A pyrazoloquinoline derivative having the formula (I): ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 independently represent a hydrogen atom or a lower alkyl group; R.sup.4 represents a hydrogen atom, a lower alkyl group, a halogen-substituted lower alkyl group, or a lower alkoxycarbonyl group; the dotted line means that the pyrazole ring has two conjugated double bonds; and R.sup.4 is bonded to the nitrogen atom at the 1-position or 2-position, or pharmacologically acceptable salts thereof. These compounds exhibit excellent anti-inflammatory activity and hepatic insufficiency treating activity.

FIELD OF THE INVENTION 
This invention relates to 3-aminopyrazolo[4,3-c]quinolin-4-one derivatives 
useful as anti-inflammatory agents and treating agents for hepatic 
insufficiency. 
BACKGROUND OF THE INVENTION 
Compounds having a 3-aminopyrazol[4,3-c]quinolin-2-one skeleton are 
unknown. 3-Amino-6,7,8,9-tetrahyiropyrazolo[4,3-c]quinolin-4-one 
derivatives represented by formula: 
##STR2## 
wherein R represents a hydrogen atom or a methyl group, which are deemed 
structurally relevant to the compounds of the present invention are 
described in Journal of Chemical Society, Pirkin I, p. 857 (1978), but 
their pharmacological activities are entirely unknown. 
SUMMARY OF THE INVENTION 
An object of the present invention is to provide a 
3-aminopyrazolo[4,3-c]quinolin-4-one derivative having excellent 
anti-inflammatory activity or hepatic insufficiency treating activity. 
The present invention relates to a pyrazoloquinoline derivative having the 
formula (I): 
##STR3## 
wherein R.sup.1, R.sup.2, and R.sup.3 independently represent a hydrogen 
atom or a lower alkyl group; R.sup.4 represents a hydrogen atom, a lower 
alkyl group, a halogen-substituted lower alkyl group or a lower 
alkoxycarbonyl group; the dotted line means that the pyrazole ring has two 
conjugated double bonds; and R.sup.4 is bounded to the nitrogen atom at 
the 1-position or 2-position, or pharmacologically acceptable salts 
thereof. These compounds are hereinafter collectively referred to as the 
compounds of formula (I) or compound (I). 
DETAILED DESCRIPTION OF THE INVENTION 
In formula (I), the alkyl moiety in the lower alkyl, halogen-substituted 
lower alkyl and lower alkoxycarbonyl groups is a straight chain or 
branched alkyl group having from 1 to 6 carbon atoms, e.g., methyl, ethyl, 
propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 
neopentyl, or hexyl groups. 
The halogen-substituted lower alkyl group has from 1 to 3 halogen atoms 
which may be the same or different, e.g., fluorine, chlorine, bromine, or 
iodine atoms. 
Salts of the compounds of formula (I) preferably include pharmacologically 
acceptable acid addition salts. 
The pharmacologically acceptable acid addition salts of the compound of 
formula (I) include inorganic acid salts, e.g., hydrochloride, sulfate, or 
phosphate; and organic acid salts, e.g., acetate, maleate, fumarate, 
tartrate, and citrate. 
Compounds of formula (I) wherein R.sup.4 is a hydrogen atom generally exist 
as tautomers represented by formulae (I-1) and (I-2): 
##STR4## 
For the sake of convenience, these tautomers will hereinafter be 
inclusively represented by formula (I-1). 
ORGANIC SYNTHESIS 
The compounds of formula (I) can be prepared, for example, by Processes (a) 
to (e) illustrated below. 
##STR5## 
In the above formulae, the definition of R.sup.1, R.sup.2, R.sup.3 and 
R.sup.4 have the same significance as defined above; R.sup.4a represents 
lower alkyl, halogen-substituted lower alkyl or lower alkoxycarbonyl 
groups in the definition of R.sup.4 ; and R.sup.3a represents a lower 
alkyl group in the definition of R.sup.3. 
In Step 1 of (a), 1 mol of compound (II) is reacted with 2 to 5 mols of 
hydrazine hydrate in an alcohol solvent, e.g., methanol, ethanol, or 
propanol, at room temperature to 100.degree. C. for 0.5 to 3 hours. Thus 
compound (III) can be obtained. 
Compound (II) wherein R.sup.1 is a methyl group is known as disclosed in 
Indian J. Chem. Section B, 24B(1), 62 (1985). Compound (II) wherein 
R.sup.1 is other than a methyl group can be synthesized according to the 
process disclosed therein. 
In Step 2 of (a), 1 mol of compound (III) is reacted with 1 to 5 mols of an 
isothiocyanate (R.sup.2 -NCS) in a solvent, e.g., dimethylformamide, 
pyridine, dimethylacetamide, or dimethyl sulfoxide to obtain compound 
(Ia). The reaction is carried out at 50.degree. to 130.degree. C. for 3 to 
40 hours preferably first at 50.degree. to 70.degree. C. for about 1 to 3 
hours and then at an elevated temperature of 90.degree. to 130.degree. C. 
for 3 to 40 hours. 
In process (b), compound (Ib) or (Ic) is obtained by displacing a hydrogen 
atom of the pyrazole ring of compound (Ia) with an alkyl group or an 
alkoxycarbonyl group. 
Alkylating agents for introduction of an alkyl group include alkyl halides, 
e.g., methyl iodide, ethyl iodide, propyl iodide, isopropyl iodide, butyl 
iodide, or butyl bromide. Introduction of an alkoxycarbonyl group is 
preferably effected by using methyl chlorocarbonate, ethyl 
chlorocarbonate, etc. From 1 to 10 mols of the alkylating or 
alkoxycarbonylating agent is reacted with per mol of compound (Ia) in a 
solvent, e.g., dimethylformamide, dimethylacetamide, or dioxane at room 
temperature to 50.degree. C. for 1 to 20 hours. To accelerate the 
reaction, the reaction may be carried out in the presence of a 
deacidifying agent, e.g., sodium hydride, potassium carbonate, sodium 
carbonate, triethylamine, or pyridine. Pyridine may also serve as a 
solvent. 
The reaction of process (b) generally produces compound (Ib) as a main 
product. Separation of compound (Ib) from compound (Ic), unreacted 
components and other products can be performed by usual purification means 
such as silica gel column chromatography and the like. 
Step 1 of (c) is carried out by treating compound (IV) with phosphorus 
oxychloride at room temperature to 140.degree. C. for 1 to 5 hours to 
obtain compound (V). 
Compound (IV) wherein R.sup.1 is a methyl group is known as described in J. 
Heterocycl. Chem., 16(8), 1605 (1979). Other compounds (IV) are 
synthesized according to the process disclosed therein. 
In Step 2 of (c), 1 mol of compound (V) is reacted with 2 to 5 mols of a 
substituted hydrazine (R.sup.4 NHNH.sub.2) in an alcohol solvent, e.g., 
methanol, ethanol, propanol, or 2-methoxyethanol. Thus, compound (Id) and 
(Ie) are obtained. The reaction is performed at room temperature to 
100.degree. C. for 1 to 5 hours. The reaction products, compound (Id) and 
compound (Ie), can be separated into each component by usual purification 
techniques, such as silica gel column chromatography. 
In process (d), a mono- or disubstituted compound (If) can be obtained by 
reacting compound (Ib) or (Id) with an alkylating agent, preferably in the 
presence of a deacidifying agent. Alkylating agents to be used include 
alkyl halides of the above-mentioned (b). The alkylating agent is used in 
an amount of 1 to 10 mols per mol of compound (Ib) or (Id) in a solvent, 
e.g., pyridine, dimethylformamide or dimethylacetamide. The reaction is 
preferably carried out at room temperature to 100.degree. C. for 1 to 10 
hours. Suitable deacidifying agents are potassium carbonate, sodium 
carbonate, triethylamine, or pyridine. 
In process (e), compound (Ig) can be obtained according to the same 
procedure as process (d) except that compound (Ic) or (Ie) are used 
instead of compound (Ib) or (Id). 
All the intermediate products and desired products obtained in the 
above-described processes can be isolated and purified by purification 
techniques commonly employed in organic synthesis, such as filtration, 
extraction, washing, drying, concentration, recrystallization, or 
chromatographic methods. Alternatively, the intermediate product may be 
subsequently reacted as is without purification. 
When compound (I) in the form of a salt is desired, a product obtained in 
the form of a salt is purified as such, or a product obtained in the free 
form is converted to its salt by dissolving or suspending it in an 
appropriate solvent and adding an acid thereto. 
Some compounds (I) or their pharmacologically acceptable salts exist in the 
form of an addition product with water or various solvents. Such addition 
products are also included in the scope of the present invention. 
Specific embodiments of various compounds according to formula (I) obtained 
by processes (a) to (e) are shown in Tables 1 and 2 below. 
TABLE 1 
______________________________________ 
##STR6## 
Compound 
No. R.sup.1 R.sup.2 R.sup.3 
R.sup.4 
______________________________________ 
1 (CH.sub.2).sub.2 CH.sub.3 
CH.sub.3 H H 
2 (CH.sub.2).sub.2 CH.sub.3 
(CH.sub.2).sub.3 CH.sub.3 
H H 
3 (CH.sub.2).sub.2 CH.sub.3 
CH.sub.3 H CO.sub.2 CH.sub.3 
4 (CH.sub.2).sub.2 CH.sub.3 
CH.sub.3 H (CH.sub.2).sub.3 CH.sub.3 
5 (CH.sub.2).sub.2 CH.sub.3 
(CH.sub.2).sub.3 CH.sub.3 
H CO.sub.2 CH.sub.3 
______________________________________ 
TABLE 2 
______________________________________ 
##STR7## 
Compound 
No. R.sup.1 R.sup.2 R.sup.3 
R.sup.4 
______________________________________ 
6 (CH.sub.2).sub.2 CH.sub.3 
H H CO.sub.2 CH.sub.3 
7 (CH.sub.2).sub.2 CH.sub.3 
H H C(CH.sub.3).sub.3 
8 (CH.sub.2).sub.2 CH.sub.3 
H H CH.sub.2 CF.sub.3 
9 (CH.sub.2).sub.2 CH.sub.3 
CH.sub.3 CH.sub.3 
CH.sub.2 CF.sub.3 
10 (CH.sub.2).sub.2 CH.sub.3 
H CH.sub.3 
CH.sub.2 CF.sub.3 
______________________________________ 
PHARMACEUTICAL APPLICATIONS 
Compound (I) or pharmacologically acceptable salts thereof can be used as 
it is or in various forms of preparations. Preparations can be obtained by 
uniformly mixing an effective amount of compound (I) or a 
pharmacologically acceptable salt thereof as an active ingredient with 
pharmacologically acceptable carriers. The preparations preferably have a 
unit dose form suitable for oral administration or injection. 
For preparation of dose forms for oral administration, any useful and 
pharmacologically acceptable carriers can be used. For example, liquid 
preparations, e.g., suspensions or syrups, can be prepared by using water, 
saccharides, e.g., sucrose, sorbitol, or fructose; glycols, e.g., 
polyethylene glycol or propylene glycol; oils, e.g., sesame oil, olive 
oil, or soybean oil; antiseptics, e.g., p-hydroxybenzoic esters; or 
flavors, e.g., strawberry flavor or peppermint. Powders, pills, capsules, 
or tablets can be prepared by using vehicles, e.g., lactose, glucose, 
sucrose, or mannitol; disintegrators, e.g., starch or sodium alginate; 
lubricants, e.g., magnesium stearate or talc; binders, e.g., polyvinyl 
alcohol, hydroxypropyl cellulose, or gelatin; surface active agents, e.g., 
fatty acid esters; or plasticizers, e.g., glycerin. Tablets or capsules 
are the most useful unit dose forms for oral administration because of 
their ease of application. For preparation of tablets or capsules, solid 
carriers are employed. 
Injectable solutions can be prepared by using carriers, such as distilled 
water, a salt solution, a glucose solution, or a mixture of a salt 
solution and a glucose solution. 
For an aerosol for inhalation, the compound is dissolved in an appropriate 
pharmaceutically acceptable solvent, e.g., ethyl alcohol or a mixture of 
ethyl alcohol and a miscible solvent, and the solution is mixed with a 
pharmaceutically acceptable atomizing base. 
The effective dose level and number of doses of compound (I) or a 
pharmacologically acceptable salt thereof vary depending on the 
administration route and the age, body weight and symptoms of a patient. A 
recommended daily dose is usually 1 to 50 mg/kg in 3 to 4 divided doses. 
The present invention is now illustrated in greater detail with reference 
to the following Examples.

EXAMPLE 1 
4-Hydrazino-1-propylquinolin-2(1H)-one (Compound a) 
In 140 ml of ethanol was dissolved 6.02 g (27 mmol) of 
4-chloro-1-propylquinolin-2(1H)-one, and 140 ml of hydrazine monohydrate 
was added thereto, followed by refluxing for 3 hours. The reaction mixture 
was concentrated to an about half of its original volume and then allowed 
to cool to obtain 5.53 g (94%) of the titled compound as a pale yellow 
crystal. 
Melting point: 181.degree.-186.degree. C. 
Elementary Analysis for C.sub.12 H.sub.15 N.sub.3 O: Calcd. (%): C 66.34; H 
6.96; N 19.34. Found (%): C 66.50, H 7.18; N 19.62. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1642, 748. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.12 (1H, s), 7.94-7.91 
(1H, m), 7.57-7.50 (1H, m), 7.43-7.40 (1H, m), 7.16-7.10 (1H, m), 5.86 
(1H, s), 4.24 (2H, brs), 4.13-4.07 (2H, m), 1.62-1.53 (2H, m), 0.92 (3H, 
t, J=7Hz). 
EXAMPLE 2 
4-Chloro-1,2-dihydro-1-propyl-2-oxo-3-quinolinecarbonitrile (Compound b) 
In 10 ml of phosphorus oxychloride was refluxed 1.0 g (4.1 mmol) of 
1,2-dihydro-4-hydroxy-1-propyl-2-oxo-3-quinolinecarbonitrile for 1 hour. 
The reaction mixture was dried under reduced pressure, and the residue was 
partitioned between chloroform and water. The chloroform layer was dried 
under reduced pressure to obtain 0.44 g (41%) of the titled compound as a 
yellow crystal. 
Melting point: 203.degree.-205.degree. C. 
Elementary Analysis for C.sub.13 H.sub.11 ClN.sub.2 O: Calcd. (%): C 63.29; 
H 4.49; N 11.36. Found (%): C 63.23, H 4.33; N 11.45. 
IR (KBr) .nu..sub.max (cm.sup.-1): 2232, 1645, 762. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.12-8.08 (1H, m), 
7.94-7.87 (1H, m), 7.79-7.76 (1H, m), 7.53-7.47 (1H, m), 4.27-4.22 (2H, 
m), 1.71-1.63 (2H, m), 0.97 (3H, t, J=7Hz). 
EXAMPLE 3 
3-Methylamino-5-propyl-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (Compound 1) 
In 18 ml of N,N-dimethylformamide (DMF), 2.08 g (9.6 mmol) of Compound a 
prepared in Example 1 and 1.59 g (21.7 mmol) of methylthioisocyanate were 
stirred at 140.degree. C. for 20 hours. Water was added to the reaction 
mixture, and the mixture was cooled and allowed to stand. The crystal thus 
formed was washed with ethyl acetate and then recrystallized from 
DMF-ethanol to obtain 0.76 g (30%) of the titled compound as a pale yellow 
crystal. 
Melting 267.degree.-270.degree. C. 
Elementary Analysis for C.sub.14 H.sub.16 N.sub.4 O: Calcd. (%): C 65.60; H 
6.29; N 21.86. Found (%): C 65.39; H 6.58; N 21.71. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1645, 748. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 12.68 (1H, brs), 
8.04-8.01 (1H, m), 7.57-7.51 (2H, m), 7.28-7.23 (1H, m), 5.53 (1H, brs), 
4.20-4.14 (2H, m), 2.88 (3H, d, J=5Hz), 2.56-2.49 (2H, m), 0.94 (3H, t, 
J=7Hz). 
MS, m/e: 256 (M.sup.+). 
EXAMPLE 4 
3-Butylamino-5-propyl-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (Compound 2) 
In 150 ml of DMF, 15.0 g (69 mmol) of Compound a and 18.9 g (157 mmol) of 
butylthioisocyanate were stirred at 140.degree. C. for 40 hours. Water was 
added to the reaction mixture, followed by cooling. The precipitate thus 
formed was subjected to silica gel column chromatography using a 30:1 (by 
volume) mixed solvent of chloroform and methanol as an eluent. The main 
fraction was collected, dried under reduced pressure, and recrystallized 
from water-containing ethanol to obtain 2.0 g (10 %) of the titled 
compound as a pale yellow crystal. 
Melting point: 169.degree.-172.degree. C. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1660, 1581, 747. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 12.6 (1H, brs), 
8.03-8.00 (1H, m), 7.58-7.52 (2H, m), 7.29-7.23 (1H, m), 5.60 (1H, brs), 
4.19-4.13 (2H, m), 3.30-3.25 (2H, m), 1.70-1.54 (4H, m), 1.44-1.30 (2H, 
m), 0.97-0.87 (6H, m). 
MS, m/e: 298 (M.sup.+). 
EXAMPLE 5 
1-Methoxycarbonyl-3-methylamino-5-propyl-1H-pyrazolo[4,3-c]quinolin-4(5H)-o 
ne (Compound 3) 
In 70 ml of DMF was suspended 1.69 g (6.6 mmol) of Compound 1, and 0.33 g 
(8.3 mmol) of 60% sodium hydride was added and dissolved therein. To the 
mixture was added 0.80 ml (10 mmol) of methyl chlorocarbonate, followed by 
stirring at room temperature for 1 hour. The reaction mixture was dried 
under reduced pressure, and the residue was partitioned between chloroform 
and water. The chloroform layer was dried under reduced pressure, passed 
through a silica gel column, and eluted with chloroform. The main fraction 
collected was dried under reduced pressure and recrystallized from 
water-containing ethanol to obtain 1.03 g (50%) of the titled compound as 
a colorless crystal. 
Melting point: 160.degree.-163.degree. C. 
Elementary Analysis for C.sub.16 H.sub.18 N.sub.4 O.sub.3 : Calcd. (%): C 
61.13; H 5.77; N 17.82. Found (%): C 61.08, H 6.01; N 17.94. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1749, 1660. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.93-8.89 (1H, m), 
7.69-7.67 (2H, m), 7.35-7.29 (1H, m), 6.26 (1H, brq, J=5Hz), 4.30-4.24 
(2H, m), 4.02 (3H, s), 2.90 (3H, d, J=5Hz), 1.72-1.63 (2H, m), 0.96 (3H, 
t, J=7Hz). 
MS, m/e: 314 (M.sup.+). 
EXAMPLE 6 
1-Butyl-3-methylamino-5-propyl-1H-pyrazolo[4,3-clquinolin-4(5H)-one 
(Compound 4) 
In 70 ml of DMF was suspended 1.00 g (3.9 mmol) of Compound 1, and 0.20 g 
(5.0 mmol) of 60% sodium hydride was added and dissolved therein. To the 
mixture was added 0.88 ml (7.7 mmol) of butyl iodide, followed by stirring 
at room temperature for 1 hour. The reaction mixture was dried under 
reduced pressure, and the residue was partitioned between chloroform and 
water. The chloroform layer was dried under reduced pressure, passed 
through a silica gel column, and eluted with chloroform. The main fraction 
collected was dried under reduced pressure and recrystallized from 
water-containing ethanol to obtain 0.55 g (45%) of the titled compound as 
a colorless crystal. 
Melting point: 125.degree.-127.degree. C. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1645, 750. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.06-8.03 (1H, m), 
7.60-7.55 (2H, m), 7.36-7.30 (1H, m), 4.45 (2H, t, J=7Hz), 4.22-4.17 (2H, 
m), 2.88 (3H, s), 1.83-1.59 (4H, m), 1.42-1.34 (2H, m), 0.95 (3H, t, 
J=7Hz), 0.92 (3H, t, J=7Hz). 
MS, m/e: 312. 
EXAMPLE 7 
3-Butylamino-1-methoxycarbonyl-5-propyl-1H-pyrazolo[4,3-c]quinolin-4(5H)-on 
e (Compound 5) 
In 60 ml of dioxane was suspended 1.40 g (4.7 mmol) of Compound 2, and 1.0 
ml (7.2 mmol) of triethylamine and 0.73 ml (9.4 mmol) of methyl 
chlorocarbonate were added thereto, followed by stirring at room 
temperature for 2 hours. The reaction mixture was dried under reduced 
pressure, and the residue was partitioned between chloroform and water. 
The chloroform layer was dried under reduced pressure, and the residue was 
passed through a silica gel column and eluted with a 3:1 (by volume) mixed 
solvent of hexane and ethyl acetate. The main fraction collected was 
recrystallized from hexane-ethyl acetate to obtain 0.67 g (40%) of the 
titled compound as a colorless crystal. 
Melting point: 147.degree.-149.degree. C. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1740, 1661, 762. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.93-8.90 (1H, m), 
7.70-7.67 (2H, m), 7.36-7.30 (1H, m), 6.14 (1H, brt, J=6Hz), 4.30-4.27 
(2H, m), 4.02 (3H, s), 3.35-3.23 (2H, m), 1.72-1.57 (4H, m), 1.43-1.34 
(2H, m), 0.97 (3H, s, J=7Hz), 0.93 (3H, s, J=7Hz). 
MS, m/e: 356 (M.sup.+). 
EXAMPLE 8 
3-Amino-2-methoxycarbonyl-5-propyl-2H-pyrazolo[4,3-c]quinolin-4(5H)-one 
(Compound 6) 
In 60 ml of methanol were refluxed 2.00 g (8.1 mmol) of Compound b prepared 
in Example 2 and 1.10 g (12.2 mmol) of methoxycarbonylhydrazine for 6 
hours. The reaction mixture was cooled to obtain 1.32 g (54%) of the 
titled compound as a colorless crystal. 
Melting point: 180.degree.-184.degree. C. 
Elementary Analysis for C.sub.15 H.sub.16 N.sub.4 O.sub.3 : Calcd. (%): C 
59.99; H 5.37; N 18.66. Found (%): C 60.21, H 5.42; N 18.36. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1746, 1651. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.03-8.00 (1H, m), 
7.61-7.54 (1H, m), 7.47-7.44 (1H, m), 7.36 (2H, brs), 7.26-7.21 (1H, m), 
4.14-4.08 (2H, m), 4.02 (3H, s), 1.67-1.62 (2H, m), 0.95 (3H, t, J=7Hz). 
MS, m/e: 300 (M.sup.+). 
EXAMPLE 9 
3-Amino-2-t-butyl-5-propyl-2H-pyrazolo[4,3-c]quinolin-4(5H)-one (Compound 
7) 
In a mixture of 60 ml of ethanol and 5 ml of triethylamine, 2.00 g (8.1 
mmol) of Compound b and 2.00 g (16 mmol) of t-butylhydrazine hydrochloride 
were refluxed for 4 hours. The reaction mixture was dried under reduced 
pressure, and the residue was partitioned between chloroform and water. 
The chloroform layer was dried under reduced pressure, and the residue was 
passed through a silica gel column and eluted with a 3:1 (by volume) mixed 
solvent of hexane and ethyl acetate. The main fraction collected was dried 
under reduced pressure to obtain 2.11 g (87%) of Compound 7 as a colorless 
crystal. The product was treated with ethyl acetate saturated with 
hydrogen chloride to obtain a hydrochloride of Compound 7. 
Melting point: 175.degree.-177.degree. C. 
Elementary Analysis for C.sub.17 H.sub.22 N.sub.4 O.HCl: Calcd. (%): C 
60.98; H 6.92; N 16.73. Found (%): C 61.10, H 7.22; N 16.80. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1662, 760. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.00-7.97 (1H, m), 
751-7.41 (2H, m), 7.22-7.16 (1H, m), 6.17 (2H, brs), 4.15-4.10 (2H, m), 
1.71-1.58 (2H, m), 1.65 (9H, s), 0.94 (3H, t, J=7Hz). 
MS, m/e: 298 (M.sup.+). 
EXAMPLE 10 
3-Amino-5-propyl-2-(2,2,2-trifluoroethyl)-2H-pyrazolo[4,3-c]quinolin-4(5H)- 
one (Compound 8) 
In 60 ml of ethanol, 2.00 g (8.1 mmol) of Compound b and 1.94 ml (16 mmol) 
of 2,2,2-trifluoroethylhydrazine were refluxed for 6 hours. The reaction 
mixture was cooled to obtain 1.73 g (66%) of a colorless crystal. The 
product was treated with ethyl acetate saturated with hydrogen chloride to 
obtain a hydrochloride. 
Melting point: 235.degree.-237.degree. C. 
Elementary Analysis for C.sub.15 H.sub.15 F.sub.3 N.sub.4 O.HCl: Calcd. 
(%): C 49.94; H 4.47; N 15.53. Found (%): C 50.23, H 4.40; N 15.18. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1640, 766. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 7.97-7.94 (1H, m), 
7.54-7.42 (2H, m), 7.23-7.17 (1H, m), 6.81 (2H, brs), 5.10 (2H, q, J=9Hz), 
4.16-4.10 (2H, m), 1.70-1.56 (2H, m), 0.95 (3H, t, J=7Hz). 
MS, m/e: 324 (M.sup.+). 
EXAMPLE 11 
3-Dimethylamino-5-propyl-2-(2,2,2-trifluoroethyl)-2H-pyrazolo[4,3-c]quinoli 
n-4(5H)-one (Compound 9) and 
3-Methylamino-5-propyl-2-(2,2,2-trifluoroethyl)-2H-pyrazolo[4,3-c]quinolin- 
4(5H)-one (Compound 10) 
In 150 ml of DMF was dissolved 2.26 g (7.0 mmol) of a hydrochloride of 
Compound 8 obtained in Example 10, and 0.42 g (11 mmol) of 60% sodium 
hydride was added to the solution. After stirring at room temperature for 
30 minutes, 0.87 ml (14 mmol) of methyl iodide was added thereto, followed 
by stirring for 1 hour. The reaction mixture was dried under reduced 
pressure, and the residue was partitioned between chloroform and water. 
The chloroform layer was dried under reduced pressure, and the residue was 
passed through a silica gel column and eluted with chloroform. The first 
main fraction collected was dried under reduced pressure to obtain 0.65 g 
(25%) of Compound 9 as a colorless crystal. 
Melting point: 142.5.degree.-145.5.degree. C. 
Elementary Analysis for C.sub.17 H.sub.19 F.sub.3 N.sub.4 O: Calcd. (%): C 
57.95; H 5.43; N 15.90. Found (%): C 57.97, H 5.10; N 15.90. 
IR (KBr) .nu..sub.max (cm.sup.-1): 1661, 1174, 747. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.14-8.11 (1H, m), 
7.62-7.52 (2H, m), 7.31-7.25 (1H, m), 5.21 (2H, q, J=9Hz), 4.24-4.18 (2H, 
m), 2.86 (6H, s), 1.71-1.62 (2H, m), 0.98 (3H, t, J=7Hz). 
MS, m/e: 352 (M.sup.+), 337, 323. 
The second main fraction was collected and dried under reduced pressure to 
obtain 1.10 g (47%) of a colorless crystal (Compound 10), which was then 
treated with ethyl acetate saturated with hydrogen chloride to obtain a 
hydrochloride of Compound 10. 
Melting point: 168.0.degree.-168.5.degree. C. 
IR (KBr) .nu..sub.max (cm.sup.-1): 3324, 1616, 1159, 752. 
.sup.1 H-NMR (DMSO-d.sub.6, 270 MHz) .delta. (ppm): 8.01-7.97 (1H, m), 
7.53-7.40 (2H, m), 7.22-7.16 (1H, m), 5.13 (2H, q, J=9Hz), 4.15-4.09 (2H, 
m), 3.90 (brs, lH), 3.27 (3H, s), 1.66-1.58 (2H, m), 0.96 (3H, t, J=7Hz). 
MS, m/e: 338 (M.sup.+), 309, 296. 
EXAMPLE 12 
Pharmaceutical Composition 
Tablets were prepared from the following components in a usual manner. 
______________________________________ 
Compound 1 50 mg 
Lactose 113 mg 
Potato starch 30 mg 
Hydroxypropyl cellulose 6 mg 
Magnesium stearate 0.6 mg 
______________________________________ 
EXAMPLE 13 
Pharmaceutical Composition 
A powder was prepared from the following components in a usual manner. 
______________________________________ 
Compound 1 
50 mg 
Lactose 750 mg 
______________________________________ 
EXAMPLE 14 
Pharmaceutical Composition 
A syrup was prepared from the following components in a usual manner. 
______________________________________ 
Compound 1 50 mg 
Purified sugar 75 mg 
Ethyl p-hydroxybenzoate 100 mg 
Propyl p-hydroxybenzoate 
25 mg 
Strawberry flavor 0.25 cc 
Water to make 100 cc 
______________________________________ 
EXAMPLE 15 
Pharmaceutical Composition 
Capsules were prepared from the following composition in a usual manner. 
______________________________________ 
Compound 150 mg 
Microcrystalline cellulose 
69.5 mg 
Magnesium stearate 0.5 mg 
______________________________________ 
The above components were mixed and filled in gelatin capsules. 
EXAMPLE 16 
Pharmaceutical Composition 
An injectable solution was prepared from the following components in a 
usual manner. 
______________________________________ 
Compound 1 10 mg 
Buffer adequate amount 
Water to make 1.0 ml 
______________________________________ 
Typical pharmacological activities of compound (I) are demonstrated by 
Examples 17 and 18. 
EXAMPLE 17 
Effect on Type III Allergic Pleurisy in Rats 
1. Preparation of IgG fraction of rabbit anti-egg white (anti-OA) 
IgG was purified from rabbit anti-OA serum prepared in advance by the 
method of Koda et al. [Folia Pharmacol., Japon, 66, 237 (1970)]in the 
following manner. 
A saturated solution of ammonium sulfate (half volume of the serum) was 
added to the anti-OA serum, and the mixture was left for one hour at 
4.degree. C. The precipitate was taken by centrifugation (3,000 rpm, 30 
min, 4.degree. C.) and dissolved in phosphate buffered saline of Dulbecco. 
Then, ammonium sulfate fractionation was carried out three times in the 
same manner as above, whereby a purified IgG fraction was obtained. 
2. Type III allergic reaction-induced pleurisy 
Male Wister rats weighing 225-250 g were pre-bred for several days and 
fasted overnight prior to experiment. The test compound (100 mg/kg) was 
orally administered to the animals, and after 30 minutes, IgG of rabbit 
anti-OA (0.2 ml, 5 mg protein/ml) was injected into the pleural cavity of 
the animals under anesthesia with ether. Thirty minutes after the 
injection of IgG, OA (albumin egg grade III; Sigma Chemical Co.) was 
intravenously injected into the animals as an inducer of pleurisy. After 
two hours, Evans Blue (25 mg/kg) was intravenously injected, and four and 
half hours after the injection of pleurisy, the animals were killed by 
bleeding. Then, an exudate in the pleural cavity was obtained, and the 
volume of the exudate was measured. The pleural cavity was rinsed with 5 
ml of physiological saline and the rinsings were added to the exudate. The 
number of infiltrated cells in the mixture was counted and th volume of 
the dye in the mixture was determined by the absorption at 625 nm [Agents 
and Actions, 25, 326 (1988)]. The suppression rates for the volume of the 
exudate, the number of infiltrated cells and the volume of the dye in the 
pleural cavity were calculated by the following equation. 
##EQU1## 
S.V: the value obtained with the group administered with the test compound 
and in which pleurisy is induced 
N.V: the value obtained with the group in which pleurisy is not induced 
P.V: the value obtained with the group administered with no test compound 
and in which pleurisy is induced 
TABLE 3 
______________________________________ 
INHIBITION OF ALLERGIC PLEURISY IN RATS 
Suppression rate (%) 
Volume of Number of 
Volume of dye in the 
infiltrated cells 
Compound exudate exudate in the exudate 
______________________________________ 
3 8.5 41.2 48.2 
4 26.4 45.6 24.1 
*8Sa 52.9 52.3 36.2 
______________________________________ 
*Sa means an hydrochloride of compound 8. 
EXAMPLE 18 
Inhibition of Hepatic Insufficiency Model 
Effect of test compounds on hepatic insufficiency was measured by the 
following method [Acta. Hepatol. Japon, 26, 1438 (1985)]. Blood cells of 
Propionibacterium acnes (1 mg/mouse) was applied to 8-week-old male BALB/c 
mice (30 mice per group) by intravenous injection at the tail. After 7 
days, 1 .mu.g/mouse of lipopolysaccharide from Salmonella enteritidis was 
intravenously injected to induce acute hepatic insufficiency. At the same 
time, 100 mg/kg of compound (I) suspended in 0.3% carboxymethyl cellulose 
(CMC) was orally administered to mice (only 0.3% CMC was given to the 
control group). Mortality of animals were measured at 7 and 24 hours 
following the injection of lipopolysaccharide. The suppression effect of 
mortality of mice due to hepatic insufficiency were shown in Table 4. In 
Table 4, the value are calculated based on the decrease in mortality from 
control (untreated mice). 
TABLE 4 
______________________________________ 
INHIBITION OF MORTALITY OF MICE DUE TO 
HEPATIC INSUFFICIENCY 
Mortality 
Compound No. At 7 Hrs. 
At 24 Hrs. 
______________________________________ 
1 39.2 17.9 
3 42.0 13.9 
Control 86.7 96.7 
______________________________________ 
According to the present invention, there are provided 
3-aminopyrazolo[4,3-c]quinolin-4-one derivatives exhibiting excellent 
anti-inflammatory activity and hepatic insufficiency treating activity. 
While the invention has been described in detail and with reference to 
specific examples thereof, it will be apparent to one skilled in the art 
that various changes and modifications can be made therein without 
departing from the spirit and scope thereof.