• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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  • 优先权
    • 专利摘要:
    A 1,2,3,5-tetrahydroimidazothienopyrimidin- 2- one represented by the formula: wherein one of Z1, Z2 and Z3 is a sulfur atom and the remaining two of Z1, Z1 and Z3 represent CH, R1 and R2 each represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, a phenyl group, a chlorine atom or, when taken together R1 and R2 represent an alkylene chain of 3 to 5 carbon atoms, and R3 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and a pharmaceutically acceptable acid addition salt thereof, which exhibit an excellent blood platelet anti-aggregatory activity and are useful as anti-thrombotic agents. The invention also provides a process for the preparation of said compounds and a pharmaceutical composition comprising at least one of said compounds. I
    公开号:SU880252A3
    申请号:SU792798503
    申请日:1979-08-10
    公开日:1981-11-07
    发明作者:Исикава Фумиеси；Асида Синитиро
    申请人:Дайити Сейяку Ко, Лтд (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing new 1,2,3,5-tetragI roimidazothienopyrimidin-2-ones of the general formula, where one of the ry and the other two are from. , he;,. R and R 2. f each means a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms, a phenyl group, a chlorine atom, or R and R taken together are an alkylene chain containing from 3 to 5 carbon atoms. atom R is a hydrogen atom or an alkyl group having from 1 to 5 carbon atoms, however, when a sulfur atom is present, R and Rj. cannot be an alkylene chain, or their salts with activity against blood platelet aggregation, and can be used as antithrombotic agents. A method of producing l, .2, J, b tetrahydroimidazo- (2,1-) -quinazolin-2-ones is known, which consists in that 2-chloro-3-ethoxycarbonylmethyl-5,6-dimethylquinazoline is reacted with ammonia in a medium Alcohol TlJ The purpose of the invention is the synthesis of new compounds with valuable properties that allow their use in medicine. A method for the preparation of compounds of the formula I is proposed, comprising a compound of the formula CHCOjK, where Zjj, Zj., X. | - chlorine above values, or bromine / R4. - lower alkyl, subjected to interaction with ammonia. in a sealed vessel at 100–150 ° C, mostly at 120–130 ° C, in an alcohol medium with a subsequent release of the target product in free form or in the form of a salt. Pharmaceutically acceptable salts are attached with an acid of compounds of Formula I can be easily obtained by adding a selected non-toxic acid to the methanol solution of Compound I. Suitable pharmaceutically acceptable addition salts with non-toxic acids are hydrochloride, hydrobromide, alkyl or aryl sulfonate, phosphate, sulfate, fumarate maleate succinate, tartrate, citrate, and other salts of non-toxic acids commonly used in the art. In the examples below, unless otherwise indicated, parts, percentages, are weight parts and percents. Example. Preparation of 2-chloro-5, 6-dimethyl-3, 4-dihydrothieno- (2,3-d) -pyrimidine. To a solution of 4.66 g of 2,4-dichloro-5,6-dimethyl-teno- (2,3-d) -pyrimidine in 150 ml of a mixture of ethanol-hl-form (1: 1 by volume, slowly add with stirring 2.32 g of borohydride The mixture was stirred at room temperature for 6 hours and the solvent was distilled off in vacuo. 50 ml of water was added to the solid residue and the insoluble product was filtered, washed with water, dried and recrystallized from benzene, yielding 2.05 g of 2- chloro-5,5-dimethyl-3, 4-dihydrothieno- (2,3-d) -pyrimidine, m.p. 170-172s, Found,%: C 47.73; H 4.47; N 13.68. C6HpC N2S: Calculated,%: C, 47.88; H, 4.52; N, 13.96. Analogously to example 1, but using an equimol of the amount of substituted 2,4-dichlorotheno pyrimidine instead of 2,4-dichloro-5,6 dimethylthieno- (2, 3-d) -pyrimidine used in example 1, the following substituted 2-halo-3,4 digydrothienopyrimidine compounds (compounds from 2A to 17A) of the formula | In this example, the reaction is carried out at 40 for compounds 5A, 7A, 8A, 15A and 17A, for BOBO C for compound 9A, at 40 -45 ° C for Compound 16A and at room temperature for the remaining compounds. A list of the compounds obtained and their melting points is given in Table 1. Note,. As a rule, these compounds do not give a clear melting point or decomposition due to instability when heated, i.e. when heated, these compounds gradually become wet and then solidify upon subsequent decomposition. 2. The number in parentheses indicates the temperature of decomposition after solidification. Froze Preparation of 6/7-dimethyl-, 2,3,5-tetrahydroimidazo- (1,) -. -thieno- (2,3-O) -pyrimidine -2-one. A mixture of 6.0 g of 2-chlorop-5, b-dimethyl-3, 4-dihydrothieno -. (2,) -pyrimidine, 5.52 g of ethyl bromoacetate and 12.5 g of powdered potassium carbonate in 300 ml of methyl ethyl ketone are heated with reverse by stirring under nitrogen for 4 hours. After cooling, the insoluble inorganic salt is filtered off and the filtrate is concentrated in vacuo to give crude 2-chloro-3-ethoxycarbrynylmethyl-5; 6-dimethyl-3, 4-dihydrothieno- (2 ., 3-d) -pyrimidine. Due to the instability of the compound obtained, the crude oil is used in the subsequent reaction. A mixture of the crude oil obtained above in 50 ml of a 10% ammonia-ethanol solution is heated in a sealed tube at 120-30 s in an oil bath for 5 hours. After cooling, the precipitated crystals are filtered, washed with water and dried, to obtain 3.0 g of 6,7-dimethyl, 2,3,5-tetrahydroimidazo- (, 2-a) thieno- (2,3-d) -pyrimidine-2- she is. The hydrochloride salt of the resulting compound is obtained by reacting the free compound with hydrochloric acid in methanol in the usual manner. The product has a mp. 249-255s (with diff.). Found,%: C 46.66; H, 4, n. c oH c N oCalculated,%: C 46.60, H 4.69, N 16.30. Analogously to example 3, but using an equimolar amount of the substituted 2-halo-3,4-dihydrothienopyrimidine, which is obtained in example 2, instead of 2-chloro-5, 6-dimethyl-3, 4-dihydrothieno (2,3-d) - pyrimidine (lA) used in Example 3, compounds 2-17 of formula I are obtained, given in t% bl.2.
    Table 1
    "S a: sh at fd
    X
    t w
    a
    s
    X W with; and s e- 3 t
    3
    (C H
    X
    «« About and
    权利要求:
    Claims (1)
    [1]
    m. Claim 1. A method for producing 1,2,3,5-tetrahydroimidazoenothyridine-2-one where one of the Radikshovs Z., Z and 2, is a sulfur atom, and the other two of the radicals 2, Z 2. and Z are is a CH2 R group. Each is a hydrogen atom, an AlCyl group, 1-5 carbon atoms, a phenyl group, a chlorine atom, or R and R taken together represent an alkylene chain with 3-5 carbon atoms; R 5 is a hydrogen atom or an alkyl group having 1-5 carbon atoms, however, when Z is a sulfur atom, RR 2 and iv can be an alkylene chain, or their salts, O. is different because the compound of the general formula: co, ti where Z is .ZZ, R, Rj and R are as defined above, X is chlorine or bromine, R4 is a lower alkyl group, is reacted with ammonia in a sealed vessel at 100-15 ° C, preferably at 120-130 ° C, in an alcoholic medium with subsequent concentration of the target product in free form or in the form of a salt. Sources of information taken into account during the examination 1. Patent OUR 3932407, class 260-256,4, published 1976.
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    同族专利:
    公开号 | 公开日
    AU529068B2|1983-05-26|
    IL57923D0|1979-11-30|
    DE2961552D1|1982-02-04|
    YU41170B|1986-12-31|
    PH15530A|1983-02-09|
    EP0008408A1|1980-03-05|
    GR73839B|1984-05-04|
    DK153844C|1989-01-30|
    IL57923A|1982-09-30|
    ZA793909B|1980-10-29|
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    DK336779A|1980-02-12|
    AU4973579A|1980-02-14|
    MX6242E|1985-01-28|
    US4284773A|1981-08-18|
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    引用文献:
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    DE2411273A1|1974-03-06|1975-09-18|Schering Ag|Thieno pyrimidinone derivs - for use as anti-inflammatories and inters, for antimicrobials|US4287340A|1979-08-27|1981-09-01|Warner-Lambert Company|Dihydro-oxo-pyrido[1,2-a]thienopyrimidine compounds|
    ZW11781A1|1980-06-27|1982-01-20|Hoffmann La Roche|Pyrimidine derivatives|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    JP53097832A|JPS627914B2|1978-08-11|1978-08-11|
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