Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-05-18
2002-05-14
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S247000, C514S252120, C514S252130, C514S255050
Reexamination Certificate
active
06387904
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to the use of piperazinyl-heterocyclic compounds of the formula I, as defined below, for the treatment of glaucoma and ischemic retinopathy.
The piperazinyl-heterocyclic compounds of formula I and their utility for the treatment of psychotic disorders, including schizophrenia, are referred to in U.S. Pat. Nos. 4,831,031 and 4,883,795, which issued, respectively, on May 16, 1989 and Nov. 28, 1989. The ulitity of such compounds for the treatment of obsessive-compulsive disorder and Tourette's syndrome is referred to in U.S. Provisional Application 60/057,987, which was filed on Sep. 5, 1997. The utility of such compounds for the treatment of certain psychiatric disorders that have as symptoms behavioral disturbances (e.g., anxiety, bipolar disorder, major depressive disorder, autistic disorder, conduct disorder, dementias including dementias associated with Alzheimer's disease, and drug induced and neurodegeneration based dyskinesias is referred to in U.S. Provisional Application 60/068,069, which was filed on Dec. 18, 1997. All of the foregoing patents and patent applications are assigned in common with the present application.
Current treatments for glaucoma include the use of beta-adrenergic antagonists such as timolol and betaxolol, which, like the compounds administered in the methods of this invention (i.e., compounds of the formula I, as defined below), are effective in reducing intraocular pressure. The compounds of formula I, however, do not exhibit beta-adrenergic blocking activity and thus do not have associated with them the negative cardiac side effects that are associated with beta-adrenergic blockers (e., systemic absorption leading to slowing of the heart).
Methods of preparing the novel compounds of the formula I and their pharmaceutically acceptable salts are referred to in each of the following: U.S. Pat. Nos. 4, 831,031 and 4,883,795, referred to above, and in U.S. Pat. Nos. 5,206,366 and 5,338,846, which were issued, respectively, on Apr. 27, 1993 and Aug. 16, 1994. All of the foregoing patents are assigned in common with the present application and incorporated herein by reference in their entireties.
SUMMARY OF THE INVENTION
The present invention also relates to a method of treating a disorder or condition that can be treated by decreasing intraocular pressure in a mammal, including a human, comprising administering to said mammal a therapeutically effective amount of a compound of the formula
or a pharmaceutically acceptable acid addition salt thereof, wherein
Ar is benzoisothiazolyl or an oxide or dioxide thereof each optionally substituted by one fluoro, chloro, trifluoromethyl, methoxy, cyano or nitro; naphthyl optionally substituted by fluoro, chloro, trifluoromethyl, methoxy, cyano or nitro; quinolyl; 6-hydroxy-8-quinolyl; isoquinolyl; quinazolyl; benzothiazolyl; benzothiadiazolyl; benzotriazolyl; benzoxazolyl; benzoxazolonyl; indolyl; indanyl optionally substituted by one or two fluoro; 3-indazolyl optionally substituted by 1-trifluoromethylphenyl; or phthalazinyl;
n is 1 or 2; and
X and Y together with the phenyl to which they are attached form a cyclic ring system selected from quinolyl; 2-hydroxyquinolyl; benzothiazolyl; 2-aminobenzothiazolyl; benzoisothiazolyl; indazolyl; 2-hydroxyindazolyl; indolyl; oxindolyl optionally substituted by spirocycloalkyl wherein said cycloalkyl moiety contains from 4 to 7 carbon atoms, or by one to three of (C
1
-C
3
)alkyl, or by one of chloro, fluoro or phenyl wherein said phenyl is optionally substituted by one chloro or fluoro; benzoxazolyl; 2-aminobenzoxazolyl; benzoxazolonyl; 2-aminobenzoxazolinyl; benzothiazolonyl; benzoimidazolonyl; and benzotriazolyl.
The present invention also relates to a method for treating glaucoma (e.g., open angle glaucoma, wide angle glaucoma, aphakic glaucoma and secondary glaucoma) or ischemic retinopathy (i.e., ischemic retinal degeneration) in a mammal, including a human, comprising administering to said mammal a therapeutically effective amount of compound of the formula
or a pharmaceutically acceptable acid addition salt thereof, wherein
Ar is benzoisothiazolyl or an oxide or dioxide thereof each optionally substituted by one fluoro, chloro, trifluoromethyl, methoxy, cyano or nitro; naphthyl optionally substituted by fluoro, chloro, trifluoromethyl, methoxy, cyano or nitro; quinolyl; 6-hydroxy-8-quinolyl; isoquinolyl; quinazolyl; benzothiazolyl; benzothiadiazolyl; benzotriazolyl; benzoxazolyl; benzoxazolonyl; indolyl; indanyl optionally substituted by one or two fluoro; 3-indazolyl optionally substituted by 1-trifluoromethylphenyl; or phthalazinyl;
n is 1 or 2; and
X and Y together with the phenyl to which they are attached form a cyclic ring system selected from quinolyl; 2-hydroxyquinolyl; benzothiazolyl; 2-aminobenzothiazolyl; benzoisothiazolyl; indazolyl; 2-hydroxyindazolyl; indolyl; oxindolyl optionally substituted by spirocycloalkyl wherein said cycloalkyl moiety contains from 4 to 7 carbon atoms, or by one to three of (C
1
-C
3
)alkyl, or by one of chloro, fluoro or phenyl wherein said phenyl is optionally substituted by one chloro or fluoro; benzoxazolyl; 2-aminobenzoxazolyl; benzoxazolonyl; 2-aminobenzoxazolinyl; benzothiazolonyl; benzoimidazolonyl; and benzotriazolyl.
This invention also relates to a method of treating a disorder or condition that can be treated by improving blood flow in the retina of a mammal, including a human, comprising administering to said mammal a therapeutically effective amount of a compound of the formula
or a pharmaceutically acceptable acid addition salt thereof, wherein
Ar is benzoisothiazolyl or an oxide or dioxide thereof each optionally substituted by one fluoro, chloro, trifluoromethyl, methoxy, cyano or nitro; naphthyl optionally substituted by fluoro, chloro, trifluoromethyl, methoxy, cyano or nitro; quinolyl; 6-hydroxy-8-quinolyl; isoquinolyl; quinazolyl; benzothiazolyl; benzothiadiazolyl; benzotriazolyl; benzoxazolyl; benzoxazolonyl; indolyl; indanyl optionally substituted by one or two fluoro; 3-indazolyl optionally substituted by 1-trifluoromethylphenyl; or phthalazinyl;
n is 1 or 2; and
X and Y together with the phenyl to which they are attached form a cyclic ring system selected from quinolyl; 2-hydroxyquinolyl; benzothiazolyl; 2-aminobenzothiazolyl; benzoisothiazolyl; indazolyl; 2-hydroxyindazolyl; indolyl; oxindolyl optionally substituted by spirocycloalkyl wherein said cycloalkyl moiety contains from 4 to 7 carbon atoms, or by one to three of (C
1
-C
3
)alkyl, or by one of chloro, fluoro or phenyl wherein said phenyl is optionally substituted by one chloro or fluoro; benzoxazolyl; 2-aminobenzoxazolyl; benzoxazolonyl; 2-aminobenzoxazolinyl; benzothiazolonyl; benzoimidazolonyl; and benzotriazolyl.
The term “treating”, as used herein, refers to reversing, alleviating, inhibiting the progress of, or preventing the disorder or condition to which such term applies, or one or more symptoms of such disorders or condition. The term “treatment”, as used herein, refers to the act of treating, as “treating” is defined immediately above.
The term “therapeutically effective amount”, as used herein, refers to an amount of a compound of the formula I, or a pharmaceutically acceptable salt thereof, that is effective in treating the disorder or condition for which such compound or salt is being administered.
A preferred embodiment of this invention relates to any of the inventive methods described above wherein the compound of formula I or pharmaceutically acceptable salt is administered is for the treatment of glaucoma.
Another preferred embodiment of this invention relates to any of the inventive methods described above wherein the compound of formula I or pharmaceutically acceptable salt is administered for the treatment of ischemic retinopathy.
Another preferred embodiment of this invention relates to any of the inventive methods described above wherein the compound of formula I or pharmaceutically acceptable salt that is administered is one wherein Ar is benzoisothi
Delacroix-Muirheid C.
Fay Zohreh
Ginsburg Paul H.
Pfizer INC
Richardson Peter C.
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