GB2056437A - Secoergoline derivatives - Google Patents
Secoergoline derivatives Download PDFInfo
- Publication number
- GB2056437A GB2056437A GB8015589A GB8015589A GB2056437A GB 2056437 A GB2056437 A GB 2056437A GB 8015589 A GB8015589 A GB 8015589A GB 8015589 A GB8015589 A GB 8015589A GB 2056437 A GB2056437 A GB 2056437A
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- Prior art keywords
- secoergoline
- dimethyl
- methoxy
- methyl
- general formula
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/90—Benzo [c, d] indoles; Hydrogenated benzo [c, d] indoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
There are provided 6,7- secoergolines of the formula I <IMAGE> wherein R1=C1-C4alkyl, benzyl or phenethyl; R2=OH, acyloxy, alkoxy, NH2, CN, NH2CO, substituted or unsubstituted heterocyclic group, the ring of which is formed by 5 or 6 atoms of which at least one is N and carries the bond to the methylene group, not more than 3 are N and/or O and/or S and the remainder are C, or SR5, NHR5, <IMAGE> or CHR7R8 where R5 = substituted or unsubstituted heterocyclic group, the ring of which is formed by 5 or 6 atoms of which at least 1 is N, not more than 3 are N and/or O and/or S and the remainder are C, X=O or S, n=0 or 1; R6=C1-C4 aliphatic group, benzyl, NH2 or substituted NH2; R7=H or CN; R8=H or alkoxycarbonyl or NH2CO; R3=H or CH3O; and R4=H or CH3. These compounds are useful alpha -adrenergic blocking agents, hypotensives, central nervous system depressants, antispasmodics, analgesics and antiprolactin agents and can be incorporated into pharmaceutical compositions.
Description
SPECIFICATION
Secoergoline derivatives
The invention relates to secoergoline derivatives and to processes for their preparation.
The invention provides 6,7-secoergolines of the general formula I:
wherein R, represents an alkyl group having from 1 to 4 carbon atoms or a benzyl or phenethyl group; R2 represents a hydroxy, acyloxy, alkoxy, amino, cyano or carbamoyl group, or a substituted or unsubstituted heterocylic group, the ring of which is formed by 5 or 6 atoms of which one at least is a nitrogen atom and carries the bond to the methylene group, not more than 3 are nitrogen and/or oxygen and/or sulphur atoms, and the remainder are carbon atoms, or a group of the general formula SR5, NHR5,
or CHR7R8 wherein R5 represents a substituted or unsubstituted heterocyclic group, the ring of which is formed by 5 or 6 atoms of which at least 1 is a nitrogen atom, not more than 3 are nitrogen and/or oxygen and/or sulphur atoms, and the remainder are carbon atoms, X represents an oxygen or sulphur atom, n is O or 1, R6 represents an aliphatic group having from 1 to 4 carbon atoms, a benzyl group or a substituted or unsubstituted amino group, R7 represents a hydrogen atom or a cyano group and R8 represents a hydrogen atom or an alkoxycarbonyl or carbamoyl group; R3 represents a hydrogen atom or a methoxy group; and R4 represents a hydrogen atom or a methyl group.
The compounds of the general formula I may be prepared according to the invention by reacting a compound of the general formula Ill wherein R2, R3 and R4 have the meanings ascribed to them above with a halide of the general formula RaY wherein R, has the meaning ascribed to it above and Y represents a halogen atom and hydrogenating the resultant quaternary ammonium salt of the general formula IV in an anhydrous or aqueous aliphatic alcohol or in an inert solvent in the presence of a suitable catalyst.
The catalyst may be any conventional hydrogenation catalyst such as platinum, palladium, their salts or oxides, either as such as deposited on a suitable support such as carbon, barium sulphate or calcium carbonate.
The hydrogenation-hydrogenolysis is preferably carried out at or above atmospheric pressure at ambient temperature for a period of from 2 to 6 hours. The catalyst is filtered off and the filtrate evaporated to dryness in vacuo to obtain the crude product which can be isolated and purified.
The compounds of the general formula Ill may be obtained by condensing a compound of the general formula II
wherein R3 and R4 have the meanings ascribed to them above with a compound of the general formula
R2H wherein R2 has the meaning ascribed to it above.
Secoergoline derivatives according to the invention are yellowish or white oils or white crystalline solids. They are obtained as mixtures of their 8R and 8S diastereoisomers. The mixtures can be separated by chromatography or crystallisation.
Secoergoline derivatives according to the invention and their pharmaceutically acceptable salts are useful as a-adrenergic blocking agents, hypotensives, central nervous system depressants, antispasmodics, analgesics and antiprolactin agents. Accordingly the invention further provides a pharmaceutical composition comprising a 6,7-secoergoline derivatives of the formula I or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically diluent or carrier.
The following Examples illustrate the invention.
EXAMPLE 1 6-Methyl-8-chloromethyl-8,9-didehydro- 70-methoxy-ergoline-(II: R3=OCH3, R4=H)
A stirred mixture of 1 g of 6-methyl-8-hydroxymethyl-8,9-didehydro-l O-methoxy-ergoline, 0,147 g of lithium chloride and 0.509 ml of s-collidine in 5 ml of dimethylformamide was treated dropwise, after cooling to OOC with 0.301 ml of methanesulphonyl chloride. Stirring was continued at OOC for 1 hour, whereafter the reaction mixture was poured over iced water and extracted with cold chloroform.
Evaporation off of the solvent in vacuo left a residue that was crystallized from diethyl ether to give 0.7 g of the title compound, m.p. 148-1 500C.
EXAMPLE 2 6-Methyl-8-(2-ethoxycarbonyl-2-cyano-ethylJ-8,9-dideDydro- 10-methoxy-ergoline (Ill: R2=C2H5OOC.CH(CN) R3=OCH3, R4=H)
A mixture of 0.446 g sodium ethyl cyano acetate and 1 g of 6-methyl-8-chloromethyl-8,9didehydro-1 0-methoxy-ergoline, prepared as described in Example 1, in 10 ml of dimethylsulphoxide was stirred at room temperature for 2 hours. The solution was poured into cold water, and the precipitate was filtered off and chromatographed on an aluminium oxide column, using acetone as eluant, to give 0.6 g of the title compound as a foam.
EXAMPLE 3 6-Methyl-8-rdimethylcarbamoyl-aminomethyl)-8,9-didehydro- 1 0-methoxy-ergoline (Ill: R2=(CH3)2N-C0NH, R3=OCH3, R4=H)
0.8 g of 6-methyl-8-aminomethyl-8,9-didehydro-1 0-methoxy-ergoline in 10 ml of pyridine were cooled to --1 OOC and reacted with 0.34 ml of dimethylcarbamoyl chloride. The reaction mixture was kept at this temperature for 10 minutes and then for 10 minutes at room temperature. It was then diluted with chloroform and methanol and washed with aqueous sodium carbonate. The chloroform was evaporated from the chloroform layer and the residue was chromatographed on a silica gel column using chloroform followed by 1% methanol in chloroform as eluting solvent.The evaporation off of the solvent gave the title compound as an oil in 35% yield.
EXAMPLE 4 6,6-Dimethyl-8-hydroxymethyl- 1 0-methoxy-6, 7-secoergoline
1.6 ml of methyl iodide were added at room temperature to a suspension of 4 g of 6-methyl-8hydroxymethyl-8,9-didehydro- 1 0-methoxy-ergoline in 40 ml of nitromethane. The mixture was left under stirring overnight and then 80 ml of diethyl ether were added. The solid obtained was filtered off, dissolved in 250 ml of methanol and hydrogenated at room temperature and atmospheric pressure for 6 hours in the presence of 3 g of platinum dioxide catalyst. After filtration off of the catalyst and evaporation off of the solvent, the residue was dissolved in water, made basic by addition of sodium bicarbonate and extracted with chloroform. Evaporation off of the chloroform gave 3 g of 6,6-dimethyl 8-hydroxymethyl- 1 0-methoxy-6,7-secoergoline as a foam.
PMR Spectrum (CDCl3) 0.9-1.23 a (m, Me), 2.43 and 2.49 a (2 s. Me2N), 2.87 and 2.96 a (2 s, MeO).
IR (KBr):
1075 and 1035 cm-l (v C=O)
MS: m/e 302 (M+), 287 (M-Me).
EXAMPLE 5 6,6-Dimethyl-8-{3,5-dimethyl-pyrrole-2-carboxymethyly- 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4 but employing 6-methyl-8-(3,5-dimethyl-pyrrole-2-carboxymethyl) 8,9-didehydro-1 0-methoxy-ergoline the title compound was obtained as a foam in 45% yield.
EXAMPLE 6 1,6, 6-Trimethyl-8-(5-bromonicotinoyloxymethyl)- 1 0-methoxy-6, 7-secoergollne Operating as in Example 4, but employing 1 ,6-dimethyl-8-(5-bromonicotinoyloxymethyl)-8,9didehydro-1 0-methoxy-ergoline, the title compound was obtained in 35% yield.
PMR Spectrum (CDCl3) 0.95 a and 1.08 S (2d, CHCH3 2.42 ov and 2.48 S (2s, N(CH3)2), 2.95 a (s, OCH3).
EXAMPLE 7 6,6-Dimethyl-8-r2-ethoxy-carbonyl-2-cyano-ethyl) -1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing the compound of Example 2, the title compound was obtained as a foam in 60% yield.
EXAMPLE 8 6, 6-Dimethyl-8-(2-carbamoyl-2-cyano-ethyl)- 1 0-methoxy-6, 7-secoergollne Operating as in Example 4, but employing 6-methyl-8-(2-carbamoyl-2-cyano-ethyl)-8,9didehydro-1 0-methoxy-ergoline, the title compound was obtained as an oil in 65% yield.
EXAMPLE 9 6, 6-Dimethyl-8-(2-carbamoyl-2-cyano-ethyl)-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-(2-carbamoyl-2-cyano-ethyl)-8,9didehydro-ergololine, the title compound was obtained as an oil in 55% yield.
EXAMPLE 10 6,6-Dimethyl-8-morpholinomethyl- 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-morpholinomethyl-8,9-didehydro-10- methoxy-ergoline, in turn prepared by reaction of the product of Example 1 with morpholine, the title compound was obtained as an oil in 70% yield.
EXAMPLE 11 6,6-Dimethyl-8-[{2-pyrimidinylamino)-methyll 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-[(2-pyrimidinyl-amino)-methyl]-8,9- didehydro-1 0-methoxy-ergoline, in turn prepared by reaction of the product of Example 1 with 2aminopyrimidine, the title compound was obtained as an oil in 50% yield.
EXAMPLE 12 6, 6-Dimethyl-8-[(2-pyridyl)-thiomethyl]- 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-[(2-pyridyl)-thiomethyl]-8,9- didehydro-1 0-methoxy-ergoline, in turn prepared by reaction of the product of Example 1 with 2mercaptopyridine, the title compound was obtained as an oil in 45% yield.
EXAMPLE 13 6,6-Dime thyi-8-[(2-pyrimidin yI)-thiom e thyl]-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-[(2-pyrimidyl)-thiomethyl]-8,9-didehydro- ergoline, the title compound was obtained as an oil in 55% yield.
EXAMPLE 14 6, 6-Dimethyl-8-l -methyl-2-imidazolylJ-thiomethyl]- 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-[(1-methyl-2-imidazolyl)-thiomethyl]-8,9- didehydro-1 0-methoxy-ergoline, in turn prepared by reaction of the product of Example 1 with 1 methyl-2-mercapto-imidazole, the title compound was obtained as an oil in 45% yield.
EXAMPLE 15 6,6-Dimethyl-8-{dimethylcarbamoyl-aminomethyl) 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing the compound of Example 3, the title compound was obtained as an oil in 55% yield.
EXAMPLE 1 6 6, 6-Dimethyl-8-(benzyloxycarbonyl-aminomethyl)- 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing 8-(benzyloxycarbonyl-aminomethyl)-6-methyl-8,9- didehydro-1 O-methoxy-ergoline, the title compound was obtained as a foam in 45% vield.
EXAMPLE 17 6,6-Dimethyl-8-{ethoxycarbonyl-aminomethyl)- 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-(ethoxycarbonyl-aminomethyl)-8,9- didehydro-1 O-methoxy-ergoline, the title compound was obtained as an oil in 70% yield.
EXAMPLE 18 6,6-Dimethyl-8-{benzyloxycarbonyl-aminomethyl)-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-(benzyloxycarbonyl-aminomethyl)-8,9- didehydro-ergoline, the title compound was obtained as a foam in 35% yield.
PMR Spectrum (CDCl3) 0.96 8 and 1.03 8 (2d, CHCH3), 2.248 (s, N(CH3)2).
EXAMPLE 19 6,6-Dimethyi-8-(dimethyicarbamoyi-aminomethyl)-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-(dimethylcarbamoyl-aminomethyl)-8,9didehydro-ergoline, the title compound was obtained as a foam in 60% yield.
PMR Spectrum (CDCl3) 0.53 8 to 1.17 8 (m, CHCH3), 2.22 8 (s, N(CH3)2).
EXAMPLE 20 6,6-Dimethy!-8-(dimethyithiocarbamoyi-aminomethyi)-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-(dimethylthiocarbamoyl-aminomethyl)-8,9- didehydro-ergoline, the title compound was obtained as an oil in 70% yield.
PMR Spectrum (CDCl3) 0.93 s to 1.37 8 (m, CHCH3, CH(CH3)2), 2.30 6 (s, N(CH3)2).
EXAMPLE 21 6, 6-Dimethy!-8-(5-bromonicotino yioxymethyi)- 1 0-methoxy-6, 7-secoergoline
Operating as in Example 4, but employing 6-methyl-8-(5-bromonicotinoyloxymethyl)-8,9didehydro-1 0-methoxy-ergoline, the title compound was obtained as a foam in 40% yield.
PMR Spectrum (CDCl3) 0.96 8 and 1.08 8 (2d, CHCH3), 2.42 S and 2.47 S (2s, N(CH3)2), 2.98 8 (s, OCH3).
EXAMPLE 22 6,6-Dimethyl-8-benzoyloxymethyl- 1 O-methoxy-6, 7-secoergoline Operating as in Example 4, but employing 6-methyl-8-benzoyloxymethyl)-8,9-didehydrn-1 0- methoxy-ergoline, the title compound was obtained as a foam in 60% yield.
PMR Spectrum (CDCl3) 1.00 S and 1.108 (2d, CHCH3), 2.42 8 (s, N(CH3)2).
Claims (25)
1. A 6,7-secoergoline of the general formula I as herein defined or a pharmaceutically acceptable salt thereof.
2. 6,6-Dimethyl-8-hydroxymethyl- 1 0-methoxy-6,7-secoergoline.
3. 6,6-Dimethyl-8-(3,5-dimethyl-pyrrole -2-carboxymethyl)- 1 0-methoxy-6,7-secoergoline.
4. 1 ,6,6-Trimethyl-8-(5-bromonicotinoyloxymethyl)- 1 0-methoxy-6,7-secoergoline.
5. 6,6-Di methyl-8-(2-ethoxycarbonyl-2-cyano-ethyl)-1 0-methoxy-6,7-secoergoline.
6. 6,6-Dimethyl-8-(2-carbamoyl-2-cyano-ethyl )-1 0-methoxy-6,7-secoergoline.
7. 6,6-Dimethyl-8-(2-carbamoyl-2-cyano-ethyl)-6,7-secoergoline.
8. 6,6-Dimethyl-8-morpholinomethyl-1 0-methoxy-6,7-secoergoline.
9. 6,6-Dimethyl-8-[(2-pyrimidinylamino)-methylj- 1 0-methoxy-6,7-secoergoline.
10. 6,6-Dimethyl-8-[(2-pyridyl)-thiomethyl]-1 O-methoxy-6,7-secoergoline.
11. 6,6-Dimethyl-8-[(2-pyrimidinyl)-thiomethyl]-6,7-secoergoline.
12. 6,6-Dimethyl-8-[( 1 -methyl-2-imidazolyl)-thiomethyl]- 1 0-methoxy-6,7-secoergoline.
13. 6,6-Dimethyl-8-(dimethylcarbamoyl-aminomethyl)-1 0-methoxy-6,7-secoergoline.
14. 6,6-Dimethyl-8-(benzyloxycarbonyl-a minomethyl)- 1 0-methoxy-6,7-secoergoline.
1 5. 6,6-Dimethyl-8-(ethoxycarbonyl-a minomethyl)- 1 0-methoxy-6,7-secoergoline.
16. 6,6-Dimethyl-8-(benzyloxycarbonylaminomethyl)-6 ,7-secoergoline.
1 7. 6,6-Dimethyl-8-(dimethylcarbamoyl-aminom
18. 6,6-Dimethyl-8-(dimethylthiocarbamoylami
19. 6,6-Dimethyl-8-(5-bromonicotinoyloxymethyl)- O-methoxy-6,7-secoergoline.
20. 6,6-Dimethyl-8-benzoyloxymethyl- 1 0-methoxy-6,7-secoergoline.
21. A process for the preparation of a 6,7-secoergogine of the general formula I as herein defined, the process comprising reacting a compound of the general formula Ill as herein defined with a halide of the general formula RgY as herein defined and hydrogenating the resultant quaternary ammonium salt in an anhydrous or aqueous aliphatic alcohol or in an inert solvent in the presence of a suitable catalyst.
22. A process according to claim 21 in which the catalyst for the hydrogenation is platinum, palladium, or a salt or an oxide of platinum or palladium, optionally supported on carbon, barium sulphate or calcium carbonate.
23. A process according to claim 21 or claim 22 in which the hydrogenation is carried out at or above atmospheric pressure, at ambient temperature, for a period of from 2 to 6 hours.
24. A process according to claim 21 substantially as described herein with reference to any of
Examples 4 to 22.
25. A pharmaceutical composition comprising a 6,7-secoergoline derivative according to any of claims 1 to 20 or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable diluent or carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8015589A GB2056437A (en) | 1979-08-07 | 1980-05-12 | Secoergoline derivatives |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7927525 | 1979-08-07 | ||
| GB8015589A GB2056437A (en) | 1979-08-07 | 1980-05-12 | Secoergoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2056437A true GB2056437A (en) | 1981-03-18 |
Family
ID=26272459
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8015589A Withdrawn GB2056437A (en) | 1979-08-07 | 1980-05-12 | Secoergoline derivatives |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2056437A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4632928A (en) * | 1983-03-06 | 1986-12-30 | Richter Gedeon Vegyeszeti Gyar R.T. | Pyrazole derivatives with an ergoline skeleton, their acid addition salts, and a process for the preparation thereof |
| US4657914A (en) * | 1982-04-30 | 1987-04-14 | Farmitalia Carlo Erba S.P.A. | Ergoline derivatives |
| US4675404A (en) * | 1981-07-21 | 1987-06-23 | Farmitala Carlo Erba S.P.A. | 8-pyridazinylcarbamoyl ergolines |
| US4690929A (en) * | 1983-04-28 | 1987-09-01 | Farmitalia Carlo Erba | Ergolines exhibiting protactin secretion inhibition activity |
| US4704395A (en) * | 1985-12-20 | 1987-11-03 | Eli Lilly And Company | Cyclic ether esters of 2-substituted-6-(substituted and unsubstituted) dihydrolysergic acid useful as 5HT receptor antagonists |
| US4713457A (en) * | 1985-02-21 | 1987-12-15 | Maruko Seiyaku Co., Ltd. | Ergoline derivatives and acid addition salts thereof |
| US4742075A (en) * | 1984-07-27 | 1988-05-03 | Lilly Industries Limited | Substituted hexahydro-4H-indolo[6,5,4-cd]indoles |
| US4843073A (en) * | 1986-06-25 | 1989-06-27 | Farmitalia Carlo Erba S.P.A. | 1-t-butyl ergolines useful in the treatment of cerebral insufficiency and senile dementia |
| US4861793A (en) * | 1986-04-11 | 1989-08-29 | Farmitalia Carlo Erba, S.P.A | D-nor-7-ergoline derivatives having anti-Parkinson and antipsychosis activity and pharmaceutical compositions containing them |
| WO1998000424A1 (en) * | 1996-06-27 | 1998-01-08 | Pharmacia & Upjohn S.P.A. | Antineurodegenerative ergoline derivatives |
-
1980
- 1980-05-12 GB GB8015589A patent/GB2056437A/en not_active Withdrawn
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4675404A (en) * | 1981-07-21 | 1987-06-23 | Farmitala Carlo Erba S.P.A. | 8-pyridazinylcarbamoyl ergolines |
| US4657914A (en) * | 1982-04-30 | 1987-04-14 | Farmitalia Carlo Erba S.P.A. | Ergoline derivatives |
| US4632928A (en) * | 1983-03-06 | 1986-12-30 | Richter Gedeon Vegyeszeti Gyar R.T. | Pyrazole derivatives with an ergoline skeleton, their acid addition salts, and a process for the preparation thereof |
| US4690929A (en) * | 1983-04-28 | 1987-09-01 | Farmitalia Carlo Erba | Ergolines exhibiting protactin secretion inhibition activity |
| US4742075A (en) * | 1984-07-27 | 1988-05-03 | Lilly Industries Limited | Substituted hexahydro-4H-indolo[6,5,4-cd]indoles |
| US4841056A (en) * | 1984-07-27 | 1989-06-20 | Lilly Industries Limited | Substituted hexahydro-4H-indolo[6,5,4-cd]indoles |
| US4713457A (en) * | 1985-02-21 | 1987-12-15 | Maruko Seiyaku Co., Ltd. | Ergoline derivatives and acid addition salts thereof |
| AU591094B2 (en) * | 1985-02-21 | 1989-11-30 | Maruko Seiyaku Co., Ltd. | Ergoline derivatives and acid addition salts thereof |
| US4704395A (en) * | 1985-12-20 | 1987-11-03 | Eli Lilly And Company | Cyclic ether esters of 2-substituted-6-(substituted and unsubstituted) dihydrolysergic acid useful as 5HT receptor antagonists |
| US4861793A (en) * | 1986-04-11 | 1989-08-29 | Farmitalia Carlo Erba, S.P.A | D-nor-7-ergoline derivatives having anti-Parkinson and antipsychosis activity and pharmaceutical compositions containing them |
| US4843073A (en) * | 1986-06-25 | 1989-06-27 | Farmitalia Carlo Erba S.P.A. | 1-t-butyl ergolines useful in the treatment of cerebral insufficiency and senile dementia |
| WO1998000424A1 (en) * | 1996-06-27 | 1998-01-08 | Pharmacia & Upjohn S.P.A. | Antineurodegenerative ergoline derivatives |
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