6-Aminoisoquinoline Compounds
AssigneeAerie Pharmaceuticals, Inc.
InventorsMitchell A. deLong, Susan M. Royalty, Jill Marie Sturdivant, Geoffrey Richard Heintzelman
Life of this patent
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Abstract
6-Amino isoquinoline compounds are provided that influence, inhibit or reduce the action of a kinase. Pharmaceutical compositions including therapeutically effective amounts of the 6-aminoisoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, obesity and glaucoma are also provided.
Claims43
A compound according to Formula (I):
- wherein A is —CH2NH—,
- —SCH2—, —CH2S(O)—, —CH2S(O)(O)—, —S(O)CH2—, —S(O)(O)CH2—, —CH2CH2—, —CH(R10)CH2—, —CH2CH(R10)—, —CH═CH—,
- wherein R10 is hydrogen, unsubstituted C1-C4 alkyl, C1-C4 alkenyl, C1-C4 alkynyl, or amino;
- wherein R1, and R2 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;
- and
- wherein R3 is hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, amino, cyano, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, carbonyl, carbonylamino, thioalkyl, sulfonyl, sulfonylamino, acyl, or carboxyl.
A compound according to Formula II:
- wherein R1 and R2 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;
- wherein R4 is hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, amino, cyano, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, carbonyl, carbonylamino, thioalkyl, sulfonyl, sulfonylamino, acyl, or carboxyl;
- and
- wherein B is a chain containing from 0 to 3 member atoms, X represents n independently chosen member atoms which together form a ring structure and n is an integer from about 0 to about 5.
A compound according to Formula III:
- wherein one of X1, X2 and X3 is independently selected from CH2, O, S, S(O), S(O)(O),
- and the other two of X1, X2 and X3 are independently selected from CH2, O, S, S(O), S(O)(O),
- and bond;
- wherein R1, and R2 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 and C1-C4 carboxyl;
- and
- wherein R5 and R10 are independently hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, amino, cyano, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, carbonyl, carbonylamino, thioalkyl, sulfonyl, sulfonylamino, acyl, or carboxyl.
A compound according to Formula IV
- wherein A is a substituted or unsubstituted linker consisting of at least one member atom and at most 4 member atoms wherein the linker may be mono- or disubstituted with halogen, cyano, nitro or C1-C4 alkyl, or the substituted atoms may attach back to the main chain to form a ring;
- wherein R1, and R2 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;
- and
- wherein R3 is hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, amino, cyano, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, carbonyl, carbonylamino, thioalkyl, sulfonyl, sulfonylamino, acyl, or carboxyl.
A pharmaceutical composition comprising:
- a) a 6-aminoisoquinoline derivative having the structure
- wherein R1, and R2 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;
- and
- wherein R4 is hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, amino, cyano, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, carbonyl, carbonylamino, thioalkyl, sulfonyl, sulfonylamino, acyl, or carboxyl;
- and
- b) a carrier.
A method of treating a condition comprising administering to a subject in need of treatment a safe and effective amount of a 6-aminoisoquinoline derivative, wherein the condition is selected from the group consisting of eye disease, bone disorder, obesity, heart disease, hepatic disease, renal disease, pancreatitis, cancer, myocardial infarct, gastric disturbance, hypertension, fertility control, nasal congestion, neurogenic bladder disorder, gastrointestinal disorder, and dermatological disorder.
A compound selected from the following:
Dependencies are inferred from the claim text.