Claims
- 1. A compound of formula ##STR89## wherein X is --CH.dbd.CH-- or S; R.sub.1 is lower alkyl, lower alkoxy or trifluoromethyl;
- R.sub.2 is hydrogen, lower alkyl, lower alkoxy, hydroxy or acetyloxy;
- R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy;
- s is an integer from 0 to 1, provided that when s is 1, R.sub.2 cannot be hydroxy, lower alkoxy or acetyloxy;
- R.sub.5 is a radical of the formula
- R.sub.7 --O--(CH.sub.2).sub.m --C.tbd.C-- wherein R.sub.6 and R.sub.7 are naphthyl, phenyl or phenyl or naphthyl mono-, di- , or trisubstituted by chlorine, fluorine, lower alkoxy or lower alkoxy or a heterocyclic radical selected from the group consisting of pyridinyl, imidazolinyl, thienyl, furyl, pyrimidinyl, oxazolinyl, ##STR90## which can be substituted by one or two substitutents selected from the group consisting of lower alkyl, lower alkoxy, chlorine and fluorine, n is an integer of from 0 to 2 and m is an integer of from 1 to 2, provided that, when n is 0R.sub.6 must be attached through a carbon to carbon bond, and provided that R.sub.7 is always attached through a carbon to oxygen bond, or, when at least one asymmetric carbon is present, an enantiomer or racemate thereof, or a pharmaceutically acceptable acid addition salt thereof.
- 2. A compound in accordance with claim 1. wherein s is 0.
- 3. A compound, in accordance with claim 1, wherein s is 1.
- 4. A compound, in accordance with claim 2, wherein X is
- 5. A compound, in accordance with claim 2, wherein X is S.
- 6. A compound, in accordance with claim 4, wherein ##STR91##
- 7. A compound, in accordance with claim 4, wherein ##STR92##
- 8. A compound, in accordance with claim 5, wherein ##STR93##
- 9. A compound, in accordance with claim 5, wherein ##STR94##
- 10. A compound, in accordance with claim 8, wherein R.sub.6 is a heterocyclic radical.
- 11. A compound, in accordance with claim 9, wherein R.sub.7 is
- 12. A compound, in accordance with claim 10, wherein R.sub.1, is methyl or ethyl, R2 is hydrogen, R is fluorine or chlorine, R.sub.4 is hydrogen, s is 0 and n is 1 or 2.
- 13. A compound, in accordance with claim 10, wherein R.sub.1 is methyl, R.sub.2 is hydrogen, R is fluorine or chlorine at the 2-position of the phenyl moiety. R.sub.4 is hydrogen. s is 0, n is 1 and R.sub.6 is hetero-bicyclic or hetero-tricyclic group.
- 14. A compound, in accordance with claim 10, wherein R.sub.1 is methyl, R.sub.2 is hydrogen, R.sub.3 is chlorine and at the 2-position of the phenyl moiety, R.sub.4 is hydrogen, n is 1 and R.sub.6 is selected from the group consisting of ##STR95## which can be substituted by one or two substituents selected from the group consisting of lower alkyl, lower alkoxy, chlorine and fluorine.
- 15. A compound, in accordance with claim 11, wherein R.sub.1 is methyl or ethyl. R.sub.2 is hydrogen, R.sub.3 is fluorine or chlorine and R.sub.4 is hydrogen.
- 16. A compound, in accordance with claim 11, wherein R.sub.1 is methyl, R.sub.2 is hydrogen, R.sub.3 is fluorine or chlorine at the 2-position of the phenyl moiety, R.sub.4 is hydrogen, m is and R.sub.7 is phenyl, naphthyl or phenyl or naphthyl mono-, di- or trisubstituted by chlorine, fluorine, lower alkyl or lower alkoxy.
- 17. A compound, in accordance with claim 9, wherein R.sub.1 is methyl, R2 is hydrogen, R.sub.3 is chlorine and at the 2-position of the phenyl moiety, R.sub.4 is hydrogen, n is 1 and R.sub.7 is phenyl, naphthyl or pyridyl.
- 18. A compound, in accordance with claim 1, 1-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3.2-f][1,2,4][4,3-a][4,1]diazepin-2-yl]-2-propynyl]-benz[cd]-indol-2(1H)-one.
- 19. A compound, in accordance with claim 1, 5-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazol 4,3-a][4,1]diazepin-2-yl]-2-propynyl}-phenanthridin-6(5H)-one.
- 20. A compound, in accordance with claim 1, 4-(2-chlorophenyl)-2-[3-(1,2.3,4-tetrahydro-9H-carbazol-9-yl)1-propynyl]-9-methyl-6H-thi.RTM.no-[3,2-f]1,2,4]triazolo[4,3-a][1,4]diazepine.
- 21. A compound, in accordance with claim 1, 1-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-2-yl]-2-propynyl}-3,4-dihydro2(1H)-quinolinone.
- 22. A compound, in accordance with claim 1, 4-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-2H-4,1-benzoxazin-3(4H)-one.
- 23. A compound, in accordance with claim 1, 1-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-1H-indole2,3-dione.
- 24. A compound in accordance with claim 1 1-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl].1,3-dihydro 2H-indol-2-one.
- 25. A compound, in accordance with claim 1. 2-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-1,2,4triazolo[4,3-a]pyridin-3(2H)-one.
- 26. A compound, in accordance with claim 1, 2-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-1,2-benziso-thiazol-3(2H)-one 1,1-dioxide.
- 27. A compound, in accordance with claim 1, 4-(2-Chlorophenyl)-2-[3-(1H-indazol-1-yl)-1-propynyl]-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepine.
- 28. A compound, in accordance with claim 1, 2-[3-(1H-Benzimidazol-1-yl)-1-propynyl]-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine.
- 29. A compound, in accordance with claim 1, 2-[3-[6-(2-Fluorophenyl)-1-methyl-4H-[1,2 4]triazolo [4,3-a][4,1]benzodiazepin-8-yl]-2-propynyl]-1H-isoindole-1,3(2H)-dione.
- 30. A compound, in accordance with claim 1, 4-[3-[6-(2-Fluorophenyl)-1-methyl-4H-[1,2,4]triazolo [4,3-a][4,1]benzodiazepin-8-yl]-2-propynyl]-2H-4,1-benzoxazin-3(4H)-one.
- 31. A compound, in accordance with claim 1, 4-(2-chlorophenyl)-9-methyl-2-[3-(3-pyridyloxy-1-propynyl)-6H. thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepine.
- 32. A pharmaceutical composition comprising an effective amount of a compound of formula ##STR96## wherein X is --CH.dbd.CH-- or S; R.sub.1 is lower alkyl, lower alkoxy or trifluoromethyl;
- R.sub.2 is hydrogen, lower alkyl, lower alkoxy, hydroxy or acetyloxy;
- R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy;
- s is an integer from 0 to 1, provided that when s is 1 , R.sub.2 cannot be hydroxy, lower alkoxy or acetyloxy;
- R.sub.5 is a radical of the formula
- R.sub.6 --(CH.sub.2).sub.n --C.tbd.C-- or R.sub.7 --O--(CH.sub.2).sub.m --C.tbd.C-- wherein R.sub.6 and R.sub.7 are naphthyl, phenyl or phenyl or naphthyl mono-, di- or trisubstituted by chlorine, fluorine, lower alkyl or lower alkoxy or a heterocyclic radical selected from the group consisting of pyridinyl, imidazolinyl, thienyl, furyl, pyrimidinyl, oxazolinyl, ##STR97## which can be substituted by one or two substituents selected from the group consisting of lower alkyl, lowr alkoxy, chlorine and fluorine, n is an integer of from 0 to 2 and m is an integer of from 1 to 2, provided that, when n is 0, R.sub.6 must be attached through a carbon to carbon bond, and provided that R.sub.7 is always attached through a carbon to oxygen bond, or, when at least one asymmetric carbon is present, an enantiomer or racemate thereof, or a pharmaceutically acceptable acid addition salt thereof, and an inert carrier material.
- 33. A pharmaceutical composition, in accordance wirh claim 32, wherein s is 0.
- 34. A pharmaceutical composition, in accordance with claim 33, wherein s is 1.
- 35. A pharmaceutical composition, in accordance with claim 33, wherein X is --CH.dbd.CH--.
- 36. A pharmaceutical composition, in accordance with claim 34, wherein X is S.
- 37. A pharmaceutical composition, in accordance with claim 35, wherien R.sub.5 is ##STR98##
- 38. A pharmaceutical composition, in accordance with claim 35, wherein R.sub.5 ios ##STR99##
- 39. A pharmaceutical composition, in accordance with claim 36, wherein R.sub.5 is ##STR100##
- 40. A pharmaceutical composition, in accordance with claim 36, wherein R.sub.5 is ##STR101##
- 41. A pharmaceutical composition, in accordance with claim 32, wherein the compound of formula I is 2-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-1H-benz[de]isoquinoline-1,3(2H)-dione.
- 42. A pharmaceutical composition, in accordance with claim 32, wherein the compound of formula I is 1-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-benz[cd]indol-2(1H)-one.
- 43. A pharmaceutical composition, in accordance with claim 32, wherein the compound of formula I is 4-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-2H-1,4-benzoxazin-3(4H)-one.
- 44. A pharmaceutical composition, in accordance with claim 32, wherein the compound of formula I is 5-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-2-yl]-2-propynyl]-phenanthridin-6(5H)-one.
- 45. A pharmaceutical composition, in accordance with claim 32, wherein the compound of formula 1 is 4-(2-chlorophenyl)-2-[3-(1,2,3,4-tetrahydro-9H-carbazol-9-yl)1-propynyl]-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo[4,3-a][4,1]diazepine.
- 46. A pharmaceutical composition, in accordance with claim 32, wherein the compound of formula I is 1-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno-[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl}-3,4-dihydro-2 (1H)-quinolinone.
- 47. A method which comprises administering to a host requiring a paltelet activating factor antagonist an effecting amount of a compound of the formula ##STR102## wherein X is --CH.dbd.CH-- or S; R.sub.1 is lower alkyl, lower alkoxy or trifuloromethyl;
- R.sub.2 is hydrogen, lower alkyl, lower alkoxy, hydroxy or acetyloxy;
- R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lowr alkyl or lower alkoxy;
- s is an integer from 0 to 1, provided that when s is 1, R.sub.2 cannot be hydroxy, lower alkoxy or acetyloxy;
- R.sub.5 is a radical of the formula
- R.sub.6 --(CH.sub.2).sub.n --C.tbd.C-- or R.sub.7 --O--(CH.sub.2).sub.m --C.tbd.C-- wherein R.sub.6 and R.sub.7 are naphthyl, phenyl or phenyl or naphthyl mono-, di- or trisubstituted by chlorine, fluorine, lower alkyl or lower alkoxy or a heterocyclic radical selected from the group consisting of pyridinyl, imidazolinyl, thienyl, furyl, pyrimidinyl, oxazolinyl, ##STR103## which can be substituted by one or two substituents selected from the group consisting of lower alkyl, lower alkoxy, chlorine and fluorine, n is an integer of from 0 to 2 and m is an integer of from 1 to 2, provided that, when n is 0, R.sub.6 must be attached trhough a carbon to carbon bond, and provided that R.sub.7 is always attached through a carbon to oxygen bond,
- or, when at least one asymmetric carbon is present, an enantiomer or racemate thereof, or a pharmaceutically acceptable acid addition salt thereof.
- 48. A method, in accordance with claim 47, wherein s is 0.
- 49. A method, in accordance with claim 47, wherein s is 1.
- 50. A method, in accordance with claim 48, wherein X is --CH.dbd.CH--.
- 51. A method, in accordance with claim 48, wherein X is S.
- 52. A method, in accordance with claim 50, wherein ##STR104##
- 53. A method, in accordance with claim 50, wherein ##STR105##
- 54. A method, in accordance with claim 51, wherein ##STR106##
- 55. A method, in accordance with claim 51, wherein ##STR107##
- 56. A method, in accordance with claim 47, wherein the compound of formula I is 2-[3-[4-(2-Chlorophenyl)-9-methyl6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-2-yl]-2propynyl]-1H-benz[de]isoquinoline-1,3(2H)-dione.
- 57. A method, in accordance with claim 47, wherein the compound of formula I is 1-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-proponyl]-benz[cd]indol-2(1H)-one.
- 58. A method, in accordance with claim 47, wherein the compound of formula I is 4-[3-[4-(2-Chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl]-2H-4,1-benzoxazin-3(4H)-one.
- 59. A method, in accordance With claim 47, wherein the compound of formula I is 5-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl}-phenanthridin-6(5H)-one.
- 60. A method, in accordance with claim 47, wherein the compound of formula I is wherein the compound of formula 1 is 4-(2-chlorophenyl)-2-[3-(1,2,3,4-tetrahydro-9H-carbazol-9-yl)-1-propynyl]-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[-triazolo -4,3-a][4,1]diazepine;
- 61. A method, in accordance with claim 47, wherein the compound of formula I is 1-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno-[3,2-f][1,2,4]triazolo[4,3-a][4,1]diazepin-2-yl]-2-propynyl}-3,4-dihydro-2(1H)-quinolone.
- 62. A compound in accordance with claim 1, 1-{3-[4-(b 2-chlorphenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo[4,3-a][1,4]diazepin-2-yl]-2-propynyl}-1,3-dihydro-3-methyl-2H-benzimidazo -2-one.
- 63. A compound in accordance with claim 1, 1{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo triazolo [4,3-a][1,4]diazepin-2-yl]-2-propynyl}-1,3-dihydro-3-methyl-2,4(1H,3H)-quinzolinedione.
- 64. A compound in accordance with claim 1, 1-{3-[4-(b 2-chlorphenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo[4,3-a][1,4]diazepin-2-yl]-2-propynyl}-1,3-dihydro-3-phenyl-2H-benzimidazo 2-one.
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of U.S. application Ser. No. 227,948, filed Aug. 3, 1988 now abandoned, which in turn is a continuation-in-part of U.S. application Ser. No. 134,726, filed Dec. 18, 1987 now abandoned.
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Continuation in Parts (2)
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