Compounds for treating autoimmune and demyelinating diseases

A method of treating a patient suffering from demyelinating condition, comprising:

• administering to said patient a therapeutically effective amount of a compound of formula (A) or a pharmaceutically acceptable salt thereof:
• wherein:
• R is —H, an optionally substituted alkyl, a hydroxyl, an alkoxy group, a halogen, a group represented by the following structural formula
• or, R and R5 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• or R and R4 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• R2 is —H, an optionally substituted C1-C10 alkyl or an optionally substituted aryl or heteroaryl;
• R3 is —(CH2)n—NRaRb, wherein n=1-5, and Ra and Rb, each independently are hydrogen or an optionally substituted alkyl, or —NRaRb is an N-morpholinyl or N-pyrazinyl optionally substituted at one or more substitutable carbons with methyl, hydroxyl, or methoxy group, and wherein the N-pyrazinyl is optionally N′-substituted with C1-C4 alkyl or C1-C4 alkyl substituted with —NRcRd, wherein Rc and Rd are individually —H, methyl or ethyl;
• R4, R5 and R6, are each independently —H, —OH, a halogen or a C1-C6 alkoxy;
• or
• R5 and R5 taken together with their intervening carbon atoms, form a 5, 6 or 7 member, optionally substitited cycloalkyl or non-aromatic heterocycle.

A method of treating a patient suffering from multiple sclerosis, comprising:

• administering to said patient a therapeutically effective amount of a compound of formula (A) or a pharmaceutically acceptable salt thereof:
• wherein:
• R is —H, an optionally substituted alkyl, a hydroxyl, an alkoxy group, a halogen, a group represented by the following structural formula
• or, R and R5 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• or R and R4 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• R2 is —H, an optionally substituted C1-C10 alkyl or an optionally substituted aryl or heteroaryl;
• R3 is —(CH2)n—NRaRb, wherein n=1-5, and Ra and Rb, each independently are hydrogen or an optionally substituted alkyl, or —NRaRb is an N-morpholinyl or N-pyrazinyl optionally substituted at one or more substitutable carbons with methyl, hydroxyl, or methoxy group, and wherein the N-pyrazinyl is optionally N′-substituted with C1-C4 alkyl or C1-C4 alkyl substituted with —NRcRd, wherein Rc and Rd are individually —H, methyl or ethyl;
• R4, R5 and R6, are each independently —H, —OH, a halogen or a C1-C6 alkoxy;
• or
• R5 and R5 taken together with their intervening carbon atoms, form a 5, 6 or 7 member, optionally substitited cycloalkyl or non-aromatic heterocycle.

A method of promoting remyelination of nerve cells in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of formula (A) or a pharmaceutically acceptable salt thereof:

• wherein:
• R is —H, an optionally substituted alkyl, a hydroxyl, an alkoxy group, a halogen, a group represented by the following structural formula
• or, R and R5 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• or R and R4 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• R2 is —H, an optionally substituted C1-C10 alkyl or an optionally substituted aryl or heteroaryl;
• R3 is —(CH2)n—NRaRb, wherein n=1-5, and Ra and Rb, each independently are hydrogen or an optionally substituted alkyl, or —NRaRb is an N-morpholinyl or N-pyrazinyl optionally substituted at one or more substitutable carbons with methyl, hydroxyl, or methoxy group, and wherein the N-pyrazinyl is optionally N′-substituted with C1-C4 alkyl or C1-C4 alkyl substituted with —NRcRd, wherein Rc and Rd are individually —H, methyl or ethyl;
• R4, R5 and R6, are each independently —H, —OH, a halogen or a C1-C6 alkoxy;
• or
• R5 and R5 taken together with their intervening carbon atoms, form a 5, 6 or 7 member, optionally substitited cycloalkyl or non-aromatic heterocycle.

A composition comprising a therapeutically effective amount of a compound of formula (A) below, or pharmaceutically acceptable salt thereof, and an anti-inflammatory agent:

• wherein:
• R is —H, an optionally substituted alkyl, a hydroxyl, an alkoxy group, a halogen, a group represented by the following structural formula
• or, R and R5 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• or R and R4 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• R2 is —H, an optionally substituted C1-C10 alkyl or an optionally substituted aryl or heteroaryl;
• R3 is —(CH2)n—NRaRb, wherein n=1-5, and Ra and Rb, each independently are hydrogen or an optionally substituted alkyl, or —NRaRb is an N-morpholinyl or N-pyrazinyl optionally substituted at one or more substitutable carbons with methyl, hydroxyl, or methoxy group, and wherein the N-pyrazinyl is optionally N′-substituted with C1-C4 alkyl or C1-C4 alkyl substituted with —NRcRd, wherein Rc and Rd are individually —H, methyl or ethyl;
• R4, R5 and R6, are each independently —H, —OH, a halogen or a C1-C6 alkoxy;
• or
• R5 and R5 taken together with their intervening carbon atoms, form a 5, 6 or 7 member, optionally substitited cycloalkyl or non-aromatic heterocycle.

A method of reversing paralysis in a patient resulting from a demyelinating disease, comprising administering to the patient a compound in an amount sufficient to inhibit lymphocyte infiltration of immune cells in the spinal cord to promote remyelination of nerve cells in the spinal cord and thereby treating paralysis in said patient, wherein the compound is of formula formula (A) or a pharmaceutically acceptable salt thereof:

• wherein:
• R is —H, an optionally substituted alkyl, a hydroxyl, an alkoxy group, a halogen, a group represented by the following structural formula
• or, R and R5 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• or R and R4 taken together with their intervening carbon atoms form a 5, 6 or 7 member, optionally substituted, cycloalkyl or non-aromatic heterocycle;
• R2 is —H, an optionally substituted C1-C10 alkyl or an optionally substituted aryl or heteroaryl;
• R3 is —(CH2)n—NRaRb, wherein n=1-5, and Ra and Rb, each independently are hydrogen or an optionally substituted alkyl, or —NRaRb is an N-morpholinyl or N-pyrazinyl optionally substituted at one or more substitutable carbons with methyl, hydroxyl, or methoxy group, and wherein the N-pyrazinyl is optionally N′-substituted with C1-C4 alkyl or C1-C4 alkyl substituted with —NRcRd, wherein Rc and Rd are individually —H, methyl or ethyl;
• R4, R5 and R6, are each independently —H, —OH, a halogen or a C1-C6 alkoxy;
• or
• R5 and R5 taken together with their intervening carbon atoms, form a 5, 6 or 7 member, optionally substitited cycloalkyl or non-aromatic heterocycle.