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US 2016/0243105 A1Published application
Combination therapy
AssigneeAerie Pharmaceuticals, Inc.
InventorsCasey Kopczynski, Cheng-Wen Lin, Jill Marie Sturdivant, Mitchell A. deLong
Life of this patent
Estimating the term…
Abstract
Described herein are compounds and compositions for treating glaucoma and/or reducing intraocular pressure. Compositions may comprise an isoquinoline compound and a prostaglandin or a prostaglandin analog. Compounds described herein include those in which an isoquinoline compound is covalently linked to a prostaglandin or a prostaglandin analog, and those in which an isoquinoline compound and a prostaglandin free acid together form a salt.
Claims45
A composition comprising:
- a) a compound according to formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 and R2 are independently selected from the group consisting of hydrogen and C1-C4 alkyl, or R1 and R2 are taken together with the nitrogen atom to which they are attached to form a ring of 3, 4, 5, 6, 7 or 8 member atoms;
- A is selected from the group consisting of —CH2NH—, —CH(R10)—, —C(CH3)(R10)—, —CH2CH2—, —CH(R10)CH2—, —CH2CH2CH(R10)—, —CH2CH(R10)—, and —C(CH3)(R10)CH2—;
- each R10 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, amino, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, any of which may be optionally substituted;
- and
- X1 and X2 are independently selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, amino, nitro, cyano, carbonyl, carbonylamino, alkoxy, aryloxy, sulfonyl, sulfonamido, thioalkyl, and carboxyl;
- and
- b) a prostaglandin or a prostaglandin analog.
6 more elements
A compound according to formula (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- Y is selected from the group consisting of alkylene, aryl, heteroaryl, cycloalkyl, and heterocyclyl, any of which may be optionally substituted;
- B is selected from the group consisting of —NR1R2, —CH2NR1R2, —CH(R10)R2, —CCH3(R10) R2, —NHCH(R10)R2, —N(CH3)R2, —CH2CH2R2, —CH(R10)CH2R2, and —CH2CH(R10)R2;
- R1, R2 and R10 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, amino, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, any of which may be optionally substituted;
- X1 and X2 are independently selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, amino, nitro, cyano, carbonyl, carbonylamino, alkoxy, aryloxy, sulfonyl, sulfonamido, thioalkyl, and carboxyl;
- and
- PG is the acyl radical of a prostaglandin or a prostaglandin analog.
4 more elements
A compound of formula (III):
- wherein:
- R1 and R2 are independently selected from the group consisting of hydrogen and C1-C4 alkyl, or R1 and R2 are taken together with the nitrogen atom to which they are attached to form a ring of 3, 4, 5, 6, 7 or 8 member atoms;
- A is selected from the group consisting of —CH2NH—, —CH(R10)—, —C(CH3)(R10)—, —CH2CH2—, —CH(R10)CH2—, —CH2CH2CH(R10)—, —CH2CH(R10)—, and —C(CH3)(R10)CH2—;
- each R10 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, amino, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, any of which may be optionally substituted;
- X1 and X2 are independently selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, amino, nitro, cyano, carbonyl, carbonylamino, alkoxy, aryloxy, sulfonyl, sulfonamido, thioalkyl, and carboxyl;
- and
- PG⊖ is a deprotonated free acid of a prostaglandin or a prostaglandin analog.
4 more elements
A composition comprising:
- a) (rac)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide hydrochloride;
- and
- b) a prostaglandin selected from the group consisting of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, latanoprostene bunod, unoprostone, PGF2α and fluprostenol.
A composition comprising:
- a) (R)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide hydrochloride;
- and
- b) a prostaglandin selected from the group consisting of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, latanoprostene bunod, unoprostone, PGF2α and fluprostenol.
A composition comprising:
- a) (S)-2-(dimethylamino)-N-(1-hydroxyisoquinolin-6-yl)-2-(thiophen-3-yl)acetamide hydrochloride;
- and
- b) a prostaglandin selected from the group consisting of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, latanoprostene bunod, unoprostone, PGF2α and fluprostenol.
A composition comprising:
- a) (rac)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimesylate;
- and
- b) a prostaglandin selected from the group consisting of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, latanoprostene bunod, unoprostone, PGF2α and fluprostenol.
A composition comprising:
- a) (R)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimesylate;
- and
- b) a prostaglandin selected from the group consisting of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, latanoprostene bunod, unoprostone, PGF2α and fluprostenol.
A composition comprising:
- a) (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimesylate;
- and
- b) a prostaglandin selected from the group consisting of latanoprost, bimatoprost, travoprost, tafluprost, AR-102, cloprostenol, latanoprostene bunod, unoprostone, PGF2α and fluprostenol.
Dependencies are inferred from the claim text.