JPH0254344B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention discloses the general formula () useful as a vasodilator, an antihypertensive agent, etc. [In the formula, R ₁ is a group selected from a chlorine atom, an amino group, an alkoxy group, and a piperidino group, R ₂ is a group selected from an amino group and a piperidino group, and R ₃ is a general formula

[Formula] (In the formula, R ₄ represents a lower alkyl group.) A group represented by the general formula -NH(CH ₂ ) _o NH ₂ (In the formula, n represents an integer from 4 to 10.) group, formula

A group selected from the groups represented by [Formula]. However, R ₁ and
Both R ₂ cannot be amino groups. ] and its acid addition salts. Specific examples of the compound represented by the above general formula () include the following compounds. (1) 1-(4-amino-2-chloro-6-quinazolinesulfonyl)-4-(2-ethoxy-2-phenylethyl)piperazine (2) N-(4-aminobutyl)-4-amino-2-
Chlor-6-quinazolinesulfonamide (3) N-(10-aminodecyl)-4-amino-2-
Chlor-6-quinazolinesulfonamide (4) 1-(2-chloro-4-piperidino-6-quinazolinesulfonyl)-4-(2-ethoxy-2
-phenylethyl)piperazine (5) 1-(2-chloro-4-piperidino-6-quinazolinesulfonyl)-4-cinnamylpiperazine (6) N-(4-aminobutyl)-2-chloro-4-
Piperidino-6-quinazolinesulfonamide (7) 1-(2-amino-4-piperidino-6-quinazolinesulfonyl)-4-(2-ethoxy-2
-phenylethyl)piperazine 8 1-(4-amino-2-piperidino-6-quinazolinesulfonyl)-4-(2-ethoxy-2
-phenylethyl)piperazine (9) 1-(2-methoxy-4-piperidino-6-
Quinazolinesulfonyl)-4-(2-ethoxy-
2-phenylethyl)piperazine (10) 1-(2-isobutoxy-4-piperidino-
6-quinazolinesulfonyl)-4-(2-ethoxy-2-phenylethylpiperazine) Furthermore, the present invention provides an acid addition salt of a 2,4-disubstituted-6-quinazolinesulfonamide derivative represented by the general formula (). The salts are pharmaceutically acceptable non-toxic salts, such as inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and acetic acid, citric acid, tartaric acid, lactic acid, succinic acid, etc. acids, fumaric acid, maleic acid, methanesulfonic acid, p-
Organic acids such as toluenesulfonic acid can be mentioned. The 2,4-disubstituted-6-quinazolinesulfonamide derivative represented by the general formula () provided by the present invention can be synthesized, for example, according to the following formula. (In the formula, R ₂ and R ₃ have the same meanings as above.) That is, when R ₁ is a chlorine atom, the formula () obtained by reacting 2,4-dichloroquinazoline with ammonia or piperidine at a low temperature 4-Amino-2-chloroquinazoline or 2-
Using chlor-4-piperidinoquinazoline as a raw material,
4-Amino- obtained by sulfonation and acid chloride
It can be obtained by reacting 2-chloro-6-quinazolinesulfonic acid chloride and 2-chloro-4-piperidino-6-quinazolinesulfonic acid chloride with a compound corresponding to R ₃ H (). In the above sulfonation and acid chloride reactions, the compound represented by the formula () is reacted with a sulfonation reagent such as oleum, and then 4-amino-2-chloro-6-quinazolinesulfonic acid, 2
-Chloro-4-piperidino-6-quinazoline sulfonic acid, and then reacted with a halogenating reagent such as thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, etc. to produce 4- Amino-2-chloro-6-quinazolinesulfonic acid chloride and 2-chloro-4-piperidino-6-quinazolinesulfonic acid chloride can be obtained by heating the compound represented by formula () with chlorosulfonic acid, for example. , or by heating the compound represented by the formula () with chlorosulfonic acid and a halogenating reagent such as thionyl chloride, phosphorus oxychloride, or phosphorus pentachloride, the 4-amino- represented by the formula () can be prepared at once.
2-chloro-6-quinazolinesulfonic acid chloride and 2-chloro-4-piperidino-6-quinazolinesulfonic acid chloride can be obtained. 4-Amino-2-chloro-6-quinazolinesulfonic acid chloride or 2
- Reacts with chloro-4-piperidino-6-quinazoline sulfonic acid chloride and is represented by the formula ()
Examples of R ₃ H include 1,4-diaminobutane,
1,w-diaminoalkanes such as 1,6-diaminohexane and 1,10-diaminodecane (w represents an integer from 4 to 10), such as 1-(2-ethoxy-2-phenylethyl)piperazine 1-(2-alkoxy-2-phenylethyl)
Piperazines or 1-cinnamylpiperazine can be mentioned. In the reaction between the sulfonic acid chloride represented by the formula () and the compound represented by the formula (), an acid acceptor may be present. Acid acceptors used include sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, inorganic bases such as sodium methylate, pyridine, trimethylamine, triethylamine, triethylenediamine, etc. Examples include organic tertiary amines. Examples of the reaction solvent include alkanols such as methanol and ethanol, halogenated hydrocarbons such as dichloromethane and chloroform, ethers such as tetrahydrofuran and dioxane, acetonitrile, and dimethylformamide. The reaction proceeds at room temperature or under mild heating conditions, and the target 4-amino- or 4-piperidino-2-
Chloro-6-quinazoline sulfonamides can be obtained. A 2-alkoxy-4-substituted-6-quinazolinesulfonamide represented by the general formula () in which R ₁ is an alkoxy group can be synthesized as described above, for example.
2 represented by the general formula () where R ₁ is a chlorine atom
It can be synthesized using -chloro-4-substituted-6-quinazolinesulfonamide as a raw material according to the following formula. (In the formula, R ₂ and R ₃ have the same meaning as above and represent an R ₄ alkyl group.) That is, it can be obtained by reacting 2-chloro-substituted-6-quinazolinesulfonamide with an alkali metal alkoxide. . The alkali metal alkoxides used include sodium methoxide, sodium ethoxide, potassium n-propoxide, sodium n-propoxide, sodium n-propoxide, potassium isopropoxide, sodium n-butoxide, sodium isobutoxide, potassium isobutoxide, etc., and the reaction proceeds rapidly at room temperature or under mild heating conditions, and the target product, 2-alkoxy-
A 4-substituted-6-quinazoline sulfonamide derivative is produced. The 2-amino- or 2-piperidino-4-substituted-6-quinazolinesulfonamide derivatives represented by the general formula () in which R ₁ is an amino group or a piperidino group are similar to the 2-alkoxy derivatives, and the 2-amino- or 2-piperidino-4-substituted-6-quinazolinesulfonamide derivatives represented by the formula ()
It can be synthesized by using the 2-chloro-4-substituted-6-quinazolinesulfonamide derivative represented by as a raw material by reaction with ammonia or piperidine, but it can also be synthesized according to the following formula. (In the formula, R ₁ and R ₂ represent an amino group or a piperidino group, and R ₃ represents the same meaning as above.) That is, 2-chloro-4-substituted quinazoline is reacted with ammonia or piperidine, and 2
-Amino- or 2-piperidino-4-substituted quinazoline is obtained, which is sulfonated and acid chloridated to give 2-amino- or 2-piperidino-4-substituted-6-quinazoline sulfonic acid chloride (), and further By reacting with R ₃ H, the 2-amino- or 2-amino-
-Piperidino-4-substituted-6-quinazolinesulfonamide derivatives can be obtained. The sulfonation, acid chloridation, and reaction with R ₃ H can be achieved by the same method as described above for the compound in which R ₁ is a chlorine atom. The compound represented by the general formula () and its pharmaceutically acceptable acid addition salt provided by the present invention are:
According to the research of the present inventors, it has a strong smooth muscle relaxing effect, a platelet aggregation inhibiting effect, a vasodilator,
It is a substance useful as a cerebral circulation improving agent, a therapeutic agent for angina pectoris, and a preventive and therapeutic agent for thrombosis in the cerebrovascular system. The effect of the compound of the present invention on smooth muscle was revealed by the relaxing effect on the superior mesenteric artery of domestic rabbits, and it was also revealed that the compound of the present invention inhibited human platelet aggregation induced by collagen at 2.5 μg/ml. Summer. The smooth muscle relaxing effect is obtained by suspending the superior mesenteric artery isolated from a rabbit in the form of a spiral, contracting it with a potassium chloride solution, and then adding the compound of the present invention to this, which relaxes the artery. For example, when 1-(4-amino-2-chloro-6-quinazolinesulfonyl)-4-(2-ethoxy-2-phenylethyl)piperazine is added, the concentration that causes 50% relaxation (ED50) is defined as complete relaxation being 100%. was 1.9 μM. Furthermore, when the compounds of the present invention are administered intravenously for the purposes mentioned above, no significant toxicity is observed, e.g. 1-(4-amino-2-chloro-
6-quinazolinesulfonyl)-4-(2ethoxy-
Acute toxicity value of 2-phenylethyl)piperazine
LD50 is 88mg/intravenous administration to male mice.
It was Kg. EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto. Example 1 20 g of chlorsulfonic acid and 7.0 g of phosphorus pentachloride were added to 3.0 g of 4-amino-2-chloroquinazoline,
The reaction was carried out at 100°C for 6 hours. The reaction solution was carefully poured into ice water and extracted with chloroform. The chloroform layer was washed successively with saturated sodium bicarbonate water and water, dried over anhydrous sodium sulfate, and then concentrated until the reaction solution volume was 50 ml. 4-Amino-2-chloro-6- thus obtained
A solution of quinazoline sulfonic acid chloride in chloroform contains 2.3 g of anhydrous potassium carbonate and 3.9 g of 1-(2-ethoxy-2-phenylethyl)piperazine.
was added and stirred at room temperature for 18 hours. The reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (chloroform) using 100 g of silica gel to obtain 5.24 g of 1-(4-amino-2-chloro-6-quinazolinesulfonyl)-4-(2-ethoxy-2-phenylethyl)piperazine. Ta. Yield 66% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ) 3400,
1370, 1160 Nuclear magnetic resonance spectrum (δ, CDCl ₃ ): 1.1 (3H,
t, CH ₃ ), 2.2-3.0 (10H, 5×NCH ₂ ), 3.35
(2H, q, OCH ₂ ), 4.4 (1H, CH), 7.2 (5H),
7.4-8.5 (3H) Mass spectrum (m/e): 423, 430, 342,
340 Example 2 A chloroform 50 ml solution of 4-amino-2-chloro-6-quinazoline sulfonic acid chloride prepared from 3.0 g of 4-amino-2-chloroquinazoline in the same manner as in Example 1 was added to 5.0 g of 1,4-diaminobutane.
The mixture was added dropwise to a 50 ml solution of chloroform under ice cooling, and the mixture was stirred at room temperature for 2 hours. Add the reaction solution to 10 ml of 5% NaOH water,
After washing with water and drying over anhydrous magnesium sulfate, chloroform was distilled off. Remove residue with silica gel
Column chromatography (chloroform to 2% methanol-chloroform) was performed using 300 g of N-(4-aminobutyl)-4-amino-2-
1.86 g of chloro-6-quinazoline sulfonamide was obtained. Yield 27% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 3400,
1600, 1550, 1370, 1160 Nuclear magnetic resonance spectrum (δ, _CDCl3 ): 1.5-2.3
(4H, 2×CH ₂ ), 2.9-3.3 (4H, 2×NCH ₂ ),
7.5-8.3 (3H), 2.5 (2H, _NH2 ) Mass spectrum (m/e): 331, 329, 273,
271 Example 3 In Example 2, 1,4-cyaminobutane 5.0
2.6 g of N-(10-aminodecyl)-4-amino-2-chloro-6-quinazolinesulfonamide is obtained in the same manner as in Example 2, except that 10 g of 1.10-diaminodecane is used instead of 1.10 g. Yield 38% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 3400,
1595, 1450, 1365, 1170 Nuclear magnetic resonance spectrum (δ, _CDCl3 ): 1.2-2.1
(16H, 8×CH ₂ ) 3.3 (2H, NH ₂ ), 3.7-4.1 (4H,
2×NCH ₂ ), 7.5-8.3 (3H) Mass spectrum (m/e): 415, 413, 273,
271 Example 4 2-chloro-4-piperidinoquinazoline 1.26g
6 g of chlorosulfonic acid and 1 g of phosphorus pentachloride were added to the mixture, and the mixture was heated at 100°C for 6 hours. The reaction solution was carefully poured into ice water and extracted with chloroform. The chloroform layer was washed successively with saturated sodium bicarbonate water and water, and after drying over anhydrous sodium sulfate, the chloroform was concentrated so that the reaction solution became 30 ml.
To a chloroform solution of the thus obtained 2-chloro-4-piperidino-6-quinazolinesulfonic acid chloride was added 0.70 g of anhydrous potassium carbonate, 1-(2-
Ethoxy-2-phenylethyl)piperazine 1.20
g and stirred at room temperature for 12 hours. The reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (chloroform) using 100 g of silica gel to obtain 1-(2-chloro-4-piperidino-6-
Quinazolinesulfonyl)-4-(2-ethoxy-2
1.0 g of -phenylethyl)piperazine was obtained. Yield 36% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 1600,
1550, 1440, 1340, 1180 Nuclear magnetic resonance spectrum (δ, CDCl ₃ ) 1.1 (3H,
t, CH ₃ ), 1.8 (6H, 3×CH ₂ ), 2.3-4.2 (16H,
1 x OCH ₂ + 7 x NCH ₂ ), 4.3 (1H, m, CH),
7.3 (5H, s), 7.4-8.3 (3H) Mass spectrum (m/e): 545, 543, 409,
410, 312, 248 Example 5 2-chloro-4-piperidinoquinazoline 3.6 g
17 g of chlorosulfonic acid and 6 g of phosphorus pentachloride were added to the mixture, and the mixture was stirred at 100°C for 6 hours. The reaction solution was treated in the same manner as in Example 4 to obtain a 90 ml solution of 2-chloro-4-piperidino-6-quinazolinesulfonic acid in chloroform. To this solution were added 2.0 g of anhydrous potassium carbonate and 3.0 g of 1-cinnamylpiperazine, and the mixture was stirred at room temperature for 12 hours. The reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (chloroform) using 100 g of silica gel.
1-(2-chloro-4-piperidino-6-quinazolinesulfonyl)-4-cinnamylpiperazine 3.3
I got g. Yield 44% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 1600,
1550, 1350, 1160 Nuclear magnetic resonance spectrum (δ, CDCl ₃ ): 1.8 (6H,
3×CH ₂ ), 2.3-2.8 (4H, 2×NCH ₂ ), 2.8-3.3
(6H, 3×NCH ₂ ), 3.8-4.1 (4H, 2×NCH ₂ ),
5.9-6.7 (2H, 2xCH), 7.2 (5H), 7.8-8.2 (3H) Mass spectrum (m/e): 511, 513, 476,
421, 423, 391, 393, 339, 341, 303, 305, 202 Example 6 2-chloro-4-piperidinoquinazoline 2.0 g,
A chloroform 50 ml solution of 2-chloro-4-piperidino-6-quinazolinesulfonic acid chloride obtained according to the method of Example 4 from 9.4 g of chlorosulfonic acid and 0.4 g of phosphorus pentachloride was added with 2.2 g of anhydrous potassium carbonate and 1 , 3.5 g of 4-diaminobutane were added thereto, and the mixture was stirred at room temperature for 12 hours. Wash the reaction solution with water,
After drying over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (chloroform) using 200 g of silica gel.
1.28 g of N-(4-aminobutyl)-2-chloro-4-piperidino-6-quinazolinesulfonamide was obtained. Yield 40% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 1610,
1550, 1470, 1360, 1160 Nuclear magnetic resonance spectrum (δ, _CDCl3 ): 1.2-2.2
(10H, 5×CH ₂ ), 2.9 (2H, NH ₂ ), 3.0-4.5
(8H, 4×NCH ₂ ), 7.5-8.7 (3H) Mass spectrum (m/e): 399, 397, 341,
339, 312, 310 Example 7 2-amino-4-piperidinoquinazoline 2.0g
was stirred at 100° C. for 6 hours with 10 g of chlorosulfonic acid and 0.4 g of phosphorus pentachloride. To a chloroform 50 ml solution of 2-amino-4-piperidino-6-quinazolinesulfonic acid chloride obtained according to the method of Example 4, 1.2 g of anhydrous potassium carbonate was added to the reaction solution.
2.1 g of 1-(2-ethoxy-2-phenylethyl)piperazine was added, and the mixture was stirred at room temperature for 12 hours.
The reaction solution was washed with water, dried over anhydrous magnesium sulfate, and then chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (chloroform) using 200 g of silica gel to obtain 1-(2-amino-4-piperidino-6-quinazolinesulfonyl)-4-(2
-ethoxy-2-phenylethyl)piperazine
2.2g was obtained. Yield 48% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 3400,
1600, 1440, 1360, 1280, 1260, 1160 Nuclear magnetic resonance spectrum (δ, CDCl ₃ ): 1.2 (3H,
CH ₃ ), 1.8 (6H, 3×CH ₂ ), 2.9 to 4.5 (16H, 7×
NCH ₂ + OCH ₂ ), 5.2 (1H, CH), 7.2 (5H), 7.8
~8.7 (3H) Mass spectrum (m/e): 524, 389, 293,
229 Example 8 1- (4-amino-2-piperidino-6-quinazolinesulfonyl)-4-(2-
Ethoxy-2-phenylethyl)piperazine 3.4
get g. Yield 74% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 3400,
1640, 1450, 1370, 1180, 1100 Nuclear magnetic resonance spectrum (δ, CDCl ₃ ): 1.1 (3H,
CH ₃ ), 1.7 (6H, 3×CH ₂ ), 2.9×4.5 (16H, 7×
NCH ₂ + OCH ₂ ), 5.2 (1H, CH), 7.3 (5H), 7.7
~8.6 (3H) Mass spectrum (m/e): 524, 389, 293,
229 Example 9 Dissolve 1.9 g of 1-(2-chloro-4-piperidino-6-quinazolinesulfonyl)-4-(2-ethoxy-2-phenylethyl)piperazine in 50 ml of dimethylformamide, and dissolve 1.8 g of sodium methoxide.
A 5 ml methanol solution of 10 g was added thereto, and the mixture was reacted at room temperature for 15 hours. The reaction solution was diluted with water, extracted with chloroform, dried over anhydrous magnesium sulfate, and then chloroform was distilled off under reduced pressure. The residue was subjected to column chromatography (chloroform) using 60 g of silica gel to obtain 1-(2-methoxy-4-piperidino-6-
Quinazolinesulfonyl)-4-(2-ethoxy-2
-Phenylethyl)piperazine (1.1 g) was obtained. Yield 58% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 1600,
1560, 1450, 1360, 1175 Nuclear magnetic resonance spectrum (δ, CDCl ₃ ): 1.1 (3H,
t, CH ₃ ), 1.8 (6H, 3×CH ₂ ), 2.5-3.5 (14H,
6×NCH ₂ + OCH ₂ ), 3.8 (4H, 2×NCH ₂ ), 4.0
(3H, s, OCH ₃ ), 4.4 (1H, CH) 7.2 (5H), 7.7
~8.3 (3H) Mass spectrum (m/e): 405 (M-135) Example 10 In Example 9, a solution of 2.0 g of sodium isobutoxide and 5 ml of isobutyl alcohol is used instead of a solution of 1.8 g of sodium methoxide in 5 ml of methanol. Except for this, 1-
(2-isobutoxide-4-piperidino-6-quinazolinesulfonyl)-4-(2-ethoxy-2-
0.95 g of phenylethyl)piperazine was obtained. yield
47% Infrared absorption spectrum (ν ^cap _nax , cm ^-1 ): 1550,
1365, 1170 Nuclear magnetic resonance spectrum (δ, _CDCl3 ): 0.8-1.4
(9H, 3×CH ₃ ), 1.8 (7H, 3×CH ₂ ×CH), 3.0
~4.7 (18H, 7×NCH ₂ +2×OCH ₂ ), 5.2 (1H,
CH), 7.3 (5H), 7.9-8.6 (3H) Mass spectrum (m/e): 582, 536, 447, 391 Test example 1 Relaxation effect on mesenteric artery Domestic rabbit (Japanese native species, weight approximately 3 kg ) is exsanguinated to death, the abdomen is opened, and the superior mesenteric artery is removed. Blood vessels are measured in a spiral shape of 2 mm x 25 mm according to the usual method, and 95%
OB: Suspended in a 20ml organ bath filled with Krebs-Hensleit nutrient solution passed through a gas mixture of 5% _CO2 . When one side of the blood vessel is connected to an isometric transducer and a load of 1.5 g is applied, the contraction and relaxation reactions of the blood vessel are recorded as the load applied to the transducer (Nihon Kohden FD Pickup TB-912T). The compound of the present invention was added under conditions of contraction of approximately 1/2 of the maximum contraction of KCl at 15 to 20 mM KCl, and its relaxing effect was observed. The complete relaxation is taken as 100%,
The concentration that causes 50% relaxation (ED50 value) is shown in Table-1.

【table】

[Table] Test Example 2 Effect on platelet aggregation reaction The experiment was conducted according to the conventional method (Journal of Physiology, Vol. 168, p. 178, 1963). Citric acid-treated platelet-rich plasma (PRP) was heated at 1000 rpm for 20 minutes. Obtained by centrifugation and used in experiments. Table 2 of the results
Shown below.

【table】

[Table] Test Example 3 Acute Toxicity Table 3 shows the LD50 values when administered intravenously to ddY male mice.

【table】

Claims (1)

[Claims] 1 General formula () [In the formula, R ₁ is a group selected from a chlorine atom, an amino group, an alkoxy group, and a piperidino group, R ₂ is a group selected from an amino group and a piperidino group, and R ₃ is a general formula (In the formula, R ₄ represents a lower alkyl group.) A group represented by the general formula -NH(CH ₂ ) _o NH ₂ (In the formula, n represents an integer from 4 to 10.) formula This is a group selected from the groups shown in . however,
R ₁ and R ₂ are never both amino groups. ] A 2,4-disubstituted-6-quinazolinesulfonamide derivative and an acid addition salt thereof. 2. The compound according to claim 1, wherein R ₁ is a chlorine atom. 3. The compound according to claim 1, wherein R ₁ is an amino group. 4. The compound according to claim 1, wherein R ₁ is an alkoxy group. 5. The compound according to claim 4, wherein the alkoxy group has 1 to 4 carbon atoms. 6. The compound according to claim 1, wherein R ₁ is a piperidino group. 7. The compound according to claim 1, wherein R ₂ is an amino group. 8. The compound according to claim 1, wherein R ₂ is a piperidino group. 9. The compound according to claim 1, wherein R ₃ is a group represented by the general formula [Formula] (wherein R ₄ represents a lower alkyl group). 10. The compound according to claim 9, wherein R ₄ is a lower alkyl group having 1 to 4 carbon atoms. 11 Claim 1 in which R ₄ is an ethyl group
Compound according to item 0. 12. The compound according to claim 1, wherein _R3 is a group represented by -NH( _CH2 ) _oNH2 (in the formula, _n represents an integer of 4 to 10). 13. The compound according to claim 1, wherein R ₃ is a group represented by the formula: 14. The compound according to claim ₁ , wherein R 1 is a chlorine atom and R ₂ is an amino group. 15. The compound according to claim 14, wherein R ₁ is a chlorine atom, R ₂ is an amino group, and R ₃ is a group represented by the formula [formula] (wherein R ₄ represents a lower alkyl group). . 16. The compound according to claim 15, wherein the lower alkyl group is an ethyl group. 17 R ₁ is a chlorine atom, R ₂ is an amino group, R ₃ is a formula -
The compound according to claim 14, represented by NH(CH ₂ ) _o NH ₂ (wherein n represents an integer of 4 to 10). 18 Claim 1 in which n is 4 or 10
Compound according to item 7. 19. The compound according to claim _{1, wherein R 1} is a chlorine atom and R ₂ is a piperidino group. 20 The compound according to claim 19, wherein R ₁ is a chlorine atom, R ₂ is a piperidino group, and R ₃ is a group represented by the formula [formula] (wherein R ₄ represents a lower alkyl group) . 21. The compound according to claim 20, wherein the lower alkyl group is an ethyl group. 22. The compound according to claim 19, wherein R ₁ is a chlorine atom, R ₂ is a piperidino group, and R ₃ is a group represented by the formula [Formula]. 23 A patent claim in which R ₁ is a chlorine atom, R ₂ is a piperidino group, and R ₃ is a group represented by the formula -NH(CH ₂ ) _o NH ₂ (wherein n represents an integer from 4 to 10). A compound according to Range 19. 24. The compound according to claim 23, wherein 24n is 4. 25. The compound according to claim _{1, wherein R 1} is an amino group, R ₂ is a piperidino group, and R ₃ is a group represented by the formula [formula] (wherein R ₄ represents a lower alkyl group). . 26. The compound according to claim 25, wherein the lower alkyl group is an ethyl group. 27 The compound according to claim 1, wherein R ₁ is a piperidino group, R ₂ is an amino group, and R ₃ is a group represented by the formula [formula] (wherein R ₄ represents a lower alkyl group) . 28. The compound according to claim 27, wherein the lower alkyl group is an ethyl group. 29 R ₁ is an alkoxy group, R ₂ is a piperidino group,
2. The compound according to claim 1, wherein R ₃ is a group represented by the formula: [Formula] (wherein R ₄ represents a lower alkyl group). 30. The compound according to claim 29, wherein the lower alkyl group is an ethyl group. 31. The compound according to claim 30, wherein the alkoxy group has 1 to 4 carbon atoms. 32. The compound according to claim 31, wherein the alkoxy group is a methoxy group or an isobutoxy group.