IE41428B1 - 6-methyl-8 -n,n-dimethyl sulphamoylaminoergoline i - Google Patents
6-methyl-8 -n,n-dimethyl sulphamoylaminoergoline iInfo
- Publication number
- IE41428B1 IE41428B1 IE2048/78A IE204878A IE41428B1 IE 41428 B1 IE41428 B1 IE 41428B1 IE 2048/78 A IE2048/78 A IE 2048/78A IE 204878 A IE204878 A IE 204878A IE 41428 B1 IE41428 B1 IE 41428B1
- Authority
- IE
- Ireland
- Prior art keywords
- compound
- formula
- methyl
- addition salt
- acid addition
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 150000003839 salts Chemical group 0.000 claims description 6
- 239000012458 free base Substances 0.000 claims description 5
- JHWDWUPYEQIICX-UFGOTCBOSA-N (6ar,9s,10ar)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-amine Chemical compound C1=CC([C@@H]2[C@H](NC[C@H](C2)N)C2)=C3C2=CNC3=C1 JHWDWUPYEQIICX-UFGOTCBOSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000003946 Prolactin Human genes 0.000 description 2
- 108010057464 Prolactin Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229940097325 prolactin Drugs 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- JHWDWUPYEQIICX-HRBVQNPCSA-N (6ar,10ar)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-amine Chemical compound C1=CC([C@@H]2[C@H](NCC(C2)N)C2)=C3C2=CNC3=C1 JHWDWUPYEQIICX-HRBVQNPCSA-N 0.000 description 1
- KGUBZNRUCSWDAU-ZKYQVNSYSA-N (6ar,9s,10ar)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-amine Chemical compound C1=CC([C@H]2C[C@H](N)CN([C@@H]2C2)C)=C3C2=CNC3=C1 KGUBZNRUCSWDAU-ZKYQVNSYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000011121 vaginal smear Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
6-tnathyl-8c(-N ,N-dimethylsulDhamoylaninoergoline I This invention relates to 6-methyl-8a-N,Ndimethylsulphamoyl aminoergoline i of formula I The compound may be obtained by acylating 6-methyl5 8a-aminoergoline i'with a reactive functional derivative of an acid of formula (CH3)2.N SOjH.
The process may be carried out in conventional manner for such acylations. A suitable reactive functional derivative is the chloride or bromide. The process may be effected as follows (all temperatures are in degrees Centigrade and are uncorrected): 2,41 g (10 millimols) of 6-methyl-8a-aminoergoline I are dissolved in a mixture of 200 cc of .· methylene chloride and 25 cc of absolute pyridine, and a solution of 3.58 g (25 millimols) of dimethyl15 sulphamyl chloride in 25 cc of methylene chloride is added dropwise with stirring at room temperature.
After stirring for 12 hours, the reaction solution is poured into an excess of a .2 normal sodium carbonate solution,the - 2 414 3 8 precipitate is filtered off, dried in the air and subsequently chromatographed on silicagel. The title compound is eluted with 2% of methanol in methylene chloride. M.P. 223-226° C from ethanol; yellowish needles. [«]2°= -51.6° (c = 0.5 in pyridine).
Acid addition salt forms of the compound of formula I may be obtained in conventional manner from the free base form, and vice versa.
The compound of formula I exhibits pharmacolo10 gical activity. In particular, the compound exhibits prolactin secretion inhibition activity as indicated in standard tests, for example, in rats by an inhibition of ovum implantion as follows: The compound under investigation is administered 15 to female rats 5 days after coitus and shown to be sperm positive according to the vaginal smear test. The rats are sacrificed on day 12 and their uteri are examined by means of the Salewski reaction for proof that the nidation process has been interrupted (Arch.exp.Path.
Pharm. 247, 367 (1967)].
The compound is, therefore, indicated for use as an prolactin secretion inhibitor agent. For this use an indicated daily dose is frcm 0.05 mg to 10 mg, conveniently administered in divided --344428 doses 2 to 4 times a day in unit dosage form containing from 0.01 to 5 mg, or in sustained release form.
The compound of formula I may be administered 5 in pharmaceutically acceptable acid addition salt form. Such acid addition salt forms exhibit the same order of activity as the free base form and are readily prepared in conventional manner. The present invention also provides a pharmaceutical composition comprising a compound of formula X, in free base form or In pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent. Such compositions may be formulated in conventional manner, so as to be, for example, a solution or a tablet.
Claims (5)
1. A process for tne production of a compound of formula I, which comprises acylating 6-methyl~8a-aminoergoline I 5 with a reactive functional derivative of an acid of formula (CH 3 ) 2 NSO 3 H.
2. A process for the production of a compound of formula X, as stated in claim 1, substantially as hereinbefore describted with reference to 10 the Example.
3. A compound of formula I, whenever produced by a process according to claim 1 or 2,
4. A compound of formula I, as defined in claim 1. 15 5. A compound according to claims 3 or 4 in free base form. - 5 4442© 6. A compound according to claim 3 or 4 in acid addition salt form. 7. A pharmaceutical composition comprising a compound according to claim 3 or 4 in free base
5. Form or in pharmaceutically acceptable acid addition salt form in association with a pharmaceutical carrier or diluent.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH998374A CH605936A5 (en) | 1974-07-19 | 1974-07-19 | 8-Alpha-(Amino-or cyanomethyl)-ergoline derivs |
| CH1103174A CH605938A5 (en) | 1974-08-13 | 1974-08-13 | 8-Alpha-(Amino-or cyanomethyl)-ergoline derivs |
| IE1596/75A IE41426B1 (en) | 1974-07-19 | 1975-07-17 | 8 -substituted ergoline i derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE41428L IE41428L (en) | 1976-01-19 |
| IE41428B1 true IE41428B1 (en) | 1980-01-02 |
Family
ID=27176349
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2048/78A IE41428B1 (en) | 1974-07-19 | 1975-07-17 | 6-methyl-8 -n,n-dimethyl sulphamoylaminoergoline i |
| IE2047/78A IE41427B1 (en) | 1974-07-19 | 1975-07-17 | 6-methyl-8 -cyanomethylergoline i |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2047/78A IE41427B1 (en) | 1974-07-19 | 1975-07-17 | 6-methyl-8 -cyanomethylergoline i |
Country Status (1)
| Country | Link |
|---|---|
| IE (2) | IE41428B1 (en) |
-
1975
- 1975-07-17 IE IE2048/78A patent/IE41428B1/en unknown
- 1975-07-17 IE IE2047/78A patent/IE41427B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE41428L (en) | 1976-01-19 |
| IE41427B1 (en) | 1980-01-02 |
| IE41427L (en) | 1976-01-19 |
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