6-and 7-amino isoquinoline compounds and methods for making and using the same

A 7-aminoisoquinoline compound according to Formula (II)

• any optical isomer, diastereomer, or enantiomer of Formula II or a physiologically acceptable salt or solvate thereof,
• wherein R1 is hydrogen, a lower alkyl group, an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, the stereocenter being either ‘R’ or ‘S’ in configuration,
• R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group or R1 and R7 combine to form a ring, of at least three and at most 8 member atoms,
• R2, and R3 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, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group;
• or R2 and R3 combine to form a ring of at least five and at most 8 member atoms,
• X is a carbonyl group, a sulfone group, thiocarbonyl or methylene, and
• R4 and R5 are independently, halogen, hydrogen, hydroxy, alkyl, alkoxy, amino, carbonyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl.

A pharmaceutical composition comprising

• a) a 6-aminoisoquinoline derivative according to Formula I
• any optical isomer, diastereomer, or enantiomer of Formula I or a physiologically acceptable salt or solvate thereof,
• wherein R1 is an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, the stereocenter being either ‘R’ or ‘S’ in configuration,
• R7 is hydrogen, C1-C4 alkyl, cyano, or R1 and R7 combine to form a ring of at least three and at most eight member atoms,
• R2, and R3 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, C1-C4 carboxyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, or C1-C4 alkyl heteroaryl;
• or R2 and R3 combine to form a ring of at least five and at most eight member atoms,
• X is a carbonyl group, a sulfone group, thiocarbonyl or methylene, and
• R4 and R5 are independently, halogen, hydrogen, hydroxy, alkyl, alkoxy, amino, carbonyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, alkenyl, alkynyl, nitro, cyano, C1-C4 carbonylamino, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl or C1-C4 carboxyl,
• or
• a 7-isoquinoline derivative according to Formula II
• any optical isomer, diastereomer, or enantiomer of Formula II or a physiologically acceptable salt or solvate thereof,
• wherein R1 is hydrogen, a lower alkyl group, an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, the stereocenter being either ‘R’ or ‘S’ in configuration,
• R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group or R1 and R7 combine to form a ring, of at least three and at most 8 member atoms,
• R2, and R3 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, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group;
• or R2 and R3 combine to form a ring of at least five and at most 8 member atoms,
• X is a carbonyl group, a sulfone group, thiocarbonyl or methylene, and
• R4 and R5 are independently, halogen, hydrogen, hydroxy, alkyl, alkoxy, amino, carbonyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, and
• b) a carrier.

A method for treating a disease in a mammal comprising:

• administering to a mammal a safe and effective amount of a 6-aminoisoquinoline derivative according to Formula I
• any optical isomer, diastereomer, or enantiomer of Formula I or a physiologically acceptable salt or solvate thereof,
• wherein R1 is an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, the stereocenter being either ‘R’ or ‘S’ in configuration,
• R7 is hydrogen, C1-C4 alkyl, cyano, or R1 and R7 combine to form a ring of at least three and at most eight member atoms,
• R2, and R3 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, sulfonyl, C1-C4 sulfonylamino, thioalkyl, C1-C4-carboxyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, or C1-C4 alkyl heteroaryl;
• or R2 and R3 combine to form a ring of at least five and at most eight member atoms,
• X is a carbonyl group, a sulfone group, thiocarbonyl or methylene, and
• R4 and R5 are independently, halogen, hydrogen, hydroxy, alkyl, alkoxy, amino, carbonyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, alkenyl, alkynyl, nitro, cyano, C1-C4 carbonylamino, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl or C1-C4 carboxyl,
• wherein the disease comprises at least one 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 method for treating a disease in a mammal comprising:

• administering to a mammal a safe and effective amount of 7-isoquinoline derivative according to Formula II
• any optical isomer, diastereomer, or enantiomer of Formula II or a physiologically acceptable salt or solvate thereof,
• wherein R1 is hydrogen, a lower alkyl group, an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, the stereocenter being either ‘R’ or ‘S’ in configuration,
• R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group or R1 and R7 combine to form a ring, of at least three and at most 8 member atoms,
• R2, and R3 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, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group;
• or R2 and R3 combine to form a ring of at least five and at most 8 member atoms,
• X is a carbonyl group, a sulfone group, thiocarbonyl or methylene, and
• R4 and R5 are independently, halogen, hydrogen, hydroxy, alkyl, alkoxy, amino, carbonyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl,
• wherein the disease comprises at least one 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 method for influencing the action of a kinase in a cell, a tissue, or a living mammal comprising:

• administering to or contacting with a cell, a tissue, or a mammal a therapeutically effective amount of a first therapeutic agent comprising at least one of a 6-aminoisoquinoline derivative according to Formula I
• any optical isomer, diastereomer, or enantiomer of Formula I or a physiologically acceptable salt or solvate thereof,
• wherein R1 is an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, the stereocenter being either ‘R’ or ‘S’ in configuration,
• R7 is hydrogen, C1-C4 alkyl, cyano, or R1 and R7 combine to form a ring of at least three and at most eight member atoms,
• R2, and R3 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, C1-C4 carboxyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, or C1-C4 alkyl heteroaryl;
• or R2 and R3 combine to form a ring of at least five and at most eight member atoms,
• X is a carbonyl group, a sulfone group, thiocarbonyl or methylene, and
• R4 and R5 are independently, halogen, hydrogen, hydroxy, alkyl, alkoxy, amino, carbonyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, alkenyl, alkynyl, nitro, cyano, C1-C4 carbonylamino, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl or C1-C4 carboxyl,
• a 7-isoquinoline derivative according to Formula II
• any optical isomer, diastereomer, or enantiomer of Formula II or a physiologically acceptable salt or solvate thereof,
• wherein R1 is hydrogen, a lower alkyl group, an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, the stereocenter being either ‘R’ or ‘S’ in configuration,
• R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group or R1 and R7 combine to form a ring, of at least three and at most 8 member atoms,
• R2, and R3 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, aryl group, heteroaryl group, alkyl aryl group, cycloalkyl group or heterocycloalkyl group;
• or R2 and R3 combine to form a ring of at least five and at most 8 member atoms,
• X is a carbonyl group, a sulfone group, thiocarbonyl or methylene, and
• R4 and R5 are independently, halogen, hydrogen, hydroxy, alkyl, alkoxy, amino, carbonyl, cycloalkyl, heterocycloalkyl, aryl, C1-C4 alkyl aryl, heteroaryl, C1-C4 alkyl heteroaryl, or
• combination thereof,
• wherein the action of a kinase is influenced.