Pyrido[3,4-b]indoles and methods of use

A compound of the formula (A):

• wherein:
• R1 is H, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, carboxyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy, or R1 and R2a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R1 and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• each R2a and R2b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R2a and R2b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R2a and R1 are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R2a and R3a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety, or R2a and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• each R3a and R3b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, nitro, hydroxyl, alkoxy, substituted or unsubstituted amino, cycloalkyl, aryl, heteroaryl, heterocyclyl, acylamino or acyloxy or R3a and R3b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R3a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R3a and R2a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety, or R3a and R10a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• each R10a and R10b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, hydroxyl, alkoxy cyano, nitro, or R10a and R10b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R10a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R10a and R2a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R10a and R3a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• each X7, X8, X9 and X10 is independently N or CR4;
• each R4 is independently H, hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, C1-C8 alkoxy, aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;
• m and q are independently 0 or 1;
• each R8a, R8b, R8c and R8d is independently H, hydroxyl, halo, alkoxy, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted C2-C8alkenyl, C1-C8 perhaloalkyl, carboxyl, carbonylalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or is taken together with a geminal R8(a-d) to form a substituted or unsubstituted methylene moiety or a moiety of the formula —OCH2CH2O—, or is taken together with a geminal R8(a-d) and the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety;
• each R11 and R12 is independently H, halo, alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C3-C8 cycloalkyl, carboxy, carbonylalkoxy or C1-C8 perhaloalkyl and the bond indicates the presence of either an E or Z double bond configuration, or R11 and R12 are taken together to form a bond or are taken together with the carbon atoms to which they are attached to form a substituted or unsubstituted C3-8 cycloalkenyl or substituted or unsubstituted heterocyclyl moiety;
• Q is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted amino, alkoxy, aminoacyl, acyloxy, carboxyl, carbonylalkoxy, cyano, alkynyl, aminocarbonylalkoxy or acylamino;
• provided that the compound conforms to one of provisions (i)-(vi):
• (i) R1 and R2a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• (ii) R1 and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• (iii) R1 and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• (iv) R2a and R3a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety;
• (v) R2a and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• and (vi) R3a and R10a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula (II):

• wherein:
• R2b is H, halo, or substituted or unsubstituted C1-C8 alkyl;
• each R3a and R3b is independently H, halo, or substituted or unsubstituted C1-C8 alkyl;
• each R10a and R10b is independently H, halo, or a substituted or unsubstituted C1-C8 alkyl;
• p is 1 or 2;
• each X7, X8, X9 and X10 is independently N or CR4;
• each R4 is independently H, hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, C1-C8 alkoxy, aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;
• m and q are independently 0 or 1;
• n is 1;
• each R8a, R8b, R8c, R8d, R8e and R8f is independently H, hydroxyl, alkoxy, halo, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted C2-C8alkenyl, C1-C8 perhaloalkyl, carboxyl, carbonylalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or is taken together with a geminal R8(a-f) to form a substituted or unsubstituted methylene moiety or a moiety of the formula —OCH2CH2O—, or is taken together with a geminal R8(a-f) and the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or is taken together with a vicinal R8(a-f) and the carbon atoms to which they are attached to form a substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, or substituted or unsubstituted heterocyclyl moiety, or is taken together with a vicinal R8(a-f) to form a bond provided when an R8(a-f) is taken together with a vicinal R8(a-f) to form a bond, the geminal R8(a-f) is other than hydroxyl;
• and
• Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted amino, alkoxy, aminoacyl, acyloxy, carboxyl, carbonylalkoxy, cyano, alkynyl, aminocarbonylalkoxy or acylamino;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula (B):

• wherein:
• R2b is H, halo, or substituted or unsubstituted C1-C8 alkyl;
• each R3a and R3b is independently H, halo, or substituted or unsubstituted C1-C8 alkyl;
• each R10a and R10b is independently H, halo, or a substituted or unsubstituted C1-C8 alkyl;
• p is 1 or 2;
• each X7, X8, X9 and X10 is independently N or CR4;
• each R4 is independently H, hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, C1-C8 alkoxy, aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;
• m and q are independently 0 or 1;
• each R8a, R8b, R8c and R8d is independently H, hydroxyl, alkoxy, halo, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted C2-C8alkenyl, C1-C8 perhaloalkyl, carboxyl, carbonylalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or is taken together with a geminal R8(a-d) to form a substituted or unsubstituted methylene moiety or a moiety of the formula —OCH2CH2O—, or is taken together with a geminal R8(a-d) and the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety;
• each R11 and R12 is independently H, halo, alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C3-C8 cycloalkyl, carboxy, carbonylalkoxy or C1-C8 perhaloalkyl and the bond indicates the presence of either an E or Z double bond configuration, or R11 and R12 are taken together to form a bond or are taken together with the carbon atoms to which they are attached to form a substituted or unsubstituted C3-8 cycloalkenyl or substituted or unsubstituted heterocyclyl moiety;
• and
• Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted amino, alkoxy, aminoacyl, acyloxy, carboxyl, carbonylalkoxy, cyano, alkynyl, aminocarbonylalkoxy or acylamino;
• or a pharmaceutically acceptable salt thereof.

A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of a compound of the formula (I-1):

• wherein:
• R1 is H, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, carboxyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy, or R1 and R2a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R1 and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• each R2a and R2b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R2a and R2b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R2a and R1 are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R2a and R3a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety, or R2a and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• each R3a and R3b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, nitro, hydroxyl, alkoxy, substituted or unsubstituted amino, cycloalkyl, aryl, heteroaryl, heterocyclyl, acylamino or acyloxy or R3a and R3b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R3a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R3a and R2a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety, or R3a and R10a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• each R10a and R10b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, hydroxyl, alkoxy cyano, nitro, or R10a and R10b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R10a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R10a and R2a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R10a and R3a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• each X7, X8, X9 and X10 is independently N or CR4;
• each R4 is independently H, hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, C1-C8 alkoxy, aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;
• m and q are independently 0 or 1;
• n is 1;
• each R8a, R8b, R8c, R8d, R8e and R8f is independently H, hydroxyl, alkoxy, halo, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted C2-C8alkenyl, C1-C8 perhaloalkyl, carboxyl, carbonylalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or is taken together with a geminal R8(a-f) to form a substituted or unsubstituted methylene moiety or a moiety of the formula —OCH2CH2O—, or is taken together with a geminal R8(a-f) and the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or is taken together with a vicinal R8(a-f) and the carbon atoms to which they are attached to form a substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, or substituted or unsubstituted heterocyclyl moiety, or is taken together with a vicinal R8(a-f) to form a bond provided when an R8(a-f) is taken together with a vicinal R8(a-f) to form a bond, the geminal R8(a-f) is other than hydroxyl;
• Q is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted amino, alkoxy, aminoacyl, acyloxy, carboxyl, carbonylalkoxy, cyano, alkynyl, aminocarbonylalkoxy or acylamino;
• provided that the compound conforms to one of provisions (i)-(vi):
• (i) R1 and R2a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• (ii) R1 and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• (iii) R1 and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• (iv) R2a and R3a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety;
• (v) R2a and R10a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
• and (vi) R3a and R10a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
• or a pharmaceutically acceptable salt thereof.