%; H--5.14%; 
N--26.39%. 
Example 23 
5-Methyl-6-[1'-(6-methyl-2-picolyl)-benzotriazol-5'-yl]-4,5-dihydro-3(2H)-p 
yridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-[3'-amino-4'-(6-methyl-2-picolylamino)-phenyl]-4,5-dihydro-3(2H 
)-pyridazinone. 
Yield: 40% of theory. 
Melting point of the hydrochloride: 213.degree.-218.degree. C. 
C.sub.18 H.sub.18 N.sub.6 O.times.HCl (370.85). 
Calculated: C--58.30%; H--5.16%; N--22.66%; Cl--9.56%; 
Found: C--58.37%; H--5.01%; N--23.29%; Cl--9.71%. 
Example 24 
5-Methyl-6-[1'-(3,5-dichloro-4-amino-benzyl)-benzotriazol-5'-yl]-4,5-dihydr 
o-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-[3'-amino-4'-(3,4-dichloro-4-aminobenzyl-amino)-phenyl]-4,5-dih 
ydro-3(2H)-pyridazinone. 
Yield: 10.5% of theory. 
Melting point: 250.degree.-252.degree. C. 
C.sub.18 H.sub.18 N.sub.6 OCl.sub.2 (401.27). 
Example 25 
5-Methyl-6-[1'-(.alpha.-methyl-.alpha.-phenyl-propionyl)-benzotriazol-5'-yl 
]-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-[3'-amino-4'-(.alpha.-methyl-.alpha.-phenyl-propionyl-amino)-ph 
enyl]-4,5-dihydro-3(2H)-pyridazinone. 
Yield: 36.4% of theory. 
Melting point: 196.degree.-198.degree. C. 
C.sub.21 H.sub.21 N.sub.5 O.sub.2 (375.4). 
Calculated: C--67.18%; H--5.64%; N--18.65%; Found: C--67.00%; H--5.66%; 
N--18.65%. 
Example 26 
5-Methyl-6-(1'-acetyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-acetylamino-phenyl)-4,5-dihydro-3(2H)-pyridazinone 
. 
Yield: 8.0% of theory. 
Melting point: 213.degree.-215.degree. C. 
Example 27 
5-Methyl-6-(1'-n-hexanoyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinon 
e 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-n-hexanoylamino-phenyl)-4,5-dihydro-3(2H)-pyridazi 
none. 
Yield: 55.5% of theory. 
Melting point: 147.degree.-149.degree. C. 
C.sub.17 H.sub.21 N.sub.5 O.sub.2 (327.4). 
Calculated: C--62.37%; H--6.47%; N--21.39%; Found: C--62.43%; H--6.42%; 
N--21.38%. 
Example 28 
5-Methyl-6-(1'-p-methoxybenzoylbenzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyrida 
zinone 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(3'-amino-4'-p-methoxybenzoylamino-phenyl)-4,5-dihydro-3(2H)-py 
ridazinone. 
Yield: 61.3% of theory. 
Melting point: 220.degree.-225.degree. C. 
C.sub.19 H.sub.17 N.sub.5 O.sub.3 (363.4). 
Calculated: C--62.80%; H--4.72%; N--19.27%; Found: C--62.98%; H--4.84%; 
N--19.37%. 
Example 29 
5-Methyl-6-(1'-cyclohexanoyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazi 
none. 
This compound was prepared analogous to Example 1 from 
5-methyl-6-(1'-amino-4'-cyclohexanoylamino-phenyl)-4,5-dihydro-3(2H)-pyrid 
azinone. 
Yield: 76.3% of theory. 
Melting point: 218.degree.-221.degree. C. 
C.sub.18 H.sub.21 N.sub.5 O.sub.2 (339.4). 
Calculated: C--63.70%; H--6.24%; N--20.63%; Found: C--64.13%; H--6.11%; 
N--20.45%. 
The compounds of the present invention, that is, those embraced by formula 
I above and their non-toxic, pharmacologically acceptable acid addition 
salts, have useful pharmacodynamic properties. More particularly, they 
exhibit cardiovascular properties, namely cardiotonic, hypotensive and 
antithrombotic activities in warm-blooded animals such as rats. 
The above pharmacological properties of the compounds of the present 
invention were ascertained by the standard test methods described below, 
and the results of these tests for a few representative species of the 
genus are shown in the tables, where 
A=5-Methyl-6-(1'-p-methoxybenzoyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyr 
idazinone, 
B=5-Methyl-6-(1'-cyclohexanoyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyrida 
zinone, 
C=5-Methyl-6-(1'-isopropyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazino 
ne, 
D=5-Methyl-6-(1'-ethyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone, 
E=5-Methyl-6-(1'-p-methoxybenzyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyri 
dazinone, 
F=5-Methyl-6-[1'-(2-dimethylaminoethyl)-benzotriazol-5'-yl]-4,5-dihydro-3(2 
H)-pyridazinone, and 
G=5-Methyl-6-(1'-methyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone. 
1. Determination of the thrombocyte aggregation according to Born and Cross 
[J. Physiol. 170, 397 (1964) 
The thrombocyte aggregation was determined in platelet-rich plasma from 
healthy human test subjects. The course of decrease in optical density 
after the administration of standard commercial collagen (made by the 
Sigma Co., St. Louis, Mo.) containing 1 mg of collagen fibrils per ml was 
measured photometrically and recorded. The rate of aggregation (V.sub.max) 
was deduced from the angle of inclination of the density curve. The point 
on the curve where there was most light transmittance was used to 
calculate the optical density (O.D.). To initiate maximum aggregation, 
about 0.01 ml of the collagen solution was added to 1 ml of platelet-rich 
plasma. 
The following Table shows the results obtained: 
______________________________________ 
Compound EC.sub.50 in mol/liter 
______________________________________ 
A 2.7 .times. 10.sup.-7 
B 2.8 .times. 10.sup.-7 
C 3.3 .times. 10.sup.-8 
D 4.1 .times. 10.sup.-8 
F 3.0 .times. 10.sup.-7 
G 5.1 .times. 10.sup.-8 
______________________________________ 
2. Determination of hypotensive and positive inotropic activity in the 
anesthetized cat 
The tests were carried out on cats which had been anesthetized with sodium 
pentobarbital (40 mg/kg i.p.). The animals breathed spontaneously. The 
arterial blood pressure was measured in the aorta abdominalis using a 
Statham pressure transducer (P 23 Dc). To determine the positive inotropic 
effect, the pressure in the left ventricle of the heart was measured using 
a catheter-tip manometer (Milliar Pc-350 A). From this, the contractility 
parameter (dp/dt.sub.max was obtained by means of an analog 
differentiator. 
The test compounds were injected into a vena femoralis. Physiological 
saline solution of Polydiol 200 was used as the solvent. Each compound was 
tested on at least 3 cats in a dosage of 0.1 or 2.0 mg/kg i.v. The 
duration of activity of the test compounds was at least 45 minutes in each 
case. 
The following Table contains the average values: 
______________________________________ 
Dosage Change in blood pressure 
Increase in 
Compound 
mg/kg i.v. 
in mm Hg dp/dt in % 
______________________________________ 
A 0.1 -16/-16 +105 
B 2.0 -60/-37 +154 
C 0.1 -27/-33 +116 
D 0.1 -30/-32 +125 
E 0.1 -48/-48 +167 
G 0.1 -33/-38 +168 
______________________________________ 
3. Acute toxicity 
In therapeutic doses the test substances are non-toxic. For example, 
compound B has a peroral LD.sub.50 of &gt;50 mg/kg in the mouse. 
In view of their pharmacological properties, the compounds of the formula 
I, the optically active enantiomers thereof, and their non-toxic, 
pharmacologically acceptable addition salts with inorganic or organic 
acids are useful for the treatment of chronic cardiac insufficiency or 
angina pectoris and for the prophylaxis of arterial thromboembolism and 
arterial occlusion. 
For pharmaceutical purposes the compounds of the present invention are 
administered to warm-blooded animals perorally, parenterally or rectally 
as active ingredients in customary pharmaceutical compositions, that is, 
compositions consisting essentially of an inert pharmaceutical carrier and 
an effective amount of the active ingredient, such as tablets, coated 
pills, capsules, wafers, powders, solutions, suspensions, emulsions, 
syrups, suppositories and the like. An effective amount of the compounds 
of the present inventions is from 0.14 to 0.71 mgm/kg, preferably 0.29 to 
0.57 mgm/kg body weight i.v., and from 0.71 to 2.14 mgm/kg, preferably 
1.07 to 1.43 mgm/kg body weight p.o., 1 to 4 times daily. 
The following examples illustrate a few pharmaceutical compositions 
comprising a compound of the present invention as an active ingredient and 
represent the best modes contemplated of using the invention. The parts 
are parts be weight unless otherwise specified. 
Example 30 
Tablets containing 100 mg of 
5-methyl-6-(1'-methylbenzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
The tablet composition is compounded from the following ingredients: 
______________________________________ 
Active ingredient 100.0 parts 
Lactose 50.0 parts 
Polyvinyl pyrrolidone 5.0 parts 
Carboxymethylcellulose 19.0 parts 
Magnesium stearate 1.0 parts 
175.0 parts 
______________________________________ 
The active ingredient and lactose are mixed homogeneously moistened with an 
aqueous solution of the polyvinyl pyrrolidone. 
Moist screening: 1.5 mm-mesh. 
Drying: Circulating air drier at 50.degree. C. 
Dry-screening: 1 mm-mesh. 
The remaining excipients are added to the granulate, and the finished 
mixture is compressed into tablets. 
Weight of tablet: 175 mg. 
Punch: 8 mm .phi.. 
Example 31 
Coated tablets containing 50 mg of 5-methyl-6-(1'-methyl 
benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
The tablet core composition is compounded from the following ingredients: 
______________________________________ 
Active ingredient 50.0 parts 
Dried corn starch 20.0 parts 
Soluble starch 2.0 parts 
Carboxymethylcellulose 7.0 parts 
Magnesium stearate 1.0 parts 
80.0 parts 
______________________________________ 
The active ingredient and starch are mixed and homogeneously moistened with 
an aqueous solution of the soluble starch. 
Moist screening: 1.0 mm-mesh. 
Drying: 50.degree. C. in a circulating air drier. 
Dry screening: 1.0 mm-mesh. 
The granulate and remaining excipients are mixed together and compressed 
into tablet cores. 
Weight of core: 80 mg. 
Punch: 6 mm. 
Radius of curvature: 5 mm. 
The finished cores are coated with a sugar shell in a coating vessel in the 
usual way. 
Weight of the coated tablet: 120 mg. 
Example 32 
Suppositories containing 75 mg of 5-methyl-6-(1'-methyl 
benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
The suppository composition is compounded from the following ingredients: 
______________________________________ 
Active ingredient 75.0 parts 
Suppository base (e.g. 
1625.0 parts 
cocoa butter) 
1700.0 parts 
______________________________________ 
Preparation 
The suppository base is melted. At 38.degree. C. the ground active 
substance is homogeneously dispersed in the melt. It is then cooled to 
35.degree. C. and poured into pre-cooled suppository molds. 
Weight of suppository: 1.7 gm 
Example 33 
Hypodermic solution containing 25 mg of 
5-methyl-6-(1'-methyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
The solution was compounded from the following ingredients: 
______________________________________ 
Active ingredient 25.0 parts 
Sodium chloride 45.0 parts 
Polyethyleneglycol 600 
1000.0 parts by vol. 
Solubilizer (e.g. hydroxy- 
ethylated hydrogenated 
castor oil) 500.0 parts by vol. 
Water for injection q.s. ad 
5000.0 parts by vol. 
______________________________________ 
Preparation 
In a suitable calibrated vessel, the active ingredient is dissolved in a 
mixture of polyethyleneglycol, solubilizer and about half the water, while 
stirring. After everything has dissolved, the sodium chloride is added, 
and the solution is made up to the stated volume with water. 
Example 34 
Suspension containing 75 mg of 
5-methyl-6-(1'-methyl-benzotriazol-5'-yl)-4,5-dihydro-3(2H)-pyridazinone 
per 100 ml 
The suspension is compounded from the following ingredients: 
______________________________________ 
Active ingredient 1.5 parts 
Carboxymethylcellulose 
0.1 parts 
Methyl p-hydroxybenzoate 
0.05 parts 
Propyl p-hydroxybenzoate 
0.03 parts 
Sucrose 10.0 parts 
Glycerol 5.0 parts 
70% sorbitol solution 
20.0 parts 
Flavoring 0.3 parts 
Distilled water q.s. ad 
100.0 parts by vol. 
______________________________________ 
Preparation 
The distilled water is heated to 70.degree. C. The methyl and propyl 
p-hydroxybenzoates and the glycerol and carboxymethyl-cellulose are 
dissolved therein by stirring. The solution is cooled to room temperature, 
and the active substance is added and homogeneously dispersed therein by 
stirring. After the suger, sorbitol solution and flavoring have been added 
and dissolved, the suspension is evacuated, while stirring, to remove air. 
Any one of the other compounds embraced by formula I or a non-toxic, 
pharmacologically acceptable acid addition salt thereof may be substituted 
for the particular active ingredient in Examples 30 through 34. Likewise, 
the amount of active ingredient in these illustrative examples may be 
varied to achieve the dosage unit range set forth above, and the amounts 
and nature of the inert pharmaceutical carrier ingredients may be varied 
to meet particular requirements. 
While the present invention has been illustrated with the aid of certain 
specific embodiments thereof, it will be readily apparent to others 
skilled in the art that the invention is not limited to these particular 
embodiments, and that various changes and modifications may be made 
without departing from the spirit of the invention or the scope of the 
appended claims.