Indolyl compounds for treating migraine

• US 5,466,699 A
• Filed: 12/05/1994
• Issued: 11/14/1995
• Est. Priority Date: 06/07/1990
• Status: Expired due to Term

• Current Assignee: Astrazeneca UK Limited (Astrazeneca PLC)
• Original Assignee: Burroughs Wellcome and Co.
• Inventors: Robertson, Alan D., Glen, Robert C., Hill, Alan P., Martin, Graeme R.
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US08/341,206
• Time in Patent Office: 344 Days
• Field of Search: 546/201, 548/229, 548/181, 548/312.1, 548/504, 514/323, 514/369, 514/389, 514/397, 514/414
• US Class Current: 514/323
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

##STR1## The present invention is concerned with compounds of formula (I), wherein n is an integer of from 0 to 3: W is a group of formula (i), (ii), or (iii), wherein R is hydrogen or C_1-4 alkyl, X is --O--, --S--, --NH--, or --CH₂ --, Y is oxygen or sulphur and the chiral center (*) in formula (i) or (ii) is in its (S) or (R) form or is a mixture thereof in any proportions: and Z is a group of formula (iv), (v), or (vi), wherein R¹ and R² are independently selected from hydrogen and C_1-4 alkyl and R³ is hydrogen or C_1-4 alkyl; and their salts, solvates and physiologically functional derivatives, with processes for their preparation, with medicaments containing them and with their use as therapeutic agents, particularly in the prophylaxis and treatment of migraine.

Claims

1. A compound of formula (I) ##STR37## wherein n is an integer of from 0 to 3;

W is a group of formula (i), (ii), or (iii) ##STR38## wherein R is hydrogen or C_1-4 alkyl, X is --O--, --S--, --NH--, or --CH₂ --, Y is oxygen or sulphur and the chiral center * in formula (i) or (ii) is in its (S) or (R) form or is a mixture thereof in any proportions; and

Z is a group of formula (iv) or (vi) ##STR39## wherein R¹ and R² are independently selected from hydrogen and C_1-4 alkyl and R³ is hydrogen or C_1-4 alkyl;

or a physiologically acceptable salt or solvate thereof.

2. A compound of formula (I) according to claim 1, wherein n is 1 or W is a group of formula (i).

3. A compound of formula (I) according to claim 1 wherein n is 1, W is a group of formula (i) wherein R is hydrogen, X is --O-- and Y is oxygen, and Z is a group of formula (iv) or (vi) wherein R¹ =R² =hydrogen or methyl.

4. A compound of formula (I) as claimed in claim 1, which compound is N,N-dimethyl-2-[5-2-oxo-1,3-oxazolidin-4-ylmethyl)-1H-indole -3-yl]ethylamine or 3-(1-methyl-4-piperidyl)-5-(2-oxo-1,3-oxazolidin-4-ylmethyl) 1-H-indole in either its (S) or (R) form or as a mixture thereof in any proportions.

5. A method of treating or preventing migraine comprising administering to a patient in need of same an effective amount of a compound of claim 1.

6. A pharmaceutical composition comprising an effective amount of a compound of formula (I) as claimed in claim 1 with a pharmaceutically acceptable carrier.

7. The pharmaceutical composition of claim 6 which is in the form of a tablet or capsule.

8. The compound (S)-N,N-dimethyl-2-[5-(2-oxo-1,3-oxazolidin -4-ylmethyl)-1H-indole-3-yl]ethylamine or a pharmacologically acceptable salt or solvate thereof.

9. A method of treating or preventing migraine comprising administering to a patient in need of same an effective amount of a compound of claim 8.

10. A pharmaceutical composition comprising an effective amount of a compound of claim 8 with a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 which is in the form of a tablet or capsule.