JPH03167186A - Xanthine derivative and use thereof - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [R1 is carboxyl, carbamoyl, cyano, vinyl, OH, acetyl, -NR3(R4) (R3 and R4 are H or lower alkyl) or -COOR6 (R5 and R6 are lower alkyl); R2 is H or 4-methoxybenzyl; n is 1-3]. EXAMPLE:[2,3,6,7-tetrahydro-7-(4-methoxybenzyl)-2,6-dioxo-3-n-propyl-1 H-purine-1- yl] ethyl acetate. USE:Used as bronchodilator, cerebral function-improver and antipepticulcer agent. PREPARATION:3,7-dihydro-7-(4-methoxybenzyl)-3-n-propyl-1H-purine-2,6-d ione expressed by formula II is reacted with halogen compound expressed by formula III (X is halogen) in a solvent in the presence of a base as a deoxidizer.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to novel xanthine derivatives and pharmacologically acceptable salts thereof, as well as bronchodilators, brain function improving agents, and anti-digestive agents containing them as active ingredients. It relates to an ulcer agent and is useful as a medicine.

Conventional technology Theophylline [Merck Index (Th6 Merc
kIndex), 10th edition, 9114) or bentoxifylline [The Merck Index (The Merck Index)
Xanthine derivatives, such as those represented by Index), IO edition, 700 2), are widely used clinically as therapeutic agents for closed airway diseases or brain function diseases.

Problem to be Solved by the Invention The main drawback of treatment with xanthine derivatives is that the drugs often cause serious side effects, such as gastric disorders or convulsions. Therefore, in the clinical setting, there is a strong desire to develop new drugs that exhibit fewer side effects.

Means for Solving the Problems As a result of intensive research in view of the above circumstances, the present inventors have found that the novel xanthine derivative according to the present invention is useful for the treatment of obstructive airway diseases, brain function diseases, and peptic ulcers. The present invention was completed based on the discovery that it has a bronchodilating effect, a brain function improving effect, and an anti-peptic ulcer effect.

That is, the present invention is based on the following general formula (I) (wherein Rl is a carboxyl group, a carbamoyl group, a cyano group, a vinyl group, a hydroxyl group, an acetyl group, -N/R· group.
one. 4. Base. Yo. . O R a group, \R4 R1 is a hydrogen atom or 4-methoxybenzyl group, n is 1
represents an integer from 3 to 3, where R1 and R4 are the same or different and each represents a hydrogen atom or a lower alkyl group, and R$ and R represent a lower alkyl group. ) The present invention relates to xanthine derivatives and pharmacologically acceptable salts thereof, as well as bronchodilators, brain function improving agents, and antipeptic ulcer agents containing these as active ingredients.

In the general formula (I) of the present invention, R. a. Rs. As the lower alkyl group represented by, for example, a methyl group. Ethyl group. n-probyl group. iso-probyl group, cycloprobyl group, n-butyl group. iso-butyl group. Examples include see-butyl group and terL-butyl group.

Further, the pharmacologically acceptable salts of the compound represented by the general formula (I) of the present invention include alkali addition salts and acid addition salts, and examples of the alkali addition salts include sodium, potassium, calcium. Inorganic alkali salts such as ammonium, or ethylenediamine. Ethanolamine, N. Salts of organic bases such as N-dialkylethanolamine and triethanolamine are used as acid addition salts such as hydrochloric acid, specific hydrochloric acid, etc. Hydroiodic acid, sulfuric acid. Mineral acid salts such as nitric acid and phosphoric acid, or acetic acid and maleic acid. Fumaric acid, citric acid, oxalic acid. Succinic acid. Tartaric acid, malic acid, methanesulfonic acid. 10-camphorsulfonic acid. Examples include organic acid salts such as mandelic acid.

The novel xanthine derivative represented by the general formula (I) of the present invention can be produced by various methods.

According to the first mode of the method for producing a compound according to the present invention,
The compound in which R in the general formula (I) is a 4-methoxybenzyl group is a 3,7-dihydro-
7-(4-methoxybenzyl)-3-n-proyl-I
H-purine-2,6-dione has the following general formula (III)
R I- (C H t)- X (
A halogen compound represented by I[I] (wherein R1 has the same meaning as above and X represents a halogen atom) is reacted in an organic solvent in the presence of a base as a deoxidizing agent. It can be manufactured by

Examples of the organic solvent used in the method of the present invention include methanol. Ethanol, n-propanol.
Alcohol solvents such as isopropanol and n-butanol, tetrahydrofuran, acetonitrile, N.I. N-dimethylformamide. N-methyl-2-pyrrolidone. Examples include aprotic polar solvents such as dimethyl sulfoxide, and bases used include, for example, metallic sodium. Sodium hydride. Sodium amide, sodium hydroxide, potassium hydroxide. sodium carbonate. Examples include potassium carbonate, and the reaction is carried out at a temperature ranging from water cooling to the reflux temperature of the solvent.

The formula (I) used as the starting material in the production method of the present invention
The compound represented by I) can be produced as follows.

(In the formula, Y represents a halogen atom.) According to the second mode of the method for producing a compound according to the present invention,
In the general formula (I), R! is a hydrogen atom, a 7-penzylxanthine derivative represented by the following general formula CPJ) (where RI and n represent the same meanings as above) is prepared by adding a free radical to a 7-penzylxanthine derivative without a solvent or in an organic solvent. It can be produced by treatment with an acid in the presence of a scavenger.

Examples of the organic solvent used in the method of the present invention include benzene, toluene. Xylene. Carbon tetrachloride.
13 2-dichloroethane etc., and as the free radical scavenger, for example, anisole. Examples of acids include thioanisole, trifluoroacetic acid, trifluoromethanesulfonic acid, and sulfuric acid. Examples include hydrochloric acid and hydrobromic acid. Further, the reaction is carried out at a temperature ranging from room temperature to the reflux temperature of the solvent.

According to the third mode of the method for producing a compound according to the present invention,
The compound in which R+ in the general formula (I) is a carboxyl group is produced by hydrolyzing a compound in which R1 in the general formula (1) is a -COORs group (R● represents the same meaning as above). can do.

This hydrolysis is carried out using an acid or alkali using a method known per se. For acidic hydrolysis, an acid such as hydrochloric acid or sulfuric acid is used, and for alkaline hydrolysis, an alkali such as sodium hydroxide or potassium hydroxide is used. , these acids or alkalis are aqueous solutions, or methanol, ethanol, n-butanol, see-butanol. It can be used in the reaction as a solution such as LerL-butanol or a solution in a water-containing organic solvent, and the reaction is carried out at a temperature ranging from room temperature to the reflux temperature of the solvent.

The bronchodilator, brain function improving agent, and antipeptic ulcer agent containing the novel xanthine derivative represented by the general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient of the present invention usually include: Capsules, tablets. Fine granules, granules, syrups. Orally administered drugs such as powders, or injections. Administered as a suppository. These preparations can be manufactured by conventional methods by adding pharmacologically and pharmaceutically acceptable additives. That is, for oral preparations and suppositories, excipients (lactose, D-mannitol, starch, crystalline cellulose, etc.), disintegrants (
Carboxymethyl cellulose. Carboxymethyl cellulose calcium, etc.), binders (hydroxybrobyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, etc.), lubricants (magnesium stearate, talc, etc.), coating agents (hydroxypropyl methyl cellulose, white sugar, etc.) , bases (polyethylene glycol, hard fat, etc.), and in the case of injections, solubilizers or solubilizers (distilled water for injections) that make up aqueous or ready-to-dissolve injections. .Physiological saline. Probylene glycol, etc.), pll! II Moderator (inorganic acid, organic acid or inorganic base). Formulative ingredients such as stabilizers are used.

The dosage of this drug for treated patients depends on the patient's symptoms, but
The usual daily dose for Bojin is 10 to 1 liter per oral administration.
000 Peng.

Examples Hereinafter, the present invention will be explained by examples and reference examples.
The invention is not limited to the specific details of these examples.

Reference example l 3.7-dihydro-7-(4-methoxybenzyl)-3
-n-Provyl-IH-Purine-2,6-Sion 3,7-dihydro-3-n-Provyl-IH-Purine-
6.68 g of 2.6-sion, 4.75 g of potassium carbonate and N. To a mixture of 70 parts of N-dimethylformamide, 4.90 wI of 4-methoxybenzyl chloride was added under stirring while cooling with water.
After adding t dropwise, the mixture was stirred at 60°C for 2 hours. After adding water to the reaction mixture, the pH was adjusted to 7 with dilute hydrochloric acid, and the precipitated crystals were collected by filtration. The obtained crystals are washed successively with water and ether to obtain 8.00 g of pale yellow crystals. Recrystallization from methanol gives colorless needle crystals with a melting point of 192-193°C.

Elemental analysis value C +sH +aN 40 *Theoretical value C
, 61.14; H, 5.77; N. 17.82 Experimental value C. 61.17;H. 5.88;N. 17
．． 73 implementation fPII (2.3.6.7-tetrahydro-7-(4-methoxybenzyl)-2.8-dioxo-3101 brobyl-I
H-purin-1-yl]ethyl acetate 3,7-dihydro-
7-(4-methoxybenzyl)-3-n-proyl-I
H-purine-2,θ-dione 4.00 g, potassium carbonate 2.17 g, N. A mixture of 24 N-dimethylformamide and 1.10 d of ethyl bromoacetate is stirred at 60-70° C. for 8 hours. The reaction mixture was poured into ice water, and the precipitated crystals were collected by filtration. The obtained crystals are washed successively with water and n-hexane to obtain 4.39 g of colorless crystals. Recrystallization from isopropyl ether gives colorless crystals with a melting point of 106.5-107.5°C.

Elemental analysis value C xsH! 4N 40s Theoretical value C
．． 59=99;H. 6.04: N, 13.99 experimental value C. 60.04; H, e. oa; N, 13
．． 98 According to the method of Example 1, the following compound is obtained.

Implementation N2 Ethyl 3-(2,3.6.7-tetrahydro-7-(4-methoxybenzyl)-2.8-dioxo-3-n-proyl-IH-purin-l-yl)probionic acid Properties Colorless needle-like Crystal (MeOH-H*O) Melting point 92
6 5-94.5°C Elemental analysis value C*+HtaNsOs Theoretical value C, 00.86; ii, 6.32; N
．． 13.52 Experimental value c. ao. aa;H. fL2
s:N. 13.48 Example 3 (2,3,6.7-tetrahydro-7-(4-methoxybenzyl)-2,6-dioxo-3-n-probyl-I
H-purin-l-yl]acetamide Properties Colorless needle-like product (DMF-H snow 0) Melting point 240
~241'C Elemental analysis value C ++H tlN●04 Theoretical value C. 5
8.21. H. 5.70; N, 18.86 experimental value C. 58.2U H. 5.74; N, 19.02
Example 4 3-(2.3.6.7-tetrahydro-7-(4-methoxybenzyl)-2.6-dioxo-3-n-proyl-IH-purin-l-yl)probionamide Properties Colorless crystals ( ELOH) Melting point 196-198℃ Elemental analysis value C +wH tsN 80 4 Theoretical value C
．． 59.21;H. a. ot;N. 18.17 Experimental value C, 59.16; H. 5.88; N, 18
．． 45 Example 5 (2,3,6,7-tetrahydro-7-(4-methoxybenzyl)-2,6-dioxo-3-n-propyl I
H-purin-l-yl]acetonitrile Properties Pale colored needle-like product (AcOEt-n-hexan
e) Melting point 128-130℃ Elemental analysis value C +*H +sN so s Theoretical value C
．． (11.18; H. 5.42; N, 19.82
Experimental value C, 61.09; H, 5.52; N, 1
9.67 Example 6 3-(2.3.6.7-tetrahydro-7-(4-methoxypenzyl)-2.6-dioxo3-n-proyl-IH-purin-l-yl)brobio Nitrile properties Colorless prismatic crystals (IltOH) Melting point 83-8
4℃ Elemental analysis value C+eH*lNsOs Theoretical value C. 62.11;H. 5.76; N. 1
9.06 Experimental value c. at. oz; H, 5.87;
N. 18.97 Example 7 3,7-dihydro-7-(4-methoxybenzyl)-1
-(2-oxoprovir)-3-n-provir-I H
-Purine-2,6-dione Properties Colorless needle crystals (Me0
11) Melting point 12θ~127°C Elemental analysis value C +sH ttN ao a Theoretical value C
, 61.61; H, 5.99. N, 15.13 experimental value c. at. 4a; H, 5.90; N, 15
．． 12 Example 8 3.7-dihydro-7-(4-methoxybenzyl)-1
-(3-oxobutyl)-3-n-propyl-IH-purine-2,6-dione Properties Colorless prismatic crystals (iso-PrOH) Melting point
118-119℃ Elemental analysis value C Snow●HxaNaO< Theoretical value C. 62.49; H, 6.29; N. 1
4.57 Experimental value C. 62.29; H, 6.15;
N, 14.68 Example 9 3.7-dihydro-1-(2-hydroxyethyl)-7
- (4-methoxybenzyl)-3-n-proyl-I
H-purine-2,6-dione Properties Colorless needle crystals (^c
otlt) Melting point 138-140℃ Elemental analysis value C r*H *lN 40 4 Theoretical value C
,60.32. H, 6.19; N, 15.63 experimental value C. 60.08i H. e. 1o; N. 15
．． 64 Example 10 3.7-dihydro-1-(3-hydroxybrobyl)-
7-(4-methoxybenzyl)-3-n-probyl-
1}1-purine-2,8-sion Properties Colorless needle crystals (
AcQIEL-n-hexane) Melting point 99-10
1”C Elemental analysis value C I#H 14N 40 4 Theoretical value C
, 61.28. H, 6. so; N, 15.04 experimental value C. 61. l4. H. 6.41. N, 14
．． 94 Example 11 l-(2-dimethylaminoethyl)-3,7-dihydro-7-(4-methoxybenzyl)-3-n-probyl-
IH-purine-2,6-dione Properties Colorless needle crystals (
iso-PrtO) Melting point: 76-78°C Elemental analysis value: C. H*tN*Oa Theoretical value C, 62.32; H, 7.06; N, 1
8.17 Experimental value C. 62.26. H. 7.05;
N, 18.24 Example 12 l-(3-dimethylaminoprobyl)-3.7-dihydro-7-(4-methoxybenzyl)-3-n-probyl-1}1-purine-2.6- Dione properties Pale colored viscous liquid IR spectroscopy v <KBr) cm-' 21
650. 1700 (C=0) NMR spectrum δ (CDCIs) ppIn '0
．． 96 (3+1.L, J=7.5Hz). t
．． 50-2. 10(4}1.+n),2. 20
-2. 70 (211, m). 2. 28(6}1
．． s). 3. 80 (311, s), 3. 90
-4. 20 (411, m). 5. 41 (211
, s), 6. 88 (211, d, J=9.O
llz), 7. 31 (211, d, J:9.
Ollz), 7. 50 (IH.s) High resolution mass spectrum: C*+HtsNsOs theoretical value m/
z: 399.2270 experimental value mix:
399.2294 Example 13 3.7-dihydro 7-(4-methoxybenzyl)-1
-(2-methoxyethyl)-3-n-proyl-IH-
Purine-2,6-dione Properties Colorless crystals (iso-PrtO) Melting point 93~
94℃ Elemental analysis value C IIH! 4N 40 4Theoretical value C
．． 81.28; H, 6.50; N. 15.04 Experimental value C, 61.03; H, e. aa; N, 15
．． 09 Example 14 l-(2-ethoxyethyl)-3.7-dihydro-7-
(4-methoxybenzyl)-3-n-proyl-IH-
Purine-2.6-dione Properties Colorless needle crystals (ELOII) Melting point 110-112℃ Elemental analysis value C msH ssN 40 4 Theoretical value C
．． 62. l6. H, 6.78. N, 14.50 experimental value C, 61.99; H, e. eo; N, 14
．． 76 Example 15 3.7-dihydro 7-(4-methoxybenzyl)-1
-(2-propenyl)-3-n-propyl-IH-purine-2,6-dione Properties Colorless needles (iso-Pr, O) Melting point 98
~100℃ Elemental analysis value CI●H 1! N 40 g theoretical value C, 64.39; H, 6.26; N, 15.8
1 Experimental value C. 64.24; H, 6, 33; N,
15.85 Example 16 l-(3-butenyl)-3,7-dihydro7-(4-methoxybenzyl)-3-n-propyl-IH-purine-
2.6-dione properties Pale brown crystals (AcO[!L-n-1+exan
e) Melting point 75-77°C Elemental analysis value C t*H ! 4N aos theoretical value C
．． 65.20; H, 6.57; N. 15.21 Experiment 1ia C, 64.95. H, 6.42; N
, 15.29 Example 17 (2,3.6.7-tetrahydro-2.6-dioxo-
3-n-propyl-IH-purin-1-yl)ethyl acetate (2,3.6.7-tetrahydro-7-(4-methoxybenzyl)-2,6-dioxo-3101propyl-I
H-brin-I-yl]ethyl acetate 4.00 g. Anisole l. 0.15+yJ of concentrated sulfuric acid was added to a mixture of 52- and trifluoroacetic acid 20- while stirring at room temperature, and the mixture was heated under reflux for 8 hours. After evaporating the solvent and adding water and isobrobyl ether to the residue, the solution was adjusted to p116 with a 20% aqueous sodium hydroxide solution, and the precipitated crystals were collected by filtration. The obtained crystals are washed successively with water and isopropyl ether to obtain 2.57 g of colorless crystals. Recrystallized from methanol, melting point 1
Colorless platelet crystals with a temperature of 71.5-173°C are obtained.

Elemental analysis value C ItH +@N s0 4 theory @
C, 51.42; H. 5.75;N. 19.99
Experimental value C. 51.32;H. 5.83; N, 2
0.10 Example 18 (2.3,6.7-tetrahydro-2.6-dioxo-
Ethyl 3-n-propyl-IH-purin-1-yl)acetate (2,3,[1,7-tetrahydro-2,6-dioxo-3-n-propyl-IH-purin-1-yl)acetate 2 After adding 21 J of ethanol and 11.24 J of a 2N aqueous sodium monohydroxide solution to .10 g, the mixture was stirred at room temperature for 1.5 hours. After distilling off the solvent and adding water to the residue,
The pH was adjusted to 3 with dilute hydrochloric acid, and the precipitated crystals were collected by filtration. The obtained crystals are washed with water to obtain 1.85 g of colorless crystals. N. N
- Recrystallize from dimethylformamide-ethanol to obtain colorless needle crystals with a melting point of 300°C or higher.

Elemental analysis value C I@H IIN s0 4 Theoretical value C
．． 47.82; H, 4.80. N, 22.21 experimental value C. 47.77;H. 4.98; N, 22
．． 33 Following the method of Examples 17 and 18, the following compounds are obtained.

Example 19 Ethyl 3-(2,3,6.7-tetrahydro-2,6-dioxo-3-n-propyl-IH-purinyl)propionate Properties Colorless platelet crystals (MeOI+) Melting point 200-201 .5℃ Elemental analysis value C. H IIN 40a Theoretical value C.
53.05; H, 6.16; N. 19.04 Experimental value C, 52.81. H, 6.12. N. 19.
18 Example 20 3-(2.3,6.7-tetrahydro-2,6dioxo-3-n-propyl-IH-purin-l-yl)probionic acid Properties Colorless needle-like product ([lMF) Melting point 233-234°C Elemental analysis value C zH +sN 40a Theoretical value C,
49.62; H, 5.30; N, 21.04 Experimental value C. 49.66; H, 5.30; N. 21.
20? Example 2l (2,3.6.7-tetrahydro-2,6-dioxo-
3-n-propyl-IH-purin-l-yl)acetamide Properties Colorless needle crystals (DMF-11■0) Melting point 276
．． 5-278°C Elemental analysis value C1. H mouth N m O s theoretical value C, 4
7.8L; H, 5, 22; N, 27.87 Experimental value C, 47.84. H. 5.34. N. 27.7
9 Example 22 3-(2.3.6.7-tetrahydride-2.6-dioxo-3-n-propyl-IH-purine-1-yl)propionamide Properties Colorless needle-like product (MeOH) Melting point 257-259 °C Elemental analysis value CzH+sNsOs Theoretical value C, 49.81; H, 5.70. N, 2
6.40 Experimental value C. 49.7U H. 5.99.
N, 26.29 Example 23 (2.3.6.7-tetrahydro-2.6-dioxo-
3-n-propyl-IH-bryl-l-yl)acetonitrile Properties Colorless needle crystals (ELOH) Melting point 209-211'C Elemental analysis value C +*H zN so t theory @c
,si. so; 1-1. 4.75; N, 30.0
3 Experimental values C. 51.41;H. 4.97; N,
29.93 Example 24 3-(2,3,8.7-tetrahydro-2,6-dioxo-3-n-proyl-IH-purin-1-yl)probionitrile Properties Colorless prism product (iso-Pr011 ) melting point
183-185°C Elemental analysis value C zH +sN so t theoretical value C.
53.43; H, 5.30; N, 28.32 Experimental value C. 53.64; H, 5.51; N. 211
．． 13 Example 25 3.7-dihydro 1-(2-oxobutylene 3-n
-Provil-IH-purine-2,θ-dione Properties Pale gray needle crystals (EtOH) Melting point 199 to 200.5°C Elemental analysis value C H x N 40 m Theoretical value C. 5
2.79i H, 5.64; N. 22.39 Experimental valueC. 52.83;H. 5.61; N, 22.48 Example 26 3.7-dihydro-1-(3-year-old xobutyl)-3101 proyl-IH-purine-2.6-dione Properties Colorless needle-like product (EIOI1 ) Melting point 198-199℃ Elemental analysis value CI! H l@N so s Theoretical value C
, 54.54; H. a. to; Experimental value C. 54.
52;H. 5.96. N, 21.20 N, 21.19 Example 27 3.7-dihydro-1-(2-hydroxyethyl)-3
-n-propyl-LH-purine-2.6-dione Properties Colorless needle crystals (81011) Melting point 204-206°C Elemental analysis value CI@HraNaOs Theoretical value C. 50.41, H, 5.92. N. 2
3.52 Experimental value C. 50.38; H, 5.82;
N , 23.42 Example 28 3.7-dihydro 1-(3-hydroxyprobyl)-
3-n-propyl-IH-purine-2,6-sion Properties Colorless needle crystals (iso-PrOI+) Melting point 1
46-148°C Elemental analysis value C++H+sN<Ox Theoretical value c, sz. a7; H, 6,39; N, 2
2.21 Experimental value C, 52.17; H. 6.17;
N. 21.90 Example 29 1-(2-dimethylaminoethyl)-3,7-dihydro an-propyl-IH-purine-2,6-sion.
Hydrochloride properties Colorless crystals (IILOH) Melting point 235-240'C (decomposed) IR spectrum v CKBr) an-': 16
54. 1718 (C=O) NMR spectrum δ (DMSO-da) p1116
'0.90 (38.t, J:7.58Z). 1.50
-2.00 (2H.m), 2. 83 (6H.s).
3. 31 (2H, L. J=6.0}1z)
, 3. 98(2}1.t.J=7.511z
). 4. 23 (2H, t. J=6.0Hz)
, 8.02 (IH.s) High-resolution mass spectrum: C ++ H +sN so
Theoretical value tact: 2B5.1539 Experimental value m/z: 265.1543 Example 30 l-(3-dimethylaminopropyl)-3.7-dihydro-3-n-propyl-IH-purine-2,8 -Sion/hydrochloride Properties Colorless crystal (iso-PrOH) Melting point 220
~225°C (decomposition) IR spectrum v (Kllr) am-': 1
658. 1704. 1718 (C=O) NMR spectrum δ (DMSO-da) 11p11 :0.
89 (3H, L.J=7.5HZ), 1.
36-2. 33 (4L m), 2. 72 (68.
s). 3. 07 (20.m). 3. 97 (4
H. m). 7.99 (IH, s), 13.20 (IH
,br s) High-resolution mass spectrum: C eye H ghost +N
*Ot theoretical value m/z: 279.1695 experimental value +11/Z: 279.1689 Example 3l 3.7-dihydro 1-(2-methoxyethyl)-3-
n-probyl-IH-purine-2,6-dione Properties Colorless crystal (AcO[1t) Melting point 148-150℃ Elemental analysis value C ++H l@N 40 1 Theoretical value C
．． 52.37;H. 6.39; Experimental value C, 52.
58; H, 6, 2l:N, 22.21 N, 22.43 Example 32 l-(2-ethoxyethyl)-3.7-dihydro-3-
n-propyl-IH-purine-2.6-dione Properties colorless needle crystals (benzene) Melting point 153.5-154.5°C Elemental analysis value C +tH +*N so s Theoretical value C
, 54.12; H. 6.81. N, 21.04 Experimental value C, 53.9U H, 6.75. N. 20.
92 Example 33 3.7-dihydro-1-(2-bropenyl)-3-n-
Provil-IH-purine-2,6-dione Properties Colorless plate-like product (^cOEL) Melting point 161-163℃ Elemental analysis value C IIH 14N <O t Theoretical value C
．． 56.40. H, 6.02. N, 23.92 experimental value C. 56.43. H. 6.03. N. 24
．． 03 Example 34 l-(3-butenyl)-3.7-dihydro-3101propyl-18-purine-2.6-dione Properties Colorless platelet crystals (AcOIIL) Melting point 201-203°C! R spectrum ν0[Br) roscline: 1664.
1708 (C=O) NMR class h) 6 (DM
SO-dl) I)l)m:0. 87 (3H,
L. J=7. 0Hz). 1. 71 (2H,
SeXL. J=7. 0Hz), 2. 33 (2H.
q. J=7. OHx). 3. 97 (4H.t
．． J=7.0Hz). 4.88-5.08 (2H, m)
．． 5.82 (IH.m). 7. 96 (IH, s).
13. 43 (IH. br s) High resolution mass spectrum: C tmH INN 40 g theoretical value ra
ft: 248.1273 experimental value m/z:
24B. 1259 Effects of the Invention According to the present invention, a new pharmaceutical product containing a xanthine derivative or a pharmacologically acceptable salt thereof as an active ingredient is provided.

That is, the novel bovine santhin derivative represented by the general formula (I) of the present invention and its pharmacologically acceptable salt have excellent bronchodilatory effects, brain function-improving effects, and anti-peptic ulcer effects. , extremely useful as a medicine.

Claims (4)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 is a carboxyl group, carbamoyl group, cyano group, vinyl group, hydroxyl group, acetyl group, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ group, -OR_5 group or -COOR
_6 group, R_2 represents a hydrogen atom or a 4-methoxybenzyl group, n represents an integer from 1 to 3, R_3 and R_4 are the same or different and each represents a hydrogen atom or a lower alkyl group, R_5 and R_6 represents a lower alkyl group. ) A xanthine derivative and a pharmacologically acceptable salt thereof. (2) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 is a carboxyl group, carbamoyl group, cyano group, vinyl group, hydroxyl group, acetyl group, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ group, -OR_5 groups or COOR_
6 groups, R_2 represents a hydrogen atom or a 4-methoxybenzyl group, n represents an integer from 1 to 3, where R_3 and R
_4 are the same or different and each represents a hydrogen atom or a lower alkyl group, and R_5 and R_6 represent a lower alkyl group. ) A bronchodilator containing as an active ingredient a xanthine derivative and a pharmacologically acceptable salt thereof. (3) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 is a carboxyl group, carbamoyl group, cyano group, vinyl group, hydroxyl group, acetyl group, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ group, -OR_5 group or -COOR
_6 group, R_2 represents a hydrogen atom or a 4-methoxybenzyl group, n represents an integer from 1 to 3, R_3 and R_4 are the same or different and each represents a hydrogen atom or a lower alkyl group, R_5 and R_6 represents a lower alkyl group. ) A brain function improving agent containing a xanthine derivative represented by the following and a pharmacologically acceptable salt thereof as an active ingredient. (4) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 is a carboxyl group, carbamoyl group, cyano group, vinyl group, hydroxyl group, acetyl group, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ group, -OR_5 group or -COOR
_6 group, R_2 represents a hydrogen atom or a 4-methoxybenzyl group, n represents an integer from 1 to 3, R_3 and R_4 are the same or different and each represents a hydrogen atom or a lower alkyl group, R_5 and R_6 represents a lower alkyl group. ) An anti-peptic ulcer agent containing a xanthine derivative represented by the following formula and a pharmacologically acceptable salt thereof as an active ingredient.