Details for Patent: 5,985,920

Title:	Difluoroprostaglandin derivatives and their use
Abstract:	A fluorine-containing prostaglandin derivative of the formula (1) (or a salt thereof) and a medicine containing it, particularly, a preventive or therapeutic medicine for an eye disease: ##STR1## wherein A is a vinylene group or the like, R.sup.1 is an aryloxyalkyl group or the like, R.sup.2 and R.sup.3 are hydrogen atoms or the like, and Z is OR.sup.4 (wherein OR.sup.4 is a hydrogen atom or an alkyl group) or the like.
Inventor(s):	Shirasawa; Eiichi (Ikoma, JP), Kageyama; Masaaki (Ikoma, JP), Nakajima; Tadashi (Ikoma, JP), Nakano; Takashi (Yokohama, JP), Mori; Nobuaki (Yokohama, JP), Sasakura; Hideshi (Yokohama, JP), Matsumura; Yasushi (Yokohama, JP), Morizawa; Yoshitomi (Yokohama, JP)
Assignee:	Asahi Glass Company Ltd. (Tokyo, JP) Santen Pharmaceutical Co., Ltd. (Osaka, JP)
Filing Date:	Aug 03, 1998
Application Number:	09/127,804
Claims:	1. A fluorine-containing prostaglandin derivative of the following formula (1) or a salt thereof: ##STR4## wherein A is an ethylene group, a vinylene group, an ethynylene group, --OCH.sub.2 -- or --SCH.sub.2 --, R.sup.1 is a substituted or unsubstituted C.sub.3-8 alkyl group, a substituted or unsubstituted C.sub.3-8 alkenyl group, a substituted or unsubstituted C.sub.3-8 alkynyl group, a substituted or unsubstituted C.sub.3-8 cycloalkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryloxyalkyl group, each of R.sup.2 and R.sup.3 which are independent of each other, is a hydrogen atom or an acyl group, or forms a single bond together with Z, X is --CH.sub.2 --, --O-- or --S--, Z is --OR.sup.4 --, --NHCOR.sup.5 --, --NHSO.sub.2 R.sup.6 -- or --SR.sup.7 --, or forms a single bond together with R.sup.2 or R.sup.3, each of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 which are independent of one another, is an alkenyl group, an alkynyl group, a cycloalkyl group, or an aralkyl group, and a dual line consisting of solid and broken lines is a single bond, a cis-double bond or a trans-double bond. 2. The compound according to claim 1, wherein A is an ethylene group or a vinylene group. 3. The compound according to claim 1, wherein X is --CH.sub.2 --. 4. The compound according to claim 1, wherein both R.sup.2 and R.sup.3 are hydrogen atoms. 5. The compound according to claim 1, wherein Z is --OR.sup.4. 6. A medicine containing the compound according to claim 1 as an active ingredient. 7. The medicine according to claim 6, which is a preventive or therapeutic medicine for an eye disease. 8. The medicine according to claim 7, wherein the eye disease is glaucoma or ocular hypertension. 9. The medicine according to claim 6, 7 or 8, wherein A is an ethylene group or a vinylene group. 10. The medicine according to claim 6, 7, or 8, wherein X is --CH.sub.2 --. 11. The medicine according to claim 6, 7 or 8, wherein both R.sup.2 and R.sup.3 are hydrogen atoms. 12. The medicine according to claim 6, 7, or 8, wherein Z is --OR.sup.4. 13. A fluorine-containing prostaglandin derivative of the following formula (1) or a salt thereof: ##STR5## wherein A is --OCH.sub.2 -- or --SCH.sub.2 --, R.sup.1 is a substituted or unsubstituted C.sub.3-8 alkyl group, a substituted or unsubstituted C.sub.3-8 alkenyl group, a substituted or unsubstituted C.sub.3-8 alkyl group, a substituted or unsubstituted C.sub.3-9 cycloalkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryloxyalkyl group, each of R.sup.2 and R.sup.3 which are independent of each other, is a hydrogen atom or an acyl group, or forms a single bond together with Z, X is --CH.sub.2 --, --O-- or --S--, Z is --OR.sup.4 --, --NHCOR.sup.5 --, --NHSO.sub.2 R.sup.6 -- or --SR.sup.7 --, or forms a single bond together with R.sup.2 or R.sup.3, each of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 which are independent of one another, is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or an aralkyl group, and a dual line consisting of solid and broken lines is a single bond, a cis-double bond or a trans-double bond. 14. A fluorine-containing prostaglandin derivative of the following formula (1) or a salt thereof: ##STR6## wherein A is an ethylene group, a vinylene group, an ethynylene group, --OCH.sub.2 -- or --SCH.sub.2 --, R.sup.1 is a substituted or unsubstituted C.sub.3-8 alkyl group, a substituted or unsubstituted C.sub.3-8 alkenyl group, a substituted or unsubstituted C.sub.3-8 alkynyl group, a substituted or unsubstituted C.sub.3-8 cycloalkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryloxyalkyl group, each of R.sup.2 and R.sup.3 which are independent of each other, is an acyl group, or forms a single bond together with Z, X is --CH.sub.2 --, --O-- or --S--, Z is --OR.sup.4 --, --NHCOR.sup.5 --, --NHSO.sub.2 R.sup.6 -- or --SR.sup.7 --, or forms a single bond together with R.sup.2 or R.sup.3, each of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 which are independent of one another, is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or an aralkyl group, and a dual line consisting of solid and broken lines is a single bond, a cis-double bond or a trans-double bond. 15. A fluorine-containing prostaglandin derivative of the following formula (1) or a salt thereof: ##STR7## wherein A is an ethylene group, a vinylene group, an ethynylene group, --OCH.sub.2 -- or --SCH.sub.2 --, R.sup.1 is a substituted or unsubstituted C.sub.3-8 alkyl group, a substituted or unsubstituted C.sub.3-8 alkenyl group, a substituted or unsubstituted C.sub.3-8 alkynyl group, a substituted or unsubstituted C.sub.3-8 cycloalkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryloxyalkyl group, each of R.sup.2 and R.sup.3 which are independent of each other, is a hydrogen atom or an acyl group, or forms a single bond together with Z, X is --O-- or --S--, Z is --OR.sup.4 --, --NHCOR.sup.5 --, --NHSO.sub.2 R.sup.6 -- or --SR.sup.7 --, or forms a single bond together with R.sup.2 or R.sup.3, each of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 which are independent of one another, is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or an aralkyl group, and a dual line consisting of solid and broken lines is a single bond, a cis-double bond or a trans-double bond. 16. A fluorine-containing prostaglandin derivative of the following formula (1) or a salt thereof: ##STR8## wherein A is an ethylene group, a vinylene group, an ethynylene group, --OCH.sub.2 -- or --SCH.sub.2 --, R.sup.1 is a substituted or unsubstituted C.sub.3-8 alkyl group, a substituted or unsubstituted C.sub.3-8 alkenyl group, a substituted or unsubstituted C.sub.3-8 alkyl group, a substituted or unsubstituted C.sub.3-8 cycloalkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryloxyalkyl group, each of R.sup.2 and R.sup.3 which are independent of each other, is a hydrogen atom or an acyl group, or forms a single bond together with Z, X is --CH.sub.2 --, --O-- or --S--, Z is --NHCOR.sup.5 --, --NHSO.sub.2 R.sup.6 -- or --SR.sup.7 --, or forms a single bond together with R.sup.2 or R.sup.3, each of R.sup.5, R.sup.6 and R.sup.7 which are independent of one another, is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or an aralkyl group, with the proviso that R.sup.6 is not an alkyl group or an aryl group, and a dual line consisting of solid and broken lines is a single bond, a cis-double bond or a trans-double bond. 17. The compound according to claim 13, wherein X is --CH.sub.2 --. 18. The compound according to claim 13, wherein both R.sup.2 and R.sup.3 are hydrogen atoms. 19. The compound according to claim 13, wherein Z is --OR.sup.4. 20. A medicine containing the compound according to claim 13 as an active ingredient. 21. The medicine according to claim 20, which is a preventive or therapeutic medicine for an eye disease. 22. The medicine according to claim 21, wherein the eye disease is glaucoma or ocular hypertension. 23. The medicine according to claim 20, 21 or 22, wherein X is --CH.sub.2 --. 24. The medicine according to claim 20, 21 or 22 wherein both R.sup.2 and R.sup.3 are hydrogen atoms. 25. The medicine according to claim 20, 21 or 22 wherein Z is --OR.sup.4. 26. The compound according to claim 14, wherein A is an ethylene group or a vinylene group. 27. The compound according to claim 14, wherein X is --CH.sub.2 --. 28. The compound according to claim 14, wherein Z is --OR.sup.4. 29. A medicine containing the compound according to claim 14 as an active ingredient. 30. The medicine according to claim 29, which is a preventive or therapeutic medicine for an eye disease. 31. The medicine according to claim 30, wherein the eye disease is glaucoma or ocular hypertension. 32. The medicine according to claims 29, 30 or 31, wherein A is an ethylene group or a vinylene group. 33. The medicine according to claims 29, 30, or 31 wherein X is --CH.sub.2 --. 34. The medicine according to claims 29, 30 or 31 wherein Z is --O.sup.4. 35. The compound according to claim 15, wherein A is an ethylene group or a vinylene group. 36. The compound according to claim 15, wherein both R.sup.2 and R.sup.3 are hydrogen atoms. 37. The compound according to claim 15, wherein Z is --OR.sup.4. 38. A medicine containing the compound according to claim 15 as an active ingredient. 39. The medicine according to claim 38, which is a preventive or therapeutic medicine for an eye disease. 40. The medicine according to claim 39, wherein the eye disease is glaucoma or ocular hypertension. 41. The medicine according to claims 38, 39, or 40 wherein A is an ethylene group or a vinylene group. 42. The medicine according to claims 38, 39, or 40 wherein both R.sup.2 and R.sup.3 are hydrogen atoms. 43. The medicine according to claims 38, 39, or 40 wherein Z is --OR.sup.4. 44. The compound according to claim 16, wherein A is an ethylene group or a vinylene group. 45. The compound according to claim 16, wherein X is --CH.sub.2 --. 46. The compound according to claim 16, wherein both R.sup.2 and R.sup.3 are hydrogen atoms. 47. A medicine containing the compound according to claim 16 as an active ingredient. 48. The medicine according to claim 47, which is a preventive or therapeutic medicine for an eye disease. 49. The medicine according to claim 48, wherein the eye disease is glaucoma or ocular hypertension. 50. The medicine according to claims 47, 48, or 49, wherein A is an ethylene group or a vinylene group. 51. The medicine according to claims 47, 48, or 49, wherein X is --CH.sub.2 --. 52. The medicine according to claims 47, 48, or 49 wherein both R.sup.2 and R.sup.3 are hydrogen atoms.