Maxi-k channel blockers, methods of use and process for making the same
View Patent ↗This invention relates to the use of potent potassium channel blockers or a formulation thereof in the treatment of glaucoma and other conditions related to elevated intraocular pressure in the eye of a patient. This invention also relates to the use of such compounds to provide a neuroprotective effect to the eye of a mammalian species, particularly humans.
1. A compound of structural formula I:
or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer or mixture thereof, wherein,
R 1 and R 1a independently are:
R 2 is:
(a) CO 2 C 1-6 alkyl,
(b) H,
(c) OH, or
(d) C 1-6 alkyl,
when a double bond is not present at b;
R 3 is:
(a) H,
(b) (C═O)OC 1-6 alkyl or
(c) C 1-6 alkyl optionally substituted with OH, N(R 6 ) 2 , or CO 2 R 6 ;
R 4 is
(a) H, provided that R 3 is not H,
(b) C 1-6 alkyl optionally substituted with OH, N(R 6 ) 2 , or CO 2 R 6 or
R 5 is:
(a) H,
(b) OH, or
(c) OC 1-6 alkyl;
R 6 is:
(a) H, or
(b) C 1-6 alkyl;
R 7 is H, or C 1-6 alkyl optionally substituted with OH, N(R 6 ) 2 , or CO 2 R 6 ;
R 8 is H, C 1-6 alkyl, CH 2 -phenyl, CH 2 -hydroxyphenyl, CH 2 -indolyl, CH 2 -imidazolyl, CH 2 OR 6 , CH(OR 6 )CH 3 , (CH 2 ) n C(O)NR 6 , (CH 2 ) n CO 2 R 6 , (CH 2 ) n SR 6 , (CH 2 ) n (N + R 6 ) 3 ,
n is 0-4, and
is a double bond optionally and independently present at a or b.
2. A compound according to claim 1 wherein R 1 , R 1a and R 3 are hydrogen.
3. A compound according to claim 1 wherein R 4 is
4. A compound according to claim 1 wherein R 2 and R 7 are hydrogen and R 4 is
5. A compound which is:
or a pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer or mixture thereof.
6. A composition comprising a compound of formula I as recited in claim 1 and a pharmaceutically acceptable carrier.