	US 7,507,730 B2
	Substituted pyrazolo[1,5-a]pyrimidines as potassium channel activators
Wei Han, Yardley, Pa. (US); and Zilun Hu, Jamison, Pa. (US)
Assigned to Bristol-Myers Squibb Company, Princeton, N.J. (US)
Filed on Aug. 28, 2006, as Appl. No. 11/511,154.
Claims priority of provisional application 60/712497, filed on Aug. 30, 2005.
Prior Publication US 2007/0203157 A1, Aug. 30, 2007
Int. Cl. C07D 487/04 (2006.01); C07D 291/06 (2006.01); A61K 31/519 (2006.01); A61K 31/541 (2006.01); C07D 413/12 (2006.01); A61K 31/5355 (2006.01); A61P 25/06 (2006.01); A61P 9/06 (2006.01); A61P 25/08 (2006.01); A61P 1/04 (2006.01); A61P 11/08 (2006.01)

U.S. Cl. 514—222.2 [514/234.2; 514/259.3; 544/2; 544/117; 544/281]

14 Claims

1. A compound having the structure

or stereoisomers thereof or a phannaceutically acceptable salt thereof,

wherein Q is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl,

which is aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R¹and R²are the same or different and are independently selected from H, alkyl, substituted alkyl, halogen, carbocyclo, substituted carbocyclo, aryl, substituted aryl, heterocyclo, substituted heterocyclo, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, CO₂R^a, CONR^bR^c, NR^dR^e, So₂NR^fR^gor SO₂R^hRⁱwhere R^a, R^b, R^c, R^d, R^e, R^f, R^g, R^hand Rⁱare the same or different and are independently selected from H, alkyl or aryl;

R³is

where R⁸is aryl, substituted aryl, carbocyclo, substituted carbocyclo, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkyl, substituted alkyl, heterocyclo, or substituted heterocyclo; and

R⁹is H, alkyl, substituted alkyl, cycloalkyl or substituted cycloalkyl;

and wherein R⁸and R⁹together with the atoms to which they are bonded may optionally form a heterocyclic group or a substituted heterocyclic group;

R⁴is alkyl or substituted alkyl;

R⁵is H, alkyl or substituted alkyl;

R⁶and R⁷are the same or different and are independently selected from H, alkyl, substituted alkyl or polyhaloalkyl;

wherein

the term “substituted alkyl” refers to alkyl groups substituted with one or more groups selected from alkyl, aryl (optionally substituted), substituted aryl, heterocyclo, substituted heterocyclo, carbocyclo, substituted carbocyclo, halo, hydroxy, arylalkoxy (optionally substituted), alkoxy (optionally substituted), aryloxy (optionally substituted), alkylester (optionally substituted), arylester (optionally substituted), alkanoyl (optionally substituted), aroyl (optionally substituted), cyano, nitro, amino, substituted amino, amido, lactam, urea, urethane, and sulfonyl;

the term “substituted alkenyl” refers to alkenyl groups substituted with one or more groups selected from alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, carbocyclo, substituted carbocyclo, halo, hydroxy, alkoxy (optionally substituted), aryloxy (optionally substituted), alkylester (optionally substituted), arylester (optionally substituted), alkanoyl (optionally substituted), aroyl (optionally substituted), cyano, nitro, amino, substituted amino, amido, lactam, urea, urethane, and sulfonyl;

the term “substituted alkynyl” refers to alkynyl groups substituted with one or more groups selected from alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, carbocyclo, substituted carbocyclo, halo, hydroxy, alkoxy (optionally substituted), aryloxy (optionally substituted), alkylester (optionally substituted), arylester (optionally substituted), alkanoyl (optionally substituted), aroyl (optionally substituted), cyano, nitro, amino, substituted amino, amido, lactam, urea, urethane, and sulfonyl;

the term “substituted aryl” refers to aryl groups substituted with one or more groups selected from alkyl, substituted alkyl, alkenyl (optionally substituted), aryl (optionally substituted), heterocyclo (optionally substituted), halo, hydroxy, alkoxy (optionally substituted), aryloxy (optionally substituted), alkanoyl (optionally substituted), aroyl, (optionally substituted), alkylester (optionally substituted), arylester (optionally substituted), cyano, nitro, amino, substituted amino, amido, lactam, urea, urethane, and sulfonyl, where optionally one or more pair of substituents may together with the atoms to which they are bonded form a 3 to 7 member ring;

the terms “substituted carbocyclo”, “substituted cycloalky” and “refer to cycloalkyl groups ” refer to cycloalkyl groups and cycloalkenyl groups substituted with one or more groups selected from alkyl, substututed alkyl, aryl substituted aryl, heterocyclo, substituted heterocyclo, carbocyclo, substituted carbocyclo, halo, hydroxy, alkoxy (optionally substituted), aryloxy (optionally substituted), alkylester (optionally substituted), arylester (optionally substituted), alkanoyl (optionally substituted), aroyl (optionally substituted), cyano, nitro, amino, substituted amino, amido, lactam, urea, urethane, and sulfonyl; and

the terms “substituted heterocyclo” , “substituted cycloheteroalkyl” and “substituted heteroaryl” refer to heterocyclo, cycloheteroalkyl and heteroaryl groups, respectively, substituted with one or more groups selected from alkyl, substituted alkyl, alkenyl, oxo aryl, substituted aryl, heterocyclo, substituted heterocyclo, carbocyclo (optionally substituted), halo, hydroxy, alkoxy (optionally substituted), aryloxy (optionally substituted), alkanoyl (optionally substituted), aroyl (optionally substituted), alkylester (optionally substituted), arylester (optionally substituted), cyano, nitro, amido, amino, substituted amino, lactam, urea, urethane, and sulfonyl, where optionally one or more pair of substituents together with the atoms to which they are bonded form a 3 to 7 member ring.