• 专利附录
  • 专利说明
  • 权利要求
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    • 专利摘要:
    The novel ergoline derivatives of the general formula I …<CHEM>… wherein R1 represents an ally or alkoxy group having from 1 to 4 carbon atoms, phenyl, a 5- or 6-membered heterocyclic ring which is preferably saturated, an amino group, a substituted amino group of the formula NHR min (wherein R min represents an alkyl group having from 1 to 4 carbona toms, a cycloalkyl group, a benzyl group or a phenyl group), or a substituted amino group of the formula NR sec R''' (wherein R sec and R''' both represent alkyl groups having from 1 to 4 carbon atoms);… R2 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms or a phenyl group;… R3 represents a halogen atom, a cyano group, a halogenated lower alkyl group, methylthio, methylsulfonyl or sulfonamido group, an alkoxy group having from 1 to 4 carbon atoms, an acyl group, having from 2 to 5 carbon atoms or a benzoyl group;… R4 represents a hydrocarbon group having from 1 to 4 carbon atoms;… R<5> represents a hydrogen atom or a methoxy group;… R6 is hydrogen, a halogen atom or a methyl group;… R7 is hydrogen or a methyl group;… and the pharmaceutically acceptable addition salts with organic or inorganic acids thereof exhibit antihypertensive and antiprolactinic activity. Their preparation is described, e.g. 2-cyano3- (6 min -methyl-ergoline-8 min beta )-propionic acid ethyl ester is obtained by reacting sodium ethyl cyanoacetate with 6-methyl-8 beta -tosyloxymethylergoline.
    公开号:SU906377A3
    申请号:SU792807706
    申请日:1979-09-06
    公开日:1982-02-15
    发明作者:Мантегани Серджо；Аркари Джулиана；Мария Караваджи Анна；Босисио Джермано
    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 ergoline derivatives of the general formula I not described in the literature
    . * 7 where is alkyl with 1-4 carbon atoms, phenyl, piperidino, pyrrolidino, morpholino or 4-methylpiperazino group, alkoxy group with 1-4 carbon atoms, amino group, group of the formula -NHR · 1 , where R 1 is alkyl with 1-4 carbon atoms, cycloalkyl, benzyl or phenyl, or a group of the formula -NR * "R"", where R" and R 'is alkyl with 1-4 carbon atoms,
    Rq · is hydrogen, alkyl with 1-4 carbon atoms or phenyl,
    R 3 is cyano, methylsulfonyl group, alkoxy group with 1-4 carbon atoms, acyl with 2-5 carbon atoms or benzyl,
    Id - alkyl with -1-4 carbon atoms Yu or alkenyl with 2-4 carbon atoms,
    Rj is hydrogen or methoxy;
    R & is hydrogen, halogen or methyl; is hydrogen or methyl having pharmacological activity15.
    A known method of producing cl-alkyl substituted derivatives of carboxylic acids, which consists in. alkylation of carboxylic acid derivatives with 20 esters of η-toluenesulfonic acid [1}.
    The purpose of the invention is a method for the synthesis of new pharmacologically active ergoline derivatives of the general formula I, based on the use of a known reaction.
    The goal is achieved by the fact that according to the method for producing ergoline derivatives of the general formula I, the compound of the general formula II
    'where, Rj, R & and R 7 have the above meanings, are reacted with an alkaline salt of a compound of general formula III R ^ R ^ CHCOR ^, where R, -, 20 R 2 and R 3 have the above meanings, in a polar aprotic solvent such as dimethylsulfoxide, dimethylformamide in the presence of sodium iodide at 50-100 ° C followed by 25 You are a target product division.
    Ergoline derivatives of general formula I relieve increased stress and have moderate activity with respect to prolactin. thirty
    Example 1. 2-Cyano ~ 3 “(6'-methyl rgol in -8’ ft) propionic acid, ethyl ether.
    A mixture of 16.9 g of sodium ethyl cyanoacetate-35 ta, 41 g of 6-methyl-8 ft-tosyloxymethyl * ergoline and 16 g of potassium iodide in 250 ml of dimethyl sulfoxide and 50 ml of ethyl cyanoacetate is heated with stirring for 5 hours at 70 ° C. A solution of 40 is poured out into 7 L of ice water, the resulting precipitate is filtered off, dried and purified by silica gel column chromatography using chloroformts as eluent. 24 g of the expected product are obtained. '202-200 ° C.
    Example 2. 2-Cyano-3 ~ (6 * -methylergolin-8 'ft) -N-propionylmorpholine.
    A mixture of 0.85 g of sodium cyanoacetyl-50 morpholine, 2 g of 6-methyl-8 (B-tosyloxymethylergoline, 0.6 g of sodium iodide in 10 ml of dimethyl sulfoxide and 2 g of cyanoacetylmorpholine is heated with stirring for 10 hours at 80 ° C. 55 the target is poured into 500 ml of water and the resulting precipitate is filtered off, dried and chromatographed on silica gel to give 1.7 g of the compound, mp 220-221 ° C.
    Example 3. 2-Cyano-Z 6 ( E methylergolin-8 (b1-N-phenylpropionamide.
    Under the conditions of Example 2, using sodium cyanoacetanilide, 2-cyano-3 ~ (6 ’-methylzrgoline-8 ft) -N-phenylpropionamide was obtained in a 60% yield, mp 180-181 ° C.
    Example 4. 2-Cyano-Z ’'- (6' -methylergoline-8'ft) -N-propionyl (I-methyl) -piperazine.
    Under the conditions of Example 2, using sodium cyanoacetyl-N-methylpiperazine, a compound was obtained in 60% yield, mp. 206-207 ° C.
    Example 5. 2-Cyano-3 ~ (6 '-methylergolin-8 1 ft) -N-ethylpropionamide.
    Under the conditions of Example 2, using sodium-N-ethylcyanoacetamide, a compound with a melting point of 65% was obtained. 225-22b ° C.
    Example 6. 2-Cyano ~ 3 “(6'-methylerg < Lin-8 'ft) -N-benzylpropionamide.
    Under the conditions of Example 2, a compound was obtained in 75% yield from sodium N-benzylcyanacetamide, mp. 233 ~ 234 ° C.
    Example 7. 2-Cyano-3 ~ (6'-methylergolin-8 ’) -N-propionylpiperidine.
    Under the conditions of Example 2, a compound is obtained from sodium cyanoacetylpiperidine in 77% yield, mp. 252253 ° C.
    Example 8. 2-Cyano-3 _ (6'-methylergolin-8 ft) -N-propionamide.
    Under the conditions of Example 2, a compound is obtained from sodium-anoacetamide in 45% yield, mp. 248-25-0 ° C.
    Example 9. 2-Cyano-3 - (6'-ethylene-ergoline-8'ft) -propionamide.
    Under the conditions of Example 8, from 42-ethyl-8 / B-tosyloxymethylergoline, a compound was obtained in 42% yield, mp. 243-245 ° C.
    Example 10. 2-Cyano-3 - (6'-allylergolin-8'ft) -propionamide.
    Under the conditions of Example 8, from 6-allyl-8 | L-tosyloxymethylergoline, a compound is obtained in 40% yield. Example 11. 2-Cyano-3 - (6'-methylergolin-8'ft) -N-propionylpyrrolidine.
    Under the conditions of Example 2, a compound is obtained from sodium cyanoacetylpyrrolidine in 68% yield, mp. 219 220 ° C.
    Example 12. ' 2-Cyano-3 (1 ’, 6’-dimethylergoline-8’ft) -propionamide.
    Under the conditions of Example 8, from 1,6-dimethyl-8ft-tosyloxymethylergoline, a compound is obtained in 80% yield, mp. 19b-197 ° C.
    Example 13- 2-Cyano-3 - (6'-me-5-tyl-1 0 '-methoxyergolin-8' (¾) -propion amide.
    Under the conditions of Example 8, the compounds were obtained in 45% yield from 6-methyl-10-methox and-8 | L-tosylox of imethylergoline in 45% yield. 207 _ 208 ° C.
    Example 14. 2-Cyano ~ 3 ~ (1 ', 6' -dimethyl-1 0 ’-methoxyergolin-8’!%) -Propionamide.
    Under the conditions of Example 8, from 1, 6-dimethyl-1 0-methoxy-8 (L-tosyloxymethylergoline), the compound is obtained in 81% yield, mp 190-192 ° C.
    Example 15.2-Cyano-Z - (2'bromo-6'-methylergolin-8'ft j -propion-2 (amide.
    Under the conditions of Example 8, from 2-bromo-6-methyl-8ft-tosyloxymethylergoline, a compound of 5 mp was obtained in 41% yield. 171-173 ° C. 2J
    Example 16. 2-Acetyl-3 “(6'-methylergolin-8'ft / propionic acid, ethyl ether.
    Under the conditions of Example 1, a compound is obtained from sodium ethyl acetoacetate in 70% yield. 1/8179 ° C.
    Example 17. 3 ~ Acetyl-4- (6'-methylergolin-8'ft) -butanone.
    Under the conditions of Example 1, from sodium-3 ″ acetylacetone, a compound is obtained in 75% yield, mp. 210-212 ° C.
    Example 18. 2-Cyano-2-ethyl “3” (6’-methylergolin-8'β> -propionamide.
    In the conditions of example 8 from sodium-4 (ethylcyanoacetamide receive compound in 43% yield, mp 217 ° C
    PRI me R 19. 2-Cyano-2-phenyl “3 (6 '-methylergoline-8’ | bj-propionamide.
    Under the conditions of Example 8, a compound is obtained from sodium phenylcyanoacetamide in 45% yield, mp. 232 ° C;
    Example 20. 2-Cyano-3 - (1 *, 6'-dimethylergoline-8 'ft) -N-ethylpropionic amide.
    Under the conditions of Example 5, from 1, 6-dimethyl-8 (6-tosyloxymethylergoline, a compound is obtained in 60% yield, mp 194-19 ° C.
    Example 21. 2-Cyano-Z- (1 ’, 6 '-dimethylergolin-8’ |>) - Ν “ΠΡΟπμοημτιpyrrolidine.
    Under the conditions of Example 11, from 1, 6-dimethyl-8y-tosyloxymethylergoline, a compound was obtained in 55% yield, mp. 207 _ 209 ° C.
    Example 22.2-Cyano-Z - (1 *, 6'-dimethylergoline-8'ft) -N-benzylpropionamide.
    Under the conditions of Example 6, from a 1,6-dimethyl-8B-tosyloxymethylergoline, a compound is obtained in 40% yield, mp. 175-177 ° C.
    Example 24. 2-Methylsulfonyl-3- (6’-methylergolin-8 Ίό) -N-benzyl-propionamide.
    Under the conditions of Example 1, a compound is obtained in 70% yield from sodium ethyl 8-methylsulphonyl acetate in a yield of 70 ° C. 199 ~ 201 ° C.
    Example 25. 2-B'etipsulfonyl-3 ”(6 1 -methylergoline-8'ft) -propionamide,
    Under the conditions of Example 2, a compound is obtained from sodium-S-benzylmethylsulfonylacetamine in 60% yield, mp. 285-287 ° C.
    Example 26. 2-Methylsulfonyl-3 “(6'-methylergolin-8'ft) -N-propionylpyrrolidine.
    Under the conditions of Example 2, a compound is obtained from sodium methylsulfonylacetylpyrrolidine in 69% yield, mp. 235-237 ° C.
    Example 27. 2-Methylsulfonyl-3- (6'-methyl-ergolin-8.'B) -N-ethylpropionamide.
    Under the conditions of Example 2, from 60% yield of sodium-N-ethylmethylsulfonylacetamide, the compound was obtained, i.e. pl. 227-229 ° C.
    Example 28. 2-Acetyl-3 - (6'-methylergolin-8'ft) -propionamide.
    Under the conditions of Example 2, a compound is obtained from sodium acetylacetamide in 40% yield, mp. 225 - 227 ° C.
    Example 29. 2-Cyano-3 “(2’-chloro-6 * -methylergolin-8’B) -propionamide.
    Under the conditions of Example 8, from 2-chloro-6-methyl-8-tosyloxymethylergoline, a compound is obtained in 45% yield, mp. 245-2464.
    Example 30. 2-Cyano-3 -> (2 ', 6’-dimethylergoline-8'ft) -propionamide.
    In the conditions of example 8, from 2,6-dimethyl-8 (L-tosyloxymethylergoline, a compound is obtained with a mp of 270-272 ° C in 5θ%
    Example 31. 2-Cyano-3- (6’-methylergolin-8 * ft) - cyclohexylpropionam id.
    Under the conditions of Example 2, from the sodium N-cyclohexyl cyanoacetamide above 7, 906377, the title compound was obtained as a foam in 45% yield.
    Example 32. 2-Cyano-3- (6'-methylergolin-8 '(b) -N-diethylpropionamide.
    the conditions of example 2 from N-diethylcyanoacetamide sodium receive the above compound in the form of a foam with a yield of 52%.
    权利要求:
    Claims (1)
    [1]
    The goal is achieved in that according to the method of obtaining ergoline derivatives of general formula I, the compound of general formula II: Cr - where R, J Rr, R t and R7 have the above meanings, is reacted with an alkaline salt of a compound of general formula III RnRaCHCOR, where R Rri and R have the above values in a polar aprotic solvent such as dimethyl sulfoxide, dimethylformamide in the presence of sodium iodide at 50-100 ° C, followed by separation of the target product. Ergoline derivatives of general formula I relieve an increased stress state and have moderate activity with respect to prolactin. Example K 2-Cyano-3- (6-methyl ergoline-8) propionic acid, ethyl ester. . A mixture of 16.9 g of sodium ethyl cyanoacetate, AI g of 6-methyl-8 (L-tosyloxymethyl ergoline and 16 g of potassium iodide in 250 ml of dimethyl sulfoxide and 50 ml of ethyl cyanoacetate is heated with stirring for 5 hours at 70 ° C. ice, the precipitate obtained is filtered off, dried and purified by chromatography on a column of silica gel using chloroform as eluent.) 2 g of the expected product are obtained, mp. i202-200 ° C. Example 2-. 2-Cyano-3- (6-methylergoline-8 | i) -N-propionylmorpholine. A mixture of 0.85 g of sodium cyanoacetylmorpholine, 2 g of 6-methyl-8 (1-tosyloxymethyl ergoline, 0.6 g of sodium iodide in 10 ml of dimethyl sulfoxide and 2 g of cyanoacetylmorpholine is heated under stirring for 10 hours at. The solution is poured into 500 ml of water and the semi-precious precipitate is filtered off, dried and chromium is etched on silica gel to give 1.7 g of the compound, mp 220-221 ° C. Example 3. 2-Cyano-3-6 (-methylergolium-8 (i) -N- Phenylpropionamide. Under the conditions of Example 2, using sodium cyanoacetanilide, 2-cyano-3- (6-methylergoline-8 | i) -N-phenylpropionamide is obtained with an yield of mp ISO-ISI C. p k. 2-Cyano-3 - (6 -methyl ergoline-8 (b) -N-propionyl (M-methyl-piperazine. Under the conditions of Example 2, using sodium cyano-cetyl-N-methyl-piperazine, the compound is obtained in 60; mp 206-207 ° C. Example 5. 2-Cyano-3- (6-methylergoline-8 fi) -N-ethylpropionamide Under the conditions of Example 2. Using sodium-ethyl cyanoacetamide, get with b5% - The yield is the compound with mp 225-22b ° C. Example 6. 2-Cyano-3- (6-methylergdlin-8 ft) -N-benzylpropionamide. The 8 conditions of example 2 from sodium-N-benzyl cyanacetamide are obtained with the yield compound, so pl. 23323 ° C. Example 7. 2-14iano-3- (C | -methyl ergoline-8) -N-propiochylpiperidine. Under the conditions of Example 2, sodium cyanoacetylpiperidine produces the compound in 77% yield, mp. 252253 ° C. PRI me R 8. 2-Cyano-3-G6 -methyl ergoline-8 fb) -W-propionamide. Under the conditions of Example 2, sodium cyanoacetamide gives the compound with a C% yield, m.p. 248-25-0С. Example 9. 2-Cyano-3- (6-Etilenergolin-8 fi) -propionamide. Under the conditions of Example 8, from b-ethyl-8 / J-tosyloxymethylergoline, the compound was obtained in 42% yield, m.p. 2 3-245 ° C. Example 0. 2-Cyano-3- (6-allylhergoline -8 / i) -propionamide. Under the conditions of Example 8, from 6-allyl-81b-tosyloxymethylergoline, the compound is obtained in 0% yield. Example 11. 2-Cyano-3- (6-methylergoline-8 ft) -N-propionylpyrrolidine. Under the conditions of Example 2, cyanoacetylpyrrolidine sodium is obtained with 68% vol. square 219 output of the compound, 220 C. Example 12. 2-Cyano-3- (1, 6-dimethylergolin-8 (J) -propionamide. 5 Under the conditions of example 8, from 1,6-dimethyl-8 (L-tosyloxymethyl-ergoline) is obtained with an 80% yield, the compound is mp 19b-197 ° C. Example 13 2-Cyano-3- (6-methyl-1 O-methoxy-ergoline-8 | b) -propionamide. Under the conditions of Example 8 from 6-methyl-10-methoxy-8i-tosyloxymethyl-ergoline, a compound is obtained in 45% yield, mp 207-208 c. Example T4. 2-Cyano-3-SG, 6-dimethyl-1 O-methoxy-ergoline-8 % -propionamide. Under the conditions of Example 8 from 1,6-dimethyl-1, 0-methoxy-8 (L-tosyloxymethyl ergonine is obtained in 8K5% yield with solid, mp 190-192 ° C. Example 15. 2-Cyano-3- (2 Bromo-6 -methylergoline-8 (B j-propion-amide. Under the conditions of Example 8 of 2-bromo-6 - Methyl-8-tosyloxymethyl-ergoline yields a compound of mp 171-173 ° C with I i-HbiM. Example 16. 2-Acetyl-3 (6-methylergoline-8 (1} propionic acid, ethyl ether. In condition x of Example 1 from sodium ethyl acetoacetate is obtained with the release of the compound, with mp 1/8179 C. Example 17. 3 Acetyl - - (6-methylergoline-8 (L 1-butanone. Under the conditions of Example 1, sodium acetylacetone is obtained with a yield, compound, mp 210-212 C. Example 18. 2-Cyano-2- ethyl 3 (6-methylergoline-8y-propiones Under the conditions of example 8, a compound is obtained from the sodium ethyl cyanoacetamide with yield, mp. Example 19. 2-Cyano-2-c |) enyl 3 (6-methyl ergoline-8 | b - propiones Under the conditions of example B, sodium nilcyanoacetamide is obtained with the yield of the compound, mp. Example 20. 2-Cyano-3- (1, 6 -dimethylergoline-8 (L1 -N-ethyl-propio amide. Under the conditions of example 5 of 1 , 6-dime-8-(tosyloxymethyl ergoline n Compound is obtained with the release, mp 19 -1964. Example 21. 2-Cyano-3- (, 6-dimethylergoline-8) -Y-propionylpyrrolidine. Under conditions of example 11 from 1,6-tym-8 | 1-tosyloxymethyl ergoline obtained 7 UT with the release of the compound, mp 207-205 ° C. Example 22. 2-Cyano-3- (1, 6-dimethylergoline-8 -N-benzylpropionamide. Under the conditions of Example 6 of 1, 6-dimethyl-8 4-tosyloxymethyl ergoline is obtained with the release of the compound, mp 175-177 ° C. Example 2h. 2-Methylsulfonyl-3- (6-methylergoline-8To) -N-benzyl-propionamide. Under the conditions of Example 1, sodium ethyl 8-methylsulfonyl acetate gives, in 70-g. Yield, a compound, m.p. 199-2010С. Example 25. 2-Ketipsulfonyl-3 (6-methyl ergoline-8 ft) -propionamide, Under the conditions of Example 2, sodium-3-benzylmethylsulfonylacetamine gives the compound with yield, m.p. 285-287 ° C. Example 26. 2-Methylsulfonyl3 (6 -methyl ergoline-8 | b1 -N-propionylpyrrolidine. Under the conditions of example 2, sodium methylsulfonylacetylpyrrolidine under conditions of example 2) gives the title compound, m.p. 235-237 ° C. Example 27. 2-Methylsulfonyl 3 (6-methylergoline-8.) -N-ethylpropionamide. Under the conditions of Example 2, sodium-N-ethylmethyl sulfonyl acetamide is semi- | Compound: With a 60% yield, the compound: t. square 227-229 ° C. Example 28. 2-Acetyl-3- (6-methylergoline-8 Ib) -propionamide. Under the conditions of Example 2, sodium acetylacetamide gives the compound with a 0% yield, m.p. . Example 29. 2-Cyano-3- (2-chloro-6-methyl ergoline-8 (il-propionamide. Under the conditions of example B from 2-xg), p-6-methyl-8-tosyloxymethyl ergoline is obtained in 5% yield compound, mp 2 5-24b C. Example 30. 2-Cyano-3 -; (2,6-dimethyl ergolin-8 (3) -propionamide. Under the conditions of Example 8 of 2,6-dimethyl-8 | -tosyloxymethyl ergoline gives a compound with mp 270-272® C in 50% yield. Example 31 2-Cyano-3- (6-methylergoline-B (b) - -cyclohexylpropionamide. Under conditions of example 2, sodium cyclohexyl cyanoacetamide sodium the above I, the coupled compound is obtained as a foam with an exit, Example 32. 2-Cyano-3 (6-methylergoline-8 (B) -N-diethylpropionamide 8 conditions of example 2 from N-diethyl sodium cyanoacetamide, the above compound is obtained in the form of a foam, yield 52, The invention The method for preparing ergoline derivatives of general formula I wherein R is alkyl with -k carbon atoms, phenyl, piperidino, pyrolidino, morpholino or A-methylpiperazino, alkyl alkoxy group with -k carbon atoms, amino group, a group of the formula NHR, where R is alkyl with carbon atoms, cycloalkyl, benzyl, or phenyl, or a group of the formula NR R where R and R are alkyl with carbon atoms, hydrogen, alkyl with 1 - carbon atoms lerod or phenyl. 7 cyano, methylsulfonylgroup, alkoxy group with 1 - carbon atoms, acyl with 2-5 carbon atoms or benzyl, R - alkyl with carbon atoms or alkenyl with 2 - A carbon atoms Rj - hydrogen or methoxy group. hydrogen, halogen or methyl. R is hydrogen or methyl. characterized in that the compound of the general formula IIB-or R ", R, R, or Rf has the above-mentioned meanings, is reacted with an alkaline salt of the compound of the general formula III RjjRiCHCOR, where R, Rn and Rl have the above values, in a polar aprotic solvent such as dimethyl sulfoxide, dimethylformamide, in the presence of sodium iodide at 50-100 ° C, followed by isolation of the target product. Sources of information taken into account in the examination 1.. Weigand-Hilgetag. Methods of an experiment on organic chemistry. M. Chemistry, 1968, p. 755.
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    同族专利:
    公开号 | 公开日
    GR71867B|1983-07-07|
    FI792776A|1980-03-09|
    JPS6221792B2|1987-05-14|
    YU217479A|1983-02-28|
    DK375279A|1980-03-09|
    AU526764B2|1983-01-27|
    IE48550B1|1985-03-06|
    ZA794682B|1980-11-26|
    AT1354T|1982-08-15|
    DK148419C|1985-12-09|
    JPS5589282A|1980-07-05|
    DK148419B|1985-07-01|
    CA1128502A|1982-07-27|
    IE791705L|1980-03-08|
    EP0008802A1|1980-03-19|
    US4252941A|1981-02-24|
    DE2963371D1|1982-09-09|
    HU179450B|1982-10-28|
    EP0008802B1|1982-07-21|
    YU41347B|1987-02-28|
    US4321381A|1982-03-23|
    FI66613C|1984-11-12|
    FI66613B|1984-07-31|
    IL58182A|1983-07-31|
    AU5045579A|1980-03-13|
    CS208135B2|1981-08-31|
    引用文献:
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    GB8318790D0|1983-07-12|1983-08-10|Erba Farmitalia|Anorexigenic ergot derivatives|
    GB8501078D0|1985-01-16|1985-02-20|Erba Farmitalia|Piperazin-1-yl-ergo-line derivatives|
    GB2173189B|1985-02-21|1988-04-27|Maruko Pharmaceutical Co|Ergoline derivatives and salts thereof and pharmaceutical compositions thereof|
    US4801712A|1985-06-24|1989-01-31|Eli Lilly And Company|2-Alkylthio-6-n-alkylergolines are dopamine D-1 antagonists without D-2 agonist activity|
    US4704396A|1985-12-20|1987-11-03|Eli Lilly And Company|Phenacyl esters of 1-substituted-6- dihydrolysergic acids useful as 5HT receptor antagonists|
    JPH04106090U|1991-02-27|1992-09-11|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB7836080|1978-09-08|
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