Ophthalmic compositions for treating ocular hypertension

A method for treating macular edema or macular degeneration comprising administration to a patient in need of such treatment a pharmaceutically effective amount of a compound of structural formula I:

• 11
• or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
• wherein,
• R1 represents hydrogen or C1-6 alkyl;
• R2, R3a and R3b independently represent hydrogen, alkylsilyl, C1-10 alkyl, C3-10 cycloalkyl, C4-10 heterocycloalkyl, C4-10 heteroaryl, NH2, or C6-10 aryl said alkyl, aryl or heteraryl optionally substituted with 1-3 groups of Rx;
• Rx represents C1-6 alkyl, halogen, CF3, C1-6 alkoxy, NR1R1, or NO2, or NH2;
• R4 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, or halogen;
• R5 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, nitro, amino, cyano, C1-6 alkylamino, or halogen and
• R6 represents hydrogen, halogen or C1-6 alkyl.

A method for increasing retinal and optic nerve head blood velocity or increasing retinal and optic nerve oxygen tension comprising administration to a patient in need of such treatment an effective ocular hypertensive formulation containing a potassium channel blocker of structural formula I:

• 15
• or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
• wherein,
• R1 represents hydrogen or C1-6 alkyl;
• R2, R3a and R3b independently represent hydrogen, alkylsilyl, C1-10 alkyl, C3-10 cycloalkyl, C4-10 heterocycloalkyl, C4-10 heteroaryl, NH2, or C6-10 aryl said alkyl, aryl or heteraryl optionally substituted with 1-3 groups of Rx;
• Rx represents C1-6 alkyl, halogen, CF3, C1-6 alkoxy, NR1R1, or NO2, or NH2;
• R4 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, or halogen;
• R5 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, nitro, amino, cyano, C1-6 alkylamino, or halogen and
• R6 represents hydrogen, halogen or C1-6 alkyl.

A method for providing a neuroprotective effect comprising administration to a patient in need of such treatment a therapeutically effective amount of structural formula I:

• 19
• or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
• wherein,
• R1 represents hydrogen or C1-6 alkyl;
• R2, R3a and R3b independently represent hydrogen, alkylsilyl, C1-10 alkyl, C3-10 cycloalkyl, C4-10 heterocycloalkyl, C4-10 heteroaryl, NH2, or C6-10 aryl said alkyl, aryl or heteraryl optionally substituted with 1-3 groups of Rx;
• Rx represents C1-6 alkyl, halogen, CF3, C1-6 alkoxy, NR1R1, or NO2, or NH2;
• R4 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, or halogen;
• R5 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, nitro, amino, cyano, C1-6 alkylamino, or halogen and
• R6 represents hydrogen, halogen or C1-6 alkyl.

A method for treating ocular hypertension or glaucoma comprising administration to a patient in need of such treatment a therapeutically effective amount of structural formula I:

• 23
• or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
• wherein,
• R1 represents hydrogen or C1-6 alkyl;
• R2, R3a and R3b independently represent hydrogen, alkylsilyl, C1-10 alkyl, C3-10 cycloalkyl, C4-10 heterocycloalkyl, C4-10 heteroaryl, NH2, or C6-10 aryl said alkyl, aryl or heteraryl optionally substituted with 1-3 groups of Rx;
• Rx represents C1-6 alkyl, halogen, CF3, C1-6 alkoxy, NR1R1, or NO2, or NH2;
• R4 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, or halogen;
• R5 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, nitro, amino, cyano, C1-6 alkylamino, or halogen and
• R6 represents hydrogen, halogen or C1-6 alkyl.

A method of preventing repolarization or hyperpolarization of a mammalian cell wherein the cell contains a potassium channel comprising the administration to a mammal, including a human, in need thereof, of a pharmacologically effective amount of a potassium channel blocker of structural formula I:

• 27
• or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
• wherein,
• R1 represents hydrogen or C1-6 alkyl;
• R2, R3a and R3b independently represent hydrogen, alkylsilyl, C1-10 alkyl, C3-10 cycloalkyl, C4-10 heterocycloalkyl, C4-10 heteroaryl, NH2, or C6-10 aryl said alkyl, aryl or heteraryl optionally substituted with 1-3 groups of Rx;
• Rx represents C1-6 alkyl, halogen, CF3, C1-6 alkoxy, NR1R1, or NO2, or NH2;
• R4 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, or halogen;
• R5 represents hydrogen, C1-6 alkoxy, C1-6 alkyl, CF3, nitro, amino, cyano, C1-6 alkylamino, or halogen and R6 represents hydrogen, halogen or C1-6 alkyl.