• 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:
    Compounds having the general formula (I): <CHEM> wherein: R<1> is hydrogen or fluorine; R<2> is hydroxy, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, acetylamino or methanesulfonylamino; and the pharmaceutically acceptable salts thereof are useful in potentiating the antineoplastic activity of known oncolytic drugs.
    公开号:SU965351A3
    申请号:SU792786502
    申请日:1979-07-02
    公开日:1982-10-07
    发明作者:Миллз Джэк；Курт Шмигель Клаус；Юджин Туми Ричард
    申请人:Эли Лилли Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    39653 IIj / IL (lHCH2 HC-HC // OH ,,: 5 is reduced with palladium on charcoal and the resulting product is isolated as a racemate or an optically active isomer .., / o. Example N - (2.nip-2 -hydroxyethyl) -1,1-Dimethyl-3- (4.hydroxyphenyl) propylamine. To a solution of 72.9 g of 1,1-dimbyl-3- (4. 1, -, -methoxyphenyl). propylamine in 10OO ml of diethyl ether. A solution of 37.8 g of 2-bromoacetophenone in 450 ml of diethyl ether is added over 1 hour with stirring. After the addition of the reagents has been completed, the reaction mixture is heated at reflux and stirred in t One week. Then the reaction mixture is cooled to room temperature and filtered, resulting in 53 g of unreacted amine in the form of its hydrochloric acid salt. The filtrate is washed with water, dried and the solvent is removed by distillation, resulting in 20 from crystallization from ethanol and ethyl acetate (20 2-hydroxyethyl) -1,1-dimetic-3- (4-methoxyphenyl) -. 0 propylamine with mp 180-181.5 C. The amine obtained in this way is dissolved in 200 ml of aqueous bromo; hydrochloric acid, heat the resulting acid solution with a reflux condenser and stir it for 12 hours. The reaction mixture is cooled to room temperature, resulting in crystallization of the crude reaction product. The crystalline precipitate is separated by filtration and recrystallized twice from ethanol to obtain 13.0 g of M- (2m} yunil-2-oxoethyl) -1,1-dimethyl-3- (4-hydroxyphenyl) -propylaminohydrobromide with m. Pl. 213 С (with salivation, 45%). A solution of 13.0 g of N- (2-fesh1L-2-oxoethyl) -1.1-Dimethyl-3- (4-hydroxyphenyl) propylaminohydrobromide in 235 ml of 9O% solution of ethanol in water, 50 containing 2 g of 5% palladium on coal, stirred for 2 hours and 15 minutes in a hydrogen atmosphere under pressure. The reaction mixture was then filtered and the resulting filtrate was concentrated by distilling off the solvent, 55 to give a solid. In this way, after lerekristaplizayi, 5.5 g of M- (2-phenyl-2-hyrpxyethyl) -1 1 - Dimetip-3- (4-hydroxyphenip) -propylaminohydrobromide with m.p. 1b9-170S. Calculated; S oO.OO; H 6.89; I3.68 0, Ynz, MO.Vg Found, C 6O, 16;, H 6.59; | 3.61 The resulting hydrobromic acid and amine salt is pactored in 50 ml of methanol and stirred at room temperature, while adding a solution of g, hydrogen chloride and diethyl feno acid amine salt precipitates and ll. g®® collect after filtration. The obtained, J P is recrystallized from metal and ethyl acetate, the result is 1 "- (2Chenyl-2-hydroxyethyl) -1,1 methyl-3- (4-hydroxyphenyl) -propylamine chloride with mp. I80-182 fc In the letter: C 67.91; H 7.80; N / -4.17 Found: C 68.13; H 7.59; N4.22 Compounds according to the invention are useful for enhancing the activity of known oncological agents used on a large scale for neoplasms. These drugs include, for example, cytoxan. An-t timetabolitic sredsgaa, in particular-. 5-fluorouracil and 6-mercaptopurine, and vegetable alkaloids, such as quindesine, vincristine and vinbdastine. A similar result allows the use of the proposed compounds against neoplasms in reduced amounts compared to the known ones, obtaining a therapeutic effect, which can even exceed the effect due to the use of well-known drugs in their present therapeutic means. agents against neoplasms, as well as non-toxic with respect to: to the cells in the doses used, have greater strength and less toxicity than when using known drugs designed to be treated tumors. Formula of the Invention 7 Method for preparing M- (2Ni-2-hydroxyethyl) -1,1-dimethyl-3- (4-hydroxyphenyl) -propipamine hydrochloride of the form DY I / ONSI II u -CHCHN No.H-C-CHO N about-SNSNoZH-Сv l / i (jjj
    5965351 "
    in the form of the racemate or optically active;
    isomer, which differs by extinction and the resulting product is reduced to
    the fact that the carbonyl combination of the for-vidb racemate or optically active,
    Mupy (). isomer,
    . L5 Sources of information
    mI / - Printed into consideration during examination
    С frHf, .NH - с - Cif I tH 2 ijy ОИ1. GCCP patent application
    It “2С73556 / 23-Ю4, cl. C O7 C 91/06,
    CH51977,
    权利要求:
    Claims (1)
    [1]
    The formula is invented and I A method for the preparation of M- (2-4-phenyl-2-hydroxyethyl) -1,1-dimeti p-3- (4-hydroxyphenyl) propipamine hydrochloride of the formula (*) as a racemate or an optically active isomer, characterized in that, a carbonyl compound of the formula (··)
    CH Oe was reduced with palladium on carbon and the product was isolated as a racemic or optically active, isomer.
    $ Sources of information taken into account in the examination
    1. USSR patent for application No. 2G73556 / 23-O4, cl. C 07 C 91/06, 1977.
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    同族专利:
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    JPS559100A|1980-01-22|
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    EP0007206B1|1983-02-23|
    PT69840A|1979-07-01|
    DK268579A|1980-01-04|
    CA1120058A|1982-03-16|
    RO83053B|1984-02-28|
    YU154879A|1983-04-30|
    FR2430409B1|1981-05-29|
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    IL57670D0|1979-10-31|
    PH15650A|1983-03-11|
    AU521744B2|1982-04-29|
    GR72546B|1983-11-17|
    IE48436B1|1985-01-23|
    NZ190859A|1984-09-28|
    GB2028800B|1982-11-03|
    BG40480A3|1986-12-15|
    BE877392A|1980-01-02|
    BG40482A3|1986-12-15|
    FI792080A|1980-01-04|
    MY8500596A|1985-12-31|
    HK44087A|1987-06-12|
    ZA793295B|1981-02-25|
    ES482153A1|1980-08-16|
    LU81456A1|1979-10-30|
    RO77731A|1981-11-24|
    JPS636058B2|1988-02-08|
    SU931102A3|1982-05-23|
    IE791231L|1980-01-03|
    AU4848879A|1980-01-10|
    PL123990B1|1982-12-31|
    AR222727A1|1981-06-15|
    HU179170B|1982-08-28|
    GB2028800A|1980-03-12|
    EG14400A|1983-12-31|
    PL222867A1|1981-01-02|
    AT370408B|1983-03-25|
    AR222658A1|1981-06-15|
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    EP0047536A2|1982-03-17|
    CS208660B2|1981-09-15|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US7994315B2|2005-07-22|2011-08-09|Mitsubishi Tanabe Pharma Corporation|Intermediate compound for synthesizing pharmaceutical agent and production method thereof|NL6610530A|1966-07-27|1968-01-29|
    BE757005A|1969-10-02|1971-04-02|Bristol Myers Co|SUBSTITUTED PHENETHANOLAMINES AND PROCESS FOR THEIR PREPARATION|
    US3801631A|1972-02-16|1974-04-02|Mead Johnson & Co|2'-hydroxy-5'-ethyl)meth-anesulfonanilide and its salts|EP0006735B1|1978-06-28|1983-06-15|Beecham Group Plc|Secondary amines, their preparation, pharmaceutical compositions containing them and their use|
    NL8105170A|1980-12-10|1982-07-01|Thomae Gmbh Dr K|NEW PHENYL ALKYLAMINS, METHOD FOR THE PREPARATION THEREOF AND THE USE THEREOF AS MEDICINES.|
    EP0068669A1|1981-06-20|1983-01-05|Beecham Group Plc|Secondary phenylethanol amines, processes for their preparation and their pharmaceutical application|
    CA1219865A|1982-05-14|1987-03-31|Leo Alig|Aziridine phenethanolamine derivatives|
    CA1258454A|1982-08-10|1989-08-15|Leo Alig|Phenethanolamines|
    EP0102213A1|1982-08-21|1984-03-07|Beecham Group Plc|Ethanolamine derivatives, pharmaceutical compositions containing them, and processes for preparing them|
    EP0204948B1|1983-01-31|1990-03-28|Eli Lilly And Company|Growth promotion of animals with phenethanol amines|
    US4849453A|1983-01-31|1989-07-18|Eli Lilly And Company|Growth promotion|
    US4569801A|1984-10-15|1986-02-11|Eli Lilly And Company|Alkylsulfonamidophenylalkylamines|
    JPS62155213A|1985-12-20|1987-07-10|Lilly Co Eli|Tumoral cell breaker|
    EG18188A|1986-05-01|1992-09-30|Pfizer Ltd|Process for preparation anti-arhythmia agents|
    US5135955A|1988-04-25|1992-08-04|Eli Lilly And Company|Propanamine derivatives|
    US5051423A|1988-07-13|1991-09-24|Schering Ag|Derivatized alkanolamines as cardiovascular agents|
    US5561142A|1994-04-26|1996-10-01|Merck & Co., Inc.|Substituted sulfonamides as selective β3 agonists for the treatment of diabetes and obesity|
    US5541197A|1994-04-26|1996-07-30|Merck & Co., Inc.|Substituted sulfonamides as selective β3 agonists for the treatment of diabetes and obesity|
    CN1073983C|1994-10-31|2001-10-31|中国科学院成都有机化学研究所|Method for synthesis of beta-adrenomimetic excitant type fodder additive|
    EP1402890B1|2001-06-08|2008-01-09|Institute of Medicinal Molecular Design, Inc.|Sulfonamide derivatives|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US92166878A| true| 1978-07-03|1978-07-03|
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