Treatments for alzheimer's related diseases and disorders

A method of alleviating a neuropsychiatric behavioral symptom associated with Alzheimer's disease comprising administering to a subject in need thereof an effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof:

• wherein, represents a single or double bond;
• R1 and R2 are both hydrogen or taken together R1 and R2 are ═O;
• R3 is chosen from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• R4 is chosen from hydrogen, halogen, hydroxy, amino, alkoxy, C1-C20 alkyl and substituted C1-C20 alkyl;
• R5 and R6 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• alternatively, R5 and R6 together form a carbonyl or a vinyl substituent;
• independently R7 and R8 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• alternatively, R7 and R8 together form an —O— or —S— group;
• and
• R9 is selected from —C(O)N(R20)(R21), —C(S)N(R20)(R21), aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

A method of alleviating a neuropsychiatric behavioral symptom associated with Alzheimer's disease comprising administering to a subject in need thereof an effective amount of a compound of Formula IA or a pharmaceutically acceptable salt thereof:

• wherein, represents a single or double bond;
• R1 and R2 are both hydrogen or taken together R1 and R2 are ═O;
• R3 is chosen from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• R4 is chosen from hydrogen, halogen, hydroxy, amino, alkoxy, C1-C20 alkyl and substituted C1-C20 alkyl;
• R5 and R6 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• alternatively, R5 and R6 together form a carbonyl or a vinyl substituent;
• each R20 and R21 is independently selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R7 and R8 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• alternatively, R7 and R8 together form an —O— or —S— group;
• and,
• R9 is selected from —C(O)N(R20)(R21), —C(S)N(R20)(R21), aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

A method of alleviating a neuropsychiatric behavioral symptom associated with Alzheimer's disease comprising administering to a subject in need thereof an effective amount of a compound of Formula IB or a pharmaceutically acceptable salt thereof:

• wherein, represents a single or double bond;
• m is 0, 1, 2 or 3;
• X is CH2, NR20, S, S(O)2 or O;
• R3 is chosen from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• and
• R21 is selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl and substituted aryl.

A compound of Formula IB or a pharmaceutically acceptable salt thereof:

• wherein, represents a single or double bond;
• m is 0, 1, 2 or 3;
• X is CH2, NR20, S, S(O)2 or O;
• R3 is chosen from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• and
• R21 is selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl and substituted aryl.

A method of treating a disease or disorder, or a symptom of a disease or disorder mediated by an N-methyl-D-aspartate (NMDA) receptor comprising the step of administering a compound of Formula I, or a pharmaceutically acceptable salt thereof, to a subject in need thereof:

• wherein, represents a single or double bond;
• R1 and R2 are both hydrogen or taken together R1 and R2 are ═O;
• R3 is chosen from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• R4 is chosen from hydrogen, halogen, hydroxy, amino, alkoxy, C1-C20 alkyl and substituted C1-C20 alkyl;
• R5 and R6 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• Alternatively R5 and R6 together form a carbonyl or a vinyl substituent;
• each R20 and R21 is independently selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R7 and R8 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• alternatively, R7 and R8 together form an —O— or —S— group;
• and,
• R9 is selected from —C(O)N(R20)(R21), —C(S)N(R20)(R21), aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycyl and substituted heterocyclyl.

A method of treating a disease or disorder, or a symptom of a disease or disorder mediated by an N-methyl-D-aspartate (NMDA) receptor comprising the step of administering a compound of Formula IA, or a pharmaceutically acceptable salt thereof, to a subject in need thereof:

• wherein, represents a single or double bond;
• R1 and R2 are both hydrogen or taken together R1 and R2 are ═O;
• R3 is chosen from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• R4 is chosen from hydrogen, halogen, hydroxy, amino, alkoxy, C1-C20 alkyl and substituted C1-C20 alkyl;
• R5 and R6 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• Alternatively, R5 and R6 together form a carbonyl or a vinyl substituent;
• each R20 and R21 is independently selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R7 and R8 are independently selected from hydrogen, halogen, —OR20, —SR20, —NR20R21, —C(O)R20, —C(O)OR20, —C(O)NR20R21, —N(R20)C(O)R21, —CF3, —CN, —NO2, —N3, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• alternatively, R7 and R8 together form an —O— or —S— group;
• and,
• R9 is selected from —C(O)N(R20)(R21), —C(S)N(R20)(R21), aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycyl and substituted heterocyclyl.

A method of treating a disease or disorder, or a symptom of a disease or disorder mediated by an N-methyl-D-aspartate (NMDA) receptor comprising the step of administering a compound of Formula IB, or a pharmaceutically acceptable salt thereof, to a subject in need thereof:

• wherein, represents a single or double bond;
• m is 0, 1, 2 or 3;
• X is CH2, NR20, S, S(O)2 or O;
• R3 is chosen from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl;
• and,
• R21 is selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl and substituted aryl.