Method of preparing purine derivatives or their salts

专利摘要:
Novel 2-amino substituted adenine compounds and their use as antiviral compounds are disclosed. In particular the compound 2-amino-9-(2-hydroxyethoxymethyl) adenine is particularly advantageous as an antiviral in that it has high oral absorption and that upon metabolism in mammals, it has the property of being converted to 9-(2-hydroxyethoxymethyl) guanine which is also a highly active antiviral.
公开号:SU784777A3
申请号:SU792780252
申请日:1979-06-18
公开日:1980-11-30
发明作者:Джон Шаффер Ховард
申请人:Дзе Велкам Фаундейшн Лимитед (Фирма)；
IPC主号:

专利说明:

The invention relates to a method for producing new derivatives of purine having antiviral activity, which may find application in medicine.
The known reaction of hydrolysis of halogen derivatives of condensed pyrimidines to the corresponding hydroxy derivatives or conversion to mercapto derivatives by the action of, for example, sodium hydrosulfide, thiourea or thioacetamide [1].
The purpose of the invention is a method for producing new derivatives of purine with antiviral activity.
The goal is achieved through
sob receiving purine derivativescommon formulas20R N ΪΓ h 11 / a). N CH ₂ OCH _g CH ₂ OH, 25
The method consists in the fact that the compound of General formula
X
CH ₂ 0CH ₂ CH ₂ 0H, where X is halogen, hydrolyzed or converted to a mercapto derivative, followed by isolation of the target product in the form of a base or salt.
Organic acids such as lactic, acetic, malic or p-luol sulfonic acid, and inorganic acids such as hydrochloric or sulfuric are used as acids for the preparation of salts of compound I.
Derivatives of purine of the general formula I exhibit antiviral activity against various DNA and RNA viruses. In particular, the compounds are active against cytomegalovirus, adenovirus, in particular adenovirus 5, infectious mononucleosis, rhinovirus, Mengo virus and Sindbis virus. These are where R is an hydroxy or mercapto group, or their salts. - 30, including the simplest zoster, and in mammals these diseases, such as herpetic keratitis and herpetic encephalitis, compounds are especially active "against cowpox and vesicular vesicles, varicella, Russes cause rabbits in mice, for example.
When methyl) -thioguanine.
To a boiling solution of 1.27 g of 2-amino-6-chloro-9- (2-benzoyloxyethoxymethyl) -purine in isopropanol (40 ml) was added 0.28 g of thiourea. The reaction mixture was continued to boil for another 1.5 hours, then cooled. 0.58 g of 9- (2-benzoyloxyethoxymethyl) -thioguanine is filtered off, so pl. 199-202 ° C. It is introduced into 40 ml of aqueous ammonia (“7 N”) and the mixture is heated in a water bath for 10 minutes, then it is continued stirring overnight at room temperature. Water and ammonia are distilled off in vacuo, the residue is triturated with acetone and then with ether (to remove benzamide). The remaining solid was recrystallized twice from water to give 0.26 g of 9- (2-hydroxyethoxymethyl) thioguanine as a melting point. 251-254 ° C.
'Example methyl) guanine.
A solution of 0.75 mg in 7.5 ml (1 mol) of a methanolic solution of sodium methylate is added to a solution of 0.89 g of 2-amino-6-chloro-9- (2-benzoyloxyethoxymethyl) -purine in 150 ml of methanol. The reaction mixture is boiled. 3 hours under nitrogen. ' The solvent was distilled off in vacuo and the residue was dissolved in water. The aqueous solution is heated for 2 hours in a water bath, cooled, acidified with acetic acid to pH 5.0. The white substance formed is filtered off, washed well with ice water and ether, recrystallized from methanol, and 9- (2-hydroxymexyloxymethyl) -guanine is obtained in 45% yield; so pl. 256.5-257 ° C.
yellow flakes;
2.
9- (2-0xyethoxy2-mercaptoethanol

权利要求:
Claims (1)
[1]
The compounds are particularly active in J: POTHB cowpox and cystic foramen, including protozoan zoster and varicella, in mammals these viruses cause diseases such as, for example, hirpetic keratitis in rabbits and hirpetic encephalitis in mice and. Example 1. 9- (2-Hydroxyethoxymethyl) -thioguanine. To a boiling solution of 1.27 g of 2-amino-b-chloro-9- (2-benzoyloxyethoxymethyl) -purine in isopropanol (40 ml) was added 0.28 g of thiourea. The reaction mixture is continued to boil for another 1.5 hours, then cooled. Filters give 0.58 g of 9- (2-benzoyloxyethoxime: tyl) -thioguanine, m.p. 199-202 ° C. It is introduced into 40 ml of aqueous ammonia (N) and the mixture is heated on a water bath for 10 minutes, then continued to stir until morning at room temperature. Water and ammonia are distilled off in vacuo, the residue is triturated with acetone and then with ether {to remove the benzamide). The remaining solid is twice recrystallized from water to obtain 0.26 g of 9- (2-hydroxyethoxymethyl-thioguanine as yellow flakes; mp 251-254 ° C. Example 2. 9- (2-hydroxyethoxymethyl) -guanine. Solution 0 , 75 mg of 2-mercaptoethanol in 7.5 ml (1 mol) of methanolic peicTvory sodium methoxide is added to a solution of 0.89 g of 2-amino-b-chloro-9- (2-benzylloxyethoxymethyl) -purine in 150 ml of methanol. The reaction mixture is boiled for 3 hours under nitrogen. The solvent is distilled off in vacuo and the residue is dissolved in water. The aqueous solution is heated for 2 hours in a water bath, cooled, acidified with acetic acid. Slot to pH 5.0. The white substance formed from .., 4 is filtered, washed well with ice water and ether, P1, recrystallized from methanol, 9 (2-hydroxymethyloxymethyl) -guanine is obtained in 45% yield; t. mp 256.5-257 ° C. Formula of the invention A method for producing purine derivatives of the general formula lY -.tCHnOCH SNgON, where R is hydroxy or mercapto group, or their salts, characterized in that the compound of the general formula HgT At CHjOCHtCHjOH where X is halogen , is subjected to hydrolysis or transformation into a mercapto derivative, followed by isolation of the target product in the form of Ani or salt. Sources of information taken into account in the examination 1. Chemistry of Heterocyc6ic compounds vol. 17 part 2 Viley-lntercsicuce N. Y. 1971, p. 132.

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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GB38278/74A|GB1523865A|1974-09-02|1974-09-02|Purine compunds and salts thereof|

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