JPH0344379A - N3-piperazinouracil derivative - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R<1> is H, alkoxy or halogen; R<2> is H, amino, acylamino or saccharide residue; X is H, alkyl or halogen; n is 1-5). EXAMPLE:N<1>-Amino-N<3>-[(3-phenyl-1-piperazinyl)propyl]uracil. USE:A medicine which is an active ingredient of antihypertensive agents, capable of exhibiting hypotensive action equal to or higher than that of urapidil and used for treating hypertension. The does thereof is 1-10mg/human/day amount of the active ingredient administered in one to several divided portions. PREPARATION:For example, a compound expressed by formula II is reacted with a compound expressed by formula III (Hal is halogen, such as Cl, Br or I) in a solvent, such as dimethylformamide, preferably in the coexistence of a base, such as K2CO3, and an alkali metal halide, such as NaI, at 50 deg.C to the refluxing temperature of the solvent for 30min to 10hr to afford the compound expressed by formula I.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to an N3-piperazinouracil derivative represented by the following formula (1) and an antihypertensive agent containing the compound as an active ingredient. .

K" [wherein, R1 is a hydrogen atom, an alkoxyl group, or a halogen atom, R2 is a hydrogen atom, an amino group, an acylamino group, or a sugar residue, or a hydrogen atom, an alkyl group, or a halogen atom, and n is an integer of 1 to 5. [Prior art] Currently, the mainstream treatment for hypertension is a stepwise treatment method in which diuretic antihypertensive agents and β-blockers are the first choice drugs, but in addition to the above drugs, angiotensin converting enzyme inhibitors A variety of drugs with different mechanisms of action have been developed, such as calcium channel blockers, alpha blockers, etc., and the conventional treatment methods have changed from conventional treatments to individual patients based on the severity of the disease and living conditions. It has become possible to provide customized treatment according to the patient's condition, and this is about to become a reality.

[Problem to be solved by the invention]

However, in order to make custom-made treatment a reality, there are still too few types of drugs, and the range of drug selection is extremely limited.

[Means to solve the problem]

As a result of repeated research to find a new compound with antihypertensive effect, the present inventors discovered that the N3-piperazinouracil derivative represented by the above formula CI) has an extremely unique antihypertensive effect. The invention has been completed.

Therefore, the present invention provides N3 represented by the above formula (1)
- A piperazinouracil derivative and an antihypertensive agent containing the derivative as an active ingredient.

The present invention will be explained in detail below.

The compound of the present invention is an N3-piperazinouracil derivative represented by the above formula (1).

In the formula, examples of the alkoxyl group represented by R1 include lower alkoxyl groups having 1 to 3 carbon atoms such as methoxy, ethoxy, and propoxy. Also, fluorine is a halogen atom.

Examples include halogen atoms such as iodine, chlorine, and bromine. In addition, the substitution site of R1 is ortho.

It may be either a meta or para site.

Examples of the acylamino group represented by R2 include lower acylamino groups having 2 to 4 carbon atoms such as acetylamino, propionylamino, and butyrylamino. Examples of sugar residues include pentose sugar residues such as ribofuranosyl, deoxyribofuranosyl (e.g., 2-deoxyribofuranosyl, 3-deoxyribofuranosyl, 5-deoxyribofuranosyl), arabinofuranosyl, xylofuranosyl, etc. can be exemplified.

Examples of the halogen atom represented by X include those similar to R1. Examples of the alkyl group include lower alkyl groups having 1 to 3 carbon atoms such as methyl, ethyl, and propyl.

The compounds of the present invention may be in the form of salts, such as hydrochloric acid, sulfuric acid, aqueous bromide! Inorganic acids such as Iw1 or fumaric acid, tartaric acid, succinic acid, citric acid, methanesulfonic acid,
Examples include acid addition salts with organic acids such as P-toluenesulfonic acid.

The compound of the present invention can be prepared by the following two methods.

Production method 1 A method for obtaining the compound of the present invention represented by formula (1) by reacting a compound of formula (n) below with a compound of formula Cm).

K.

[In the formula, R1R'', X and n have the same meanings as above.

Hal destroys halogen atoms such as chlorine, bromine, and iodine -] Group 1L - The following formula (II) compound and the following formula (IV) compound are reacted to obtain the following formula (V) compound (first reaction step ), and then reacting the compound of formula (V) with the compound of formula (VI) below to obtain the compound of the present invention represented by the compound of formula [■] (second reaction step).

(First reaction step) ni′ (Second reaction step) [In the formula, R1, R1, X, n, and Hal have the same meanings as above]
Production method 1 is based on formula (III) compound per mole of formula (II) compound.
) can be carried out by using 1 to 2 times the mole of the compound and reacting in a reaction solvent (amide organic solvent such as dimethylformamide, dimethylacetamide, formamide, etc.) at 50°C to solvent reflux temperature for 30 minutes to 10 hours. .

Furthermore, by allowing a base such as potassium carbonate, sodium carbonate, or triethylamine and an alkali metal halide such as sodium iodide or sodium bromide to coexist in the reaction solution, the target compound can be prepared with good yield. The amount of these bases and alkali metal halides used is 0.5 each per mole of the compound [■].
It may be appropriately selected from the range of 5 to 5 times the mole.

The compound of the present invention thus obtained can be isolated and purified by conventional isolation and purification means such as recrystallization, adsorption, and column chromatography such as ion exchange.

In the first reaction step of production method 2, 1 to 2 times the mole of the formula (IV) compound is used per mole of the formula (Ill compound), and the reaction solvent (
It can be carried out by reacting at 50 to 100° C. for 1 to 10 hours in the same method as in Production Method 1).

In addition, by allowing a base such as potassium carbonate, sodium carbonate, or triethylamine to coexist in the reaction solution,
The amount of the six bases used to enable the preparation of the target compound in good yield can be appropriately selected from the range of 1 to 2 moles per mole of the compound of formula (n).

The compound of formula (V) thus obtained is isolated and purified if necessary and subjected to a secondary second reaction step. In addition.

As the isolation and purification means, the same method as in Production Method 1 can be employed.

The second reaction step of production method 2 is the formula (V) obtained in the first reaction step.
1 to 2 mol of the compound of formula (VI) is used per 1 mol of the compound, and 30 to 10
This can be carried out by reacting at 0°C for 1 to 50 hours.

In addition, in this reaction step, as in Production Method 1, bases such as potassium carbonate, sodium carbonate, triethylamine, and alkali metal halides such as sodium iodide, potassium iodide, sodium bromide, etc. By adding .5 to 5 times the mole, the compound of the present invention can be prepared in good yield.

The compound of the present invention thus obtained can be isolated and purified by the same method as Production Method 1.

The compounds of the present invention are used for the treatment of hypertension.

When the compound of the present invention or a salt thereof is used as a medicine, the administration method is not particularly limited, and it can be administered orally or parenterally.

Orally administered preparations can be solid preparations such as powders, granules, capsules, and tablets, or liquid preparations such as syrups and elixirs. In addition, parenteral preparations include injections, rectal preparations, and skin external preparations. These formulations are manufactured according to conventional methods by adding pharmaceutically acceptable formulation auxiliaries to the compound of the present invention.

Furthermore, it is also possible to prepare a long-lasting preparation using known techniques.

To produce a solid preparation for oral administration, the compound of the present invention is mixed with excipients such as lactose, starch, crystalline cellulose, calcium lactate, calcium hydrogen phosphate, magnesium aluminate metasilicate, and silicic anhydride to form a powder. or
Furthermore, if necessary, binders such as sucrose, hydroxypropylcellulose, polyvinylpyrrolidone, and disintegrants such as carboxymethylcellulose and carboxymethylcellulose calcium are added, and wet or dry granulation is performed to produce 0 tablets. , these powders and granules can be used directly or with magnesium stearate,
These granules or tablets can be coated with an enteric base such as hydroxypropyl methyl cellulose phthalate or methyl methacrylate copolymer to form an enteric preparation, or ethyl cellulose, or ethyl cellulose. It can also be coated with carnauba wax, hydrogenated oil, etc. to make a long-lasting preparation. Furthermore, to produce capsules, powders or granules may be filled into hard capsules, or the compound of the present invention may be dissolved in glycerin, polyethylene glycol, sesame oil, olive oil, etc., and then coated with a gelatin film to form soft capsules. You can also do that.

To produce a liquid preparation for oral administration: 1. The compound of the present invention and a sweetener such as white sugar, sorbitol, or glycerin are dissolved in water to form a clear syrup, or essential oils, ethanol, etc. are added to form an elixir. Alternatively, gum arabic, tragacanth, polysorbate 80, sodium carboxymethylcellulose, etc. may be added to form an emulsion or suspension.Flavors, coloring agents, preservatives, etc. may be added to these liquid preparations as desired. good.

To produce an injection, the compound of the present invention may be mixed with sodium hydroxide, hydrochloric acid, lactic acid, sodium lactate, phosphoric acid, etc. as necessary.
Dissolved in distilled water for injection with pH adjusters such as sodium hydrogen, sodium dihydrogen phosphate, and tonicity agents such as sodium chloride and glucose, sterile-filtered, and filled into ampoules, or with mannitol, dextrin, and cyclodextrin. , gelatin, etc. are added and freeze-dried under vacuum.
It may be prepared as an injectable preparation to be dissolved at the time of use, or it may be prepared into an injectable emulsion by adding lecithin, polysorbate 80, polyoxyethylene hydrogenated castor oil, etc. to one compound of the present invention and emulsifying it in water.

To produce a rectal preparation, the compound of the present invention is heated and melted together with an emetic base such as tri-, di-, or monoglyceride of cocoa fatty acids or polyethylene glycol, and the mixture is poured into a mold and cooled. After dissolving it in polyethylene glycol, soybean oil, etc., it may be coated with a gelatin film.

To produce a skin external preparation, 1. Add the compound of the present invention to white petrolatum, beeswax, liquid paraffin, polyethylene glycol, etc., and if necessary, heat and knead to make an ointment, or add rosin, acrylic acid alkyl ester, etc. After kneading it with an adhesive such as a polymer, it is spread on a nonwoven fabric such as polyethylene to form a tape.

The dosage of the compound of the present invention varies depending on the patient's age, weight, pathological condition, etc., but is usually about 1 to 10 μg per person per day, and can be administered in a single dose or in several divided doses.

Hereinafter, the compounds of the present invention will be specifically explained by showing synthesis examples and test examples.

Synthesis Example I N1-amino-N”-((3-phenyl-
1-piperazinyl)propyl]-5-fluorouracil (R1=H, R'''=NH,, X=F, n=3=compound 1) N1-amino-5-fluorouracil 250■ (1,7
2 mmol) in dimethylformamide (DMF) 3.7
mA, and 1-phenyl-4-(3-chloropropyl)piperazine 410ag (1,72mm
ol), sodium iodide 258■ (1,72 mmo
l) and potassium carbonate 237■ (1,72 mmol)
After the 0 reaction, the reaction solution was diluted with ethyl acetate and filtered through Celite.
The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (eluent: chloroform/methanol mixed solvent (95:5) to obtain N1-amino-N''-((3-phenyl- 100 μl (yield F%) of propylg(nipiperazinyl) 5-fluorouracil was obtained.

'N-NMR (CDC1,) δ (PP!1) 1.88 (2H, m), 2.50
(2H, t, J = 6.8) 1z), 2.58 (4H, m
), 3.16 (4H, m).

4.08 (2H, t, J=7.3Hz), 4.72
(2H,s) , 6.8-7.6 (6H,m) Synthesis Example 2 N1-amino-N'-((3-phenyl-
1-piperazinyl)propyl]uracil (R'=H, R"=NH,,X=H,n=3: compound 2) N1-aminouracil 127■ (1 mmol), 1
Phenyl-4-(3-chloropropyl)piperazine 41
0■ (1,72mm*l), sodium iodide 258
■ (l, 7'2 mmol) and potassium carbonate 2
37q (1,72 mmol) was reacted in the same manner as in Synthesis Example 1 to obtain N1-amino-N3-((3-phenyl-1-piperazinyl)propyl]uracil 69, (yield: 2%).

1N-NMR (DMSO-d,) δ (ppm)], 72 (2H, m), 2
．． 37 (2H, t, J=7.6Hz), 2.49 (4
H, m), 3.09 (4H, m), 3.86 (2H
, t, J=7.2Hz), 5.52 (LH, d, J=
7.9Hz), 5.57 (IH,s), 5.58 (
IH,s), 6.7-7.3 (5H.

m), 7.64 (LH, d-J = 7.9Hz) Synthesis Example 3 N1-amino-N”-((3-phenyl-
1-piperazinyl)propyl]-5-bromouracil (R'=H, R"=NH,, X=Br, n=3=compound 3) N1-amino-5-bromouracil 206■ (1 mmo
l), 1-phenyl-4-(3-chloropropyl)piperazine 410q (1,72 mmol), sodium iodide 258 mg (1,72 mmol) and potassium carbonate 237 mg (1,72 mmol) in the same manner as in Synthesis Example 1. React to produce N1-amino-N3 [(
69 ml of 3-phenyl-1-piperazinyl)propyl]-5-bromouracil (yield 21%) was obtained.

'N-NMR (DMSO-aS) δ (ppm) 1.72 (2H, m), 2.37 (
2H,t, J=7.6Hz), 2.47(48,m),
3.09 (4H, m).

3.93 (2H, t, J=6.5Hz), 5.66
(LH, s), 5.67 (1H, s), 6.
7-7.3 (5H1m), 8.21 (LH,s
) Synthesis Example 4 N'-amino-N'-((3-phenyl-
N1-aminothymine 141■ (1 mm.l), 1-phenyl-4-(3-chloropropyl) piperazine 410■
(1,72 questions 01), sodium iodide 258■ (1,
72t+aol) and potassium carbonate 237* (1,
72 mmol) was reacted in the same manner as in Synthesis Example 1.
75IIIg (yield 22%) of 1-amino-N3-((3-phenyl-1-piperazinyl)propyl)thymine was obtained.

Elemental analysis cls H,, N, Calculated value as 02 (%
) C, 62,95; H, 7,33; N, 20.3
9 Actual measurement value (%) C, 62,66; H, 7,46; N
, 20.54 Synthesis Example 5 N'-acetamido-N3
-((3-phenyl-1-piperazinyl)propyl]-
5-fluorouracil (R1=H, R''=NHCOCH, X=F, n=3:
Compound 5) (1) N1-acetamido-5-fluorouracil 13
3■ (0,71+uiol) was dissolved in DMFo, 8-, and 150■ of 1-bromo-3-chloropropane (
0,96 mmol) and potassium carbonate 138% (1
m+aol) was added and reacted at 60°C for 2 hours.

After the reaction, the reaction solution was diluted with ethyl acetate, filtered through Celite, and concentrated under reduced pressure to remove the solvent.

The resulting residue was subjected to silica gel column chromatography (
Elution solvent: chloroform/methanol (95:5)
I got it.

(2) N1-acetamido-N3-(3-chloropropyl)-5-fluorouracil 118■ (Q, 45
v++ol) is dissolved in D M F 1 +all,
To this was added 79 μl of 1-phenylpiperazine (0.45 mmo
1), add 67 μ (0.45 mmol) of potassium carbonate and 73 μ (0.45 mmol) of sodium iodide,
The reaction was stirred at 60°C for 8 hours.

After the reaction, the reaction solution was diluted with ethyl acetate, filtered through Celite, and concentrated under reduced pressure to remove the solvent.

The resulting residue was subjected to silica gel column chromatography (
Elution solvent: Chloroform/methanol mixed solvent (95:
5)) to give N1-acetamide-N3-((3
-phenyl-1-piperazinyl)propyl)]-]5-
Fluorouracil 105 (yield: 56%) was obtained.

"N-NMR (CDCL,) δ (ppm) 1.87 (2H, m), 2.16 (
3H,s), 2.48 (2H,t, J=6.9Hz), 2.58 (4H,m), 3.17
(4H, m), 4.05 (2H, t, J=6.9H
z), 6.8-7.3 (6H, m) Synthesis Example 6 N1-acetamido-N3-((3-(2
-methoxyphenyl)-1-piperazinyl]propyl)
Uracil (R”=OCR,,R”=N HCOCH,,X=
H, n=3: compound 6) (1) N'-acetamidouracil 676■ (4, Om
mol) was dissolved in 15 mmol of DMF, and 625 kg of 1-bromo-3-chloropropane (4,0 mmol) and 552 K (1 mmol) of potassium carbonate were added thereto.
The reaction was carried out at 0°C for 2 hours.

After the reaction, one reaction solution was diluted with ethyl acetate, filtered through Celite, and concentrated under reduced pressure to remove the solvent.

The resulting residue was subjected to silica gel column chromatography (
Elution solvent: chloroform/methanol (95:5)) to give 736 ml of N1-acetamido-N'-(3-chloropropyl)uracil (yield 75%).

(2) 1 g of N”-acetamido-N3-(3-chloropropyl)uracil 724I (2,95 opening 01) in DMF
15- and 567 mg (2.95 mmol) of 1-(2-methoxyphenyl)piperazine.

407 μm (2,95+11101) of potassium carbonate and 441 μm (2,95+amol) of sodium iodide were added and reacted at 50° C. for 15 hours.

After the reaction, the reaction solution was diluted with ethyl acetate, filtered through Celite, and concentrated under reduced pressure to remove the solvent.

The resulting residue was subjected to silica gel column chromatography (
Elution solvent: Chloroform/methanol mixed solvent (95:
5)) to give N1-acetamide-N3- ((3
-(2-methoxyphenyl)piperazinyl]propyl)
769 µ of uracil (yield 65%) was obtained.

1H-NMR (CDCI,) δ (pp+m) 1.87 (2H, m), 2.16
(3H, s), 2.50 (2H, m), 2.65 (
2H, br s), 3.08 (4H, br s), 3.
85 (3H, s).

3.99 (2H, m), 5.74 (IHld, J
=8.0)lz), 6.8-7.0 (4H, m
), 7.14 (LHld, J = 8.0Hz) Synthesis Example 7 N! -amino-N”-((:3- (2-
methoxyphenyl)-1-piperazinyl)propyl)uracil (R1=OCH,, R”=NH,, X=H1n=
3=Compound 7) (1) N1-aminouracil 1.27g (10m+m
ol), 1-bromo-3-chloropropane 1.56 (1
0 mmol), potassium carbonate 1.38■ (Env+
ol) in the same manner as in Synthesis Example 5(1) to form N1
-Amino-N"-(3-chloropropyl)uracil1.
03g (yield 50%) was obtained.

(2) N1-amino-N”-(3-chloropropyl)uracil 549 mg (2,7+mmol), 1-(
2-methoxyphenyl) piperazine 5 engineering 9■ (2,7m
+aol), potassium carbonate 3'73m< (2,7
mmol) and sodium iodide 404■ (2,7-
■Nol) in the same manner as in Synthesis Example 5(2)
L-amino-N''-((3-(2-methoxyphenyl)1-piperazinyl]propyl)uracil 614° (yield 63%) was obtained.

LH-NMR (CDC1,) δ (ppm) 1. 87 (2H, m)
, 2. 50 (2H,s), 2.64 (2H
, br s).

3.07 (4H, br s), 3.85 (3H, s)
, 4.03 (2H, m), 4.68 (2H, s),
5.64 (LH, d, J=8.0Hz), 6.8-7
．． 0 (4H, m), 7.40 (LHld, J=8.
0Hz) Synthesis Example 8N'-((3-phenyl-1-piperazinyl)
Propyltouridine (R″=H, R″=β-D-ribofuranosyl group, X=H
, n = 3: Compound 8) Uridine 244 (1 mmol) was dissolved in DMFI-, and 1-phenyl-4-(3-chloropropyl) was dissolved in DMFI-.
Piperazine 286■ (1.2 mmol).

Add 166 mg (1.2 mmol) of potassium carbonate and 180 μg (1.2 mmol) of sodium iodide,
The reaction was stirred at 0° C. for 20 hours.

After the reaction, the reaction solution was concentrated under reduced pressure to remove the solvent, and the resulting residue was dissolved in a mixed solvent of chloroform and methanol (7:3
) and silica gel column chromatography (
Elution solvent: Chloroform/methanol mixed solvent (90:
10)) to give N5-((3-phenyl-l-piperazinyl)propylturidine 320μ (yield 72%)
I got it.

"H-NMR (DMSO-d,) δ (ppm) 1.73 (2H, m), 2.2
4 (2H, m), 2.49 (4H, brs), 3.
09 (4H1brs), 3.59 (2H, m), 3.
8-4.1 (4 H, m), 5.76 (LH, d, J = 8.3) 1z), 5.82 (IH, d, J = 4.8
Hz), 6.5 to 7.2 (5H, m), 7.95 (LH, d, J = 7.8Hz) Synthesis Example 91-β-D-Arabinofuranosyl N”-((
3-phenyl-1-piperazinyl)propyl]uracil (R'=H, R''=β-D-arabinofuranosyl group, X
=H, n=3: Compound 9) 1-β-D-arabinofuranosyluracil 701@g (2,87nuaol),
1-phenyl-4-(3-chloropropyl>piperazine 715■ (3.0 mmol), potassium carbonate 41
5 mg (3,0++v+ol) and 450 μm (3,0 mmol) of sodium iodide were reacted in the same manner as in Synthesis Example 8 to obtain 1-β-ri-arabinofuranosilyl N5.
-((3-phenyl-1-piperazinyl)propyl)uracil 604 µ (yield 47%) was obtained.

'H-NMR (DMSO-d,) δ (ppm) 1.90 (2H, m), 2.49 (
2H, m), 2.64 (4H, m), 3.18 (4
H, m), 3.9-4.1 (4H, m), 4.23 (2H, m), 5.71 (IH, d.

J=8.3Hz), 6.12 (IH.

d, J=3.9Hz), 6.89 (3H, m)
, 7.26 (2H, m) , 7.72 (LH
, d, J=7.8Hz) Synthesis Example 10 N3- ((3
-(2-methoxyphenyl)-1-piperazinyl]propyl)uridine (R1=OCH3, R2=β-D-ribofuranosyl group,
X=H, n=3: Compound 10) Uridine 1.0 g (3.1 mmol), 1 (
2-methoxyphenyl)-4-(3-chloropropyl)
Using 1.19 g (6.2 mmol) of piperazine, 428 μg (3.1 mmol) of potassium carbonate, and 465+ ag (3.1 mmol) of sodium iodide, a reaction was carried out in the same manner as in Synthesis Example 8 to obtain N3- ((3-( 810 ml of 2-methoxyphenyl)-1-piperazinylpropyl)uridine (yield 55%) was obtained.

Melting point: 196-199°C (hydrochloride) Synthesis Example 11 N'-((3-(2-chlorophenyl)
-nipiperazinyl]propyl) Uridine (R1=C1, R2=β-D-ribofuranosyl group, X=
H1n=3: Compound 11) Uridine 1. Og (3
, 1 mmol), 1-(2-chlorophenyl)
-4-(3-chloropropyl)piperazine 1.21 g
(6,2 mmol), potassium carbonate 428 ■ (3,
1 mmol) and sodium iodide 465■ (3,1
N”-((3
-(2-chlorophenyl)-1-piperazinyl]propyl)uridine 440 ml (yield 35%) was obtained.

'H-NMR (DMSO-d,) δ (ppm) 1.77 (2H, m), 2.67 (
2H, m), 2.99 (2H, m), 3.16 (2
H, m), 3.26 (2H, m), 3.60 (2H
, m).

3.87 (2H, m), 3.98 (IH, m), 4
．． 03 (IH, m), 5.09 (2H1m), 5
．． 38 (LH, d), 5.77 (LH, d, J = 7.8Hz), 5.83 (LHld, J = 4
．． 8Hz), 7.0-7.5°4H, m), 7.96
(IH, d, J = 7.8 Hz) Test Example I Effect of SHR on blood pressure Using 43-week-old male SHR (5 animals per group), urethane anesthesia (urethane 1000 μ/kg and α-chloralose 80 μ/kg)
, iv) A blood vessel was led out from the total artery, and blood pressure was measured 5 minutes after drug administration via a pressure transducer (MPU-05).

The drug used was dissolved in physiological saline, and the drug was administered through a cannula inserted into the femoral vein.
Doses of 00J1 g/kg were given cumulatively every 5 minutes with a common ratio of 3. The results are shown in this table.

Table 1 shows that the compound of the present invention exhibits a hypotensive effect equal to or greater than that of urapidil.

Formulation example 1 Compound 10 25 ■ Potato starch 150 ■ Light silicic anhydride
50 ■ Magnesium stearate
10 ■ Lactose 765 ■ Total amount 1000 ■ The above ingredients were mixed uniformly, and 200 ■ of each were filled into hard capsules.

Formulation Example 2 Compound 2 25 ■ Propylene Glycol 10 mg Compound 2 was dissolved in propylene glycol, filtered aseptically, and 0.0 mg was added to an ampoule.
2 pieces were filled.

〔Effect of the invention〕

The compound of the present invention exhibits a hypotensive effect equal to or superior to that of urapidil, and is useful as an antihypertensive agent.

Claims (1)

[Claims] 1) Formula [I] ▲ Numerical formulas, chemical formulas, tables, etc.▼ [I] [In the formula, R^1 is a hydrogen atom, an alkoxyl group, or a halogen atom, and R^2 is a hydrogen atom, an amino group, acylamino group or sugar residue, X represents a hydrogen atom, an alkyl group or a halogen atom, and n represents an integer of 1 to 5. ]
^3-Piperazinouracil derivative. 2) Formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] [In the formula, R^1 is a hydrogen atom, an alkoxyl group, or a halogen atom, and R^2 is a hydrogen atom, an amino group, an acylamino group, or a sugar The residue, X, is a hydrogen atom, an alkyl group or a halogen atom, and n is an integer of 1 to 5. ]
An antihypertensive agent containing a ^3-piperazinouracil derivative as an active ingredient.