• 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:
    The method of producing derivatives of 3,4,5-trioxypiperid for the general formula CEjOtt CHj SKGON CIS It- CIS i "(where from 1-d to where it is phenyl or aliphatic saturated or unsaturated hydrocarbon chain with a carbon number of 2-8, which may contain sulfonyl shsh phenyl, or groups -CHN1-0-CCH -CH2-CO-MH- (CH5) s (sh1i C, H4) NH-CO-CHf, -CH-50o-CHL-CH-g- t XZ -Y-CH2-CH2-50 CH or -CH-OR-O-CHj-, phenyl, diphenyl or the groups -C, H4-CO-NH-CH2) -, or 2 C, Hg shm-CH -CO -NH- (CH2) 2-, in order. With another irimicin of the formula BUT, they interact with the compound of the formula CHO - R - ONO at the indicated values of 2: 1 in the presence of boosted.
    公开号:SU1050563A3
    申请号:SU813280253
    申请日:1981-05-07
    公开日:1983-10-23
    发明作者:Безхаген Хорст；Юнге Бодо；Штольтефусс Юрген；Шмидт Дельф；Петер Краузе Ганс；Пульс Вальтер
    申请人:Байер Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a process for the generation of new derivatives of 3,4,5-trirxypiperidine of the general formula BUT, sonone, onon BUT - (N-CH R-OHjN, where R is phenyl or aliphatic saturated or unsaturated hydrocarbon chain with carbon atoms 2-8, which may contain sulfonyl or phenyl, or the groups -CH2-0-C H4-, -CHg-CO-NH-CC (or C, H4) -NHCO-CH2, .CH, .1G), -CH -CHpSOj-CHo - or -CH-0-I-OGSI -, where R is phenyl, biphenyl or groups. -C, H CO-NH- (or CH2-CO-MH- (CH2) 2 which can be used in medicine as a means of inhibiting in -glcosides. Derivatives of 3,4,5-trioxypnperidine, in particular, derivatives of 1-deoxinoimyrimycin, which can be used in medicine as a remedy for diabetes, hyperlipose and obesity, as well as an agent that influences the ratio of meat and fat in favor of meat. In animals, which are obtained by the interaction of 1-deoxyinomyrimycin with aldehyde in in the presence of a reducing agent. The reaction is carried out in methanol in the presence of hydrochloric acid, reduction is carried out using cyanoborohydride sodium El i. The purpose of the invention is to develop, based on a well-known method, for the preparation of new derivatives of 3,4,5-trioxypiperidine, possessing valuable headlights macologic properties. The goal is achieved by the proposed method of obtaining derivatives 3,4, 5-trioxypiperidine of the formula (I) or their salts, which consists in the fact that α-deoxinoimirimycin of the formula HO CHgOH HO-rjK-H 04 63 is reacted with a compound of the general formula CKR-R-CHO. (ill) where R has the indicated meanings, in a 2: 1 ratio in the presence of a reducing agent. The reaction is carried out in the environment of an organic solvent; complex borohydrides are used as a reducing agent. Example 1. l, 5-6HcrN, N- (l, 5-IMINO- .1,5-dideoxy-0-glucityl) -pentane. A solution of 21 g of 1-deoxynomyrimycin in 630 ml of methanol and 42.5 ml of leftover acetic acid is mixed with 28.4 ml of pentadial and cooled to -5 ° C. Then, 17.5 g of sodium cyanoborohydride is added. After 4 hours stirring at 0 ° C., stirring is continued for 18 hours at room temperature. Then the mass is concentrated, dissolved in a mixture of 200 ml of methanol and water in a volume ratio of 8: 1 and fed to a column 40 cm long and 5 cm in diameter, containing ampillite iR 120 ion exchanger (H-form). Washed with 4 liters of methanol and water in a ratio of 8: 1 and then zlyuiruyut mixture of 5% ammonia and 95% mixture of methanol and water in an 8: 1 ratio. A mixture of three substances is obtained, one of which is 1-deoxinomyrimicin. The fractions obtained are concentrated. 20.6 g of slightly colored oil are obtained. This mixture, in the form of a concentrate water solution, is fed to a column 120 cm long and 6 cm in diameter, containing cellulose as the stationary phase, as mobile acetone. Elute with acetone and then aqueous acetone with increasing water content from 10 to 30%. The resulting fractions are examined by thin layer chromatography. After separation of the by-products, the desired product is obtained by elution with a mixture of acetone and water in a ratio of 3: 1. The pure fractions are collected and concentrated. The residue obtained from evaporation is dissolved in abSOLUTNS4 methanol. After the addition of highly active bleaching, the earth and animal charcoal is filtered and concentrated. The residue obtained from evaporation is dissolved in absolute methanol. and crystallize. After adding
    highly active bleaching earth and animal carbon are filtered and concentrated. The residue obtained after evaporation is dissolved in absolute meta-zero and crystallized. After an 18-hour exposure, the precipitated crystals are sucked off and washed with methanol. Obtain 10.1 g (15.5%) of colorless crystals of Art. pp- 186-187s. ,
    And p and m e p 2. H ,, 3- (1,4-phenylene) -bis (2-propane1p) j -di- (1-deoxinoimyrimycin).
    To a mixture of 14.1 g of 1-deoxinomyrimycin in 425 ml of methanol and 29 ml of glacial acetic acid is added
    a solution of 9 g of fJ, / lphenylene-diacrolein in 270 ml of heterohydrofuran. The reaction mass is cooled to 0-5 ° C and mixed with 11.6 g of cyan: sodium borane in one step. The mixture was stirred at 20 ° C. overnight and then concentrated. The residue obtained from spraying is dissolved in 400 ppm of a mixture of methanol and water in a ratio of 8: I g and fed to a column 30 cm long and 6 cm in diameter containing Amberlite IR 120 cationite. The mixture is thoroughly washed with a mixture of methanol and water. : 1 and plans elute with 2% ammonia. Frakgschies containing the desired product are collected and concentrated. I will receive. the crude product is then cleaned in a ring, filled with cellulose in the manner described. The product crystallizes upon distillation of the metaiol. Obtain 4.1 g (5.4%) of colorless crystals with so pl. 258-260 s (decomposition).
    Analogously to examples 1 and 2, the following compounds are obtained (wherein the indicated values of P are determined using a mixture of methanol, chloroform and a 25% ammonia BI ratio of 3: 2: 2
    1.1 ,, (1,5-dideoxy-1 5-imio-O-glucitol) -yl} -butene-2,
    Yield 46.2%; R. "0.35.
    2. / Р- N, М -bis (1,5-dideox-1, 5-amio-0-glucite) -sh1} -diethylsulfone.
    Yield 32.3%; 33
    3.1,6-Cm, M-bis (1,5-dideoxy-Cc-J, 5-imino-D-glucit) -yl-H-WKtan.
    Exit 27.91; 525.
    4.1.8-1K, M bis (1,5-dideox-1G -1,5-imino-0-glucitol) -yl J-n-octane.
    Output, Rx-0.63.
    5.3 -tN - (And, 5 -dideoxy-1, 5 -imio-p-glucite) -yl-n-propylamide-3- (N-1,5-dideoxy-1, 3 -imino-D-glucit-yl ) -propionic acid. Yield 25%, Cotjggg 0.086.
    6.ol, "--tN, N -bis (1, 5-dideoxy-1, 5-imino-5-glucit) -yl} -p-xylene.
     Yield 36.8%; 33
    7. Amide N, N - 3 5 1, 5-dideoxy-1, 5-imino-0-glucityl-yl) propionic acid-trimethylene.
    Yield 16.2%; 45
    8. Bisamid N, N- {l-dehydroxyorioticimitsinil- (jn-propionic acid) -P-phenylene ...
    Output 9.7%, I, 0 ,. .
    9., H, N-6Hc (S - (N-1-desoxinoimyrimycinyl) - (zl-sulfohashatil) J - piperazine.,
    Yield 77%, mp. 175s (decomposition
    10.I ,, M-bis (1,5-dideoxy-1, 5-imio-0-gluate) yl3-butyl-2.
    Yield 10.6%; m.p. 225 C (decomposition),
    11.1,6- (H, Mbis (1,5-dideoxy-I, 5-imino-0-glucit) -yl-hexadien-2, 4.
    yield 33.3%; Ri "o, 48; m.p. 223225 With (raelozheiiv).
    12.1,4-bis 2-Y- (1,5, -dideoxy-1, 5-imio-0-gluCit) -13-ethoxy-benzene.
    The yield of 12.5%, so pl. 225-228 s.
    13.4,4 -bis {2- {n- (1, -didezoksi-l, 5imino-0-glucit) -ill-sytoxy difenip ...
    14. Benzylamide 4,4-bis 2-Cm- (G, -dideoxy-1,5-imino-0-gluc1;) - UL-etoxygbizoic acid.
    Yield 46.7%, 68.
    15.M - ((G, 5 "dideoxy-1,5-amino-0-glucitol) -yl-ethoxy} -benzyl -1-deoxyoiyyirimitsin.
    In | 1x11.4%, so pl. 155 C (decomposition).
    16.5.5-bic {N- (l, 5-c of deoxy-1, H-nmino-O-tlucite), 1-P-pheny lenepentadiene -1, 3-nx .j. & LHRD 14.1%, so pl. 230 (decomposition) ..
    17.1,6-lN, N -bis (1, 5-dizeeoxy -1,5-imio-O-glucit) sadien-2, 4.
    The output of 17.8%, so pl. 235 C (decomposition). .
    18. Feyethylamide 4,4-bis 2- {M - (l, 3-dideoxy-1, 5-imino-p-glucit) -yl} -ethoxy5-beiseic acid.
    Yield 47.2%, T.Sh1. 160-161 ° C.
    01STEMS to determine the term inhibitory ot-glucosidase activity.
    Six rats (on an empty stomach) were given orally 1 mg / kg of the 3,4,5 derivative of 3,4,5 trioxypiperidium indicated in the table together with 2 g of sucrose. After 4 h, the animals were again given 2 g of sucrose (without active substance). After 10, 20 and 30 minutes after the second administration of sucrose, the effect of the active substance on the postirandial increase in blood glucose was determined.
    Control experiments were carried out at the expense of Toroi that the animals were first given only 2 g of sucrose without the active substance, and after 4 h again only 2 g of sucrose was given.
    The results of the experiments are given in the table.
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING 3,4,5-TRIOXYPIPERIDINE DERIVATIVES of the general formula where R is where Phenyl or an aliphatic saturated or unsaturated hydrocarbon chain with 2-8 carbon atoms, which may contain sulfonyl or phenyl, or -CHCl-O-C.H ^ - groups CH 2 -C0-NH- (CH 5 ) 3 (or C, H 4 ° NH-co-cH f , -ch 2 -so2-ch 2 -ch 2 CH 2 “CH g -50 ^ € I ^ or“ CHg-O-Rt-o-CHz-, 'phenyl, diphenyl or -C groups, H 4 -C0-NH- (CH 2 ) ^ yl 2 С L Н 4 or -CKj-CO-NH-lCH ^ -, feigning that but
    0¾ CfyOH
    - SNG * - SNG but sn, he is he
    1-deoxynoyirimycin of the formula
    BUT CH 2 OH IO-L ^ C-H but is reacted with a compound of the general formula CHO - R - OH where R has the indicated values, in a 2: 1 ratio in the presence of a reducing agent.
    · "
    G
    1050563_, - 2. reacted with a compound of the general formula
    SIR - R —- SIO (in)
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1050563A3|1983-10-23|Process for preparing derivatives of 3,4,5-trihydroxypiperidine
    US4383994A|1983-05-17|Homocysteine thiolactone salts and use thereof as anti-neoplastic agents
    US2895988A|1959-07-21|Acylated trhodoaminophenylalkanoic acids and preparation thereof
    EP0068968B1|1985-09-18|Medicines containing as active ingredients compounds of the arylbenzenesulfonamide-type, and processes for their preparation
    FR2489319A1|1982-03-05|DERIVATIVES OF AMINO-4 BUTYRIC ACID AND MEDICAMENTS, PARTICULARLY ACTIVE ON THE CENTRAL NERVOUS SYSTEM, CONTAINING
    US3855285A|1974-12-17|Acylmethylthio-trifluoromethyl-benzoic acids
    EP0148094A2|1985-07-10|Anti-tumor agent comprising an O-benzylidene-L-ascorbic acid or a salt thereof, and the production of the latter compound
    DE2234651B2|1978-02-23|SQUARE CLAMP ON 1- | - 5-METHOXY-2-METHYL-3-INDOL SQUARE CLAMP ON -ACETOXYACETIC ACID, ITS SALTS WITH BASES, PROCESS FOR THEIR PRODUCTION AND PHARMACOLOGICAL PREPARATIONS
    Schoental et al.1960|Hepatotoxic activity of semi-synthetic analogues of pyrrolizidine alkaloids
    CH629218A5|1982-04-15|PROCESS FOR THE PREPARATION OF GLUCOPYRANOSE-NITROSOUREE DERIVATIVES.
    EP0061380A1|1982-09-29|Imidazo | pyrimidine derivatives, their preparation and their therapeutical use
    FR2532647A1|1984-03-09|ACETYLSALICYLIC ACID THIOESTERS, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
    EP0044238B1|1984-02-01|Cephalosporin sulfoxides, process for their preparation and pharmaceutical compositions containing them
    DE3102769A1|1982-02-04|"BIS-MORANOLINE DERIVATIVES"
    US4293700A|1981-10-06|2,6-Dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid esters and method for preparing same
    FR2503705A1|1982-10-15|PHENETHANOLAMINE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
    EP0021991A1|1981-01-07|Cystamine derivatives, their preparation and pharmaceutical compositions containing them
    EP0082040B1|1986-01-15|3,7a-diazacyclohepta|fluorene derivatives, their preparation and therapeutical use
    US4096248A|1978-06-20|Sulfonyl containing organic gold glycoside compounds and method of use
    CN112645964B|2021-10-15|Tyrosol-biotin small-molecule probe and preparation method and application thereof
    US4423236A|1983-12-27|5,6,-0-Isoalkylidene ascorbic acid derivatives
    DD141927A5|1980-05-28|PROCESS FOR THE PREPARATION OF 1,1-DISUBSTITUTED OCTAHYDROINDOLO SQUARE BRACKET TO 2,3-A CORNER CLAUSE TO CHINOLIZINES
    EP0051247B1|1985-01-09|4-thia and 4-sulfinyl pgi1 derivatives, their preparation and pharmaceutical compositions
    RU938559C|1993-11-30|S-derivatives of 5-amyno-6-mercaptopyrimidine possessing antitumoral and cytostatic activity
    BE876625R|1979-09-17|IMIDAZOLE-4-CARBOXAMIDE 5-0-ACYLES DERIVATIVES, PROCESS FOR THEIR PREPARATION AND MEDICINAL PRODUCTS CONTAINING
    同族专利:
    公开号 | 公开日
    ES8102096A1|1980-12-16|
    EP0019899A1|1980-12-10|
    IE50258B1|1986-03-19|
    DK243280A|1980-12-06|
    DE3068585D1|1984-08-23|
    IL60210A|1983-11-30|
    NO801553L|1980-12-08|
    NO852778L|1980-12-08|
    PT71308A|1980-06-01|
    DE2922760A1|1980-12-11|
    ZA803330B|1981-06-24|
    AT8500T|1984-08-15|
    JPS55164676A|1980-12-22|
    AU539847B2|1984-10-18|
    ES492143A0|1980-12-16|
    IE801149L|1980-12-05|
    HU182143B|1983-12-28|
    IL60210D0|1980-09-16|
    AU5852580A|1980-12-11|
    GR69267B|1982-05-12|
    CA1146558A|1983-05-17|
    EP0019899B1|1984-07-18|
    SU1017168A3|1983-05-07|
    US4465684A|1984-08-14|
    JPS64949B2|1989-01-10|
    FI801787A|1980-12-06|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    NO154918C|1977-08-27|1987-01-14|Bayer Ag|ANALOGUE PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE DERIVATIVES OF 3,4,5-TRIHYDROXYPIPERIDINE.|
    JPS6312063B2|1980-01-28|1988-03-17|Nippon Shinyaku Co Ltd|JPS6312063B2|1980-01-28|1988-03-17|Nippon Shinyaku Co Ltd|
    DE3873928T2|1987-11-16|1993-02-11|Medicorp Holding|DEVICE FOR DISPENSING LIQUIDS.|
    EP0344383A1|1988-06-02|1989-12-06|Merrell Dow Pharmaceuticals Inc.|Novel alpha-Glucosidase inhibitors|
    DE3936295A1|1989-11-01|1991-05-02|Bayer Ag|METHOD FOR PRODUCING INTERMEDIATE PRODUCTS AND SYNTHESISING N--2-HYDROXYMETHYL-3,4,5-TRIHYDROXYPIPERIDINE|
    US5536732A|1990-04-27|1996-07-16|Merrell Pharmaceuticals Inc.|N-derivatives of 1-deoxy nojirimycin|
    US5252587A|1990-04-27|1993-10-12|Merrell Dow Pharmaceuticals, Inc.|N-derivatives of 1-deoxy nojirimycin|
    JPH0688963B2|1990-08-15|1994-11-09|工業技術院長|Disulfone sulfonyl fluoride compound|
    AUPP942599A0|1999-03-24|1999-04-15|Commonwealth Scientific And Industrial Research Organisation|Antiviral agents|
    WO2004039373A1|2002-10-29|2004-05-13|Ranbaxy Laboratories Limited|Iminosugar derivatives as glucosidase inhibitors|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19792922760|DE2922760A1|1979-06-05|1979-06-05|NEW DERIVATIVES OF 3,4,5-TRIHYDROXYPIPERIDINE, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS A MEDICINAL PRODUCT AND IN ANIMAL FOOD|
    [返回顶部]