Treatment of conditions of abnormally increased intraocular pressure by administration of phosphonylmethoxyalkyl nucleoside analogs and related nucleoside analogs
First Claim
1. A method for reducing intraocular pressure, comprising administering to the eye an effective amount of a compound of formula I:
- ##STR8## or a pharmaceutically acceptable salt or ester thereof, wherein;
R1 and R2 are (i) or (ii) as follows;
(i) R1 is CH2 CH(OH)(CH2)n, CH2 CH(CH2)n (OH), CH2 OCH(R7),CH2 OCH(R7)(CH2)p, CH2 OCH(R7)(CH2)p O or O(CH2)p CH(R7)O;
R2 is OH or O(CH2)r H;
R7 is OH or (CH2)r OH;
n is 0-6;
r is 1-6;
p is 0-3; and
m is 0 to 3(ii) R1, R2, n, m, r and p are defined as in (i), and R1 and R2 are linked to form a cyclic ester group;
B is a pyrimidine or purine of formula (II);
##STR9## and is selected from the group consisting of pyrimidin-1-yl, pyrimidinyl-3-yl, purin-3-yl, purin-7-yl and purin9-yl; and
R3, R4, R5 and R6 are independently selected from NH2, alkylamino, aminoalkyl, hydroxyalkyl, hydrazino, H, OH, SH, alkylthio, alkyl, alkoxy, alkoxyalkyl, halide, hydroxylamino and CH3 q(hal)q in which q is 1-3 and hal is a halide; and
the amount is effective for lowering intraocular pressure.
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Abstract
Methods for treatment of conditions of abnormally increased intraocular pressure, particularly those caused by glaucoma, by administration of phosphonylmethoxyalkyl nucleoside analogs are provided. Compositions formulated and packaged for intraocular administration for use in the methods are also provided. Administration of the compound may be by intravitreal injection, aqueous humor injection, injection into the external layers of the eye, such as subconjunctival injection or subtenon injection, or may be, when penetrating derivatives are used, by topical application to the eye. The degree of reduction in pressure is dosage-dependent, and significant reduction in pressure is obtained. A single injection can produce prolonged, and perhaps permanent, lowering of the intraocular pressure.
85 Citations
37 Claims
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1. A method for reducing intraocular pressure, comprising administering to the eye an effective amount of a compound of formula I:
- ##STR8## or a pharmaceutically acceptable salt or ester thereof, wherein;
R1 and R2 are (i) or (ii) as follows;(i) R1 is CH2 CH(OH)(CH2)n, CH2 CH(CH2)n (OH), CH2 OCH(R7), CH2 OCH(R7)(CH2)p, CH2 OCH(R7)(CH2)p O or O(CH2)p CH(R7)O; R2 is OH or O(CH2)r H; R7 is OH or (CH2)r OH; n is 0-6; r is 1-6; p is 0-3; and m is 0 to 3 (ii) R1, R2, n, m, r and p are defined as in (i), and R1 and R2 are linked to form a cyclic ester group; B is a pyrimidine or purine of formula (II);
##STR9## and is selected from the group consisting of pyrimidin-1-yl, pyrimidinyl-3-yl, purin-3-yl, purin-7-yl and purin9-yl; andR3, R4, R5 and R6 are independently selected from NH2, alkylamino, aminoalkyl, hydroxyalkyl, hydrazino, H, OH, SH, alkylthio, alkyl, alkoxy, alkoxyalkyl, halide, hydroxylamino and CH3 q(hal)q in which q is 1-3 and hal is a halide; and the amount is effective for lowering intraocular pressure. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 28, 29, 30, 31, 32, 33, 34, 35, 37)
- ##STR8## or a pharmaceutically acceptable salt or ester thereof, wherein;
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2. A method for reducing intraocular pressure, comprising administering to the eye an effective amount of a compound selected from the group consisting of:
- ##STR10## or a pharmaceutically acceptable salt or ester thereof, wherein;
R7 is H, OH, or (CH2)r OH; andB is a pyrimidine or purine of formula (II);
##STR11## and is selected from the group consisting of pyrimidin-1-yl, pyrimidinyl-3-yl, purin-3-yl, purin-7-yl and purin-9-yl;R3, R4, R5 and R6 are independently selected from NH2, alkylamino, aminoalkyl, hydroxyalkyl, hydrazino, H, OH, SH, alkylthio, alkyl, alkoxy, alkoxyalkyl, halide, hydroxylamino and CH3-q (hal)q in which q is 1-3 and hal is a halide; and the amount is effective for lowering intraocular pressure. - View Dependent Claims (24, 27, 36)
- ##STR10## or a pharmaceutically acceptable salt or ester thereof, wherein;
Specification