CA1057285A - 6-NOR-6-ISOPROPYL-9,10-DIHYDRO-2'.beta.-METHYL OR ETHYL-5'.alpha.-ISOPROPYL-ERGOPEPTINE - Google Patents
6-NOR-6-ISOPROPYL-9,10-DIHYDRO-2'.beta.-METHYL OR ETHYL-5'.alpha.-ISOPROPYL-ERGOPEPTINEInfo
- Publication number
- CA1057285A CA1057285A CA229,783A CA229783A CA1057285A CA 1057285 A CA1057285 A CA 1057285A CA 229783 A CA229783 A CA 229783A CA 1057285 A CA1057285 A CA 1057285A
- Authority
- CA
- Canada
- Prior art keywords
- isopropyl
- formula
- acid
- methyl
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- 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
- C07D457/04—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/02—Ergot alkaloids of the cyclic peptide type
Abstract
6-Nor-6-Isopropyl-9,10-Dihydro-2'.beta.-Methyl Or Ethyl-5'd-Isopropyl-Ergopeptine Abstract of the Disclosure This invention provides new compounds of formula I, I
wherein R1 is alkyl of 2 to 5 carbon atoms, and R2 is methyl or ethyl, useful as anti-migraine agents.
wherein R1 is alkyl of 2 to 5 carbon atoms, and R2 is methyl or ethyl, useful as anti-migraine agents.
Description
~05~285 ..
: The pr~sent invention relates to new hetero~
cyclic compounds. ~ ;
In accordance with the inv2ntion there are provided new compounds of formula I, ~ . ~
: ~2 ~ ~ :
H ~ CO-N}I~ ~ y N -;
l B ~
CH3 \CB
: 5 wherein Rl is alkyl of 2 to 5 carbon atoms~ and ;
R2 is methyl or ethyl.
' . .. . . ' . '.. :
. i . -, . . ~ _ , , .~ :fi.... . ~
.: . '' ~''`'' '' ~: ~urther, in accordance with the invention a compound o~ formula I may be obtained by a process comprising conder.sing a reactive functional derivative ;~
of an acid of formula II, :~
COOI~ ~ ~
"
i,,~ ~ .
,' .'"1; ', ~,,~.". .. .
. , fSff7ff~si
: The pr~sent invention relates to new hetero~
cyclic compounds. ~ ;
In accordance with the inv2ntion there are provided new compounds of formula I, ~ . ~
: ~2 ~ ~ :
H ~ CO-N}I~ ~ y N -;
l B ~
CH3 \CB
: 5 wherein Rl is alkyl of 2 to 5 carbon atoms~ and ;
R2 is methyl or ethyl.
' . .. . . ' . '.. :
. i . -, . . ~ _ , , .~ :fi.... . ~
.: . '' ~''`'' '' ~: ~urther, in accordance with the invention a compound o~ formula I may be obtained by a process comprising conder.sing a reactive functional derivative ;~
of an acid of formula II, :~
COOI~ ~ ~
"
i,,~ ~ .
,' .'"1; ', ~,,~.". .. .
. , fSff7ff~si
- 2 - 100-4192 wherein Rl is as defined above, ~ -with a compound of formula III, . ,- ~`, H2~ ~ ~ III
N~o H~ ~C~
C ~3 \CH
; ~:
wherein R2 is as defined above, in pharmaceutically acceptable acid addition salt form.
Rl preferably is branched, especially in the position to the nitro~en atom to which it is bound. ,~
The reaction of the invention is a condensation ;~
~ :. -reaction for amides. It may be carried out in a manner ; analogous to known methods.
- 10 The condensation i5 effected in an inert ~ ~organic solvent or solvent mixture in the presence of an ,.: ~ : :: . .
acid-bind1ng agent.
i~ ~ For example, the condensation may be Pffected .. . . .
using as reactive functional derivative of an acid of ~ ~
. ~ :
formula II the addition product resulting from the ,, .-. :~
reaction of an acid of formula II with a chlorinating agent and an N-di(lower)alkyl-substituted acid amide of an aliphatic carboxylic acid of 1 to 3 carbon atoms~
:; `~"`,: :f ~-:, .
'. . ', . ., , ' . , :. i, , ..: ; : ' _ 3 ~ 7Z85 l00~4lg2 `~
~ such as dimethyl formamide or dimethyl acetamide. Other . ~
reactive derivatives of an acid of formula II, which may be produced in accordance with known methods, e.g. the ~ ;~
,: . .
acid chloride hydrochloride, the acid azide or mixed ~
: :: - :, .
5 anhydrides of an acid of formula II with sulphuric acid or trifluoroacetic acid, may alternativel~ be used.
Suitable organic solvents are, for example, chloroform, methylene chloride, acetonitrile or dimethyl formamide, and suitable acid-binding agents are ~ ~ ;
tertiary organic bases, e.g. pyridine or homologues thereof. Examples of chlorinating a~ents which may be used are thionyl chloride, phosgene or oxalyl chloride.
, ~ . ,:. ~ , ; The reaction may be effected at a temperature hetween -30 ~nd 0C and at normal pressure ~ ;~
It is convenient to use 1.2 to 204 mols of an . ~ . ~ . . .
acid of formula II for every mol of a compound of~
formula III in salt form. The preferred salt form of .he compounds of formula III is the hydxochloride. The course of the reaction is independent of the sequence ;~ 20 ~ o~ addition of the reagents.
The working up of the reaction mixture and isolation of the compounds of formula I may be effected in known manner.
Acid addltion salt forms may be obtalned in known manner from the free bases and vice versa. ;~
A suitable acid is tartaric acid.
. , ;, ~''~`:
.
~ i7~8~ :
; - 4 - 100-~192 The compounds of formula II, required as start.incr materials, are new and may be obtained ln accordarlce with known methods. For example, a compound -of formula IV, -~
Rl IV
N
wherein Rl is as defined above, may be saponified under mild alkaline conditions, con-, veniently by treatMent with caustic soda solutton in I an organic solvent or solvent mixture, and ~ay then be weakly acid~fied.
,~
The compounds of fo:rmula IV may be obtained by aIk~lation oS 6-nor 9,10-dihydrolysergic acid methyl ester.
; The compounds of formula III are ~nown. ;~
:. ..
.
In the following non-limitative EY.amples all temperatures are indicated in degrees Centi~xade and are ;-~
i uncorrected. Insofar as the production of the starting materials is not described, these are known or may be produced in accordance with known processes or in a manner analogous to kno~m processes.
. ~ ,, .
. '',.'.~ '' ~- :
, ;:
~, , , . ,, .. .,.. , . ., ..................... :
", " , , ~
,. . . .
_ 5 _ lOS7Z85 100-419?.
:~ ' :,',' ,: ' ; . ~
,.,'' ~'','~ '' . ~ . . .
The name of the compounds of formula I is ;~
derived from the basic structure of formula V, .. . ,:
~3 ~ ~ V
:; which is named ergopeptine or the sake of simpliclty.
I " - ~, ~, :~ . -. ;.
:, , , - - -., - - ~ ~ . :, . . . .
- 6 ~ '7~85 100-4192 EXAMPIE 1: 6-nor-6-iso~ropyl~9!lo-dihydro-2'~
5'~-isopropy1-erqo~e~tine .. .
8.6 cc of o~alyl chloride dissolved in 20 cc of acetonitrile are added dropwise, a~ -10 to -15, within 10 minutes to a solution of 300 cc of dimethyl formamide and lSO cc of acetonitrile, and stirring is effected for a further 10 minutes. 32 g of anhydrous 6-nor-6-isopropyl-9,10-dihydrolysergic acid are then sprinkled into the -solution at -20, and stirring is effected at -10 for -~
30 minutes. ~fter cooling to -20, 200 cc of pyridine and 16.3 g of (2R,SS,lOaS,lObS)-2-amino 2-methyl-5-isopropyl- ~
N~o H~ ~C~
C ~3 \CH
; ~:
wherein R2 is as defined above, in pharmaceutically acceptable acid addition salt form.
Rl preferably is branched, especially in the position to the nitro~en atom to which it is bound. ,~
The reaction of the invention is a condensation ;~
~ :. -reaction for amides. It may be carried out in a manner ; analogous to known methods.
- 10 The condensation i5 effected in an inert ~ ~organic solvent or solvent mixture in the presence of an ,.: ~ : :: . .
acid-bind1ng agent.
i~ ~ For example, the condensation may be Pffected .. . . .
using as reactive functional derivative of an acid of ~ ~
. ~ :
formula II the addition product resulting from the ,, .-. :~
reaction of an acid of formula II with a chlorinating agent and an N-di(lower)alkyl-substituted acid amide of an aliphatic carboxylic acid of 1 to 3 carbon atoms~
:; `~"`,: :f ~-:, .
'. . ', . ., , ' . , :. i, , ..: ; : ' _ 3 ~ 7Z85 l00~4lg2 `~
~ such as dimethyl formamide or dimethyl acetamide. Other . ~
reactive derivatives of an acid of formula II, which may be produced in accordance with known methods, e.g. the ~ ;~
,: . .
acid chloride hydrochloride, the acid azide or mixed ~
: :: - :, .
5 anhydrides of an acid of formula II with sulphuric acid or trifluoroacetic acid, may alternativel~ be used.
Suitable organic solvents are, for example, chloroform, methylene chloride, acetonitrile or dimethyl formamide, and suitable acid-binding agents are ~ ~ ;
tertiary organic bases, e.g. pyridine or homologues thereof. Examples of chlorinating a~ents which may be used are thionyl chloride, phosgene or oxalyl chloride.
, ~ . ,:. ~ , ; The reaction may be effected at a temperature hetween -30 ~nd 0C and at normal pressure ~ ;~
It is convenient to use 1.2 to 204 mols of an . ~ . ~ . . .
acid of formula II for every mol of a compound of~
formula III in salt form. The preferred salt form of .he compounds of formula III is the hydxochloride. The course of the reaction is independent of the sequence ;~ 20 ~ o~ addition of the reagents.
The working up of the reaction mixture and isolation of the compounds of formula I may be effected in known manner.
Acid addltion salt forms may be obtalned in known manner from the free bases and vice versa. ;~
A suitable acid is tartaric acid.
. , ;, ~''~`:
.
~ i7~8~ :
; - 4 - 100-~192 The compounds of formula II, required as start.incr materials, are new and may be obtained ln accordarlce with known methods. For example, a compound -of formula IV, -~
Rl IV
N
wherein Rl is as defined above, may be saponified under mild alkaline conditions, con-, veniently by treatMent with caustic soda solutton in I an organic solvent or solvent mixture, and ~ay then be weakly acid~fied.
,~
The compounds of fo:rmula IV may be obtained by aIk~lation oS 6-nor 9,10-dihydrolysergic acid methyl ester.
; The compounds of formula III are ~nown. ;~
:. ..
.
In the following non-limitative EY.amples all temperatures are indicated in degrees Centi~xade and are ;-~
i uncorrected. Insofar as the production of the starting materials is not described, these are known or may be produced in accordance with known processes or in a manner analogous to kno~m processes.
. ~ ,, .
. '',.'.~ '' ~- :
, ;:
~, , , . ,, .. .,.. , . ., ..................... :
", " , , ~
,. . . .
_ 5 _ lOS7Z85 100-419?.
:~ ' :,',' ,: ' ; . ~
,.,'' ~'','~ '' . ~ . . .
The name of the compounds of formula I is ;~
derived from the basic structure of formula V, .. . ,:
~3 ~ ~ V
:; which is named ergopeptine or the sake of simpliclty.
I " - ~, ~, :~ . -. ;.
:, , , - - -., - - ~ ~ . :, . . . .
- 6 ~ '7~85 100-4192 EXAMPIE 1: 6-nor-6-iso~ropyl~9!lo-dihydro-2'~
5'~-isopropy1-erqo~e~tine .. .
8.6 cc of o~alyl chloride dissolved in 20 cc of acetonitrile are added dropwise, a~ -10 to -15, within 10 minutes to a solution of 300 cc of dimethyl formamide and lSO cc of acetonitrile, and stirring is effected for a further 10 minutes. 32 g of anhydrous 6-nor-6-isopropyl-9,10-dihydrolysergic acid are then sprinkled into the -solution at -20, and stirring is effected at -10 for -~
30 minutes. ~fter cooling to -20, 200 cc of pyridine and 16.3 g of (2R,SS,lOaS,lObS)-2-amino 2-methyl-5-isopropyl- ~
3,6-dioxo-lOb-hydroxy-octahydro-8H-oxazolo[3,2-a]pyrrolo- -~ , [2,1-c]pyrazine hydrochloride are added, and stirring is effected at 0 to 2 hours. Working up is effected by add~
ing 100 cc of a buffer solution pH = 4 and distributing the reactlon mixture between methylene chloride and a 2N soda ; solution. The organic phases are washed twice with water, ;
dried with sodium sulphate and evaporated to dryness on a -~
rotary evaporator. After drying in a high vacuum, the 20 resulting crude base is dissolved in about 150 cc of etha- ~' nol and the solution is seeded. The *itle compound has an M.P. of 194 (decomp.)~ r~]D = -32.3 (c = 0.995 in meth- ~;
anol).
' '"''~ ~ .
: , '.. ~:, ', : : ' .,,,: - , . . ,. ' ~ ' :- , . ,:,- .. , ;: ' , " ' "" ' ' ' ` ' "' , . ' . :
~7~8~ :~
_ 7 _ 1~0-4192 Produçtion_of the hydrogen tartrate form.
8.3 g of the ~ase (C31E341N505) are dissolved in 120 cc of etha7l01 at about 50, and 2.22 g of L-tartaric acid dissolved in about 10 cc of ethanol are added. Aftex cooling to room temperature, the salt crystallizes. The pr~cipitated salt is separat~d from the mother liquor, is washed with a small amount of ethanol and is then dxied in a high vacuum at 80.
M.P. 200 (decomp.), [a]D= -1~.4 (c = 1.0 in ethanol). ;~
The 6-nor-6-isopropyl-9,10-dihydrolysergic acid, used as starting material, may, for example, ke -obtained by alkylation of 6-nor-9,10~dihydrolyser~ic acid methyl ester with isopropyl bromide and saponifio- ~ -~
ation of the resulting 6-nor-6-isopropyl-9,10-dihydro~
lysergic acid methyl ester (M.P. 194).
1 6-nor-6~isopropyl 9,10-dihydrolysergic acid -;
I has an M.P. of 290 (decomp.), ~20= -101 (c = 0.6 in methanol).
EXAMPLE 2: 6-nor-6-.isopropyl-9,10-dihydro-2'~
~; 20 ~ ~ et~yl-5'a-isopropyl-ergope~tine . Production in a mannar analogous to that described in Example 1. The title compound has an M.P.
of 176-I78 (decomp.), [a]20- -23 (c = 0.5 in ~`
methylene chloride.
.1 ,, .
,. . ~ ':
: ' . ' :
- :. : , : : ,. ~ : . :
.,,, , , . i ,~
. .
- 8 ~ ~S7~s 100-~192 The compounds exhibit pharmacological activity. In particular, they exhibit vasoconstrictor activity, as indicated by pressor activity indicated in standard tests, e.g. in the pithed rat test S ~Gillespie and Muir, Br.J.Pharmac. 30, 78-87 (1967)]
and in the Mellander-cat test [Angiologica 3, 77-99 --(1966~ by an arterial vasotonic effect.
The compounds are therefore further indicated for use as vasoconstrictor agents possibly for the treatment of migraine. For this use an indicated daily dose is from about 0.1 to about 3 mg, convenient~
ly administered in divided doses 2 to 4 times a day in unit dosage foxm containing from about 0002 to about 1.5 mg, or in sustained release form.
lS ~he compounds of formula I may be administered ;;
ln pharmaceutically acceptable acid additLon salt form. `~
The present 1nven~lon also`provides a pharmaceut~cal compositlon comprlslng a compound of formula I, ln free base form or in pharmaceutically acceptable acid addition salt ~orm, in association with a pharmaceutical carrier or diluent. Such compositions may ~e formulated in conventional manner so as to be, for example, a solution or a tablet. ;~;
... , , .. ~ .~:
In a pre~erred group of compounds Rl ~s isopropyl and esp~cially R2 is methyl.
.. ,.. , :
ing 100 cc of a buffer solution pH = 4 and distributing the reactlon mixture between methylene chloride and a 2N soda ; solution. The organic phases are washed twice with water, ;
dried with sodium sulphate and evaporated to dryness on a -~
rotary evaporator. After drying in a high vacuum, the 20 resulting crude base is dissolved in about 150 cc of etha- ~' nol and the solution is seeded. The *itle compound has an M.P. of 194 (decomp.)~ r~]D = -32.3 (c = 0.995 in meth- ~;
anol).
' '"''~ ~ .
: , '.. ~:, ', : : ' .,,,: - , . . ,. ' ~ ' :- , . ,:,- .. , ;: ' , " ' "" ' ' ' ` ' "' , . ' . :
~7~8~ :~
_ 7 _ 1~0-4192 Produçtion_of the hydrogen tartrate form.
8.3 g of the ~ase (C31E341N505) are dissolved in 120 cc of etha7l01 at about 50, and 2.22 g of L-tartaric acid dissolved in about 10 cc of ethanol are added. Aftex cooling to room temperature, the salt crystallizes. The pr~cipitated salt is separat~d from the mother liquor, is washed with a small amount of ethanol and is then dxied in a high vacuum at 80.
M.P. 200 (decomp.), [a]D= -1~.4 (c = 1.0 in ethanol). ;~
The 6-nor-6-isopropyl-9,10-dihydrolysergic acid, used as starting material, may, for example, ke -obtained by alkylation of 6-nor-9,10~dihydrolyser~ic acid methyl ester with isopropyl bromide and saponifio- ~ -~
ation of the resulting 6-nor-6-isopropyl-9,10-dihydro~
lysergic acid methyl ester (M.P. 194).
1 6-nor-6~isopropyl 9,10-dihydrolysergic acid -;
I has an M.P. of 290 (decomp.), ~20= -101 (c = 0.6 in methanol).
EXAMPLE 2: 6-nor-6-.isopropyl-9,10-dihydro-2'~
~; 20 ~ ~ et~yl-5'a-isopropyl-ergope~tine . Production in a mannar analogous to that described in Example 1. The title compound has an M.P.
of 176-I78 (decomp.), [a]20- -23 (c = 0.5 in ~`
methylene chloride.
.1 ,, .
,. . ~ ':
: ' . ' :
- :. : , : : ,. ~ : . :
.,,, , , . i ,~
. .
- 8 ~ ~S7~s 100-~192 The compounds exhibit pharmacological activity. In particular, they exhibit vasoconstrictor activity, as indicated by pressor activity indicated in standard tests, e.g. in the pithed rat test S ~Gillespie and Muir, Br.J.Pharmac. 30, 78-87 (1967)]
and in the Mellander-cat test [Angiologica 3, 77-99 --(1966~ by an arterial vasotonic effect.
The compounds are therefore further indicated for use as vasoconstrictor agents possibly for the treatment of migraine. For this use an indicated daily dose is from about 0.1 to about 3 mg, convenient~
ly administered in divided doses 2 to 4 times a day in unit dosage foxm containing from about 0002 to about 1.5 mg, or in sustained release form.
lS ~he compounds of formula I may be administered ;;
ln pharmaceutically acceptable acid additLon salt form. `~
The present 1nven~lon also`provides a pharmaceut~cal compositlon comprlslng a compound of formula I, ln free base form or in pharmaceutically acceptable acid addition salt ~orm, in association with a pharmaceutical carrier or diluent. Such compositions may ~e formulated in conventional manner so as to be, for example, a solution or a tablet. ;~;
... , , .. ~ .~:
In a pre~erred group of compounds Rl ~s isopropyl and esp~cially R2 is methyl.
.. ,.. , :
Claims (6)
1. A process for the production of a compound of formula I, I
wherein R1 is alkyl of 2 to 5 carbon atoms, and R2 is methyl or ethyl, comprising condensing a reactive functional derivative of an acid of formula II, II
wherein R1 is as defined above, with a compound of formula III, III
wherein R2 is as defined above, in pharmaceutically acceptable acid addition salt form.
wherein R1 is alkyl of 2 to 5 carbon atoms, and R2 is methyl or ethyl, comprising condensing a reactive functional derivative of an acid of formula II, II
wherein R1 is as defined above, with a compound of formula III, III
wherein R2 is as defined above, in pharmaceutically acceptable acid addition salt form.
2. A compound of formula I, as defined in Claim 1, whenever produced by the process of Claim 1.
3. A process for the production of a compound of formula I, as defined in Claim 1, wherein R1 is iso-propyl and R2 is methyl, comprising condensing a reactive functional derivative of an acid of formula II, as defined in Claim 1, wherein R1 is isopropyl, with a compound of formula III, as defined in Claim 1, wherein R2 is methyl.
4. 6-Nor-6-isopropyl-9,10-dihydro-2'.beta.-methyl-5'.alpha.-isopropyl-ergopeptine whenever produced by the process of Claim 3.
5. A process for the production of a compound of formula I, as defined in Claim 1, wherein R1 is isopropyl and R2 is ethyl, comprising condensing a reactive functional derivative of an acid of formula II, as defined in Claim 1, wherein R1 is isopropyl, with a compound of formula III, as defined in Claim 1, wherein R2 is ethyl.
6. 6-Nor-6-isopropyl-9,10-dihydro-2'.beta.-ethyl-5'.alpha.-isopropyl-ergopeptine whenever produced by the process of Claim 5,
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH853374A CH602767A5 (en) | 1974-06-21 | 1974-06-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1057285A true CA1057285A (en) | 1979-06-26 |
Family
ID=4341635
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA229,783A Expired CA1057285A (en) | 1974-06-21 | 1975-06-20 | 6-NOR-6-ISOPROPYL-9,10-DIHYDRO-2'.beta.-METHYL OR ETHYL-5'.alpha.-ISOPROPYL-ERGOPEPTINE |
Country Status (21)
| Country | Link |
|---|---|
| JP (1) | JPS5113798A (en) |
| AT (1) | AT356292B (en) |
| AU (1) | AU503060B2 (en) |
| BE (1) | BE830441A (en) |
| CA (1) | CA1057285A (en) |
| DD (1) | DD118088A5 (en) |
| DE (1) | DE2525962A1 (en) |
| DK (1) | DK140670B (en) |
| ES (1) | ES438704A1 (en) |
| FI (1) | FI751753A (en) |
| FR (1) | FR2275212A1 (en) |
| GB (1) | GB1499420A (en) |
| HU (1) | HU169390B (en) |
| IE (1) | IE41564B1 (en) |
| IL (1) | IL47522A (en) |
| NL (1) | NL7507177A (en) |
| NO (1) | NO752109L (en) |
| PH (1) | PH13361A (en) |
| SE (1) | SE7506758L (en) |
| YU (1) | YU157375A (en) |
| ZA (1) | ZA753967B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH601321A5 (en) * | 1975-01-06 | 1978-07-14 | Sandoz Ag | |
| CH619468A5 (en) * | 1976-01-12 | 1980-09-30 | Sandoz Ag | |
| GB0409785D0 (en) | 2004-04-30 | 2004-06-09 | Resolution Chemicals Ltd | Preparation of cabergoline |
| US7339060B2 (en) | 2005-03-23 | 2008-03-04 | Resolution Chemicals, Ltd. | Preparation of cabergoline |
| GB0505965D0 (en) | 2005-03-23 | 2005-04-27 | Resolution Chemicals Ltd | Preparation of cabergoline |
-
1975
- 1975-06-11 DE DE19752525962 patent/DE2525962A1/en not_active Withdrawn
- 1975-06-12 SE SE7506758A patent/SE7506758L/en unknown
- 1975-06-12 DK DK266475AA patent/DK140670B/en unknown
- 1975-06-12 FI FI751753A patent/FI751753A/fi unknown
- 1975-06-13 NO NO752109A patent/NO752109L/no unknown
- 1975-06-16 GB GB25527/75A patent/GB1499420A/en not_active Expired
- 1975-06-17 FR FR7518879A patent/FR2275212A1/en active Granted
- 1975-06-17 PH PH17276A patent/PH13361A/en unknown
- 1975-06-17 NL NL7507177A patent/NL7507177A/en not_active Application Discontinuation
- 1975-06-19 DD DD186767A patent/DD118088A5/xx unknown
- 1975-06-19 AU AU82273/75A patent/AU503060B2/en not_active Expired
- 1975-06-19 YU YU01573/75A patent/YU157375A/en unknown
- 1975-06-19 IE IE1375/75A patent/IE41564B1/en unknown
- 1975-06-19 IL IL47522A patent/IL47522A/en unknown
- 1975-06-19 HU HUSA2806A patent/HU169390B/hu unknown
- 1975-06-19 BE BE157509A patent/BE830441A/en unknown
- 1975-06-19 ES ES438704A patent/ES438704A1/en not_active Expired
- 1975-06-20 JP JP50074583A patent/JPS5113798A/ja active Pending
- 1975-06-20 ZA ZA3967A patent/ZA753967B/en unknown
- 1975-06-20 AT AT473575A patent/AT356292B/en not_active IP Right Cessation
- 1975-06-20 CA CA229,783A patent/CA1057285A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2275212B1 (en) | 1979-08-10 |
| DK266475A (en) | 1975-12-22 |
| AU8227375A (en) | 1976-12-23 |
| YU157375A (en) | 1982-05-31 |
| JPS5113798A (en) | 1976-02-03 |
| FI751753A (en) | 1975-12-22 |
| ATA473575A (en) | 1979-09-15 |
| DK140670B (en) | 1979-10-22 |
| PH13361A (en) | 1980-03-20 |
| DE2525962A1 (en) | 1976-01-08 |
| HU169390B (en) | 1976-11-28 |
| ZA753967B (en) | 1977-01-26 |
| FR2275212A1 (en) | 1976-01-16 |
| IL47522A0 (en) | 1975-08-31 |
| DD118088A5 (en) | 1976-02-12 |
| AT356292B (en) | 1980-04-25 |
| IE41564B1 (en) | 1980-01-30 |
| IL47522A (en) | 1977-12-30 |
| SE7506758L (en) | 1975-12-22 |
| NO752109L (en) | 1975-12-23 |
| ES438704A1 (en) | 1977-06-01 |
| DK140670C (en) | 1980-03-17 |
| IE41564L (en) | 1975-12-21 |
| AU503060B2 (en) | 1979-08-23 |
| GB1499420A (en) | 1978-02-01 |
| NL7507177A (en) | 1975-12-23 |
| BE830441A (en) | 1975-12-19 |
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