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US 5,510,347 AGranted
Thienothiadiazine sulfonamides useful as carbonic anhydrase inhibitors
AssigneeAlcon Laboratories, Inc.
InventorsThomas R. Dean, Abdelmoula Namil
Life of this patent
Estimating the term…
Abstract
New thienothiadiazine sulfonamides useful as carbonic anhydrase inhibitors are disclosed. Methods for using the compounds to control IOP are also disclosed.
Claims6
A compound having the following structure:
- ##STR5## or a pharmaceutically acceptable salt thereof wherein:
- R is H or C.sub.1-2 alkyl;
- R.sub.1 is H;
- C.sub.1-6 alkyl unsubstituted or substituted optionally with OH, C.sub.1-4 alkoxy, NR.sub.4 R.sub.5, OC(.dbd.O)R.sub.6 or C(.dbd.O)R.sub.6 ;
- R.sub.2 is H;
- C.sub.1-6 alkyl;
- C.sub.2-4 alkyl substituted with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.2-4 alkoxyC.sub.1-4 alkoxy, OC(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.7, or C(.dbd.O)R.sub.6 ;
- C(.dbd.O)R.sub.6 ;
- R.sub.3 is H;
- C.sub.1-8 alkyl;
- C.sub.1-8 alkyl substituted with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.2-4 alkoxyC.sub.1-4 alkoxy, OC(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.7, or C(.dbd.O)R.sub.6 ;
- C.sub.3-7 alkenyl unsubstituted or substituted optionally with OH, NR.sub.4 R.sub.5, or C.sub.1-4 alkoxy;
- C.sub.3-7 alkynyl unsubstituted or substituted optionally with OH, NR.sub.4 R.sub.5, or C.sub.1-4 alkoxy;
- C.sub.0-3 alkyl substituted with R.sub.7 which can be unsubstituted or substituted optionally with C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, OH, (CH.sub.2).sub.n NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, OC(.dbd.O)R.sub.6, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.8 or SO.sub.2 NR.sub.4 R.sub.5, wherein m is 0-2 and n is 0-2;
- R.sub.4 and R.sub.5 are the same or different and are H;
- C.sub.1-8 alkyl;
- C.sub.2-4 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- OH;
- C.sub.1-4 alkoxy;
- C.sub.2-4 alkoxy substituted optionally with OH, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- or R.sub.4 and R.sub.5 can be joined to form a ring of 5 or 6 atoms selected from O, S, C or N which can be unsubstituted or substituted optionally on carbon with OH, (.dbd.O), halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6 or on nitrogen with C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.8, C.sub.1-6 alkyl or C.sub.2-6 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6 or on sulfur by (.dbd.O).sub.m, wherein m is 0-2;
- R.sub.6 is C.sub.1-8 alkyl;
- C.sub.1-4 alkyl substituted optionally with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.9 ;
- C.sub.1-4 alkoxy;
- C.sub.2-4 alkoxy substituted optionally with OH, NR.sub.4 R.sub.5, halogen or C.sub.1-4 alkoxy;
- or NR.sub.4 R.sub.5 ;
- R.sub.7 is a monocyclic ring system selected from the group consisting of benzene, furan, thiophene, pyrrole, pyrazole, imidazole, triazole, tetrazole, oxazole, isoxazole, isothiazole, thiazole, thiadiazole, pyridine pyrimidine, pyridazine, and pyrazine;
- R.sub.8 is C.sub.1-4 alkyl;
- C.sub.2-4 alkyl substituted optionally with OH, NR.sub.4 R.sub.5, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- R.sub.7 which can be unsubstituted or substituted optionally with OH, (CH.sub.2).sub.n NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m C.sub.1-4 alkyl or SO.sub.2 NR.sub.4 R.sub.5 ;
- wherein m is 0-2 and n is 0-2;
- and
- R.sub.9 is C.sub.1-4 alkyl;
- C.sub.1-4 alkoxy;
- amino, C.sub.1-3 alkylamino, of di-C.sub.1-3 alkylamino.
32 more elements
A composition for lowering and controlling IOP comprising a pharmaceutically effective amount of a compound having the following structure:
- ##STR6## or a pharmaceutically acceptable salt thereof wherein:
- R is H or C.sub.1-2 alkyl;
- R.sub.1 is H;
- C.sub.1-6 alkyl unsubstituted or substituted optionally with OH, C.sub.1-4 alkoxy, NR.sub.4 R.sub.5, OC(.dbd.O)R.sub.6, or C(.dbd.O)R.sub.6 ;
- R.sub.2 is H;
- C.sub.1-6 alkyl;
- C.sub.2-4 alkyl substituted with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.2-4 alkoxyC.sub.1-4 alkoxy, OC(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.7, or C(.dbd.O)R.sub.6 ;
- C(.dbd.O)R.sub.6 ;
- R.sub.3 is H;
- C.sub.1-8 alkyl;
- C.sub.1-8 alkyl substituted with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.2-4 alkoxyC.sub.1-4 alkoxy, OC(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.7, or C(.dbd.O)R.sub.6 ;
- C.sub.3-7 alkenyl unsubstituted or substituted optionally with OH, NR.sub.4 R.sub.5, or C.sub.1-4 alkoxy;
- C.sub.3-7 alkynyl unsubstituted or substituted optionally with OH, NR.sub.4 R.sub.5, or C.sub.1-4 alkoxy;
- C.sub.0-3 alkyl substituted with R.sub.7 which can be unsubstituted or substituted optionally with C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, OH, (CH.sub.2).sub.n NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, OC(.dbd.O)R.sub.6, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.8 or SO.sub.2 NR.sub.4 R.sub.5, wherein m is 0-2 and n is 0-2;
- R.sub.4 and R.sub.5 are the same or different and are H;
- C.sub.1-8 alkyl;
- C.sub.2-4 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- OH;
- C.sub.1-4 alkoxy;
- C.sub.2-4 alkoxy substituted optionally with OH, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- or R.sub.4 and R.sub.5 can be joined to form a ring of 5 or 6 atoms selected from O, S, C or N which can be unsubstituted or substituted optionally on carbon with OH, (.dbd.O), halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6 or on nitrogen with C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.8, C.sub.1-6 alkyl or C.sub.2-6 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6 or on sulfur by (.dbd.O).sub.m, wherein m is 0-2;
- R.sub.6 is C.sub.1-8 alkyl;
- C.sub.1-4 alkyl substituted optionally with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.9 ;
- C.sub.1-4 alkoxy;
- C.sub.2-4 alkoxy substituted optionally with OH, NR.sub.4 R.sub.5, halogen or C.sub.1-4 alkoxy;
- or NR.sub.4 R.sub.5 ;
- R.sub.7 is a monocyclic ring system selected from the group consisting of benzene, furan, thiophene, pyrrole, pyrazole, imidazole, triazole, tetrazole, oxazole, isoxazole, isothiazole, thiazole, thiadiazole, pyridine pyrimidine, pyridazine, and pyrazine;
- R.sub.8 is C.sub.1-4 alkyl;
- C.sub.2-4 alkyl substituted optionally with OH, NR.sub.4 R.sub.5, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- R.sub.7 which can be unsubstituted or substituted optionally with OH, (CH.sub.2).sub.n NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m C.sub.1-4 alkyl or SO.sub.2 NR.sub.4 R.sub.5 ;
- wherein m is 0-2 and n is 0-2;
- and
- R.sub.9 is C.sub.1-4 alkyl;
- C.sub.1-4 alkoxy;
- amino, C.sub.1-3 alkylamino, of di-C.sub.1-3 alkylamino.
32 more elements
A method for lowering and controlling IOP by administering a pharmaceutically effective amount of a compound having the following structure:
- ##STR7## or a pharmaceutically acceptable salt thereof wherein:
- R is H or C.sub.1-2 alkyl;
- R.sub.1 is H;
- C.sub.1-6 alkyl unsubstituted or substituted optionally with OH, C.sub.1-4 alkoxy, NR.sub.4 R.sub.5, OC(.dbd.O)R.sub.6 or C(.dbd.O)R.sub.6 ;
- R.sub.2 is H;
- C.sub.1-6 alkyl;
- C.sub.2-4 alkyl substituted with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.2-4 alkoxyC.sub.1-4 alkoxy, OC(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.7, or C(.dbd.O)R.sub.6 ;
- C(.dbd.O)R.sub.6 ;
- R.sub.3 is H;
- C.sub.1-8 alkyl;
- C.sub.1-8 alkyl substituted with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.2-4 alkoxyC.sub.1-4 alkoxy, OC(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.7, or C(.dbd.O)R.sub.6 ;
- C.sub.3-7 alkenyl unsubstituted or substituted optionally with OH, NR.sub.4 R.sub.5, or C.sub.1-4 alkoxy;
- C.sub.3-7 alkynyl unsubstituted or substituted optionally with OH, NR.sub.4 R.sub.5, or C.sub.1-4 alkoxy;
- C.sub.0-3 alkyl substituted with R.sub.7 which can be unsubstituted or substituted optionally with C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, OH, (CH.sub.2).sub.n NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, OC(.dbd.O)R.sub.6, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.8 or SO.sub.2 NR.sub.4 R.sub.5, wherein m is 0-2 and n is 0-2;
- R.sub.4 and R.sub.5 are the same or different and are H;
- C.sub.1-8 alkyl;
- C.sub.2-4 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- OH;
- C.sub.1-4 alkoxy;
- C.sub.2-4 alkoxy substituted optionally with OH, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- or R.sub.4 and R.sub.5 can be joined to form a ring of 5 or 6 atoms selected from O, S, C or N which can be unsubstituted or substituted optionally on carbon with OH, (.dbd.O), halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6 or on nitrogen with C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m R.sub.8, C.sub.1-6 alkyl or C.sub.2-6 alkyl substituted optionally with OH, halogen, C.sub.1-4 alkoxy, C(.dbd.O)R.sub.6 or on sulfur by (.dbd.O).sub.m, wherein m is 0-2;
- R.sub.6 is C.sub.1-8 alkyl;
- C.sub.1-4 alkyl substituted optionally with OH, NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.9 ;
- C.sub.1-4 alkoxy;
- C.sub.2-4 alkoxy substituted optionally with OH, NR.sub.4 R.sub.5, halogen or C.sub.1-4 alkoxy;
- or NR.sub.4 R.sub.5 ;
- R.sub.7 is a monocyclic ring system selected from the group consisting of benzene, furan, thiophene, pyrrole, pyrazole, imidazole, triazole, tetrazole, oxazole, isoxazole, isothiazole, thiazole, thiadiazole, pyridine pyrimidine, pyridazine, and pyrazine;
- R.sub.8 is C.sub.1-4 alkyl;
- C.sub.2-4 alkyl substituted optionally with OH, NR.sub.4 R.sub.5, C.sub.1-4 alkoxy or C(.dbd.O)R.sub.6 ;
- R.sub.7 which can be unsubstituted or substituted optionally with OH, (CH.sub.2).sub.n NR.sub.4 R.sub.5, halogen, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C(.dbd.O)R.sub.6, S(.dbd.O).sub.m C.sub.1-4 alkyl or SO.sub.2 NR.sub.4 R.sub.5 ;
- wherein m is 0-2 and n is 0-2;
- and
- R.sub.9 is C.sub.1-4 alkyl;
- C.sub.1-4 alkoxy;
- amino, C.sub.1-3 alkylamino, of di-C.sub.1-3 alkylamino.
32 more elements
Dependencies are inferred from the claim text.