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    • 专利摘要:
    Compounds which in form of therapeutic compositions exhibit antihypertensive activity and are of low toxicity. These compounds are of general formula I …<CHEM>… wherein R1 represents a hydrogen atom, or a carboxy, alkoxycarbonyl, the alkoxy group having 1 to 4 carbon atoms, piperidinocarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, carbamoyl or benzylcarbamoyl group, or an alkylcarbamoyl or dialkylcarbamoyl group in which the or each alkyl group has from 1 to 4 carbon atoms,… R2 represents a hydrogen or fluorine atom, or a cyano, acetyl or carbamoyl group,… R3 represents a hydrogen atom or a methyl group and@@@ represents a single or double bond, with the proviso, that R1 and R2 do not simultaneously represent hydrogen atoms, or pharmaceutically acceptable salts thereof, their preparation and therapeutic compositions containing them.
    公开号:SU971100A3
    申请号:SU802892378
    申请日:1980-03-14
    公开日:1982-10-30
    发明作者:Темперилли Альдемио；Мантегани Серджо；Аркари Джулиана；Каравагги Анна-Мария
    申请人:Фармиталиа Карло Эрба,С.П.А.(Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing tetracyclic derivatives of indo ’ina general formula
    * 3 where R ^ is hydrogen, lower alkoxycarbonyl, piperzidinocarbonyl, 1-pyrrolidyl-, carbonyl, carbamoyl, benzylcarbamoyl, alkylcarbamoyl or dialkyl-carbamoyl in which one or each alkyl group has 1 to 4 carbon atoms; ·
    Rj is hydrogen, cyano or carbamoyl;
    Rj is hydrogen or methyl;
    - a single or double bond, provided that one of R ^ or is hydrogen, or their salts, having pharmacological activity.
    A known method of producing tetracyclic derivatives of indole of the general formula
    where R * is hydrogen or alkyl with 1-4 carbon atoms;
    R * is hydrogen, alkyl with 1-5 carbon atoms, methyl halide, hydroxymethyl, alkoxymethyl, acyloxymethyl, aminomethyl, unsubstituted or. N — substituted carbamoylmethyl, carbo-ximethyl, alkoxycarbonylmethyl, cyanomethyl, tosyloxymethyl and mesyloxymethyl, consisting in the general formula that 9-hydroxyergoline
    where K * and have the indicated meanings, ’(they are reacted with chlorine oxide, phosphorus, phosphorus bromide or phosphorus pentachloride in the presence of organic - dago base C 1 J.
    . The invention is the preparation of new pharmacologically active tetracyclic indole derivatives of the general formula (I) or their salts.
    This goal is achieved by the connection of the General formula, 15
    WHAT
    wherein Rj t has- specified value. subjected to condensation with a compound of the general formula _ r <2 cn 2 coax 2 n 5 (W) where R <j, has the above meanings, in a polar aprotic solvent at 50-100 ° C for 2-10 hours, and the resulting compound of the general formula (I) where R-1 is a carbethoxy group, hydrolysis is isolated or carried out to obtain compounds of general formula (1), where Y 1 is a carboxy group which, if necessary, is decarboxylated to obtain compounds of general formula (I), where Rf is' hydrogen, or a compound of general formula (I), wherein a carbethoxy group is treated with ammonia or an amine to obtain co compounds of general formula (1), where carbamoyl, piperidinocarbonyl, 1-pyrrolidylcarbonyl, benzylcarbamoyl, alkylcarbamoyl or dialkylcarbamoyl in which one or each alkyl group has 1 to 4 carbon atoms, or hydrolysis and decarboxylation of compounds of general formula (II) are carried out, where - carbethoxy group. Rq is the pianogroup. and the obtained propionitrile by esterification and, if necessary, subsequent treatment with ammonia or amines, is converted into a compound of the general formula (I), where ( 2 is hydrogen, a is lower alkoxycarbonyl, carbamoyl, piperidinocarbonyl, 1-pyrrolzodilcarbonyl, benzylcarbamoyl, alkylcarbamoyl, in which one or each alkyl group contains 1-4 carbon atoms, or a compound of general formula (I) obtained in any of the above steps is subjected to catalytic hydrogenation to obtain compounds of general formula (I), g de ~~~ means a simple bond, followed by isolation of the target product in free form or in the form of salt.
    As a polar aprotic solvent, dimethyl sulfoxide or dimethylformimide is used. Palladium on charcoal is used as a catalyst for hydrogenation.
    The compounds of general formula (I) or their salts have a hypotensive effect in combination with low toxicity. Example 1. Ethyl ester of 2-cyano-3- £ 5- (10 ~ * 9) abeo-9, 10-dicyhegipro-6-methylergoline-8 [L] -propionic acid.
    A mixture of 4.65 g of sodium ethyl cyanoacetate, 7 g of 5- (10- * 9) abeo-9,1O-didehydro-6-aergoline-8 β-methanol tosylate and 2.8 g of potassium iodide in 100 ml. dimetipsulfoksidai 1 ml of ethyl tsianouksus- hydrochloric acid was heated under stirring for 5 hours at 7D C 'was poured into 500 ml of ice water. The precipitate obtained is filtered off, dried and chromatographed on a silica gel column using chloroform as the mobile phase to give 3.5 g of the target compound, mp 191-193 ° C.
    Example 2. 2-cyano-3- [5- (10-¼ 9) abeo-9,10-dide hydro-6-methylergolin-8 [L J-propyrnamide.
    g of ethyl ester of 2-piano-3-L 5— (10— * 9) abeo-9,10-didehydro-6-methylergolin-8 β] -propionic acid obtained in example 1 is dissolved in 100 ml of methanol saturated with liquid ammonia. The solution was kept in a closed vessel at room temperature for 2 hours and then evaporated to dryness, 1.4 g of the target compound were obtained, so pl. 184-186 ° C.
    Example 3. 2-Cyano — 3- [5— - (10— ”©) abeo — 9,10-dIdegvdro-6-me- tylergolin-8 β] -N - ethylpropionamide.
    Performing the operations described in example 2 and using ethylamine instead of ammonia, the compound indicated in the title is obtained in the introduction of foam with a yield of 70%.
    Example 4. 2-Cyano-Z- [5 - (10— * · 9) abeo-9,10-didehydro-6-methylergolin-8 β] benzylpropionamide.
    The process is carried out analogously to example 2, but benzylamine is used instead of ammonia 5 ka. Get the target compound in the form of a foam with a yield of 60%.
    Example 5. 2-Cyano-Z- [5- (10 * 9) abeo-9,10-dide guide po-6-methyl ^ rgolin-8 ft] - N-propionylpyrrolidine.
    The process is carried out analogously to example 2, but instead of ammonia, pyrrolidine is used and the target compound is obtained in the form of a foam with a yield. 65%
    EXAMPLE IU p 6. 5- (10 * 9) 15-9,10 atseo
    T-didehydro-b-methylergoline-8 ft-propionite-.
    ril.
    1.2 g of ethyl ester 2-cyano-3- [5- (10- * 9) abeo-9, 10-didehydro-b.-methylergoline-8 ft J-propionic acid, obtained analogously to that described in example 1 , dissolved in 50 ml of methanol and treated with 0.5 g of sodium hydroxide in 20 ml of water. After stirring for 3 hours, the solution was poured into water and 25 was neutralized with diluted acetic acid. 2-cyano-3- [(10- * 9) abeo-9,10-. β-didehydro-6-methylergolin-8 ftj-propionic acid is filtered off and dissolved in 30 ml of dimethylformamide. Then. 30, the solution is heated at 120 ° C. for 24 hours to conduct decarboxylation. After evaporation of the solvent, the target compound is obtained in the form of a foam with a yield of 80%. 35
    Example 7. 5- (10- * 9) abeo-9,10 — Didehydro-6-methylergoline — 8 ft propionamide
    0.7 g of 5 (10- "9) abeo-9,10-didehydro-6-methylergoline-8 ft propionitrile obtained in Example 6 is dissolved in 50 ml of tert-butanol and treated with 1 g of potassium hydroxide. The mixture is boiled with obatnom. refrigerator for 24 hours. After evaporation of the solvent, the target compound is obtained in the form of a foam with a yield of 69%. , Example 8. 2-Cyano-3- [trans-5- (10— * 9) abeo-6-methylergolin-8 β] -propionamide. '
    A solution of 2.5 g of 2-cyano-Z- [5 (10 “* · 9) Μ abeo-9,10-dide hydro ro-6-methylergol in-8 ft] g - N-propionamide obtained according to example 2, 500 ml of ethanol are hydrogenated in the presence of 4 g of 10% palladium-carbon as a catalyst. After ethanol is evaporated, the residue is treated with a mole of oxalic acid and cis salt.
    - trans-form is separated by fractional crystallization from water in which.
    trans oxalates are less soluble. Processing trans-oxalate with potassium hydroxide gives 1 g of the target compound, so pl. 251-252 ° C.
    Example 9. Ethyl 2-cyano-3-£ trans-5 (10- * 9) abeo-6-methyl-ergoline-8p) propionic acid.
    By the repeated operation described in example 8, using ethyl 2-cyano-3- [5- (10-> 9) abeo-9,10-didehyde po-6-methylergoline-8 β] -π ropionic acid obtained by Example 1, get the target compound with a yield of 40% IT_T. pl. 182-184 ° C. _
    Example 10.2 — Cyano — 3— [trans-5- (10-> 9) abeo-6-methylergolin-8ft] -
    - N z- ethylpropionamide.
    The process is carried out analogously to example 8, but using 2-cyano-3- [5 (10 ~ * 9) abe o-9,10 - and cdehyde ro — 6 -methylergoline -8 β) -N-ethylpropionamide, obtained according to example 3. Get the target compound in the form of a foam with a yield of 40%.
    Example 11. 2-Cyano-3- [trans-5 (10- * 9) abeo — 6-methylergolin-8 ft] -
    - N-benzylpropionamide.
    The process is carried out analogously to example 8, but using 2-cyano-3- [5 (10- * 9) abeo-9,10, didehydro-6-methylergoline-8ft) -N-benzylpropionamide obtained according to ··· 4. Receive target compound in the form of a foam with a yield of 35%.
    , Example. 12. 2-Cyano-3- (trans-6 (16- * 9) abeo-6-methylergolin-8 ft] - '
    - N-propionylpyrrolidine.
    The process is carried out analogously to example 8, but using 2-cyano-3 - [5- (10 ~ * 9) abeo-9,10-didegcdro-6-methylergolin8p] -M-propionylpyrrolidine obtained in example 5. Synthesize the target compound in the form foam with a yield of 40%.
    Example 13 trans-5- (10- "9) abeo-6-Methyl ergoline-8 ft-propionitrile.
    The process is carried out analogously to example 8, but using 5- (10-> 9) abeo-9,10-Didegvdro-6-methylergene-8-β-propionitrile obtained in example 6. Synthesize the target compound with a yield of 50%, so pl. 167-169 ° C.
    Example 14.trans -5- (10- * 9) abeo-6 — Methylargolin-8β-propionamide.
    The process is carried out analogously to example 8, but 5- (10- »9) abeo-9,10-didehydrohydro-6-methylergolin-8β-propionamide obtained in example 7 is used. The target compound is synthesized with a yield of 45% in mp. 205-207 ° C.
    Example 15.trans -5- (10-> 9) abeo-6-Methylergoline-8 β-ethylpropionamide.
    971100 8 g of trone -5- (10-9) abeo-6-methyl ~ ergolin-8/3-propionitrile prepared according to example 13 in 20 ml of dioxane, 10 ml of ethanol and 10 ml of 30% KOH are heated to the opposite refrigerator for 5 hours. The solution was evaporated in vacuo and the residue was suspended in 60 ml of methanol containing 6 ml of H ^ SO 4 . After exposure at room temperature for 4 hours, the solution was diluted with 10 water, alkalized with MH 4 OH and extracted with chloroform. Evaporation of the solvent gives the residue trans-5- (10-9) abeo-6-methylergo-g lin-8 (b-propionic acid (mp 15 203-205 ° С)), which is dissolved in 50 ml of methanol and 2 ml of ethylamine.The solution is kept in a Parra pressure vessel at 100 ° C for 3 days, then evaporated to give L-, 5 g of the target 20 compound with a mp of 227-229 ° C.,
    Example 16.trans ~ 5- (10-9) abeo-b-Methylergoline-8ft - (N-benzyl-propionamide).
    The process is carried out analogously to example 15.25 but using benzylamine. Get the target compound with so pl. 185-187 ° C. Yield 60%.
    Example 17.trans.-5- (10- * 9) abeo-6-Methylenegolin-8 β-propionylpyr-30 rolvdin.
    The process is carried out · analogously to example 15, but use pyrrolidine. Get the target compound with a yield of 55%, so pl. 202204 ° C. 35
    Example 18. trans -5- (10-9) • abeo-6-Methylargolin-8 β - (N-propionylpcperylin).
    The process is carried out analogously to example 15, but piperidine is used. Get target 40 connected with a yield of 50%.
    I. ···
    Example 19.trans -6- (10-9) abeo-b-Methylargolin-8 [b - (N-allylpropion amide).
    The process is carried out analogously to example 15, but allylamine is used. Get the target compound in the form of a foam with a yield of 50%.
    Example 20. trans -5- (10-9) 50 abeo-6-Methylargolin-8p> - (N ~ n-butylpropionamyl).
    The process is carried out analogously to example 15, but using n-butylamine. Get the target compound in the form of a foam with a yield of 65%. 5
    Example 21. trans -5- (10-9) abeo — 6-Methylergo.hchn-8) 3 - (N - pietylpro pionamide).
    The process is carried out analogously to example 15, but diethylamine is used. Get the target compound in the form of a foam with a yield of 50%.
    Example 22.trans -6- (10-9) abeo-6 — Methylargolin-8 β - (N-isopropylpropionamide).
    ; The process is carried out analogously to example 15, but using isopropylamide, 'Get the target compound in the form of a foam with a yield of 60%.
    Example 23. trans -5- (10-> 9) abeo-6-Methylargolin-8 ft - (Ft-methylbu-tilpropionamide).
    The process is carried out analogously to example 15, but N-methylbutylamine is used. Get the target compound in the form of a foam with a yield of 75%.
    权利要求:
    Claims (2)
    [1]
    Example 4. 2-Cyano-3-D 5 - () abeo-9DO-diadegrin-6-methylergoline-8 fb -tbenzylpropionamide. The process is carried out analogously to example 2, but using benzylamine instead of ammonia. Get the target compound in the form of foam with a yield of 60%. Example 5. 2-Cyano-3- 5- () a6-eo-9,1O-didegiaro-6-methyl rgolin-8 (b} -N-propionylpyrrolidine. The process is carried out analogously to example 2, but pyrrolide is used instead of ammonia and get the target compound in the form of a foam with a yield of 65%. Example: 5- () aceo-9,10 idehydro-6-methylergolin-8 fi-propionitril. 1.2 g of ethyl ester 2-cyano-3-5 - () Abeo-9, U-Tide-Ishpo-.6, -methylgrolin-8 / b) -propionic acid, prepared as in Example 1, is dissolved in 50 ml of methanol and treated with 0.5 g of sodium hydroxide in 20 ml of water After stirring for 3 hours, the solution is poured into and neutralized with dilute acetic acid. 2-Cyano-3- () abeo-9DO-didehydro-6-methylergoline-8 / bD-propionic acid is filtered and dissolved in 30 ml of dimethylformamide. Then, the solution is heated at 120 ° C for 24 hours for decarboxylation. After evaporation of the solvent, the desired compound is obtained as a foam with a yield of 80%. Example 7. 5- () abeo-9,1O -Didehydro-6-methylergoline-8 p -. Propionamide 0.7 g 5 () abeo-9,1O-didehydro-6-methylergolin-8 (5-propionitrile, prepared in 40 as in example 6) is dissolved in 50 m of tert-butanol and treated with 1 g of potassium hydroxide. The mixture is refluxed for 24 hours. After evaporation of the solvent, the target compound is obtained as a foam with a yield of 69%., Example 8. 2-Cyano-3-trs ns-5- () abeo 6-methylergoline-8 p-propionamide. A solution of 2.5 g of 2-cyano-3- 5 () abeo-9,10-didehydro-6-methylzrgolin-8) g -.N-propionamide obtained in example 2, in 50 O ml of ethanol is hydrogenated in the presence of 4 g of 10% palladium on carbon in as a catalyst. After evaporation of the ethanol, the residue is treated with 1 mol of oxalic acid, and the salts of the C -Tpc salt (ns -forms are separated by fractional crystallization from water, in which the oxalates of the tr-ns-form are less soluble. Treatment of trans-oxalate with potassium hydroxide gives 1 g of the target compound, mp, 251-252 C. Example 9. 2-cyano-3-trans-5 () abeo-6-methylergoline-vr3-propionic acid ethyl ester. Repeated operation as described in Example 8, using ethyl ester of 2-iano-Z-5- () abo-9,10-gaidigidro-6-methylergolin-8 | 3-propionic acid, obtained by example 1, the desired compound is obtained with a yield of 40% and a melting point of 182-184 ° C. Example 1 O. 2-Cyano-3-tpc (ns -5- () abeo-6-methylergoline-8p-N-ethylpropionamide. Process lead analogously to example 8, H9 using 2-cyano-H-5 {10 -9) abeo-9,10-schide dehydro-6-methylergoline--8 (3-N-ethylpropionamide, prepared according to example 3. The desired compound is obtained in the form of foam with a yield of 40%. Example 11. 2-Cyano-3-trans-5 () abeo-6-methylergolin-8 | b} - M-benzylpropionamide. The process is carried out analogously to example 8, but using 2-cyano-3-5 () abeo-9,1O, didehydro-6-methylergolin-8r3-N-benzylpropionamide, prepared according to example 4. The target compound is obtained as a foam in 35% yield. . / Example. 12. 2-Cyano-3-trans-6 () abeo-6-methylergoline-8 fi} - 14-propionylpyrrolidine. The process is carried out analogously to example 8, but using 2-cyano-3 - 5- () abe o-9,1O-dide hydro-6-methyl ergol in8 (5} -N-propionylpyrrolidine obtained in example 5. Synthesize the target compound foaming with a yield of 4O%. Example 13. Trans-5 - () a6eo-6-Methylergoline-8 ji-propionitrile. The process is carried out analogously to example 8, but using 5- () abeo-9,10-Didehydro-6 α-methyl ergsB-8-propionitrile prepared according to Example 6 The target compound is synthesized with a yield of 50%, mp 167-169 C. Example 14. trans-5- () abeo b-Methylergoline-8 propionamide The process is carried out analogously to example 8 .but 5- () ab is used o-9,1O-didegitsro-6-methylergoline-8 ft-propion-MID, prepared according to example 7. The target compound is synthesized with a yield of 45% from mp 205-2O7 C. Example 15. trans-5- ( 10-.9) abeo-6-methylergoline-8 fi - ethyl propionam 2 g of TpdHC-5- () abeo-6-methyl ergolin-8/3-propionitrile, prepared according to example 13, in 20 liters of dioxane, 10 ml ethanol and 10 ml of 30% KOH are heated under reflux for 18 hours. The solution is evaporated in vacuo and the residue is suspended in 60 ml of methano; (a containing 6 ml. After aging at room temperature for 4 hours, the solution is diluted with water, alkalinized and extracted with chloroform. Evaporation of the solvent gives the residue methyl ester trans-5- () abeo-6-methylergoline-8 | b-propionic acid (m.p. 203-2O5 ° C), which is dissolved in 50 ml of methanol and 2 ml of ethylamine. The solution is kept in a Parr pressure vessel at 10 ° C for 3 days, then evaporated to give g of the title compound with m.p. 227-229 C. Example le.rprtHC- 5- () abeo 6-methylergalin-8fi - (N-benzyl-propionamide). The process is conducted as in example 15 but using benzylamine. Obtain the target compound with m. Pl. 185-187 ° C. Yield 60%. Example 17. trans. 5- () abo-6-methylergolin-8 (i-propionyl pyrrolidine. The process is similar to example 15 but pyrrolidine is used. A target compound of 55% is obtained, mp 20 204 ° C. Example 18. trans -5- () abo-6-methylergoline-8 ft - (N-propionyl 1piperidine). The process is carried out analogously to example 15 but piperidine is used. Obtain the target compound with a 50% input. I -,. Example 19. TpdHC-6- () abeo 6-methylergoline-8 (b - (N-allyl propion amide). The process is carried out analogously to example 15, but allylamine is used. The desired compound is obtained as a foam with a yield of 5O%. EXAMPLE 20 .trs (ns „5- {10-9) Abeo-6-Methyl ergoline-8 | g- (N - n-butylpropionamyl). The process is carried out analogously to example 15 but n-butylamine is used. The desired compound is obtained as a foam with a yield of 65%. Example; g1.trs1ns 5- () abeo-6-Methylergplim 8): - (N-chaethylprone). The process is carried out analogously to example 15, but diethylamine is used. The desired compound is obtained as a foam with a yield of 50%. Example 22.trans -6- () abeo-6-methylergolin-8 fb - (N-isopropyl propionamide). The process is carried out analogously to example 15, but using isopropylamide, Obtain the target compound in the form of foam with a yield of 60%. Example 23. trans-5- (9) abo-6-methylergolin-8 (b - (g-methylbutylpropionamide). The process is carried out analogously to example 15, but N-methylbutylamine is used. The desired compound is obtained as a foam in 75% yield. Formula 1. Method for producing tetracyclic | indole derivatives of the general formula I, where R is hydrogen, carboxy group, lower alkoxycarbonyl, piperidinocarbonyl, 1-pyrrolidylcarbonyl,: carbamoyl, benzylcarbamoyl, alkylcarbamoyl or dialkylcarbamoyl, in which you can take a message or have a dialkylcarbamoyl, benzylcarbamoyl, alkylcarbamoyl or dialkylcarbamoyl 4 carbon atoms; Rij is hydrogen, cyano groups a or Carbamoyl; Rj is hydrogen or methyl; is a simple or double bond, provided that one of R or R. is hydrogen, or their salts, characterized in that the compound of the general formula and where R has the above values is subjected to condensation with a compound of general formula | m, where R has the above values, in a polar aprotic solvent at 5 ° C-100 ° C for 2-1O h and the resulting compound of general formula 1, where the carbethoxy group, is isolated or hydrolyzed to obtain compounds general formula I, where Ri - carboxypropyl, which, if necessary bridges of decarboxylate to obtain compounds of general formula 1, hydrogen, or a compound of general formula 1, where F is carbox6x and the group is treated with ammonia or amine to obtain compounds of general formula 1, where carbamoyl, piperidinocarbonyl, 1-pyrrolidylcarbonyl, benzylsarbamoyl, alkylcarbamoyl or dialkylsarbamoyl in which one or each alkyl group has 1-4 carbon atoms, or hydrolysis and decarboxylation of the compounds of the general formula L, where the carbethoxy group, -.cyano group, and the resulting propionitrile esterification are carried out minutes and if necessary 00 10 posleduyushey treatment with ammonia or amines prevrashayut a compound of general formula 1, where - the hydrogen and. lower alkoxycarbonyl, carbamoyl. piperidinocarbonyl, 1-pyrrolvdylcarbonyl, benzylcarbamoyl, alkylcarbamoyl or dialkylcarbamoyl, in which one or each alkyl group contains 1-4 carbon atoms, or a compound of the general formula I, obtained in any of the above stages, is subjected to catalytic hydrogenation to prepare compounds of the I group, to prepare compounds of the formula I, prepared in any of the above mentioned stages, to prepare compounds of the composition I, which were prepared in any one of the above stages, to prepare compounds of the composition I, Formula I, where it is a direct bond followed by isolation of the desired product in free form or as a salt.
    [2]
    2. The method of claim 1, wherein and in order that dimethyl sulfoxide or dimethylformamide is used as the polar aprotic solvent. Sources of information taken into account in the examination 1. UK patent number 1482871, cl. C 2 C, 1975.
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    同族专利:
    公开号 | 公开日
    EP0016411B1|1982-09-29|
    FI66871C|1984-12-10|
    EP0016411A2|1980-10-01|
    FI66871B|1984-08-31|
    JPS55124784A|1980-09-26|
    IT1196406B|1988-11-16|
    AU526978B2|1983-02-10|
    US4317912A|1982-03-02|
    AT1598T|1982-10-15|
    DK154887B|1989-01-02|
    IE800541L|1980-09-16|
    FI800792A|1980-09-17|
    IL59507D0|1980-05-30|
    EP0016411A3|1980-11-26|
    DK108580A|1980-09-17|
    IL59507A|1984-01-31|
    DE3060888D1|1982-11-11|
    ZA801505B|1981-05-27|
    IT8020667D0|1980-03-14|
    YU70180A|1983-02-28|
    AU5631180A|1980-09-18|
    DK154887C|1989-07-03|
    HU179840B|1982-12-28|
    CA1132555A|1982-09-28|
    IE49556B1|1985-10-30|
    CS219272B2|1983-03-25|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US1482871A|1922-12-01|1924-02-05|Smith Lulu Teeter|Child's music rack|
    US3393208A|1965-10-22|1968-07-16|Mcneilab Inc|6h-benzo[5, 6] cyclohept[1, 2, 3-cd]indolin-1, 6-diones|
    US3397202A|1967-05-02|1968-08-13|Mcneilab Inc|11, 11alpha-dihydro-11alpha-hydroxy-2--11-r3-6eta-benzo [5, 6] cyclohept [1, 2, 3-cd] indolin-1, 6-diones and intermediates for their preparation|
    GB1482871A|1975-03-18|1977-08-17|Farmaceutici Italia|Tetracyclic indole derivatives|GB8419278D0|1984-07-27|1984-08-30|Lilly Industries Ltd|Pharmaceutical compounds|
    US4731472A|1986-03-03|1988-03-15|Merck & Co., Inc.|alkanoic acids and alkanimidamides|
    US4835313A|1986-03-03|1989-05-30|Merck & Co., Inc.| alkanimidamides|
    GB8608893D0|1986-04-11|1986-05-14|Erba Farmitalia|D-nor-7-ergoline derivatives|
    GB8617907D0|1986-07-22|1986-08-28|Erba Farmitalia|Tetracyclic indole derivatives|
    US5054490A|1988-05-11|1991-10-08|Lunar Corporation|Ultrasonic densitometer device and method|
    GB9407637D0|1994-04-18|1994-06-08|Erba Carlo Spa|Serotoninergic abeo-ergoline derivatives|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB7909281|1979-03-16|
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