JPS59205367A - Substituted indino-pyridazinone compound - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION Haloindeno-pyridazinone especially /-fluoro-6H
-indeno(1,2-(rypyridazin-3-one)
Engineering I Farmaco, Fid, Soi, J No. 37 (
2), pp. 163-140 (1981), it is described as having anti-moxibustion activity.

The present invention relates to substituted 6H-indeno[i,2-c)pyridazin-3-ones as cardiotonic and antihypertensive agents.

The present invention provides a novel substituted 6H-indeno[1,2-Q)-py14-ligudine-6-io/and its pharmaceutically acceptable salts useful as cardiotonic and antihypertensive agents having the structural formula Regarding.

In the above formula, 7-7 is a double bond R between two carbon atoms.

Y is -C6H)m-(rn is 1
or 2 and Ro is H or lower alkyl), CO, O or 8 and % R2 is hydrogen or lower alkyl, Q is oxygen or sulfur, R3
is hydrogen or lower alkyl, and A is (a
) to (θ) and is attached to the 6- or 4-position of the phenyl ring.

1 (wherein h R1, R' and R are independently hydrogen or lower alkyl, CH20H%BOH5,5OOHFe
o2CH5, hydroxyalkyl, halogen, C0H2
) kNR'R"' Ck is O~2 and R1 and R"' are independently hydrogen or lower alkyl (lower alkyl contains 1 to 6 carbon atoms)] or imidazole When attached to the 4 and 5 positions of the ring, together (1) a 5-, 6- or 7-membered ring which may also contain nitrogen atoms; (II) optionally halogen, hydroxy, lower Benzene ring substituted by alkyl and lower alkyloxy and O1
+1 pyridine ring can be formed, and X is a single bond * (OH2)n or 0(CH2)n+1 (n
is 1 to 4), (wherein (1) W-L
=Z=OH (II) W=Z=N and L=CH or 0ii)
L=Z=N and W=OH and X is as defined in 1a).

(0) fit,, piece X (in the formula, R4 is OH2, OlS, NR5' [in the formula, R
5 is hydrogen, alkyl, coR6 (wherein s"6 is a benzene ring optionally substituted by halogen, lower alkyl, hydroxy, lower alkoxy and CF3) or (OH2)nR6 (wherein n is 0 to 4 and R6 is as described above), (wherein n is 1 to 3), or (wherein bR7 and R8 are lower alkyl or 17- are independently Hydrogen, lower alkyl, aryl.

Aralkyl* CF3* 5- or 6-membered such as hydroxy, lower alkoxy, NHRll (wherein R11 is hydrogen, lower alkyl or lower alkanoyl) or - taken together with carbonyl or ethylenedioxy] forming a membered ring and pharmaceutically acceptable salts thereof, where X is the same as defined in 1(a)), (in the formula represents a double bond or a single bond, R12 is hydrogen or lower alkyl, M is NH%0 or S and X is either a direct bond or NH) or 18- (wherein X, M and R12 are as described above) or (6+) NHPR15R14 [wherein P is a single bond or carbonyl, R13 is a linear or branched lower alkyl, and R14 is hydrogen or Lower alkyl, herogen, NR115R1C
In the formula, R15 and R16 are each hydrogen.

straight-chain or branched lower alkyl or together with 5-membered 6- or 7-membered rings or 1(a) to
1(C)) or 5(o
)nR17 (wherein n is 0 to 2 and R17 is a straight or branched lower alkyl, phenyl) and pharmaceutically acceptable salts thereof].

Compounds of 2(11) in which R2 is hydrogen may exist in tautomeric forms, such as 3-(2H)-pyridazinone and/or 6-pyridazinone of formula (A) shown below.

(Engineering A) The present invention also provides a 2,4.4&,5-tetrahydro-
7-(Substituted)-3H-indeno(192-0)pyridazin-3-one and its pharmaceutically acceptable salts.

Another aspect of the invention is a compound of the formula (wherein R1, R', 'B, X, R2, Y and R3 are as defined above) and pharmaceutically acceptable salts thereof.

Yet another aspect of the present invention is a compound of formula 5, where the individuals in the formula are as described above in (a) and (θ). Preferred groups for A are imidazole or lower alkyl, B-lower alkyl or OH
imidazole, tetrahydrobenzimidazole, be21-zimidazole, or 1,2,4-triazole substituted by 20H. When A is as described above in (d,), the heterocyclic ring is preferably 2-2-azoline.

A specific aspect of the present invention is the following compound.

2.4.4a, 5-tetrahydro-7-(IH-imidazol-1-yl)-3H-indeno[1,2-c)pyridazin-3-one, 2,4,4a,5-tetrahydro-7 -(1-piperidinyl)-3H-indeno I”
1.2-c,) pyridazin-3-one, 2,4.4a,
5-tetrahydro-7-(4-hydroxy-1-piperidinyl)-3H-indeno-[1,2-c)pyridazin-3-one, 2,4.4a,5-tetrahydro-7-(
i,4-dioxa-8-azaspiro[4,5)-dec-
8-I#) -3H-indeno(1,2-c, 1pyridazin-3-one and 2.5-')hydro-7-(I
H-imidazol-1-yl)-3H22- -indeno[1,2-C)pyridazin-6-one.

Another aspect of the invention is an inotropic composition for increasing cardiac contractility and/or an antihypertensive composition for lowering blood pressure, comprising an effective amount of a compound of formula (1) and a pharmaceutically acceptable carrier. Regarding.

Further, the present invention provides the formula (1) as a solid or liquid usage form.
) or a pharmaceutically acceptable salt thereof, together with a pharmaceutical carrier, to the patient orally or parenterally. ) on how to lower blood pressure.

A method for preparing indenoC1,2-c)pyridazin-6-ones of formula (I) comprises a method for preparing an indenoC1,2-c)pyridazin-6-one of formula
1-Oxo-1H-2-acetic acid is reacted with R2-ML-THH2 to obtain a compound of formula (1) in which = represents a single bond and, if necessary, the product is dehydrated to form ==. It consists of making a compound exhibiting a double bond. Bromination-dehydrobromation, noble metal catalytic dehydrogenation such as palladium-catalyzed dehydrogenation or oxidation-reduction methods using MnO2 or m-nitrobenzenesulfonic acid as reagents [[J
.

med, chem, J Vol. 17, p. 273 (197
4 years)] can be used.

Compounds of formula (1) in which Q is sulfur can advantageously be prepared from corresponding compounds of formula (1) in which Q is oxygen by treatment with phosphorus pentasulfide.

The starting material of formula (V) is obtained by replacing the fluorine atom on a compound of formula (wherein Y is as defined above) with a compound corresponding to group A as defined in (a) to (e). It can be manufactured by

The displacement reaction is carried out at the boiling point of the solvent used, for example pyridine, in the presence of an anhydrous salt such as sodium or potassium carbonate and also in the presence of a catalyst such as cuprous oxide.

If the group is as defined in (dl) and is a direct bond, the A group according to (d) can be prepared by known operations from the corresponding cyanide. By reacting the atom with potassium cyanide, 25- is first substituted with a cyano group.

Compounds of the formula (■) are known and "II Farm
aco.

Ed, Sci, J No. 37 (2) Volume 133-140 (
(1981).

Compounds of formula (1) are useful in free base form and in acid addition salt form. Any form is included within the scope of the present invention. Acid addition salts are the more advantageous form for use and in fact use of the salt form is equivalent to use of the base form. In the practice of the invention, it has proven advantageous to form sulfates, phosphates or methanesulfonates. However, other suitable pharmaceutically acceptable salts within the scope of this invention include hydrochloride, sulfaminate,
Ethanesulfonate, benzenesulfonate% p-)
Mineral acids such as hydrochloric acid and sulfamic acid to give the luenesulfonate salts and the like, and organic acids such as ethanesulfonic acid, benzene 26-sulfonic acid and nato p-)luenesulfonate. Compounds of formula (1) can also form salts using acetic acid, propionic acid, oxalic acid, malonic acid, glycolic acid, maleic acid and fumaric acid.

Acid addition salts of the basic compounds can be prepared by dissolving the free base in an aqueous or aqueous alcoholic solution or other suitable solvent containing the appropriate acid and isolating the salt by evaporating the solution or by preparing the salt in an organic solvent. It is prepared by reacting a free base and an acid and obtaining the salt either by direct separation or by concentration of the solution.

The term "lower" for argyl and alkoxy is 1
It means a straight or branched hydrocarbon chain of ~6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, etc. The term "halogen" includes fluorine, chlorine, bromine and iodine, but is preferably fluorine or chlorine.

The utility of the compounds of the invention as cardiotonic agents is demonstrated by standard pharmacological test methods such as their effectiveness in producing a significant increase in myocardial contractility in pendoparbital anesthetized dogs with low or minimal hepatic frequency and changes in blood pressure. be done. This test method is as described below.

Test for in vivo myocardial inotropic activity under severe anesthesia.
It consists of determining the effect of increased intravenous doses of the compound on 6-degree frequency and aortic blood pressure.

Bendoparbital (3
Anesthetize with 5ff/l) and then deep parbital (
Maintain anesthesia by continuous infusion of 6,5"f//kf for 7 hours). Allow the animal to breathe naturally and intubate the trachea. Insert a cannula into the femoral vessel to administer the test agent. Aorta. Insert a Miller catheter tip pressure transducer or liquid-filled catheter into the ascending aorta via the femoral artery to measure blood pressure. Insert a Miller catheter tip pressure transducer into the left ventricle via the left carotid artery to measure left ventricular blood pressure. The needle electrode is placed subcutaneously to record the electrocardiogram (IOC).

Left ventricular and aortic blood pressures are recorded on a strip chart recorder. The axillary heart rate using a biotachometer triggered by the R wave of NAA and the initial induction value of left ventricular pressure (AP/AT) obtained with a differential amplifier combined with a pressure amplifier are also recorded. .

29- Obtain control data using a period of at least 30 minutes prior to administration of test compound.

Depending on solubility, add the compound to 0.9% physiological saline solution or dilute HOI! , or NaOH(0,1 or toN
) and diluted with normal physiological saline. Ethanol or dimethylacetamide can be used as solvents if reasonable dilution can be achieved.

Each dose of test compound was applied over a period of 1 minute (1
It is administered in a volume of 11111/h.

5 Compounds of the invention, such as 2,4.4a,5-tetrahydro-7-(IH
-imidazol-1-yl)-6H-indeno(1,2
-Q) Pyridazin-6-one is about 0.01 to [151
low or minimal 6 when administered intravenously at m/#
A significant dose-related increase in cardiac contractility occurs with changes in pulse frequency and a modest decrease in blood pressure. Therefore, the compound 30 of the present invention is also useful as a multiple anti-local blood pressure agent.

The following examples are presented to further illustrate the invention. However, the following examples are not intended to limit the invention.

Example 1 2.3-dihydro-5-(I H-imidazole-1-
5-Fluoro-2,6-cyhydro-1-oxo-1H-indene-2-acetic acid in pyridine 15
rmaco, Ed, Sci, J No. 37 (2) Volume 163
- Manufactured by the method on page 140 (1,981)]6.
69, anhydrous 20032.29, imidazole 1.65
A mixture of 9 and OuO[Li2a was refluxed for 24 hours. The reaction mixture is filtered, the p-liquid is diluted with water and the pH of the solution is adjusted to 5. Solid P was treated with water, washed with water and crystallized from ethanol, melting point 224-226.
2,3-sihydro-5-(I
1.62 of H-imidazol-1-yl)-1-oxo-1H-indene-2-acetic acid are obtained.

2.4.4a, 5-tetrahuman cr-7-(IH-imidazol-1-yl)-5H-indeno[1,2-Q'
1pyridazin-3-one 2,3-dihydro-5-(IH-
A solution of (imidazol-1-yl)-1-oxo-1H-inde/-2-acetic acid 14871 and 85 thihydrazine hydrate 0389 is heated to reflux for 3 hours. The reaction mixture was filtered, the residue was washed with ethanol and N was prepared by crystallization from ethanol to give the product 2,4.4L,5-tetrahydro-
7-(IH-imidazol-1-yl)-3H-indeno(1,2-0)pyridazin-3-one α7P is obtained.

The elemental analysis results for 0+ 4H12N40 are as follows.

c HN Calculated value: 66.65 4.69 22.21 Experimental value: 66.40 4.9322.25 Example 2 2.4.4 &, 5-tetrahydro-7-(1-pyRridinyl)-1H-indeno (112-Q)pyridazine-6
-one (2a) 5-fluoro-2,3-uhydro-1-oxo-IH-
A mixture of indeno-2-acetic acid 29, K2O03255p and piperidine soml is heated to reflux for 20 hours. The suspension is then poured onto Celite and the Celite is washed with methanol (50 mffi). The combined furnace liquors are evaporated under reduced pressure to yield an oil. This crude oil was dissolved in aqueous hydrochloric acid (50
ml) and extracted with ethyl acetate (50 mQ). The aqueous layer 33- is separated, filtered and brought to pH 7 with ammonium hydroxide. This mixture was then diluted with 0HOjt5/1PrOH (3
:2) Extract with 100ml. Separate the organic layer and add brine (
Wash with 100 mQ), dry (Na2SO4) and evaporate to give an oil 1.41. Add this to ethanol 25
Dissolve as needed, add 0.49 hydrazine hydrate and heat the mixture to reflux for 2 hours. The reaction mixture is cooled and filtered to give 0.7 p of product, melting point 282-284°C.

The elemental analysis results for C16H19N50 are as follows.

CHN Calculated Near 1.35 7.11 15.60 Experimental: '71.38 6.90 15.56 The following compound is prepared according to the procedure of Example 2.

2(b) 2,4,4a,5-tetrahuman cr-7-(
3-human 34-lexi1-pilysinyl)-3H-indeno(1,2
-c) Pyridazin-6-one (melting point 246-248°C)
, 2(cl 2,4,4a,5-tetrahuman C7-7-(
1,4-diokif-8-azaspiro[4,5)deku-8
-yl)-3H-indeno(1,2-c)pyridazine-
3-one (melting point 252-254°C).

Example 3 2.5-dihydro-7-(IH-imidazol-1-yl)-5H-indeno[1r2-a)pyridazin-3-one A solution of bromine (α69) in acetic acid (7 females) 100
The dihydropyridazinone (
Add dropwise to a stirred solution of α8jl). Then add 1
Heat at 10-115°C for 6 hours.

After cooling, the solid is filtered, washed with ether and air dried. Dissolve this in 20ml of water and adjust the pH of the solution to 10. The solid was filtered, washed with water and purified by chromatography on silica gel, mp 304-307.
0.259 °C (decomposition) of product is obtained.

Examples 4 to 13 Example 4 by using the preparation of Example 1 by reacting in each case 5-fluoro-2,3-dihydro-1-oxo-1H-inden-2-acetic acid with a suitable amine substrate. ~13 compounds are prepared. With the exception of Example 9, the amine substrate compounds are obtained from commercial sources.

The amine substrate of Example 9, tetrahydrobenzamidazole, is described in f-J, Prakt, Ohemie J Vol. 4, No. 2.
07 (1958).

(Example 4) 2,4,4a,5-tetrahydro-7-
(2-methyl-1H-imidazol-1-yl)-3H
-indeno[1,2-0)pyridazin-3-one [melting point 261-264°C (decomposition)], (Example 5) 2,4.4a,5-tetrahydro-7-
(2-ethyl-4-methyl-1H-imidazole-1-
I/Iz) -3H-indeno[1,2-Q)pyridazin-6-one (melting point 239-241°C).

(Example 6) 2,4.4a,5-tetrahydro-7-
(4-methyl-1H-imidazol-1-yl)-3H
-indeno[:1.2-0)pyridazin-3-one [melting point 252-253°C (decomposition)].

(Example 7) 2,4.4a,5-tetrahydro-7-
(4-hydroxymethyl-1H-imidazol-1-yl)-3H-indeno[1,2-(lypyridazine-3-
On [melting point 274-277°C (decomposition)].

(Example 8) 2,4,4a,5-tetrahydro-7-
(4-phenyl-1H-imidazol-1-yl)-3
H-indeno(1,2-a)pyridazine-3-o-3-hun [melting point 301-302°C (decomposed)].

(Example 9) 2,4.4a,5-tetrahydro-7
-(4,5,6,7-tetrahydro-1H-benzimidazol-1-yl)-5H-indeno[1,2-c)
Pyridazin-3-one (melting point 275.5-277°C),
(Example 10) 2,4.4&,5-tetrahuman I:
1-7- (I H-benzimidazol-1-yl)
-6H-indeno(1,2-c)pyridazin-3-one (272-274°C)% (Example 11) 2,4.4&,5-tetrahydrolff
-7-(iH-1,2,4-)riazol-1-yl)
-3H-indeno(1,2-o)pyridazin-3-one (melting point 302-304°C), (Examples 1 and 2) 2,4.4a,5-tetrahydro-
7-(,4-thiomorpholinyl)-3H-indeno[:
1.2-c, 1 pyridazin-3-one (melting point 265-2
(Example 15) 2,4,4a,5-tetrahydro-7-[438--(2-pyridyl)-1-piperazinylcou 3H-indeno[1,2-0)pyridazin-3-one (melting point 286
~288°C).

Examples 14 to 17 Example 14 by using the preparation of Example 2 by reacting in each case 5-fluoro-2,3-dihydro-1-oxo-1H-inden-2-acetic acid with a suitable amine substrate. ~17 compounds are produced. The amine substrate compounds in each example are obtained from commercial sources.

(Example 14) 2,4,4fL, 5-tetrahydro-
7-(1-morpholinyl)-3H-indeno(1,2-
0) pigdin-6-one (melting point 256-258°C),
(Example 15) 2,4.4a,5-tetrahydro-7
-[(3-aminopropylamino)-3H-indeno(
1,2-(ripyridacy/-6-one7) hydrochloride (melting point 2
88-290°C), (Example i6) 2,4,4a,5-tetrahydro-
7-(4-Methyl-1-piperazinyl)=roH-indeno[1,2-〇)pyridazin-3-one (melting point 244~
246°C), (Example 17) 2,4.4&,5-tetrahydro-7
-(Butylamino)-6H-indeno(1,2-(lypyridazin-3-one) (melting point 230-234°C).

Patent originator: Continued from page 1 of Warner 2 Hart Konnozony 11100 237100) (C07D 401/12 13100 (C07D 403104 (C07D 491/113 21100 317100) Priority claim February 2, 1984 ■ United States (US) Yu5
75412 0 Inventor James Arthur Bristol Michigan, United States of America (48 103) Ann Arbor Fist High Hollow Road 1921 Procedural Amendment July 20, 1980 Commissioner of the Patent Office Manabu Shiga 1, Indication of Case 1988 Patent Application No. 78797 2, Name of Invention Substituted Indeno-Pyridazinone Compound 3, Relationship with the case of the person making the amendment Patent applicant name: Werner-Lambert Kompany 4, Agent 5, Date of amendment order (voluntary) + ”, □゛Showa year
Date (Delivery date: Akira) Detailed description of the invention column Z Contents of amendment 1) The scope of claims will be amended as shown in the attached sheet.

2) On page 17, lines 6 to 9, "(in the formula, is...)" will be corrected as follows.

"[wherein R4 is CH2, OlS, NR5 (Rs is hydrogen or alkyl), COR6 (R6 is a benzene ring optionally substituted by halogen, lower alkyl, hydroxy, lower alkoxy and CF3) or (CH2)nR6 (n is 0 to 4 and R6 is as described above)], 2. Claim 1) A compound of the formula and a pharmaceutically acceptable salt thereof [the above During the ceremony,
== indicates a double 0 bond or a single bond between two carbon atoms, and Y is -(cH)m (in the formula, m
is 1 or 2 and % is H or lower alkyl), C010 or S, R2 is hydrogen or lower alkyl, R3 is hydrogen or lower alkyl, Q is oxygen or sulfur and A is the following (a) ~
(e) That is, (in the formula b Rlt R' and R are independently hydrogen or lower alkyl, 0H20H, 80H
5,800H5%5o2ar-r5, hydroxyalkyl, herogen, (OH2)kNR'R' [0 to
2 and R and R'' are independently hydrogen or lower alkyl (lower alkyl containing 1 to 6 carbon atoms) or attached to the 4 and 5 positions of the imidazole ring together with (1) a 5-, 6-, or 7-membered ring which may also contain a nitrogen atom;
I+1 a benzene ring optionally substituted by halogen, hydroxy, lower alkyl and lower alkyloxy and (can form a pyridine ring and X is a single bond *(OH2)n or 0(OH2
) n+1 (n 2- is 1 to 4), where (1) W=L=Z=CH (Ii) W=Z=N and L=CH or (lit)
L=Z=N and W=CH and X is as defined in 1(a)), is a benzene ring optionally substituted by halogen, lower alkyl, hydroxy, lower alkoxy and C'F5 ) or (CH2)nR6 (n is 0-4
and R6 is as described above)], 3- (wherein n is 1 to 3), (wherein R7 and R8 are lower alkyl or together [wherein n is R9 and RID are independently hydrogen, lower alkyl, aryl, aralkyl, OF5, hydroxy, lower alkoxy, NHRI j (wherein R11 is hydrogen, lower alkyl or lower alkanoyl), or together - carbonyl or ethylenedioxy] and pharmaceutically acceptable salts thereof, and X is 1(a
).

(In the formula, == represents a double bond or a single bond between two carbon atoms, R12 is hydrogen or lower alkyl, and M
or (e) NHPRl 3R14 [wherein P is It is a single bond or carbonyl, R13 is a linear or branched lower alkyl, and R14 is hydrogen or lower argyl, herogen, NR15R115 (
In the formula, R15 and R16 each represent hydrogen, linear or branched lower alkyl, or together represent 5
M, 6-membered or 7JA, forming a ring or group as defined in 1(a) to 1(C)) or 8(0)nRj7
(n is 0 to 2, and Rj7 is a linear or branched lower alkyl, phenyl) and a pharmaceutically acceptable salt thereof] and phenyl A compound according to claim 1 of the formula J02), which is bonded to the 6- or 4-position of the ring, and a pharmaceutically acceptable salt thereof.

6) A compound according to claim 1 of the formula and a pharmaceutically acceptable salt thereof.

4) Formula (wherein A is imidazole or lower alkyl%S-
Compounds according to claim 1fj4, which are imidazole, tetrahydrobenzimitazole, benzimidazole or 1.2.4-to')azole substituted by lower alkyl or OH20H, and pharmaceutically acceptable compounds thereof. Acid addition salt obtained.

7-5) The compound according to claim 1 of the formula (wherein A is 2-thiazoline)? and pharmaceutically acceptable acid addition salts thereof.

6) 2,4.4a,5-tetrahuman C7-7-(I
H-imidazol-1-yl)-5H-indeno(1,
2-Q) The compound according to claim 4, which is pyridazin-3-one and a pharmaceutically acceptable acid addition salt thereof.

7) 2,4,4a,5-tetrahydro-7-(1-
piperidinyl)-6H-indeno[1,2-c)pyridazin-6-one and its pharmaceutically acceptable acid addition salts, 2.4,4a,5-tetrahydro-7-(3-hydroxy-1-piperidinyl )-3H-indeno N, 2-c)
Bittacin-6-one and its pharmaceutically acceptable acid addition salts.

2.4.4a, 5-tetrahydro-7-(1,4-dioxa-8-azaspiro[4,5)dec-8-yl)-3
H-indeno(1,2-c)pyridazin-6-one and its pharmaceutically acceptable acid addition salts, 2,5-dihydro-7-(IH-imidazol-1-yl)-3H-indeno[1 ,2-Q)pyridazine-6-
2.4.4a, 5-tetrahydro-7-(2-methyl-
1H-imidazol-1-yl)-3H-indeno(1
, 2-c) pyridazin-6-one and its pharmaceutically acceptable acid addition salts.

2.4.4a, 5-tetrahydro-7-(2-ethyl-
4-Methyl-1H-imidazol-1-yl)-6H-
Indeno(1,2-0)pyridazin-3-one and its pharmaceutically acceptable acid addition salts, 2.4.4a, 5-tetrahydro-7-(4-methyl-
1H-imidazol-1-yl)-6H-indeno[1
, 2-c) Pyridazin-3-one and its pharmaceutically acceptable acid addition salts, 2.4.4a, 5-tetrahydro-
7-(4-hydroxymethyl-1H-imidazole-1
-yl)-3H-indeno(1,2-0)pyridazine-
3-one and its pharmaceutically acceptable acid addition salts, 2.4.41L, 5-tetrahydro-7-(4-phenyl-1H-imitasol-1-yl)-3H-indeno(1,2-c ) Pyridazin-3-one and its pharmaceutically acceptable acid addition salts.

10-2.4.4a, 5-tetrahydro-7-(4,5,6,
7-tetrahydro-1H-benzimidazol-1-yl)-3H-indeno(1,2-c)pyridazine-6
-one and its pharmaceutically acceptable acid addition salts.

2.4.4a, 5-tetrahydro-7-(IH-penzimitasol-1-yl)-3H-indeno(1+2-
c] Pyridazin-6-one and its pharmaceutically acceptable acid addition salts.

2+4+4'+5-tetrahuman cy-7-(1H-1
,2,4-triazol-1-yl)-3H-indeno(1,2-c)pyridazin-6-one and its pharmaceutically acceptable acid addition salts, 2.4.4a,5-tetrahydro-7 -(4-thiomorpholinyl)-3H-indeno[1,2-a)pyridazin-6-one and its pharmaceutically acceptable acid addition salts.

11-2.4,4a,5-tetrahydro-7-[4-(2-biridyl)-1-piperazinyl)-3I(-indeno(1
,2-c) Pyridazin-6-one and its pharmaceutically acceptable acid addition salt, 2.4,4a,5-tetrahydro-7-(1-morpholinyl)-3H-indeno(1,2-c) Pyridazine-6
-one and its pharmaceutically acceptable acid addition salts, 2.4,4a,5-tetrahydro-7-((3-aminopropyl)aminecu3H-indeno[1,2-c)pyridazin-3-one7 hydrochloride, 2.4.4f3. ．． 5-tetrahydro-7-(4-methyl-1-piperazinyl)-5H-indeno(1,2-(
! ,) pyridazin-3-one and its systematically acceptable acid addition salts, and 2.4.4a, 5-tetrahydro-7-(butylamino)-6H-indeno(1,2-c)pyridazine range. 1st
Method for producing the compound described in Section 1.

-3-one and its pharmaceutically acceptable acid addition salts The compound according to claim 1, which is

8) A pharmaceutical composition for increasing cardiac contractility or lowering blood pressure, comprising an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.

9) Reaction of the compound of formula with R2-NHNH2 and, if necessary, by dehydrogenation, shows that the bond is a single bond! Scope of Vv Requirement Claims 13--14= of the said patent, which consists of converting the obtained compound according to claim 1 into a corresponding compound in which == represents a double bond.

Claims (1)

[Scope of Claims] 1) A compound of the formula and its pharmaceutically acceptable salt C, in which:
== indicates a double bond or a single bond between two carbon atoms, Y is -(δH)m (where m is 1 or 2 and RO is H or lower alkyl), CO, O or S. R2 is hydrogen or lower alkyl, R3 is hydrogen or lower alkyl, Q is oxygen or sulfur, and A is
and R are independently hydrogen or lower alkyl, 0H
20be5OH5,800H5,BO2(M3, hydroxyalkyl, halogen, (OH2)kNR'R'' [in the formula, 0 to 2, and R' and R'' are independently hydrogen or lower alkyl (lower alkyl is (containing 1 to 6 carbon atoms)] or together when attached to the 4- and 5-positions of the imidazole ring (
:) 5-, 6- or 7-membered rings which may also contain nitrogen atoms, fil) optionally halogens, hydroxy,
benzene rings and (IN)pyridine rings substituted by lower alkyl and lower alkyloxy and X is a single bond, (OH2)n or 0
(OR2)H+1 (n is 1 to 4)), (wherein, (1) W=L=Z=(1!H(ii) W
=Z=N and L=CH or (lii) L=Z=N
and W=OH and is a benzene ring substituted by halogen, lower alkyl, hydroxy, lower alkoxy and CH5) or (CH2)nR6 (n is 0-4 and R
6 is as described above)], (wherein n is 1 to 3), (wherein R7 and R8 are lower alkyl or together [wherein R9 and R10 is independently hydrogen, lower alkyl, aryl, aralkyl, CH3, hydroxy, lower alkoxy, NHRll, where R11 is hydrogen, lower alkyl or lower alkanoyl, or -
together are carbonyl or ethylenedioxy]
and pharmaceutically acceptable salts thereof, where X is the same as defined in 1(a)). (In the formula, -== indicates a double bond or single bond between two carbon atoms, R12 is hydrogen or lower alkyl, and M
is NH, O or S and X is either a direct bond or NH) or (θ) NHPR15R14 C in which P is a single bond or carbonyl, R15 is linear or branched lower alkyl, R14 is hydrogen or lower alkyl, halogen, NR15R16 (wherein R15 and R16 are each 5- hydrogen, linear or branched lower alkyl or together form a 5-negative, 6-membered or 7-negative ring or a group as defined in 1(a) to 1(C)) or 5(o) nRj7 (n is D~2 and R1
7 is a straight-chain or branched lower alkyl, phenyl) and a pharmaceutically acceptable salt thereof] and is bonded to the 3- or 4-position of the phenyl ring. 1゜2) The compound according to the above-mentioned patent 'tR Claims Item 1 of the formula and a pharmaceutically acceptable salt thereof. 3) A compound according to claim 1 of the formula R2 and a pharmaceutically acceptable salt thereof. 4) of the formula (wherein A is imidazole or imidazole substituted by lower alkyl, S-lower alkyl or 0H20H, tetrahydrobenzimidazole, benzimidazole or 1.2.4- ) IJ azole) Compounds according to scope 1 and pharmaceutically acceptable acid addition salts thereof. 5) Compounds according to claim 1 of the formula (wherein A is 2-7 azoline) and pharmaceutically acceptable acid addition salts thereof. 6) 2,4,4tL,5-tetrahydro-7-(I
H-imidazol-1-yl)-3H-indeno(1,
2-c) Compounds according to claim 4 which are pyridazin-3-ones and pharmaceutically acceptable acid addition salts thereof. 7) 2,4,41L,5-tetrahydro-7-(1
-piperidinyl)-6H-indeno(1,2-c)pyridazin-6-one and its pharmaceutically acceptable acid addition salts, 2.4.4a, 5-tetrahydro-7-(3-hydroxy-1- piperidinyl)-6H-indeno(1,2-c
) Viritazin-6-one and its pharmaceutically acceptable acid addition salts, 2.4.4a, 5-tetrahydro-7-(1,4-dioxa-8-azaspiro(4,5)dec-8-yl) -3
H-indeno(1,2-e)pyridazin-3-one and its pharmaceutically acceptable acid addition salts. 2.5-:5hydro-7-(IH-imidazole-1
-yl)-3H-indeno[1,2-c)pyridazine-
3-one and its pharmaceutically acceptable acid addition salts, 2.4.4a, 5-tetrahydro-7-(2-methyl-
1H-imidazol-1-yl)-3H-indeno(1
, 2-0) pyridazin-3-one and its pharmaceutically acceptable acid addition salt, 2.4. ill&,5-tetrahydro-7-(2-ethe9-4-methyl-1H-imidazol-1-yl)-3
H-indeno(1,2-0)pyridazin-3-one and its pharmaceutically acceptable acid addition salts. 2.4.4a, 5-tetrahydro-7-(4-methyl-
1H-imidazol-1-yl)-3H-indeno(1
,2-c) Pyridazin-6-one and its pharmaceutically acceptable acid addition salts, 2.4.4&,5-tetrahydro-
7-(4-hydroxymethyl-1H-imidazole-1
-yl)-3H-indeno(1,2-a)pyridazine-
3-one and its pharmaceutically acceptable acid addition salts. 2.4.4a, 5-tetrahydro-7-(4-phenyl-1H-imidazol-1-yl)-3H-indeno(
1,2-c) Pyridazin-3-one and its pharmaceutically acceptable acid addition salts, 10-2.4.4&,5-tetrahydro-7-(4,5,6,
7-tetrahuman rt-1H-benzimidazole-1
-i/l/)-? , H-indeno(1,2-c)pyridazin-6-one and its pharmaceutically acceptable acid addition salts. 2.4.4a, 5-tetrahydro-7-(IH-benzimidazol-1-yl)-6H-indeno[1,2-
0) Pyridazin-6-one and its pharmaceutically acceptable acid addition salts, 2.4.4a, '5-tetrahydro 7- (IH-
1,2,4-triazol-1-yl)-3H-indeno(1,2-c)pyridazine and its pharmaceutically acceptable acid addition salts. 2.4.4a, 5-tetrahydro-7-(4-thiomorpholinyl)-3H-indeno[1,2-c)pyridazin-6-one and its pharmaceutically acceptable acid addition salt, 2.4.4a , 5-tetrahydro-7-, (4-(2-
pyridyl)-1-piperazinyl)-3H-indeno[1
, 2-C) Pyridazin-6-one and its pharmaceutically acceptable acid addition salts, 2.4.4a, 5-tetrahydro-7-(1-morpholinyl)-3H-indeno(1,2-c) Pyridazine-3
-one and its pharmaceutically acceptable acid addition salts. 2,,! 1.4 &, 5-tetrahydro-7-[(6-aminoprobyl)amine 3H-indeno(1,2-C
) Pyridazin-6-one monohydrochloride. 2.4.4&,5-tetrahydro-7-(4-methyl-
1-piperazinyl)-6H-indeno[1,2-0,1
Pyridazin-6-one and its pharmaceutically acceptable acid addition salts, and 2.4.4&,5-tetrahydro-7-(butylamino)-3H-indeno[1,2-C)pyridazin-3-one and a pharmaceutically acceptable acid addition salt thereof. 8) A pharmaceutical composition that increases cardiac contractility or decreases depression, comprising an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 9) Reacting the compound of formula with R,2-NHNH2 and, if necessary, by dehydrogenation, the resulting compound according to claim 1, wherein == is a double bond. A process for preparing a compound according to claim 13, which comprises converting the compound into a corresponding compound exhibiting the following.