Claims
- 1. A process for the preparation of a compound of formula (I)
- 2. A process according to claim 1 comprising:
reacting a compound of formula (II) 25wherein A is as defined above, L is a leaving group selected from alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, nitro or halogen and Q is halogen, with a compound of formula (III) 26wherein X is NR2R3, wherein R2 and R3 are defined above, or a suitable salt thereof, in the presence of a base in solvent 1, to form a compound of formula (IV) 27wherein A, L and X are as defined above, and cyclizing the compound of formula (IV) in solvent 2, optionally in the presence of a base, and optionally by treatment with a metal catalyst, to form a compound of formula (I).
- 3. A process according to claim 1 comprising:
reacting a compound of formula (II) 28wherein A is as defined above, L is a leaving group selected from alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, nitro or halogen and Q is halogen, with a compound of formula (III), 29wherein X is SR1, S(═O)R1 or S(═O)2R1, wherein R1 is defined above, or a suitable salt thereof, in the presence of a base in solvent 1, to form a compound of formula (IV) 30wherein A, L and X are as defined above, and cyclizing the compound of formula (IV) in solvent 2, optionally in the presence of a base and, optionally by treatment with a metal catalyst, to form a compound of formula (I).
- 4. A process according to claim 1 comprising:
reacting a compound of formula (II) 31wherein A is as defined above, L is a leaving group selected from alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, nitro or halogen and Q is halogen, with a compound of formula (III), 32wherein X is OR1, wherein R1 is defined above, or a suitable salt thereof, in the presence of a base in solvent 1, to form a compound of formula (IV) 33wherein A, L and X are as defined above, and cyclizing the compound of formula (IV) in solvent 2, optionally in the presence of a base and, optionally by treatment with a metal catalyst, to form a compound of formula (I).
- 5. A process according to claim 1 comprising:
transforming a compound of formula (IV) into a compound of formula (IV′) 34wherein A, L and X are as defined above, and X is transformed into X′, wherein X′ is selected from the groups defined for X, with the proviso that X′≠X, and cyclizing the compound of formula (IV′) in solvent 2, optionally in the presence of a base and, optionally by treatment with a metal catalyst, to form a compound of formula (I).
- 6. A process according to claim 1 comprising:
transforming a compound of formula (IV) 35wherein A, and L are as defined above and X is SR1, S(═O)R1 or S(═O)2R1, wherein R1 is defined above, into a compound of formula (V) 36wherein A, L and R2 and R3 are as defined above, and cyclizing the compound of formula (V) in solvent 2, optionally in the presence of a base and, optionally by treatment with a metal catalyst, to form a compound of formula (I).
- 7. A process according to claim 1, wherein the process further comprises cyclizing the compound of formula (IV) in solvent 2 in the presence of a base.
- 8. A process according to claim 1, wherein the process further comprises cyclizing the compound of formula (IV) in solvent 2 in the presence of a base and by treatment with a metal catalyst.
- 9. A process according to claim 1, wherein the process further comprises cyclizing the compound of formula (IV) in solvent 2 in the presence of a base and without a metal catalyst.
- 10. A process according claim 1, wherein the process further comprises cyclizing the compound of formula (IV) in solvent 2 without the presence of a base.
- 11. A process according to claim 1, wherein the process further comprises cyclizing the compound of formula (IV) in solvent 2 by treatment with a metal catalyst without the presence of a base.
- 12. A process according to claim 1, wherein the process further comprises cyclizing the compound of formula (IV) in solvent 2 without the presence of a base and without a metal catalyst.
- 13. A process according to claim 1, wherein the process further comprises transforming a compound of formula (I), prepared as described above, by oxidation or substitution or both, to form another compound of formula (I).
- 14. A process according to claim 1, wherein the base is selected from sodium hydroxide, potassium carbonate, cesium carbonate or potassium hydroxide.
- 15. A process according to claim 1, wherein solvent 1 is selected from diethyl ether, acetone, toluene or t-butyl-methyl ether.
- 16. A process according to claim 1, wherein solvent 2 is selected from N,N-dimethylformamide, toluene, xylene, 1-butanol, N-methyl-2-pyrrolidinone, sulfolane, dimethylsulfoxide, DMPU or water.
- 17. A process according to claim 1, wherein the metal catalyst is selected from copper bronze, copper oxide, copper chloride, copper bromide or copper iodide.
- 18. A compound selected from the group consisting of:
3-Amino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; 7-Bromo-6-chloro-3-propylaminothieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; 7-Bromo-3-(sec-butylamino)-6-chloro-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; 7-Bromo-6-chloro-3-cyclobutylamino-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Chloro-3-methylsulfanyl-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; or 6-Chloro-3-methylsulfinyl-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide+ obtained by a process according to claim 1.
- 19. A compound selected from the group consisting of:
6-Bromo-3-methylsulfanyl-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Bromo-3-methylsulfinyl-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; 3-Amino-6-bromo-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Chloro-3-ethylamino-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Chloro-3-propylamino-4H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide; 3-Isopropylamino-6-methyl-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; 6-Methyl-3-propylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide; or 3-sec-Butylamino-6-methyl-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide obtained by a process according to claim 1.
- 20. A pharmaceutical composition for the treatment or prophylaxis of Type I or Type II diabetes comprising a compound according to claim 18 and a pharmaceutically acceptable carrier.
- 21. A pharmaceutical composition for the treatment or prophylaxis of Type I or Type II diabetes comprising a compound according to claim 19 and a pharmaceutically acceptable carrier.
- 22. A method of treating Type I or Type II diabetes which comprises administering an effective or prophylactic amount of a compound according to claim 18 to a person suffering from Type I or Type II diabetes.
- 23. A method of treating Type I or Type II diabetes which comprises administering an effective or prophylactic amount of a compound according to claim 19 to a person suffering from Type I or Type II diabetes.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PA 1999 00938 |
Jun 1999 |
DK |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of PCT/DK00/00343 filed on Jun. 26, 2000, which claims priority under 35 U.S.C. 119 of Danish application no. PA 1999 00938 filed on Jun. 30, 1999, and U.S. provisional application No. 60/142,759 filed on Jul. 8, 1999, the contents of which are fully incorporated herein by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60142759 |
Jul 1999 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/DK00/00343 |
Jun 2000 |
US |
Child |
09924350 |
Aug 2001 |
US |