• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Anthracycline glycosides of the general formula (I): <CHEM> wherein R1 represents a hydrogen atom or a hydroxyl group, one of R2 and R3 represents a hydrogen atom and the other of R2 and R3 represents a hydrogen atom or a hydroxyl group; and pharmaceutically acceptable acid addition salts thereof are antitumor agents. These glycosides may be prepared from a daunomycinone derivative of formula (II): <CHEM> in which the 4-amino group is protected. 4-Demethoxy-4-amino-daunomycinone (II) and an earlier intermediate in its preparation, 4-demethoxy-4-amino-7-deoxy-daunomycinone (IX), can be diazotised followed by mild reduction to form 4-demethoxy-daunomycinone or 4-demethoxy-7-deoxy-daunomycinone respectively. 4-Demethoxy-daunomycinone can be converted into another antitumor anthracycline glycoside, 4-demethoxy-daunorubicin.
    公开号:SU1614764A3
    申请号:SU884355593
    申请日:1988-04-20
    公开日:1990-12-15
    发明作者:Карузо Микеле；Суарато Антонио；Анджелуччи Франческо；Аркамоне Федерико
    申请人:Фармиталиа Карло Эрба С.Р.Л. (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of anthracycline glycosides of the general formula
    ABOUT
    sns-oh / s /
    NH
    HE
    and-
    I)
    ten
    15
    aqueous 4-dimethyl-4-0-sulphonate, Another 0.3 g of the product is isolated by purification of a 41% solution on chromatore-Aic; a column using a mixture of toluene and acetone as eluent. Yield 80%. those on Kieselgel F254 (Merck) using a mixture of toluene and acetone (9: 1 by volume). Rf 0.26.
    Zero mass spectrometry (m) 526.
    UFDmax (MeON): 524, 490 named.
    H NMR (200 MHz, CDCl 3), f: 13.43, 13.36, (s, 2H, 11-OH, 6-OH); 8.38 (dd, J 1.3, 779 Hz, 1H, 1-H); 8.02
    (m, 2H, OSO
    F); .7,80 (dd, J
    having antitumor activity.
    The purpose of the invention is to develop a method for obtaining a new anthracycline glycoside with advantages in biological; activity,
    II p and mep 1, 4-Dimethyl-7-deoxydounomycinone,
    1.5 g of 4-dimethyldaunomycinone diluted in a mixture of 100 ml of dioxane and 100 ml of ethanol are heated in the presence of 0.3 g of 5% Pd / BaSOSO at room temperature for 3 hours. After filtration, the solvent is removed in vacuo and 4- Demethoxy-7-deoxy-dunomycinon was isolated in almost quantitative yield, those on Kieselgel F254 (Merck) using a mixture of toluene and acetone (9: 1 by volume), Rf 0.30,
    Pr im e p 2. 4-Dimethyl-4-0- (4- -fluorobenzenesulfonyl) -7-deoxidaunone micinone
    To a stirred solution of 1.0 g of 4-dimethyl-7-deoxidaunomycinone in 200 ml of anhydrous methylene dichloride containing 0.52 ml of K, M-7 ml of isopropyl amine and a catalytic amount of 4-dimethylaminopyridine, at room temperature, add 0.52 g of 4- fluorobenzenesulfonyl chloride. After 30 minutes, the conversion is complete, and the reaction mixture is washed with 0.1N. hydrochloric acid and then water.
    The organic solution is dried over anhydrous sodium sulfate, the solvent is filtered and removed in vacuo. The crude product is placed in a small amount of toluene and crystallized to obtain 0.6 g of pure product.
    20
     7.9, 8.1 Hz, 1H, 2-H); 7.62 (dd, J 1.3, 8.1 Hz, 1H, 3-H); 7.23 (m
    35
    ) - 25
    , OQ 2H, OS); 3.77 (s, 1H,
    9-OH); 3.1-2.8 (m, 4H, 7-CH2, 10-CH); 2.38 (s, AH, AHFS,); 2.0-1.9 (m, 2H, 8-CH),
    Primerz, 4-demetoksi-4-benzsh1amino-7-dvoksidaunomitsinon,
    0.8 g of the compound of Example 2 is dissolved in 100 ml of tetrahydrofuran and 0.5 ml of benzylamine is added. Receive- The mixture was extracted at 40 ° C for 36 hours with stirring, then 50 ml of 1N was added. aqueous hydrochloric acid and 100 ml of methylene dichloride. The organic phase is washed twice with water and dried over anhydrous sodium sulfate. The solvent is removed in vacuo. The crude product is chromatographed with instant evaporation using a mixture of toluene and acetone as the eluting solvent to give 0.48 g of 4-demethoxy-4-benzminamino-7-deoxidomicinone. Yield 69%.
    45 of those on the plate Kieselgel F254 CMerck) using a mixture of toluene and acetone (9: 1 by volume), Rf 0.28, Field mass spectro1; etry (M)
    457.
    I
     (MeOH): 548 nm.
    H NMR (200. MHz, eoe1z), (: 13.58 (s, 2H, 6-OH, 11-OH); 9.86 (t, J 5.7 Hz, 1H, NH-eH Ph); 7 , 64 (d, J 7.3 Hz, 1H, 1-H); 7.49 (dd, J 7.3, 8.3 Hz, 1H, 2-H); 7.4-7.2 (m , 5H,); 7.00 (d, J 8.3 Hz, 1H, - 3 W, 4.60 (d, J 5.7 Hz. 2H,); 3.1-2.9 (m, 4H, Yu-EH,
    five
    sixteen
    7-chj |); 2.37 (s, 3N, COCIb); 2, 0-1.9 (m, 2H, 3-SNg).
    PR and MER 4. 4-Demetoxy-4-amino-7-deoxidaunomycinone,
    0.45 g of 4-demethoxy-4-benzylamino-7-deoxidaunomycinone is dissolved in a mixture of 40 ml of ethanol, 20 ml of acetic acid and 0.4 ml of 37% aqueous hydrochloric acid; 0.2 g of Pd is added. / BaSO (catalyst) and the resulting mixture is hydrogenated at 1 atm for 1 hour at room temperature. After that, the catalyst is filtered off and the solvent is evaporated in vacuo. The crude product is chromatographed with instant evaporation using as eluent a mixture of toluene and acetone to obtain 0.2 g of 4-demethoxy-4-amino-7-deoxy daunicinone, 75% yield, TLC on a Kieselgel F254 plate (Merck) ; using a mixture of toluene and acetone (9: 1 by volume), Rf 0.17.
    Field mass spectrometry (M) 367,
    UV MW (MeOH): 536, 508 nm.
    H HI-IP (200 MHz, CO1H), (: 13.62, 13.55 (s, 2H, 11-OH, b-OH); 7.64 (d, J 7.7 Hz, 1-H) ; 7.46 (dd, J 7.7, 8.3 Hz, .1H, 2-H); 6.93 (d, J 8.3 Hz, 1H, 3-H); 6.8-7, 0 (broad signal), 2H, NH-i); 3.83 (s, 1H, 9-OH); 3.1-2.8 (m, 7-CHg, 10-SND); .2.37 (s, 3N, COCHj); 2.0-1.9 (m, 2H, 8-CHz).
    PRI me R 5, 4-Demetoxy-4-H-three
    fluoroacetamido-7-deoxidaunomycinone.
    About 2 g of 4-demethoxy-4-amino-7-deoxydaino chsionon is dissolved in 20 ml of anhydrous methylene dichloride, cooled to 0 ° C, and 0.3 ml of trifluoroacetic anhydride is added. After 10 minutes, sodium bicarbonate. The organic phase is washed twice with water and separated, dried over anhydrous sodium sulphate. The solvent is removed in vacuo to give a compound in quantitative yield, TLC on Kieselgel F254 (Merck) using a mixture of toluene and acetone (9: 1 by volume),
    / Rf 0.32;
    ; .
    PRI me R 6, 2-Demetoxy-4-K-trifluoroacetamide daodomycinone,
    A suspension of 0.2 g of the compound of Example 5 in 15 ml of benzene and 0.5 ml of ethylene glycol is refluxed for 4 hours in the presence of 0.015 g of p-toluenesulfonic acid, using a Dean-Stark apparatus, Obtained
    7 (
    Q j 0
    five
    ABOUT
    five
    Q 5
    .
    -46
    the mixture is cooled, washed with aqueous sodium bicarbonate and water, then evaporated to dryness to obtain 0.2 g of the target ketal.
    The resulting ketal is dissolved in 125 ml of methyl dichloride with and treated with bromine (1.7 ml of a 0.6 M solution in methylene dichloride) in the presence of 0.25 g of 2,2-azobisisobutyronitrile.
    After 3 hours, the mixture was cooled and extracted with an aqueous solution of sodium bicarbonate, then washed twice with methylene dichloride and dissolved in vacuo.
    The residue is dissolved in 3 ml of trifluoroacetic acid and 0.3 ml of water at 0 ° C and stirred for 1 hour, then extracted with methylene dichloride.
    The organic phase is washed with aqueous sodium bicarbonate and water. The solvent is filtered off, dried over anhydrous sodium sulphate and evaporated in vacuo to give 0.1 g of 4-demethoxy-4-K-trifluoroacetamido-daunone-cycine. Yield 48%. TLC on a Kiselgel F254 (Merck) plate, using CH, 2.Cl2 and acetone (95: 5 by volume), Rf 0.23,
    Field mass spectrometry (M) 479,
    Example 7. 4-demetoksi-4-ami-nodaynopybitsin (1a),
    0.08 g of 4-demethoxy-4-N-trifetropacetamide-dodomicinone prepared according to Example 6 is dissolved in anhydrous methylene dichloride, and the resulting solution is cooled to 5-10 ° C. A solution of 0.024 g of 1-chloro- N, 0-ditrifluoroacetyl daunazine prepared by a known method in diethyl ether, and a solution of 0.150 g of silver trifluoromethanesulfonate in methylene dichloride with vigorous stirring.
    After 5 minutes another 0.0 g of silver trifluoromeuansulfonate is added and after 5 minutes the reaction is quenched with collidine,
    The resulting mixture is filtered, washed with saturated aqueous sodium bicarbonate and water, dried and concentrated, in vacuo.
    The residue is chromatographed on a well with a silica gel column, eluting with methylene chloride to give 4-demethoxy-4-A-trifluoroacetamido-K-trifluoroacetyl daunorubicin (la). The compound obtained is dissolved in 10 ml of acetone and
    ten
    15 22.5
    133 167 200
    0/10 0/10 1/10
    55
    Oh oh
    IT he
    1614764
    react in anhydrous methylene chloride with 4-fluorobenzenesulfo-1-chloride in the presence of N, N-diisopropylethylethylamine and the catalytic coherence of 4-dimers of aminopyridine, the resulting -demethoxy-4-4-fluorobenzene-sulfonyl-7-ioophoxidine-4-fluorobenzene-4-fluoromethanol-i-pyridine; IV
    Oh he is about; . ten
    l with
    20
    in tetrahydrofuran, is reacted with bepsylamine for 36 hours; the benzyl group is removed from the resulting 4-demethoxy-4-benzyl-25 amino-7-deoxy daunomycinone of formula V
    Oh he oh
     he
    using catalytic hydrogenation in the presence of 5% Pd / BaSO with 1 atm at room temperature for 1 h, using a mixture of ethanol and acetic acid and a catalytic amount of aqueous hydrochloric acid as solvent, protect the 4-amino group of the resulting 4-de etoxy-4-amino-7-deoxy daunomycinone of formula VI
    Oh oh
    NH20 OH
    ten
    by reaction with trifluoro- ,. acetic anhydride in anhydrous methylene dichloride, the 7-hydroxy group is reinserted into the obtained protected compound of formula VII
    Oh he
    state of he
    using the first protection of the 13-keto group by ketalization with ethylene glycol at the reflux temperature in the presence of p-toluenesulfonic acid, the interaction of the obtained ketap with bromine in methylene dichloride in the presence of: pc. 2,2-azobisisobutyronitrile for 3 hours and subsequent treatment with 7- the brominated intermediate compound with aqueous trifluoroacetic acid at 0 ° C for 1 h to obtain 4-demethoxy-4-H-trifluoroacetamide-to-daunomycinone of formula VIlI
    Oh oh
    thirty
     OH OH
    which is subjected to interaction with a protected halo.tssahar formula IX
    35
    0
    five
    0
    R NHCOCF. OSOGS
    where Hal is a chlorine atom,
    in anhydrous methylene chloride at 5 - in the presence of silver trifluoromethanesulfonate to obtain 4-N-3, 4 -N, 0-anthracycline trifluoroacetyl - protected glycoside, from which after treatment at 3 hours O, 1 n. with aqueous sodium hydroxide, if necessary, isolate the compound of formula I as hydrochloride by treatment with methanolic hydrogen chloride.
    权利要求:
    Claims (2)
    [1]
    1/10
    9
    1614764
    I o
    by reaction at 0 ° C with trifluoro-.,
    acetic anhydride in anhydrous methylene dichloride, re-introduce the 7-hydroxy group in the resulting protected compound of formula VII
    is reacted in anhydrous methylene chloride with 4-fluorobenzenesulfonyl chloride in the presence of Ν, Ν -diisopropylethylamine and a catalytic amount of 4-dimethyl-aminopyridine, obtained by h — demetoxy — 4 — ^ 4 — fluorobenzene — sulfonyl-7-deoxa daumucinocinocinone-7-deoxyquinone-aminocinidine.
    ten
    15
    20
    in tetrahydrosrorane, is reacted with benzylamine at 40 ° C for 36 hours; the benelyl group is removed from the resulting 4-demethoxy-4-benzylamino-7-deoxy daunomycinone of formula V
    Oh he oh
    thirty
    35
    using catalytic hydrogenation in the presence of 5% RC / VAZO ^ at 1 atm, at room temperature for 1 h, using as a solvent a mixture of ethanol-acetic acid and a catalytic amount of 37% aqueous hydrochloric acid, protect the 4-amino group of the resulting 4-de - ^^ Methoxy-4-amino-7-deoxy-daunomycinone VI formula
    sock 3 yo oh he
    by first protecting the 13-keto group with ketalization with ethylene glycol at the reflux temperature in the presence of p-toluenesulfonic acid, reacting the obtained ketal at 40 * C with bromine ‘in methylene dichloride in the presence of '. ^
    [2]
    2.2 1 -azobisisobutyronitrile for 3 hours and then treating the 7-brominated intermediate with aqueous trifluoroacetic acid at 0 ° C for 1 hour to obtain 4-demethoxy-4-M-trifluoroacetamido-daunomycinone of formula VIII
    sog ^ n about he he
    which is reacted with the protected halo sugar of formula IX
    where Na1 represents a chlorine atom,
    in anhydrous methylene chloride at 5–10 ° С in the presence of silver trifluoromethanesulfonate to obtain 4-Ν-3 *, 4 ( -Ν, O-anthracycline trifluoroacetyl - protected glycoside, from which after treatment at 0 ° С for 3 h 0.1 n Aqueous sodium hydroxide, if necessary, isolates the compound of formula I as a hydrochloride by treatment with methanolic hydrogen chloride.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1614764A3|1990-12-15|Method of producing antracyclin glycozides
    EP0109253A2|1984-05-23|Epimeric azahomoerythromycin A derivative and intermediates therefor
    US4600537A|1986-07-15|Preparation of | 4-demethoxy-6 |-deoxydaunomycinone
    US4366149A|1982-12-28|Antitumor anthracycline glycosides, their preparation, intermediates therefor, and compositions and use thereof
    EP0024727B1|1982-05-26|Anthracycline glycosides, processes for their preparation and pharmaceutical composition containing them
    EP0199920B1|1988-08-17|New antitumor anthracyclines
    EP0051279B1|1985-09-04|Anthracycline glycosides, intermediate compounds, process for preparing both and pharmaceutical compositions
    US4183919A|1980-01-15|Antitumor glycosides, process for their preparation including intermediates therefor and their use
    US4003922A|1977-01-18|Synthesis of cis-1,4-cyclohexadiene dioxide
    HU198505B|1989-10-30|Process for producing antitumour anthracycline glycosides
    US4749693A|1988-06-07|Nitro anthracyclines, process for their preparation and use thereof
    CA1128503A|1982-07-27|Process for the preparation of substitutedantitumor anthracyclines
    US4965352A|1990-10-23|Anthracycline derivatives having cytostatic activity
    US4563444A|1986-01-07|Anthracycline glycosides, use and compositions containing same
    AU641644B2|1993-09-30|A process for the preparation of etoposides
    Florent et al.1989|Synthesis and antitumor activity of new anthracyclines
    US4276289A|1981-06-30|Antitumor glycosides, their preparation and use
    EP0394908A1|1990-10-31|Process for producing glucosaminyl-epi-podophyllotoxin derivatives
    SU1227117A3|1986-04-23|Method of producing anthracyclic glycosides or hydrochlorides thereof
    Hermentin et al.1989|Synthesis and Structure Elucidation of p-Methoxybenzoyl Derivatives of Rhodomycins1
    Hermentin et al.1989|Dirk Boettgerº? Hans Gerd Berscheid,"? Manfred Gerken"? and Cenek Kolarº
    同族专利:
    公开号 | 公开日
    MY103365A|1993-06-30|
    DE3855480D1|1996-09-19|
    AT83239T|1992-12-15|
    HU46335A2|1988-10-28|
    CA1318665C|1993-06-01|
    CS711788A2|1989-11-14|
    YU46455B|1993-10-20|
    GR3007163T3|1993-07-30|
    IE63510B1|1995-05-03|
    AU621222B2|1992-03-05|
    GR3021004T3|1996-12-31|
    CN88102182A|1988-12-28|
    PT101194A|1994-09-30|
    NZ224252A|1991-09-25|
    HRP920920B1|1998-08-31|
    ES2093034T3|1996-12-16|
    AU600816B2|1990-08-23|
    NO881710L|1988-10-24|
    JP2651414B2|1997-09-10|
    AU5591690A|1990-09-20|
    IL86088D0|1988-09-30|
    YU46489B|1993-10-20|
    AU1469588A|1988-10-27|
    EP0288268A2|1988-10-26|
    NO168702C|1992-03-25|
    YU94089A|1989-10-31|
    EP0288268A3|1988-12-14|
    FI881792A|1988-10-22|
    PT101194B|1999-09-30|
    HU200188B|1990-04-28|
    CS265888A2|1989-11-14|
    CS270596B2|1990-07-12|
    SI8810759A8|1996-04-30|
    DK104694A|1994-09-12|
    PT87270A|1989-05-12|
    DE3855480T2|1997-01-02|
    HRP920898A2|1997-04-30|
    CS270585B2|1990-07-12|
    MY104645A|1994-04-30|
    PT87270B|1995-05-04|
    NO881710D0|1988-04-20|
    DK174561B1|2003-06-10|
    YU75988A|1989-10-31|
    AT141251T|1996-08-15|
    DK210688D0|1988-04-18|
    ES2042737T3|1993-12-16|
    HU202810B|1991-04-29|
    NO168702B|1991-12-16|
    SU1729294A3|1992-04-23|
    CN1069722A|1993-03-10|
    DE3876482T2|1993-04-15|
    DE3876482D1|1993-01-21|
    JPS63313796A|1988-12-21|
    US4985548A|1991-01-15|
    DK210688A|1988-10-22|
    HU895388D0|1990-03-28|
    ZA882732B|1988-10-17|
    HRP920920A2|1994-04-30|
    DK170405B1|1995-08-21|
    FI89263C|1993-09-10|
    CN1022038C|1993-09-08|
    KR880012627A|1988-11-28|
    CA1315775C|1993-04-06|
    EP0426653A1|1991-05-08|
    EP0426653B1|1996-08-14|
    IE881171L|1988-10-21|
    EP0288268B1|1992-12-09|
    HRP920898B1|2000-12-31|
    CN1024545C|1994-05-18|
    FI881792A0|1988-04-18|
    FI89263B|1993-05-31|
    US4965351A|1990-10-23|
    IL86088A|1992-11-15|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE905014C|1944-09-23|1954-02-25|Cassella Farbwerke Mainkur Ag|Process for replacing the diazo group with hydrogen|
    US3803124A|1968-04-12|1974-04-09|Farmaceutici It Soc|Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives|
    GB1467383A|1974-06-12|1977-03-16|Farmaceutici Italia|Daunomycin analogues|
    GB1500421A|1975-01-22|1978-02-08|Farmaceutici Italia|Optically active anthracyclinones|
    GB1511559A|1975-09-26|1978-05-24|Farmaceutici Italia|Anthracycline glycosides|
    US4021457A|1975-11-18|1977-05-03|Research Corporation|Intermediates for polycyclic quinonoid antibiotics|
    US4012448A|1976-01-15|1977-03-15|Stanford Research Institute|Synthesis of adriamycin and 7,9-epiadriamycin|
    GB1509875A|1976-06-14|1978-05-04|Farmaceutici Italia|Optically active anthracyclinones and anthracycline glycosides|
    GB1567456A|1976-11-16|1980-05-14|Farmaceutici Italia|Daunomycin derivatives|
    US4109076A|1977-09-08|1978-08-22|Sri International|5-iminodaunomycin|
    US4348388A|1980-04-02|1982-09-07|G.D. Searle & Co.|11-Amino-11-deoxydaunorubicin and analogs|
    JPS634835B2|1980-11-01|1988-02-01|Fuarumitaria Karuro Eruba Spa|
    US4413120A|1981-04-06|1983-11-01|Purdue Research Foundation|Process for producing acosamine, daunosamine, 1-thioacosamine and related compounds|
    US4563444A|1982-05-26|1986-01-07|Farmitalia Carlo Erba S.P.A.|Anthracycline glycosides, use and compositions containing same|
    IT1168014B|1981-08-05|1987-05-20|Erba Farmitalia|PHARMACEUTICAL FORMS WITH PROTRACTED SALE|
    US4448724A|1982-12-20|1984-05-15|The Trustees Of The University Of Pennsylvania|Synthesis of 4-demethoxydaunomycinone|
    JPS61501388A|1983-10-19|1986-07-10|
    US4564674A|1983-10-31|1986-01-14|Sagami Chemical Research Center|Process for an anthracycline derivative, and an anthracyclinone derivative useful for the process|
    US4591637A|1985-01-17|1986-05-27|Sri International|Open chain-morpholino adriamycins|
    GB8617742D0|1986-07-21|1986-08-28|Erba Farmitalia|6-amino anthracyclines|
    GB8803301D0|1988-02-12|1988-03-09|Erba Carlo Spa|Process for preparation of 4-demethoxy-daunomycinone aglycone of 4-demethoxy-daunorubicin|GB8803301D0|1988-02-12|1988-03-09|Erba Carlo Spa|Process for preparation of 4-demethoxy-daunomycinone aglycone of 4-demethoxy-daunorubicin|
    GB8818167D0|1988-07-29|1988-09-01|Erba Carlo Spa|Novel 4-substituted anthracyclinones & process for their preparation|
    US5412081A|1989-02-07|1995-05-02|Farmitalia Carlo Erba S.R.L.|New 4'-epi-4'-amino anthracyclines|
    GB8904794D0|1989-03-02|1989-04-12|Erba Carlo Spa|Process for preparing anthracyclinones|
    GB8905668D0|1989-03-13|1989-04-26|Erba Carlo Spa|New 3'--and 3'--anthracycline derivatives|
    GB9019934D0|1990-09-12|1990-10-24|Erba Carlo Spa|2-hydroxy-and 2-acyloxy-4-morpholinyl anthracyclines|
    GB9216962D0|1992-08-11|1992-09-23|Erba Carlo Spa|Therapeutically active naphthalenesulfonic-pyrrolecarboxamido derivatives|
    US6645988B2|1996-01-04|2003-11-11|Curators Of The University Of Missouri|Substituted benzimidazole dosage forms and method of using same|
    US6489346B1|1996-01-04|2002-12-03|The Curators Of The University Of Missouri|Substituted benzimidazole dosage forms and method of using same|
    US6699885B2|1996-01-04|2004-03-02|The Curators Of The University Of Missouri|Substituted benzimidazole dosage forms and methods of using same|
    US5840737A|1996-01-04|1998-11-24|The Curators Of The University Of Missouri|Omeprazole solution and method for using same|
    US5948896A|1997-08-13|1999-09-07|Gem Pharmaceuticals|Processes for preparing 13-deoxy anthracycline derivatives|
    US5942605A|1998-03-03|1999-08-24|Gem Pharmaceuticals, Inc.|5-imino-13-deoxy anthracycline derivatives, their uses, and processes for preparing them|
    KR20020008297A|2000-07-21|2002-01-30|채문식|Fungicide for Plant Protection using Anthracycline Antibiotic Daunomycin|
    CA2472103A1|2002-01-25|2003-08-07|Santarus, Inc.|Transmucosal delivery of proton pump inhibitors|
    JP2006518751A|2003-02-20|2006-08-17|サンタラスインコーポレイティッド|Novel formulation for rapid and sustained suppression of gastric acid, omeprazole antacid complex-immediate release|
    US7053191B2|2003-05-21|2006-05-30|Solux Corporation|Method of preparing 4-R-substituted 4-demethoxydaunorubicin|
    US8993599B2|2003-07-18|2015-03-31|Santarus, Inc.|Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them|
    CA2531566C|2003-07-18|2013-05-07|Santarus, Inc.|Pharmaceutical formulation and method for treating acid-caused gastrointestinal disorders|
    US20050037070A1|2003-07-18|2005-02-17|Santarus, Inc.|Pharmaceutical formulatins useful for inhibiting acid secretion and methods for making and using them|
    US20070292498A1|2003-11-05|2007-12-20|Warren Hall|Combinations of proton pump inhibitors, sleep aids, buffers and pain relievers|
    US8815916B2|2004-05-25|2014-08-26|Santarus, Inc.|Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them|
    US8906940B2|2004-05-25|2014-12-09|Santarus, Inc.|Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them|
    US7353034B2|2005-04-04|2008-04-01|X One, Inc.|Location sharing and tracking using mobile phones or other wireless devices|
    US20090092658A1|2007-10-05|2009-04-09|Santarus, Inc.|Novel formulations of proton pump inhibitors and methods of using these formulations|
    US8357785B2|2008-01-08|2013-01-22|Solux Corporation|Method of aralkylation of 4′-hydroxyl group of anthracylins|
    US8846882B2|2011-04-29|2014-09-30|Synbias Pharma Ag|Method of producing 4-demethoxydaunorubicin|
    US9828405B2|2013-04-29|2017-11-28|Nerviano Medical Sciences S.R.L.|Morpholinyl anthracycline derivatives|
    RU2715902C2|2014-11-05|2020-03-04|НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л.|Functionalised derivatives of morpholinylanthracycline|
    法律状态:
    2010-07-20| REG| Reference to a code of a succession state|Ref country code: RU Ref legal event code: MM4A Effective date: 20070421 |
    优先权:
    申请号 | 申请日 | 专利标题
    GB878709353A|GB8709353D0|1987-04-21|1987-04-21|4-demethoxy-4-amino-anthracyclines|
    GB888803302A|GB8803302D0|1988-02-12|1988-02-12|Conversion of 4-demethoxy-4-amino anthracyclinones into 4-demethoxy-anthracyclinones|
    [返回顶部]