Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
AssigneeAerie Pharmaceuticals, Inc.
InventorsMitchell A. deLong, Jill Marie Sturdivant, Susan M. Royalty
Life of this patent
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Abstract
Disclosed are beta and gamma-amino isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gamma-amino isoquinoline amide compounds or substituted benzamide compounds.
Claims25
A method of treating an eye disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a compound of formula (I):
- or a pharmaceutically acceptable salt thereof;
- wherein
- R1 and R2 are, independently, hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, or C1-C4 carboxyl;
- or R1 and R2 combine to form a heterocycloalkyl ring of at least 5 and at most 8 member atoms, or R1 and R3 combine to form a heterocycloalkyl ring of at least 5 and at most 8 member atoms;
- one of R3 and R4 is an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, and the other of R3 and R4 is hydrogen or C1-C4 alkyl;
- and
- X1 and X2 are, independently, hydrogen, hydroxyl, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, amino, nitro, cyano, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, or C1-C4 carboxyl.
A method of modulating kinase activity in a cell, comprising contacting the cell with a composition in an amount effective to modulate kinase activity, wherein the composition comprises a compound of formula (I):
- or a pharmaceutically acceptable salt thereof;
- wherein
- R1 and R2 are, independently, hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, or C1-C4 carboxyl;
- or R1 and R2 combine to form a heterocycloalkyl ring of at least 5 and at most 8 member atoms, or R1 and R3 combine to form a heterocycloalkyl ring of at least 5 and at most 8 member atoms;
- one of R3 and R4 is an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, and the other of R3 and R4 is hydrogen or C1-C4 alkyl;
- and
- X1 and X2 are, independently, hydrogen, hydroxyl, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, amino, nitro, cyano, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, or C1-C4 carboxyl.
A method of reducing intraocular pressure in a subject in need thereof, comprising administering an effective amount of a composition to an eye of the subject, wherein the composition comprises a compound of formula (I):
- or a pharmaceutically acceptable salt thereof;
- wherein
- R1 and R2 are, independently, hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, or C1-C4 carboxyl;
- or R1 and R2 combine to form a heterocycloalkyl ring of at least 5 and at most 8 member atoms, or R1 and R3 combine to form a heterocycloalkyl ring of at least 5 and at most 8 member atoms;
- one of R3 and R4 is an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, and the other of R3 and R4 is hydrogen or C1-C4 alkyl;
- and
- X1 and X2 are, independently, hydrogen, hydroxyl, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, amino, nitro, cyano, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, or C1-C4 carboxyl.
Dependencies are inferred from the claim text.