IP Library › Granted Patent US 9,040,519

Granted Patent B2

US 9,040,519 · App. 13/579,911 · Granted May 26, 2015

Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use

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Quick Facts

Patent No.: US 9,040,519
App. No.: 13/579,911
Granted: May 26, 2015
Kind: B2

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Abstract

This disclosure is directed to fused tetracyclic pyrido[4,3-b>]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Claims (106)

1. A compound of the formula (VA):

or a salt thereof; wherein:

R 1 is H, hydroxyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8 perhaloalkoxy, alkoxy, aryloxy, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy, or R 1 and R 2a are taken together to form a propylene (—CH 2 CH 2 CH 2 —) moiety or a butylene (—CH 2 CH 2 CH 2 CH 2 —) moiety, or R 1 and R 3a are taken together to form a propylene (—CH 2 CH 2 CH 2 —) moiety or a butylene (—CH 2 CH 2 CH 2 CH 2 —) moiety, or R 1 and R 4 are taken together to form an ethylene (—CH 2 CH 2 —) moiety or a propylene (—CH 2 CH 2 CH 2 —) moiety;

each R 2a and R 2b is independently H, substituted or unsubstituted C 1 -C 8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro, substituted or unsubstituted amino, acyloxy, acylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, or R 2a and R 2b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R 2a and R 1 are taken together to form a propylene (—CH 2 CH 2 CH 2 —) moiety or a butylene (—CH 2 CH 2 CH 2 CH 2 —) moiety, or R 2a and R 3a are taken together to form an ethylene (—CH 2 —CH 2 —) moiety or a propylene (—CH 2 CH 2 —CH 2 —) moiety, or R 2a and R 4 are taken together to form a methylene (—CH 2 —) moiety or an ethylene (—CH 2 CH 2 —) moiety;

each R 3a and R 3b is independently H, substituted or unsubstituted C 1 -C 8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro, substituted or unsubstituted amino, acyloxy, acylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, or R 3a and R 3b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R 3a and R 1 are taken together to form a propylene (—CH 2 CH 2 CH 2 —) moiety or a butylene (—CH 2 CH 2 CH 2 CH 2 —) moiety, or R 3a and R 2a are taken together to form an ethylene (—CH 2 CH 2 —) moiety or a propylene (—CH 2 CH 2 CH 2 —) moiety, or R 3a and R 4 are taken together to form a propylene (—CH 2 CH 2 CH 2 —) moiety or a butylene (—CH 2 CH 2 CH 2 CH 2 —) moiety;

R 4 is H, substituted or unsubstituted C 1 -C 8 alkyl, halo, cyano, nitro, substituted or unsubstituted amino, hydroxyl, alkoxy, acyloxy, acylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, or R 4 and R 1 are taken together to form an ethylene (—CH 2 CH 2 —) moiety or a propylene (—CH 2 CH 2 CH 2 —) moiety, or R 4 and R 2a are taken together to form a methylene (—CH 2 —) moiety or an ethylene (—CH 2 CH 2 —) moiety, or R 4 and R 3a are taken together to form a propylene (—CH 2 CH 2 CH 2 —) moiety or a butylene (—CH 2 CH 2 CH 2 CH 2 —) moiety, or R 4 and R 7a are taken together to form a bond;

each R 5a and R 5b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 5a and a vicinal R 7(a-h) , where applicable, are taken together to form a bond;

each X 1 , X 2 , X 3 and X 4 is independently N, CH or CR 6 ;

Y 1 is CR 7a R 7b , NR 8 , O, S, S(O) or SO 2 , provided that when Y 1 is NR 8 , O, S, S(O) or SO 2 , then Y 2 is CR 7c R 7d or is taken together with Y 3 and Y 4 to form a bond,

Y 2 is CR 7c R 7d , NR 8 , O, S, S(O) or SO 2 , or Y 2 is taken together with Y 3 and Y 4 to form a bond, provided that when Y 2 is NR 8 , O, S, S(O) or SO 2 , then Y 1 is CR 7a R 7b and Y 3 is CR 7e R 7f or is taken together with Y 4 to form a bond;

Y 3 is CR 7e R 7f , NR 8 , O, S, S(O) or SO 2 , or Y 3 is taken together with Y 4 to form a bond, provided that when Y 3 is NR 8 , O, S, S(O) or SO 2 , then Y 2 is CR 7c R 7d and Y 4 is CR 7g R 7h or a bond;

Y 4 is CR 7g R 7h , NR 8 , O, S, S(O) or SO 2 , or Y 4 is a bond, provided that when Y 4 is NR 8 , O, S, S(O) or SO 2 , then Y 3 is CR 7e R 7f ;

each R 6 is independently hydroxyl, nitro, cyano, halo, C 1 -C 8 perhaloalkyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 1 -C 8 alkoxy, substituted or unsubstituted 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;

each R 7a and R 7b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7a and R 7b are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7a and R 4 are taken together to form a bond, or R 7a and R 7c , where applicable, are taken together to form a bond, or R 7a and a vicinal R 5a , where applicable, are taken together to form a bond;

each R 7c and R 7d , where applicable, is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7c and R 7d are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7c and R 7a are taken together to form a bond, or R 7c and R 7e , where applicable, are taken together to form a bond, or R 7c and a vicinal R 5a , where applicable, are taken together to form a bond;

each R 7e and R 7f , where applicable, is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7e and R 7f are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7e and R 7c are taken together to form a bond, or R 7e and R 7g , where applicable, are taken together to form a bond, or R 7e and a vicinal R 5a , where applicable, are taken together to form a bond;

each R 7g and R 7h , where applicable, is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7g and R 7h are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7g and R 7e are taken together to form a bond, or R 7g and R 5a are taken together to form a bond; and

each R 8 is independently H, hydroxyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8 perhaloalkoxy, alkoxy, aryloxy, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy;

provided that (1) at least one of X 1 , X 2 , X 3 and X 4 is CH or CR 6 ; and (2) at least one of R 5a , R 5b , R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g and R 7h is a group containing a cyclic moiety.

2. The compound of claim 1 , or a salt thereof, wherein the compound is of the formula (VA1):

wherein:

each X 1 , X 3 and X 4 is independently N or CH; and

each R 7a and R 7b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7a and R 4 are taken together to form a bond, or R 7a and R 7c , where applicable, are taken together to form a bond, or R 7a and a vicinal R 5a , where applicable, are taken together to form a bond.

3. The compound of claim 1 , or a salt thereof, wherein the compound is of the formula (VA2):

wherein:

R 1 is H or substituted or unsubstituted C 1 -C 8 alkyl;

R 4 is H, substituted or unsubstituted C 1 -C 8 alkyl, or is taken together with R 7a to form a bond;

each X 1 , X 3 and X 4 is independently N or CH;

Y 2 is O or CR 7c R 7d , or Y 2 is taken together with Y 3 and Y 4 to form a bond, provided that when Y 2 is O, then Y 1 is CR 7a R 7b and Y 3 is CR 7e R 7f or is taken together with Y 4 to form a bond;

Y 3 is O or CR 7e R 7f , or Y 3 is taken together with Y 4 to form a bond, provided that when Y 3 is O, then Y 2 is CR 7c R 7d and Y 4 is CR 7g R 7b or a bond;

Y 4 is CR 7g R 7b , or Y 4 is a bond; and

each R 7a and R 7b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7a and R 4 are taken together to form a bond, or R 7a and R 7c , where applicable, are taken together to form a bond, or R 7a and a vicinal R 5a , where applicable, are taken together to form a bond.

4. The compound of claim 3 , or a salt thereof, wherein R 4 is H or methyl.

5. The compound of claim 3 , or a salt thereof, wherein each R 5a , R 5b , R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 7g and R 7h , where applicable, is independently H, hydroxyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, or acylamino, or R 5a and a vicinal R 7(a-h) , where applicable, are taken together to form a bond.

6. The compound of claim 1 , or a salt thereof, wherein the group containing a cyclic moiety is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocyclyl.

7. The compound of claim 1 , or a salt thereof, wherein the group containing a cyclic moiety is a C 1 -C 8 alkyl, or a C 2 -C 8 alkenyl, substituted with a group selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocyclyl.

8. The compound of claim 1 , wherein the compound is of the formula (IA):

or a salt thereof;

wherein:

each X 1 , X 2 , X 3 and X 4 is independently N, CH or CR 6 ;

Y 1 is CR 7a R 7b , NR 8 , O, S, S(O) or SO 2 ;

each R 7a and R 7b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7a and R 7b are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7a and R 5a are taken together to form a bond, or R 7a and R 4 are taken together to form a bond; and

R 8 is H, hydroxyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8 perhaloalkoxy, alkoxy, aryloxy, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy.

9. The compound of claim 1 , wherein the compound is of the formula (IIA):

or a salt thereof;

wherein:

each X 1 , X 2 , X 3 and X 4 is independently N, CH or CR 6 ;

Y 1 is CR 7a R 7b , NR 8 , O, S, S(O) or SO 2 , provided that when Y 1 is NR 8 , O, S, S(O) or SO 2 , then Y 2 is CR 7c R 7d ;

Y 2 is CR 7c R 7d , NR 8 , O, S, S(O) or SO 2 , provided that when Y 2 is NR 8 , O, S, S(O) or SO 2 , then Y 1 is CR 7a R 7b ;

each R 7a and R 7b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7a and R 7b are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7a and R 7c are taken together to form a bond, or R 7a and R 4 are taken together to form a bond;

each R 7c and R 7d is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7c and R 7d are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7c and R 7a are taken together to form a bond, or R 7c and R 5a are taken together to form a bond; and

provided that when each X 1 , X 2 , X 3 and X 4 is CH, each R 2a , R 2b , R 3a , R 3b , R 4 , R 5a and R 5b is H, Y 1 is carbonyl and Y 2 is CH 2 , R 1 is other than hydrogen.

10. The compound of claim 1 , wherein the compound is of the formula (IIIA):

or a salt thereof;

wherein:

each X 1 , X 2 , X 3 and X 4 is independently N, CH or CR 6 ;

Y 1 is CR 7a R 7b , NR 8 , O, S, S(O) or SO 2 , provided that when Y 1 is NR 8 , O, S, S(O) or SO 2 , then Y 2 is CR 7c R 7d ;

Y 2 is CR 7c R 7d , NR 8 , O, S, S(O) or SO 2 , provided that when Y 2 is NR 8 , O, S, S(O) or SO 2 , then Y 1 is CR 7a R 7b and Y 3 is CR 7e R 7f ;

Y 3 is CR 7e R 7f , NR 8 , O, S, S(O) or SO 2 , provided that when Y 3 is NR 8 , O, S, S(O) or SO 2 , then Y 2 is CR 7c R 7d ;

each R 7a and R 7b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7a and R 7b are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7a and R 7c are taken together to form a bond, or R 7a and R 4 are taken together to form a bond;

each R 7e and R 7f is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7e and R 7f are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7e and R 7c are taken together to form a bond, or R 7e and R 5a are taken together to form a bond; and

11. The compound of claim 1 , wherein the compound is of the formula (IVA):

or a salt thereof;

wherein:

each X 1 , X 2 , X 3 and X 4 is independently N, CH or CR 6 ;

Y 1 is CR 7a R 7b , NR 8 , O, S, S(O) or SO 2 , provided that when Y 1 is NR 8 , O, S, S(O) or SO 2 , then Y 2 is CR 7c R 7d ;

Y 2 is CR 7c R 7d , NR 8 , O, S, S(O) or SO 2 , provided that when Y 2 is NR 8 , O, S, S(O) or SO 2 , then Y 1 is CR 7a R 7b and Y 3 is CR 7e R 7f ;

Y 3 is CR 7e R 7f , NR 8 , O, S, S(O) or SO 2 , provided that when Y 3 is NR 8 , O, S, S(O) or SO 2 , then Y 2 is CR 7c R 7d and Y 4 is CR 7g R 7h ;

Y 4 is CR 7g R 7h , NR 8 , O, S, S(O) or SO 2 , provided that when Y 4 is NR 8 , O, S, S(O) or SO 2 , then Y 3 is CR 7e R 7f ;

each R 7a and R 7b is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7a and R 7b are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7a and R 7c are taken together to form a bond, or R 7a and R 4 are taken together to form a bond;

each R 7g and R 7h is independently H, hydroxyl, halo, nitro, cyano, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkoxy, C 1 -C 8 perhaloalkyl, C 1 -C 8 perhaloalkoxy, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted amino, aminoacyl, acyl, acylamino, acyloxy, carbonylalkoxy, carboxyl, thiol, thioalkyl, aminocarbonylamino, aminocarbonylalkoxy, aminosulfonyl, or sulfonylamino, or R 7g and R 7h are taken together with the carbon to which they are attached to form a carbonyl moiety, or R 7g and R 7e are taken together to form a bond, or R 7g and R 5a are taken together to form a bond; and

12. A compound selected from the group consisting of compounds 1-12, 15-16, 18-21, 23-26, 28-62, 64-67, 69-72, 74-85, 87-90, 92-107, 109-112, 114-117, 119-122, 124-127, 129-132, 134-137, 139-142, 144-153, 155-166, 169-170, 173, 175, 177-178, 180, and 187-236, or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising (a) a compound of claim 1 or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier.

14. 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 claim 1 or a pharmaceutically acceptable salt thereof.

15. 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 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of compounds 15-16, 18-21, 23-26, 28-62, 64-67, 69-72, 74-85, 1-12, 87-90, 92-107, 109-112, 114-117, 119-122, 124-127, 129-132, 134-137, 139-142, 144-153, 155-166, 169-170, 173, 175, 177-178, 180, and 187-236.

16. A kit comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and instructions for use in the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder.

Assignments (5)

RELEASE OF SECURITY INTEREST Recorded Sep 28, 2016

From: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT

To: MEDIVATION PROSTATE THERAPEUTICS, INC.; MEDIVATION TECHNOLOGIES, INC.

Reel/Frame 040181/0177 →

CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Sep 4, 2015

From: MEDIVATION TECHNOLOGIES, INC.

To: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT

Reel/Frame 036553/0925 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2015

From: CHAKRAVARTY, SARVAJIT; HART, BARRY PATRICK

To: MEDIVATION TECHNOLOGIES, INC.