JPS58150564A - 1(2h)-isoquinolone derivative and its acid addition salt - Google Patents

Abstract

NEW MATERIAL:The 1(2H)-isoquinolone derivative of formulaI n is 0 or 1; R1 is H; R2 is H, ethoxycarbonyl, mono- or di-(lower alkyl)carbamoyl, acetyl, mono- or di-(lower alkyl)aminoethoxyacetyl, or group of formula II (R3 and R4 and H, lower alkyl, hydroxyalkyl, allyl, or form together with N heterocyclic group e.g. pyrrolidino, 4-methylpiperazino, etc.) and its acid addition salt. EXAMPLE:2-(2-Aminopropyl-4-penyl)-1(2H)-isoquinolone. USE:Gastric juice secretion suppressing agent and antiulcer agent. PROCESS:The compound of formulaIwherein NR1R2 is amino group can be prepared e.g. by (1) heating and melting 2-(chloroalkyl)-1(2H)-isoquinolone derivative and benzylamine in N2 gas stream, and (2) carrying out the catalytic reduction of the resultant 2-(benzylaminoalkyl) compound with H2 gas in a solvent in the presence of a catalyst such as Pd-C.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula [where m u Ot * rjl 0 I & the number is 82
company hydrogen, Rati Mizutake, ethyl carbonyl group, 7)
The base is a sea-furkylcarbayl group and an acedel group.

7 and 9 are di-i-class alkylaminoethoxyacetyl groups t
E represents 10OCR and NRa1+, respectively.

However, R1 and R4 each represent hydrogen, a lower alkyl group, a hydroxyalkyl group, or an allyl group; group (pyrrolidino group.

The present invention relates to a 1(211)-isoquinolone-decorated conductor and an acid addition salt thereof, which can store water with a 4-methylpiperazino group, a piperidino group, a sulfolino group, etc.).

The inorganic acid that rejects #l as the acid addition salt may be any organic acid, such as hydrochloride, sulfuric acid, methanesulfone i*m, maleic acid salt, citric acid, etc.
Preferably, a salt, a salt of stone, a salt of milk, and the like are suitable.

The target substance 1 of the present invention can be obtained by the following reaction.

That is, when NE and R1 are amino groups, aX-<taloloalyl)-1(2H)-iso-norone ms form and benzylamine are heated and melted in a nitrogen stream to obtain 2-(benzylanoalkyl). The product is then purified in a solvent such as a glacial acetic acid-ethanol mixture in the presence of a catalyst such as palladium-carbon, platinum oxide, or radium oxide by passing a bulk water gas through it at room temperature to SO'C. When NR, R, is an ethoxycarbonylamino group, the 2-(aminoalkyl) form obtained as described above is mixed with potassium carbonate and sodium carbonate in a solvent of ethanol and isopropanol. It is obtained by reacting ethyl chlorocarbonate at room temperature in the presence of a catalyst such as K.

NB, R, is N'-lower alkyl or taN', h'-
In the case of a di-lower alkylureido group, a, 2-(aminoalkyl) form can be converted into inocyanate such as methyl isocyanate or ethyl isocyanate at room temperature in a solvent such as benzene or toluene.
By reacting O-carbamyl chloride such as diethyl carbamyl chloride, useful compounds can be obtained.

When NR, B is an acedoate group, it can be obtained by reacting the 2-(aminoalkyl) form with acetic anhydride in glacial acetic acid at room temperature to heating.

In the case of a lower alkylaminoethyl ester in which NE and - are mono-t, the 2-(aminoalkyl) form is dissolved in a port medium such as almethane or chloroform, sodium hydroxide, sodium carbonate, etc. In the presence of a catalyst, chloroacetyl chloride is reacted at 0 to 10°C to obtain the 2-(chloroacetamidoalkyl) form, and then this product is converted into sodium dimethylaminoethylate, sodium diedelyatyl chloride, Sodium mono such as sodium isopropylaminoethylate, di-lower alkylaminoethylate, etc. It can be obtained by reaction at room temperature in a solvent such as methane or chloronelm.

It was. When N18g is an amino group, it is supplemented by a compound obtained by subjecting the 2-(chloroacetamidofurkyl) form obtained as described above to the Gabriel reaction. That is, by heating a mixture of 2-(chloroacetamidoalkyl), 7-taloid, and potassium carbonate at 80°C in a solvent such as dimeterformamide, the 2-
(7-talimide acetoaceta-alkyl) product was obtained, and then this product and dorazine were mixed in ethanol.

It can be obtained by reacting in a solvent such as isopropanol under heating and flowing water, and after cooling, adding diluted hydrochloric acid to the reaction solution and stirring at room temperature.

Similarly, when %NR, R4 is a lower flukylamino group, a droxyalkylamino group, an allyl group, a compound double group, etc., ti, 2-(chloroacetamidoalkyl) form and amines, such as d dimethylamine, diethera Electron, jetanolamine.

Diallylamine, sulfoline, 4-methylbiperazine, etc. can be obtained by heating and continuously flowing them in a solvent such as methanol, ethanol, or benzene.

The object '1111 butterfly of the present invention obtained in this way,
It is industrially useful as a pharmaceutical because it has excellent gastric juice secretion suppressing effects and anti-ulcer effects.

The pharmaceutical dosage of the compound related to this al11 is as follows:
The amount may be increased or decreased as appropriate depending on each individual case, taking into consideration the patient's movement and group status, but it is usually 0.5-B OqA per day for adults.
This is divided into 1 to 1fl11 and administered.

Administration is carried out in the form of tablets, capsules, powders, injections, and active agents. lll- as nine compositions
Excipients commonly used in tablets, capsules, granules, and powders for oral administration, such as charcoal-calcium, calcium phosphate, etc. *Powder m sugar, lactose, Merck, magnesium stearate, gelatin, polyvinylpyrrolidone, gum arabic, sorbitol, crystalline cellulose, "V clogol, carboxymethyl cellulose, silica may be used. Important, tablets.

-The calibrator may be coated by methods well known in the art.

Injectables may be aqueous suspensions, solutions, or powders that dissolve at the time of use. Pharmaceutical carriers well known in the art may also be included, such as macrogol, lanolin, cocoa butter, and fatty acid triglycerides.

Next, a synthesis example of the substance of the present invention and the pharmacological action of the compound synthesized by this method will be explained in more detail.Example 1 2-(2-benzylaminoprobyl)-4-phenyl-
1(2H)-isoquinolone 36.89°5%/<jdium carbon lz9. Glacial acetic acid SO- and ethanol 200d
Mix and conduct catalytic reduction by introducing hydrogen gas at 60 to 70°C. After the reaction is completed, it is filtered, the solvent is distilled off, and the residue is
Dissolve in hydrochloric acid solution. After washing with ethyl acetate, the aqueous layer is separated and neutralized with 10-sodium hydroxide solution. The precipitate is collected by filtration and recrystallized from a mixture of acetic acid and petroleum ether. Colorless prismatic crystal, melting point 104'C (D2-(2
-aminopropyl)-4-phenyl-11(2M)-isoquinolone 20.9 g (75 times) obtained O elemental analysis value (Cza H*a Nl O-278,31
Calculated value - IC,77,67Il, 6.5
2 N, 10% impurity value 61i): C, 77, 79
H, 6,57N, 10.01Next, 80 mg of Kmaleic acid containing 14 g of 2-(2-7minopropyl)-4-phenyl-1(211)-isoquinolone was added, and the mixture was heated and stirred. After cooling, the crystals precipitated are collected by filtration and recrystallized from an ethanol-acetic acid nibble mixture. 2-(2-7 Minoprobil) is a prismatic crystal with a melting point of 187'C.
-4-phenyl-1(211)-isoquinolone maleate to, 5J Obtained 0 Elemental analysis value (C,, II,, N, O.Ca H404'
- Xie, 431) Calculated value @t C, @, HH,5,
62N, ? , 10 value 61) I C, 67,07H
, 5,58N, 7.01 In addition, the raw material 2-(2-benzylaminopropyl)-4-7Eru1 (2M)-
Isoquinolones can be synthesized as follows.

2-(2-rialoprovir)-4-phenyl-1(2H
) - Inoquinolone 29.89 and benzylamine 20 - are mixed and heated and melted in a nitrogen stream. After completion of the reaction, the mixture is dissolved in warm methanol and poured into ice cubes. Filter the precipitate,
Wash with water, dry, and recrystallize from an ethyl acetate-petroleum ether solution. 2-(2-benzylaminoprobyl)-4-phenyl-1(2H)-, colorless needle crystals, melting point 118°C
30.29 (82%) of isoquinolone are obtained.

Elemental analysis value (C,, H, 4N, O"' ass, 48
B-) Calculated value ■: C, 81, 49H, 6, 57
N, 7.60 measured value (to): C, 81, 61H, 6
, 66N, 7.59 Example 2 2-(2-aminopropyl)-4-phenyl-1(2H
)-Isoquinolone 4.29. Ethyl chlorocarbonate2.
7L potassium carbonate 4.19. Mix 60% of ethanol; stir at room temperature for 3 hours. Thereafter, the solvent was distilled off, and the residue was extracted with dichloromethane. The crystals obtained by distilling off the solvent are recrystallized from ethanol. colorless prismatic crystal,
Melting point: 182° cc+2-(2-ethoxycarponylated nogrovir)-4-phenyl-1(!H)-isoquinolone 39(57) was obtained.

Elemental analysis value (CaH*) isO@m-3506421) Calculated value (11IC, 71, 9B 1f, 6.
83 N, 7.99 tli value eEJg C17l-
92H# 6-36 Ne 7-91 Example 3 2-(2-Aminoprobyl)-4-7! Nil-I C2
B)-Iso-nion bF, methyl isocyanate 1.2
g and toluene 60- were mixed and stirred at room temperature for 3 hours. After that, petroleum ether 60- was added to the reaction solution, and
Sum and overlay. Filter the precipitated crystals and recrystallize from ethanol.

Colorless needle crystals, melting point 180°C (2-<2-N'-)
4-phenyl-1 (2H)
-isoquinolone monohydrate5. Obtain IF (80 attacks).

Elemental analysis value (C, 11, N, O, .II, 0-353.
425) Calculated value ■寞C, 67, 97B, 6. Audience No. 11.89 Actual value 610.68.02 11,
6.54 N, 11.70 Example 4 2-(2-aminoprobyl)-4-yenyl 1 (2
B) -(So I? / a y 5 fi *Anhydrous vinegar 1
A mixture of 110-10- and glacial acetic acid 10-
After heating for ◎ time, pour the reaction solution into ice water and extract the precipitated crystals with dichloromethane. 5. Wash with Sosuikenka Sodium* solution, then with water. After washing, dry with Glauber's Salt.

The solvent is distilled off and the resulting crystals are recrystallized from ethanol. 4.89 (83%) of 2-(2-7-cell)-4-phenyl-1(211)-isoquinolone is obtained as colorless needle crystals with a melting point of 177'C.

Elemental analysis value (C--N, O, -3120,395) Calculated value-! C, 74, 98H, 6, 29N, 8.
Fu 4 與濶value Shin)! C, 75, IQ H, 6, 31N
, 8.71 Example 5 A mixture of 2-(2-chloroaceto7t-dogrovir)-4-7enyl-1(2H)-isoquinolone, 5 g of diethyl 7, and 50 sg of ethanol is heated under reflux for 5 hours. After distilling off the solvent and dissolving the residue in dichloromethane, washing with water and drying with sodium sulfate, the solvent was distilled off and the resulting crystals were recrystallized using ethyl acetate-soap ether. Melting point ■1° (02-(2-No.
N-diethylaminol-4-7enyl-1 (2B)-isoquinolone 5.7F (86%)
get.

Elemental analysis value (C, l, N, O, fi 3G1.51Ji
) 11 arithmetic 8 (#C, n, u H, 7, 47 Ne
10.73 Actual value 619 g C, 7B, device Mm 7
．． 62 N, 10.75 In addition, Sushina t) 2-<2-
Chloroacetamidoproyl)-4-phenyl-1(2
H)-isoquinolone can be synthesized as follows.

2-(2-aminoprobyl)-4-phenyl-1(2
H) -isochunoa y 2'l-81m diuk methane 1505g and 10-hydrolyzed sodium solution 100-
While cooling and stirring, 5° of dichloromethane containing chloratetyl chloride 134F was added dropwise to a mixture of WIK%s9c consisting of the following. After 30 minutes, the dichloromethane layer was separated, washed with water, dried with Glauber's salt, and the solvent was distilled off. The resulting crystals are recrystallized from ethyl acetate. Colorless prism crystal, melting point T/C02-
Elemental analysis value (C,H,, CJN, 0.-354.8) yielding <2-chloroacedoζV112biru)-4-yenyl-1(2H)-isoquinolone 30.52 (86%>)
40) Calculated value (5@sc, s7.yo H,5
,40N,? , 89 Ii measurement value ■: C, 67, Mouse 11,
5.47N, 7.82% Example 6 2-(2-chloroaceto7tdogrovir)-4-phenyl-1(2B)-isoquinolone 5.22% was dissolved in 100% dichloromethane, and N was added thereto.

Dissolve 10 mg of N-diethylaminoethanol and 0.46 F of potassium metal sodium, add the solution, and stir at room temperature. Add water to the reaction solution and separate the dichloromethane layer.
After washing with water and drying with an awn W4, the solvent was distilled off. Dissolve the residue in ether, extract with sulfuric acid port solution, and reduce the aqueous layer to 10%.
Neutralize with sodium hydroxide solution, collect the precipitated crystals by filtration, and recrystallize from a mixture of ethyl vinegar and petroleum ether.2-(2-N,N-diethyl) crystals with a melting point of 99°C. 4-phenyl-1(211)-isoquinolone 3F (46) is obtained.

Elemental analysis value (CsliuNaOa-435,671) Calculated value-"C1,71,7OB, 7.64 N
o 9. @5 refreshing value ■IC, F1. Viscosity H17,0N,
9.57 Example 7 2-(2-Chloq-7-doprovir)-4-phenyl-I C2M)-isoquinolone 7.111. 7 Talimide S,'lf, potassium carbonate (3.7 g) was added to dimethylformamide S〇-, and the mixture was stirred at 80°C for 5 hours. The reaction solution was poured into water, and the precipitated crystals were collected by filtration and air-dried in a water washer.Next, the crystals and 2 g of hydrazine hydrate were added to ethanol loOwt and heated under reflux for 3 hours.
Add reaction wave K11 hydrochloric acid 5- and incubate at mold temperature for 5 hours.
To push. Distill off the filtrate, add water to the residue, stir well and filter. Neutralize the filtrate with 10% sodium hydroxide solution and extract the precipitate with dichloromethane. Next, wash the extract with water, Dry. The solvent is distilled off and the resulting crystals are recrystallized from an ethyl acetate-petroleum ether mixture. colorless needles,
2-(2-aminoacetamidopropyl)-4-phenyl-1<2M)-isoquinolone with a melting point of 141°C2.
39 (34%).

Elemental analysis value (C, II,, N, as 0.-335.409) Calculated value & Qtce f 1.62 II, 6.3
1 N, 12.53 Yield value (JIG) s C, 7
1,6B II, 6.21 N, 12.44 Example $ 2-(2-7minoprovir)-4-phenyl-1(2H
)-Isoquinolone 2.8p, diethylcarbayl chloride t, sL pyridine 1.1g is heated at 900C for 1 hour. Add ethyl acetate to the reaction mixture in a refrigerator, wash with water, and dry. The solvent was distilled off and the residue was recrystallized from an ethyl acetate-petroleum ether mixture. 2- (2-N', pale yellow prismatic crystal, melting point 133°C)
N'-Dietherureidoglobil)-4-yale-1
(2H)-iso dt/a 1,6 f (441
I got the benefit.・Elemental analysis value (CaaH*嘗NsO@-3
77-491) Calculated value (%) tc*n, 18
ne7.21 N#11.1!1 Illegal value 6I9tC,
The following compounds were prepared in the same manner as in Examples 1 to 8.

Example 2-(2-aminoacetamidobumovir)-4-7x2#-1(211)-isoquinolone maleic acid Recrystallized from ethanol. Colorless prismatic crystal. Melting point 174'C0 Elemental analysis value (C, H,, N, O, -C, II, O, m4
51.483) Calculated value #: C, 11, 8! $
II, 5.58 N, 11.31 weight value 61g
IC, 6B, % 11.5.51 N, 9.2
0 Example 10 2-(2-% ruforinoacetamidoglobil)-4-phenyl-1(2)1)-isomer ethanol-ethyl acetate mixture +! I[ip et al. recrystallization. Colorless prismatic crystal. Melting point 189°c0 Elemental analysis value (Csall, N, 01m405.501
) Calculated value 619:C, 71,09B, 6.71
N, 10.36 Yield value (%): Cl 71J4
B, 6.79 N, 10.41 run #l11 2-(2-phospholinoaridamidepropyl)-4-7
Recrystallize 1(2H)-isoquinolone oleic acid from ethanol-ether mixture. Colorless needles. Melting point 122°c0 Elemental analysis value (C, H,, N, 0.@C4) 140. -5
21.575) Calculated value ■s C, 64, Xun H
，! 5.99 N, 8. %Actual value■! e, 64
．． 41 H, 5,92N, 7.93 Koji Example 12 2-(2-N,N-dimetelaminoacetamidoglobil)-4-phenyl-1(2B)-isoquinolone Recrystallized from ethyl acetate-petroleum ether mixture .

Colorless prismatic crystal. Melting point 164°C0 Elemental analysis value (C, H,, N, 0 proverb - 363,463) Calculated value -! C, 72, 70H, 6, 93N, 1
1.56 Ibuchi value ■: C, F2.62 H, 6,98N
, 11.64 Example 13 2-(2-N,N-dimethylamino-dobrovir)-4-phenyl-1(21()-isoquinolone-maleate I Recrystallization from nor-ether mixture◎ Mumo prism crystal. Melting point 1411°C0 Elemental analysis value (C, H,, N, O, C4H,04+m4
79.5 Nishiki) Calculated value ■ Zero C, 65, 12H, 6,
10N, 8.76 Yen): C, g, 21 H
, 6,03N, 8.82 Example) 4 2-(2-N,N-dietheraminoacetamidoglobil)-4-phenyl-1(21()-isoquinolone.
Maleate recrystallized from ethanol-ether mixture. Colorless needles. Melting point 140°C0 Elemental analysis value (C, 111m@NjO*・C4H404-
507,592) Calculated value (to)”Cl part, 26
H, 6,55N, 8.28 actual value) E C, 66,
35H, 6,55N, 8.15 Example 15 Recrystallization from 2-(2-N,N-diethanolanoacetamidoglobil)-4-phenyl-1(2H)-isoquinolone niol-ethyl acetate mixture . Colorless prismatic crystal, melting point 129°c.

Elemental analysis value (C, 11, N, 0.-42L as 616) Calculated value &Q* Cl 68.07 Tim 6.
90 Ne 9.92 Souren (To) I C,68,1
2Hl 6.93 N, 9.82 Example 16 2-(2-N,N-diethanolaminoacetamidoglobil)-4-phenyl-1(28)-isoquinolone hydrochloride Recrystallized from an ethanol-ether mixture. Colorless crystalline powder. Melting point: 158°C.

Elemental analysis value (C, II,, N, O, ・1ick-459
J77) Calculated value -s Co axis, @7 if, 6
47 N, 9.14 actual value ■! C, 62, FuOII
, 6.55) a, 9.07 Example 17 2-(2-Nt 14-Diallylaminoacetamidoprobyl)-4-phenyl-I C2B>-Isoquinolone Recrystallized from ethyl acetate-petroleum ether mixture.

Colorless phosphorus schistose. Melting point 132°CO Original 111 analytical value (CssliaN60m-415,540
k) Calculated value el) I C, 71$, IS B,
7.03 N, 10.11 real-value(2)! C,7
5JI H, 7,00N, 10.16 Example 18 2” (2-N,N-diarylaminoacetamidoprobyl)-4-phenyl-1(2B)-isoquinolone maleate ethanol-ether mixture Recrystallization @Colorless needle-like crystals. Melting point: 105°C0 Elemental analysis value (CssHnNaOm・C4H404-53
1,614) Calculated value $) s C, 67,78H
,6,26Ne 7JO failure value (%): C,67,91
B, 6.20 N, 7.95 Example 19 2-(2-(4-methylpiperazinoacetamide)globil)-4-phenyl-1(211)-isoquinolone Recrystallized from an ethanol-ethyl acetate mixture. Colorless needles.

Melting point 186'C.

Elemental analysis value (C,,li,)T2O, -418,543
) Calculated value ■t C, 71, 74B, ? ; 22
No 13.39 Sushi value (to) s C, 71, 78
He 7.15 No 13.4111 Example 20 2-(2-(4-methylpiperazinoacetamido)propyl)-4-7enyl-1 (2H)-isoquinolone.
Recrystallized from simaleic acid methanol-ether flA wave. Colorless needles. Melting point 181°c0 Elemental analysis value (CHHa*Na0c2XC4) 1404-
650.692) Calculated value ■: C, 60, 91H
, 5,89N, 8.61 actual measurement s Co 61.0
4H, 5,96N, 8.46 Example 21 2-(2-N,N-diethylaminoethoxyacetamidoprobyl)-4-7enyl-1<2H) -Isoquinolone Recrystallized from Fumeng salt ethanol. Colorless needles. One point 212'C
.

Elemental analysis value (C, H, N, O, -HCl-472,03
2) Calculated value (jEl: C, M, 16 B,
7.26 N, 8.90 actual measurement value -) = C, 1i
6.25 n, 7.20 N, 8.85 then,
Part of the substance 1 of the present invention obtained in this manner includes: 1
Figure 3 illustrates Illi action and acute toxicity testing.

1. Suppressing effect on gastric acid secretion 24 male Wistar rats weighing 180 to 200 g
After an hourly fast, the abdomen was opened under ether anesthesia and the pylorus was ligated. At 5 hours and 11 hours, the mosquitoes were killed, gastric juice was collected, and the amount and acidity of the gastric juice were measured. The drug may be injected into the duodenum immediately after pylorus ligation. The test results are shown in Table 1.

2-(2-7f nogrovir)-4-phenyl-1(2
1) - Suppressive effect of gastric acid secretion of isoquinolone maleate The effect was almost the same as that of provantyline bromide, and it showed a stronger effect than cimetidine ◎ 2. Stress ulcer suppressive effect 1
After fasting for 8 hours, the mice were placed in a stress cage and immersed chest-shaped in a water tank at 23°C to apply stress. 7 o'clock rIIJ
I killed the mosquitoes and removed their stomachs from Mizuhinoki. Injected 10 mg of 1% formalin into the stomach.
ii! Add 90. After fixation, the total length of the erodion generated along the greater curvature is taken as the pickle coefficient. The drug was orally administered 30 minutes before stress loading. The results are shown in Table 2.
, 2-(2-7 Minoprovir)-4-7! nyl-1<2
H)-Isoquinolone malein test IIi, Provantyline Bromide and Hokkaido showed an inhibitory effect on N-type stress ulcers.

Table 2: Stress ulcer suppression effect (1 group, 7 animals); flat Ia, two-legged deviation P < 0.01 P < 0.05 λ; recovery effect against decreased gastric mucosal flow due to blood loss; 24 Wistar male rats weighing 250-280 go;
After an hourly fast, gastric mucosal blood flow was filtered out using the aminovirine clearance method under urethane anesthesia. Blood was removed at a constant rate of 0.3% of the bale's body weight, and 5 minutes later, the blood was returned to the bird for 1 lls. - Administered intravenously 15 minutes after removal of minerals. The results are shown in Table 3, and showed a restorative effect on the decrease in gastric mucosal flow caused by blood removal.

4. Acute toxicity test weight 18-22 feddY male! Mice were starved for 18 hours and treated with 112-(2-aminopropyl)-4-phenyl-1 (
211)-Isoquinolone II maleate was orally administered, and the LD-value was determined by the up-down method using a lethal skewer at one interval of administration II.

Lo, -5s4qAa Patent sponsor Maru: 1 Pharmaceutical Co., Ltd. Kinsha Continuation of page 1 ■Submitted by: Taiho Pharmaceutical Co., Ltd. 2-chome, Kanda Tsukasa-cho, Chiyoda-ku, Tokyo No. 9

Claims (1)

[Claims] 1. General formula [wherein is an integer between 0 and l, R3 is hydrogen, it,
ti water 1b-c toxycarponyl group, 4-matasha di-lower alkyl group/(kagoyl group, acetyl group) t or di-lower alkyl group, 9-COCHg Nls Ra, respectively represent. However, Ri #R4 are each the same or independently represent hydrogen, a lower alkyl group, a hydrodialkyl group, an allyl group, and in some cases, a wing, R, Ii, together with a radical, a Qin type group. (representing a pyrrolidino group, such as a 4-methylpiperazino group, a 1 mol piperylino group, etc.)] and an acid addition salt thereof. 2. A (2B)-isoquinolone hook conductor and its acid addition salt, wherein n is 0 and NRIRg is an amino group.