Potassium channel modulators

1. A compound having formula (I-a):

or a stereoisomer thereof, or a pharmaceutically acceptable salt of the compound or stereoisomer, wherein

each T is independently G a , alkyl, halogen, haloalkyl, oxo, —CN, —NO 2 , —OR a , —NR a R b , —SR a , —S(O)R a , —S(O) 2 R a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —(CR za R zb ) m —CN, —(CR za R zb ) m —NO 2 , —(CR za R zb ) m —OR a , —(CR za R zb ) m —NR a R b , —(CR za R zb ) m —S(O)R a , —(CR za R zb ) m —S(O) 2 R a , —(CR za R zb ) m —C(O)R a , —(CR za R zb ) m —C(O)OR a , —(CR za R zb ) m —C(O)NR a R b , or —(CR za R zb ) m -G a ;

q is 0, 1, 2, 3, or 4;

X is C(O);

R 1 is G 1a or —(CR 1a R 1b ) n -G 1a ;

R 2 is alkyl;

G 1a is polycyclic cycloalkyl which is unsubstituted or substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of G a , alkyl, halogen, haloalkyl, oxo, —CN, —NO 2 , —OR a , —NR a R b , —SR a , —S(O)R a , —S(O) 2 R a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —(CR za R zb ) m —CN, —(CR za R zb ) m —NO 2 , —(CR za R zb ) m —OR a , —(CR za R zb ) m —NR a R b , —(CR za R zb ) m —SR a , —(CR za R zb ) m —S(O) 2 R a , —(CR za R zb ) m —C(O)R a , and —(CR za R zb ) m —C(O)NR a R b ;

G a , at each occurrence, is independently aryl or C 3 —C 6 cycloalkyl; each of which is independently unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, halogen, haloalkyl, oxo, —CN, —NO 2 , —OR a , —NR a R b , —SR a , —S(O)R a , —S(O) 2 R a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —(CR za R zb ) m —CN, —(CR za R zb ) m —NO 2 , —(CR za R zb ) m —OR a , —(CR za R zb ) m —NR a R b , —(CR za R zb ) m —SR a , —(CR za R zb ) m —S(O)R a , —(CR za R zb ) m —S(O) 2 R a , —(CR za R zb ) m —C(O)R a , —(CR za R zb ) m —C(O)OR a , and —(CR za R zb ) m —C(O)NR a R b ;

R a and R b , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;

R 1a and R 1b , at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl;

R za and R zb , at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl; and

m and n, at each occurrence, are each independently 1, 2, 3, or 4.

2. The compound or stereoisomer according to claim 1 , or a pharmaceutically acceptable salt of the compound or stereoisomer, wherein G 1a is optionally substituted hexahydro-2,5-methano-3a(1 H)-pentalene, optionally substituted adamantane, unsubstituted bicyclo[2.2.1]heptane, unsubstituted bicyclo[2.2.1]heptene, optionally substituted oxatricyclo[3.3.1.1 3,7 ]decane, unsubstituted bicyclo[3.2.1]octane, bicyclo[3.3.1]nonane unsubstituted or substituted with one oxo group, or unsubstituted tricyclo[3.2.1.0 2,4 ]octane.

3. The compound or stereoisomer according to claim 1 , or a pharmaceutically acceptable salt of the compound or stereoisomer, wherein the compound or stereoisomer is selected from the group consisting of:

2-(2-adamantyl)-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

2-(1-adamantyl)-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

2-(1-adamantyl)-N-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide;

2-(1-adamantyl)-N-(2-ethyl-4-oxoquinazolin-3(4H)-yl)acetamide;

(±)-exo-2-bicyclo[2.2.1]hept-2-yl-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

3-(1-adamantyl)-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)propanamide;

(±)-endo-2-bicyclo[2.2.1]hept-5-en-2-yl-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

2-[3-chloro-1-adamantyl]-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

(±)-endo-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)bicyclo[2.2.1]heptane-2-carboxamide;

(−)-exo-2-[bicyclo[2.2.1]hept-2-yl]-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

(+)-exo2-[bicyclo[2.2.1]hept-2-yl]-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

(±)-(endo)-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)bicyclo[2.2.1]hept-5-ene-2-carboxamide;

(±)-(exo)-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)bicyclo[2.2.1]hept-5-ene-2-carboxamide;

2-(1-adamantyl)-N-(7-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide;

(±)-2-[(endo)-bicyclo[2.2.1]hept-2-yl]-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide;

(±)-2-[(endo)-bicyclo[2.2.1]hept-2-yl]-N-(2-ethyl-4-oxoguinazolin-3(4H)-yl)acetamide;

N-(2-ethyl-4-oxoguinazolin-3(4H)-yl)-2-oxatricyclo[3.3.1.1 3,7 ]decane-1-carboxamide;

endo 2-[bicyclo[3.2.1]oct-3-yl]-N-(2-ethyl-4-oxoguinazolin-3(4H)-ypacetamide;

2-bicyclo[3.3.1]non-9-yl-N-(2-isopropyl-4-oxoguinazolin-3(4H)-yl)acetamide;

2-bicyclo[3.3.1]non-9-yl-N-(2-ethyl-4-oxoguinazolin-3(4H)-yl)acetamide;

(exo,exo)-N-(2-ethyl-4-oxoquinazolin-3(4H)-yl)tricyclo[3 .2.1.0 2,4 ]octane-3-carboxamide;

(exo,exo)-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)tricyclo[3.2.1.0 2,4 ]octane-3-carboxamide; and

endo-N-(2-isopropyl-4-oxoguinazolin-3(4H)-yl)-2-7-oxobicyclo[3.3.1]non-3-yl]acetamide.

4. A pharmaceutical composition comprising a therapeutically effective amount of a compound or stereoisomer of formula (I-a) according to claim 1 , or a pharmaceutically acceptable salt of the compound or stereoisomer, in combination with a pharmaceutically acceptable carrier.

5. A method for treating pain in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound or stereoisomer of formula (I-a) according to claim 1 , or a pharmaceutically acceptable salt of the compound or stereoisomer, alone or in combination with a pharmaceutically acceptable carrier.

6. A method for treating epilepsy, migraine, overactive bladder, schizophrenia, or anxiety in a subject in need thereof, said method comprises administering to the subject a therapeutically effective amount of a compound or stereoisomer of formula (I-a) according to claim 1 , or a pharmaceutically acceptable salt of the compound or stereoisomer, alone or in combination with a pharmaceutically acceptable carrier.

7. A method of activating KCNQ channels, comprising administering to a subject in need thereof a therapeutically effective amount of a compound or stereoisomer of formula (I-a) according to claim 1 , or a pharmaceutically acceptable salt of the compound or stereoisomer, alone or in combination with a pharmaceutically acceptable carrier.