Aminopyrazine analogs for treating glaucoma and other rho kinase-mediated diseases and conditions
AssigneeAlcon Inc.
InventorsMark Hellberg, Andrew Rusinko, Alan Henderson, Cheng Guo, Mark Hadden, Helene Decornez
Life of this patent
Estimating the term…
Abstract
Methods for using aminopyrazine analogs to treat rho kinase-mediated diseases or rho kinase-mediated conditions, including controlling intraocular pressure and treating glaucoma, are disclosed. Ophthalmic pharmaceutical compositions useful in the treatment of eye diseases such as glaucoma, and additionally useful for controlling intraocular pressure, the compositions comprising an effective amount of aminopyrazine analogs, are also disclosed.
Claims17
An ophthalmic pharmaceutical composition useful in the treatment of glaucoma and control of intraocular pressure, comprising an effective amount of a compound (I) of the following formula:
- in which Y is selected from the following groups:
- where:
- X═OR1, NR2R3;
- z=H, OR6, halogen, CF3, or C1-C4 alkyl;
- R is OH, OR4, or S(O)NR6;
- n is 0, 1 or 2;
- R1, R2, R3 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl or heteroaryl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl, or heteroaryl, and heterocyclyl;
- R2 and R3 together can form a heterocyclic ring;
- R4, R5 independently ═H, C1-C6 alkyl optionally substituted by OH, OR6, aryl, heterocyclyl, or heteroaryl;
- R6═C1-C6 alkyl, aryl, or CF3;
- B═NR7R8;
- R7, R8 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR6, or heterocycyl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, or heterocyclyl, and heterocyclyl;
- and
- R7 and R8 together can form a heterocyclic ring;
- and
- a pharmaceutically acceptable vehicle therefor.
A method of controlling intraocular pressure comprising:
- applying a therapeutically effective amount of an ophthalmic pharmaceutical composition useful in the treatment of glaucoma and control of intraocular pressure to the affected eye of a human or other mammal, the composition comprising an effective amount of a compound of the following formula:
- in which Y is selected from the following groups:
- where:
- X═OR1, NR2R3;
- z=H, OR6, halogen, CF3, or C1-C4 alkyl;
- R is OH, OR4, or S(O)NR6;
- n is 0, 1 or 2;
- R1, R2, R3 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl or heteroaryl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl, or heteroaryl, and heterocyclyl;
- R2 and R3 together can form a heterocyclic ring;
- R4, R5 independently ═H, C1-C6 alkyl optionally substituted by OH, OR6, aryl, heterocyclyl, or heteroaryl;
- R6═C1-C6 alkyl, aryl, or CF3;
- B═NR7R8;
- R7, R8 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR6, or heterocycyl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, or heterocyclyl, and heterocyclyl;
- and
- R7 and R8 together can form a heterocyclic ring;
- and
- a pharmaceutically acceptable vehicle therefor.
A method of treating rho kinase-mediated diseases or rho kinase-mediated conditions, which comprises administering to a human or other mammal a therapeutically effective amount of a compound of the following formula:
- in which Y is selected from the following groups:
- where:
- X═OR1, NR2R3;
- z=H, OR6, halogen, CF3, or C1-C4 alkyl;
- R is OH, OR4, or S(O)NR6;
- n is 0, 1 or 2;
- R1, R2, R3 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl or heteroaryl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl, or heteroaryl, and heterocyclyl;
- R2 and R3 together can form a heterocyclic ring;
- R4, R5 independently ═H, C1-C6 alkyl optionally substituted by OH, OR6, aryl, heterocyclyl, or heteroaryl;
- R6═C1-C6 alkyl, aryl, or CF3;
- B═NR7R8;
- R7, R8 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR6, or heterocycyl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, or heterocyclyl, and heterocyclyl;
- and
- R7 and R8 together can form a heterocyclic ring;
- and
- a pharmaceutically acceptable vehicle therefor.
A compound represented by Formula (I):
- in which Y is selected from the following groups:
- where:
- X═OR1, NR2R3;
- z=H, OR6, halogen, CF3, or C1-C4 alkyl;
- R15 is OH, OR1, or S(O)NR6;
- n is 0, 1 or 2;
- R1, R2, R3 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl or heteroaryl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, aryl, heterocyclyl, or heteroaryl, and heterocyclyl;
- R2 and R3 together can form a heterocyclic ring;
- R4, R5 independently ═H, C1-C6 alkyl optionally substituted by OH, OR6, aryl, heterocyclyl, or heteroaryl;
- R6═C1-C6 alkyl, aryl, or CF3;
- B═NR7R8;
- R7, R8 independently ═H, C1-C6 alkyl optionally substituted by NR4R5, OH, OR1, or heterocycyl, C3-C8 cyclic alkyl optionally substituted by NR4R5, OH, OR6, or heterocyclyl, and heterocyclyl;
- and
- R7 and R8 together can form a heterocyclic ring.
Dependencies are inferred from the claim text.