.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 5,436,242

« Back to Dashboard

Details for Patent: 5,436,242

Title: Tetrahydrothienopyridine derivatives, furo and pyrrolo analogs thereof for inhibiting blood platelet aggregation
Abstract:Compounds of formula (I): ##STR1## wherein R.sup.1 is hydrogen, alkyl, halogen, haloalkyl, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkanoyl, haloalkanoyl, carboxy, alkoxycarbonyl, carbamoyl, cyano, nitro, alkanesulfonyl, haloalkanesulfonyl or sulfamoyl; R.sup.2 is 5,6-dihydro-1,4,2-dioxazin-3-yl; R.sup.3 is hydrogen, hydroxy, optionally substituted alkoxy, aralkyloxy, alkanoyloxy, alkenoyloxy, cycloalkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aralkyloxycarbonylxy, phthalidyloxy, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy, (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy, optionally substituted amino or nitro; Y is --NH-- or oxygen or sulfur; n is 1 to 5; and tautomers and salts of said compounds of formula (I), have the ability to inhibit blood platelet aggregation, and can thus be used for treatment and prophylaxis of thrombosis and embolisms.
Inventor(s): Koike; Hiroyuki (Tokyo, JP), Asai; Fumitoshi (Tokyo, JP), Sugidachi; Atsuhiro (Tokyo, JP), Kimura; Tomio (Ube, JP), Inoue; Teruhiko (Ube, JP), Nishino; Shigeyoshi (Ube, JP), Tsuzaki; Yasunori (Ube, JP)
Assignee: Sankyo Company, Limited (Tokyo, JP) Ube Industries Limited (Ube, JP)
Filing Date:Dec 01, 1993
Application Number:08/161,046
Claims:1. A compound of formula (I): ##STR11## wherein: R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a halogen atom, a haloalkyl group having from 1 to 4 carbon atoms and at least one halogen atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, a haloalkoxy group having from 1 to 4 carbon atoms and at least one halogen atom, an alkylthio group having from 1 to 4 carbon atoms, a haloalkylthio group having from 1 to 4 carbon atoms and at least one halogen atom, an amino group, an alkanoyl group having from 1 to 5 carbon atoms, a haloalkanoyl group having from 2 to 5 carbon atoms and at least one halogen atom, a carboxy group, an alkoxycarbonyl group having from 2 to 5 carbon atoms, a carbamoyl group, a cyano group, a nitro group, an alkanesulfonyl group having from 1 to 4 carbon atoms, a haloalkanesulfonyl group having from 1 to 4 carbon atoms and at least one halogen atom, or a sulfamoyl group;

R.sup.2 represents a 5,6-dihydro-1,4,2-dioxazin-3-yl group; and

Y represents a group of formula --NH--, sulfur or oxygen;

R.sup.3 represents a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, a substituted alkoxy group which has from 1 to 4 carbon atoms and which is substituted by at least one substituent selected from the group consisting of substituents C, defined below, an aralkyloxy group in which the aralkyl part is as defined below, an alkanoyloxy group having from 1 to 18 carbon atoms, an alkenoyloxy group having from 3 to 6 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 8 carbon atoms, an arylcarbonyloxy group in which the aryl part is as defined below, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, an aralkyloxycarbonyloxy group in which the aralkyl part is as defined below, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a group of formula --NR.sup.a R.sup.b

wherein R.sup.a and R.sup.b are independently selected from the group consisting of hydrogen atoms, alkyl groups having from 1 to 4 carbon atoms and substituted alkyl groups which have from 1 to 4 carbon atoms and which are substituted by at least one substituent selected from the group consisting of substituents C, defined below,

an aralkylamino group in which the aralkyl part is as defined below, an alkanoylamino group having from 1 to 18 carbon atoms, an alkenoylamino group having from 3 to 6 carbon atoms, a cycloalkylcarbonylamino group having from 4 to 8 carbon atoms, an arylcarbonylamino group in which the aryl part is as defined below, an alkoxycarbonylamino group having from 2 to 5 carbon atoms, an aralkyloxycarbonylamino group in which the aralkyl part is as defined below, a phthalidylamino group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methylamino group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methylamino group or a nitro group; and

n is an integer from 1 to 5, and, when n is an integer from 2 to 5, the groups represented by R.sup.1 may be the same as or different from each other;

said substituents C are selected from the group consisting of alkoxy groups having from 1 to 4 carbon atoms, alkanoyloxy groups having from 1 to 6 carbon atoms and arylcarbonyloxy groups in which the aryl part is as defined below;

said aralkyl parts of said aralkyloxy, aralkyloxycarbonyloxy, aralkylamino and aralkyloxycarbonylamino groups are alkyl groups which have from 1 to 4 carbon atoms and which are substituted by at least one aryl group as defined below;

said aryl groups and said aryl parts of said arylcarbonyloxy groups and of said arylcarbonylamino groups have from 6 to 10 carbon atoms in a carbocyclic ring which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below; and

said substituents D are selected from the group consisting of the groups and atoms defined above for R.sup.1, other than said hydrogen atom;

or a tautomer thereof, or a pharmaceutically acceptable salt of said compound of formula (I) and of said tautomer.

2. The compound of claim 1, wherein said tautomer has the formula (Ia) or (Ib): ##STR12## wherein R.sup.1, R.sup.2, Y and n are as defined above and Z represents group of formula .dbd.NH or an oxygen atom.

3. The compound of claim 1, wherein R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a halogen atom, a fluoroalkyl group having from 1 to 4 carbon atoms and at least one fluorine atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, a fluoroalkoxy group having from 1 to 4 carbon atoms and at least one fluorine atom, an alkylthio group having from 1 to 4 carbon atoms, a fluoroalkylthio group having from 1 to 4 carbon atoms and at least one fluorine atom, an amino group, an alkanoyl group having from 1 to 5 carbon atoms, a fluoroalkanoyl group having from 2 to 5 carbon atoms and at least one fluorine atom, an alkoxycarbonyl group having from 2 to 5 carbon atoms, a carbamoyl group, a cyano group, a nitro group, an alkanesulfonyl group having from 1 to 4 carbon atoms, a fluoroalkanesulfonyl group having from 1 to 4 carbon atoms and at least one fluorine atom, or a sulfamoyl group.

4. The compound of claim 1, wherein R.sup.3 represents a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, an alkoxymethoxy group in which the alkoxy part has from 1 to 4 carbon atoms, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkanoyloxy group having from 1 to 18 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a group of formula --NR.sup.a R.sup.b

wherein R.sup.a and R.sup.b are independently selected from the group consisting of hydrogen atoms, methyl and ethyl groups or R.sup.a represents a hydrogen atom and R.sup.b represents an alkanoyloxymethyl group in which the alkanoyl part has from 1 to 5 carbon atoms,

a benzylamino group, an alkanoylamino group having from 1 to 18 carbon atoms, an alkenoylamino group having 3 or 4 carbon atoms, a cycloalkylcarbonylamino group having 6 or 7 carbon atoms, a benzoylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonylamino group having from 2 to 5 carbon atoms or a benzyloxycarbonylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below; and

said substituents D are selected from the group consisting of fluorine atoms, chlorine atoms, methyl groups and methoxy groups.

5. The compound of claim 1, wherein Y represents an oxygen atom.

6. The compound of claim 1, wherein:

R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a halogen atom, a fluoroalkyl group having from 1 to 4 carbon atoms and at least one fluorine atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, a fluoroalkoxy group having from 1 to 4 carbon atoms and at least one fluorine atom, an alkylthio group having from 1 to 4 carbon atoms, a fluoroalkylthio group having from 1 to 4 carbon atoms and at least one fluorine atom, an amino group, an alkanoyl group having from 1 to 5 carbon atoms, a fluoroalkanoyl group having from 2 to 5 carbon atoms and at least one fluorine atom, an alkoxycarbonyl group having from 2 to 5 carbon atoms, a carbamoyl group, a cyano group, a nitro group, an alkanesulfonyl group having from 1 to 4 carbon atoms, a fluoroalkanesulfonyl group having from 1 to 4 carbon atoms and at least one fluorine atom, or a sulfamoyl group;

R.sup.3 represents a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, an alkoxymethoxy group in which the alkoxy part has from 1 to 4 carbon atoms, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkanoyloxy group having from 1 to 18 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a group of formula --NR.sup.a R.sup.b

wherein R.sup.a and R.sup.b are independently selected from the group consisting of hydrogen atoms, methyl groups and ethyl groups or R.sup.a represents a hydrogen atom and R.sup.b represents an alkanoyloxymethyl group in which the alkanoyl part has from 1 to 5 carbon atoms,

a benzylamino group, an alkanoylamino group having from 1 to 18 carbon atoms, an alkenoylamino group having 3 or 4 carbon atoms, a cycloalkylcarbonylamino group having 6 or 7 carbon atoms, a benzoylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonylamino group having from 2 to 5 carbon atoms or a benzyloxycarbonylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below;

Y represents an oxygen or sulfur atom;

said substituents D are selected from the group consisting of fluorine atoms, chlorine atoms, methyl groups and methoxy groups.

7. The compound of claim 6, wherein n is from 1 to 3.

8. The compound of claim 6, wherein n is 1.

9. The compound of claim 1, wherein R.sup.1 represents a hydrogen atom, a methyl group, an ethyl group, a halogen atom, a methyl group substituted by at least one fluorine atom, a hydroxy group, a methoxy group, an ethoxy group, a methoxy group substituted by at least one fluorine atom, a methylthio group, a methylthio group substituted by at least one fluorine atom, a formyl group, an acetyl group, an acetyl group substituted by at least one fluorine atom, an alkoxycarbonyl group having from 2 to 4 carbon atoms, a carbamoyl group, a cyano group, a nitro group, a methanesulfonyl group, an ethanesulfonyl group, a methanesulfonyl group substituted by at least one fluorine atom, or a sulfamoyl group.

10. The compound of claim 1, wherein R.sup.3 represents a hydrogen atom, a hydroxy group, a methoxy group, an ethoxy group, a t-butoxy group, a methoxymethoxy group, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group, an alkanoyloxy group having from 1 to 12 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, an amino group or a t-butoxycarbonylamino group.

11. The compound of claim 1, wherein:

R.sup.1 represents a hydrogen atom, a methyl group, an ethyl group, a halogen atom, a methyl group substituted by at least one fluorine atom, a hydroxy group, a methoxy group, an ethoxy group, a methoxy group substituted by at least one fluorine atom, a methylthio group, a methylthio group substituted by at least one fluorine atom, a formyl group, an acetyl group, an acetyl group substituted by at least one fluorine atom, an alkoxycarbonyl group having from 2 to 4 carbon atoms, a carbamoyl group, a cyano group, a nitro group, a methanesulfonyl group, an ethanesulfonyl group, a methanesulfonyl group substituted by at least one fluorine atom, or a sulfamoyl group;

R.sup.3 represents a hydrogen atom, a hydroxy group, a methoxy group, an ethoxy group, a t-butoxy group, a methoxymethoxy group, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group, an alkanoyloxy group having from 1 to 12 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, an amino group or a t-butoxycarbonylamino group; and

Y represents an oxygen.

12. The compound of claim 11, wherein n is from 1 to 3.

13. The compound of claim 11, wherein n is 1.

14. The compound of claim 1, wherein R.sup.1 represents a halogen atom, a trifluoromethyl group, a hydroxy group, a difluoromethoxy group, a trifluoromethoxy group, a difluoromethylthio group, a trifluoromethylthio group, a formyl group, an acetyl group, a trifluoroacetyl group, a cyano group or a nitro group.

15. The compound of claim 1, wherein R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 10 carbon atoms, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group.

16. The compound of claim 1, wherein Y represents a sulfur atom.

17. The compound of claim 1, wherein:

R.sup.1 represents a halogen atom, a trifluoromethyl group, a hydroxy group, a difluoromethoxy group, a trifluoromethoxy group, a difluoromethylthio group, a trifluoromethylthio group, a formyl group, an acetyl group, a trifluoroacetyl group, a cyano group or a nitro group;

R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 10 carbon atoms, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group; and

Y represents a sulfur atom.

18. The compound of claim 17, wherein n is from 1 to 3.

19. The compound of claim 17, wherein n is 1.

20. The compound of claim 1, wherein R.sup.1 represents a fluorine or chlorine atom.

21. The compound of claim 1, wherein R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 6 carbon atoms or an alkoxycarbonyloxy group having from 2 to 5 carbon atoms.

22. The compound of claim 1, wherein:

R.sup.1 represents a fluorine or chlorine atom;

R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 6 carbon atoms or an alkoxycarbonyloxy group having from 2 to 5 carbon atoms.

23. The compound of claim 22, wherein n is from 1 to 3.

24. The compound of claim 22, wherein n is 1.

25. The compound of claim 1 wherein

Y represents sulfur.

26. The compound of claim 1 wherein

Y represents a group of formula --NH--.

27. The compound of claim 1 selected from the group consisting of

5-[2-chloro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-tetra hydrothieno[3,2-c]pyridine;

5-[2-fluoro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-tetra hydrothieno[3,2-c]pyridine; and

5-[2,6-difluoro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-t etrahydrothieno[3,2-c]pyridine

or a pharmaceutically acceptable salt thereof.

28. The compound of claim 27 which is 5-[2-fluoro-.alpha.(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-tetra hydrothieno[3,2-c]pyridine or a pharmaceutically acceptable salt thereof.

29. A pharmaceutical composition for the treatment of thrombosis or embolisms, comprising an effective amount of a blood platelet aggregation inhibitor in admixture with a pharmaceutically acceptable carrier or diluent, wherein said inhibitor is at least one compound of formula (I), or a tautomer or pharmaceutically acceptable salt thereof, as claimed in claim 1.

30. The composition of claim 29, wherein:

R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a halogen atom, a fluoroalkyl group having from 1 to 4 carbon atoms and at least one fluorine atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, a fluoroalkoxy group having from 1 to 4 carbon atoms and at least one fluorine atom, an alkylthio group having from 1 to 4 carbon atoms, a fluoroalkylthio group having from 1 to 4 carbon atoms and at least one fluorine atom, an amino group, an alkanoyl group having from 1 to 5 carbon atoms, a fluoroalkanoyl group having from 2 to 5 carbon atoms and at least one fluorine atom, an alkoxycarbonyl group having from 2 to 5 carbon atoms, a carbamoyl group, a cyano group, a nitro group, an alkanesulfonyl group having from 1 to 4 carbon atoms, a fluoroalkanesulfonyl group having from 1 to 4 carbon atoms and at least one fluorine atom, or a sulfamoyl group;

R.sup.3 represents a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, an alkoxymethoxy group in which the alkoxy part has from 1 to 4 carbon atoms, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkanoyloxy group having from 1 to 18 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a group of formula --NR.sup.a R.sup.b

wherein R.sup.a and R.sup.b are independently selected from the group consisting of hydrogen atoms, methyl groups and ethyl groups or R.sup.a represents a hydrogen atom and R.sup.b represents an alkanoyloxymethyl group in which the alkanoyl part has from 1 to 5 carbon atoms,

a benzylamino group, an alkanoylamino group having from 1 to 18 carbon atoms, an alkenoylamino group having 3 or 4 carbon atoms, a cycloalkylcarbonylamino group having 6 or 7 carbon atoms, a benzoylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonylamino group having from 2 to 5 carbon atoms or a benzyloxycarbonylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below;

Y represents an oxygen or sulfur atom; and

said substituents D are selected from the group consisting of fluorine atoms, chlorine atoms, methyl groups and methoxy groups.

31. The composition of claim 29 wherein:

R.sup.1 represents a hydrogen atom, a methyl group, an ethyl group, a halogen atom, a methyl group substituted by at least one fluorine atom, a hydroxy group, a methoxy group, an ethoxy group, a methoxy group substituted by at least one fluorine atom, a methylthio group, a methylthio group substituted by at least one fluorine atom, a formyl group, an acetyl group, an acetyl group substituted by at least one fluorine atom, an alkoxycarbonyl group having from 2 to 4 carbon atoms, a carbamoyl group, a cyano group, a nitro group, a methanesulfonyl group, an ethanesulfonyl group, a methanesulfonyl group substituted by at least one fluorine atom, or a sulfamoyl group;

R.sup.3 represents a hydrogen atom, a hydroxy group, a methoxy group, an ethoxy group, a t-butoxy group, a methoxymethoxy group, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group, an alkanoyloxy group having from 1 to 12 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, an amino group or a t-butoxycarbonylamino group; and

Y represents an oxygen.

32. The composition of claim 29, wherein:

R.sup.1 represents a halogen atom, a trifluoromethyl group, a hydroxy group, a difluoromethoxy group, a trifluoromethoxy group, a difluoromethylthio group, a trifluoromethylthio group, a formyl group, an acetyl group, a trifluoroacetyl group, a cyano group or a nitro group;

R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 10 carbon atoms, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group.

33. The composition of claim 29, wherein:

R.sup.1 represents a fluorine or chlorine atom;

R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 6 carbon atoms or an alkoxycarbonyloxy group having from 2 to 5 carbon atoms.

34. The composition of claim 29 wherein said blood platelet aggregation inhibitor is selected from the group consisting of

5-[2-chloro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-tetra hyrothieno[3,2-c]pyridine;

5-[2-fluoro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-tetra hydrothieno[3,2-c]pyridine; and

5-[2,6-difluoro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-t etrahydrothieno[3,2-c]pyridine

or a pharmaceutically acceptable salt thereof.

35. A method for the treatment of thrombosis or embolisms, comprising administering to a mammal an effective amount of a blood platelet aggregation inhibitor, wherein said inhibitor is at least one compound of formula (I), or a tautomer or pharmaceutically acceptable salt thereof, as claimed in claim 1.

36. The method of claim 35, wherein:

R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a halogen atom, a fluoroalkyl group having from 1 to 4 carbon atoms and at least one fluorine atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, a fluoroalkoxy group having from 1 to 4 carbon atoms and at least one fluorine atom, an alkylthio group having from 1 to 4 carbon atoms, a fluoroalkylthio group having from 1 to 4 carbon atoms and at least one fluorine atom, an amino group, an alkanoyl group having from 1 to 5 carbon atoms, a fluoroalkanoyl group having from 2 to 5 carbon atoms and at least one fluorine atom, an alkoxycarbonyl group having from 2 to 5 carbon atoms, a carbamoyl group, a cyano group, a nitro group, an alkanesulfonyl group having from 1 to 4 carbon atoms, a fluoroalkanesulfonyl group having from 1 to 4 carbon atoms and at least one fluorine atom, or a sulfamoyl group;

R.sup.3 represents a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 4 carbon atoms, an alkoxymethoxy group in which the alkoxy part has from 1 to 4 carbon atoms, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkanoyloxy group having from 1 to 18 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a group of formula --NR.sup.a R.sup.b

wherein R.sup.a and R.sup.b are independently selected from the group consisting of hydrogen atoms, methyl groups and ethyl groups or R.sup.a represents a hydrogen atom and R.sup.b represents an alkanoyloxymethyl group in which the alkanoyl part has from 1 to 5 carbon atoms,

a benzylamino group, an alkanoylamino group having from 1 to 18 carbon atoms, an alkenoylamino group having 3 or 4 carbon atoms, a cycloalkylcarbonylamino group having 6 or 7 carbon atoms, a benzoylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below, an alkoxycarbonylamino group having from 2 to 5 carbon atoms or a benzyloxycarbonylamino group which is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents D, defined below;

Y represents an oxygen; and

said substituents D are selected from the group consisting of fluorine atoms, chlorine atoms, methyl group and methoxy groups.

37. The method of claim 35, wherein:

R.sup.1 represents a hydrogen atom, a methyl group, an ethyl group, a halogen atom, a methyl group substituted by at least one fluorine atom, a hydroxy group, a methoxy group, an ethoxy group, a methoxy group substituted by at least one fluorine atom, a methylthio group, a methylthio group substituted by at least one fluorine atom, a formyl group, an acetyl group, an acetyl group substituted by at least one fluorine atom, an alkoxycarbonyl group having from 2 to 4 carbon atoms, a carbamoyl group, a cyano group, a nitro group, a methanesulfonyl group, an ethanesulfonyl group, a methanesulfonyl group substituted by at least one fluorine atom, or a sulfamoyl group;

R.sup.3 represents a hydrogen atom, a hydroxy group, a methoxy group, an ethoxy group, a t-butoxy group, a methoxymethoxy group, an alkanoyloxymethoxy group in which the alkanoyl part has from 1 to 5 carbon atoms, a benzyloxy group, an alkanoyloxy group having from 1 to 12 carbon atoms, an alkenoyloxy group having 3 or 4 carbon atoms, a cycloalkylcarbonyloxy group having from 4 to 7 carbon atoms, a benzoyloxy group, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms, a benzyloxycarbonyloxy group, a phthalidyloxy group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methoxy group, an amino group or a t-butoxycarbonylamino group; and

Y represents an oxygen.

38. The method of claim 35, wherein:

R.sup.1 represents a halogen atom, a trifluoromethyl group, a hydroxy group, a difluoromethoxy group, a trifluoromethoxy group, a difluoromethylthio group, a trifluoromethylthio group, a formyl group, an acetyl group, a trifluoroacetyl group, a cyano group or a nitro group;

R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 10 carbon atoms, an alkoxycarbonyloxy group having from 2 to 5 carbon atoms or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy group.

39. The method of claim 35, wherein:

R.sup.1 represents a fluorine or chlorine atom;

R.sup.3 represents a hydrogen atom, a hydroxy group, a pivaloyloxymethoxy group, an alkanoyloxy group having from 2 to 6 carbon atoms or an alkoxycarbonyloxy group having from 2 to 5 carbon atoms.

40. The method of claim 35 wherein the inhibitor is selected from the group consisting of:

5-[2-chloro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-tetra hyrothieno[3,2-c]pyridine;

5-[2-fluoro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-tetra hydrothieno[3,2-c]pyridine; and

5-[2,6-difluoro-.alpha.-(5,6-dihydro-1,4,2-dioxazin-3-yl)-benzyl]-4,5,6,7-t etrahydrothieno[3,2-c]pyridine

or a pharmaceutically acceptable salt thereof.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc