	US 7,531,547 B2
	Diaminopyrimidines as P2X3 and P2X2/3 modulators
Michael Patrick Dillon, San Francisco, Calif. (US); Alam Jahangir, San Jose, Calif. (US); Amy Geraldine Moore, Mountain View, Calif. (US); and Paul J. Wagner, Mountain View, Calif. (US)
Assigned to Roche Palo Alto LLC, Palo Alto, Calif. (US)
Filed on Aug. 25, 2006, as Appl. No. 11/510,216.
Claims priority of provisional application 60/713399, filed on Sep. 01, 2005.
Prior Publication US 2007/0049758 A1, Mar. 01, 2007
Int. Cl. C07D 239/48 (2006.01); C07D 239/50 (2006.01); A61K 31/505 (2006.01); A61P 11/06 (2006.01)

U.S. Cl. 514—269 [514/272; 514/275; 544/298; 544/323; 544/324]

16 Claims

1. A compound of formula (1):

or a pharmaceutically acceptable salt thereof,

wherein:

X is:

—CR₂—;

—O—;

—S(O)_n—;

or —NR^c—

wherein

n is from 0 to 2 and

R^cis hydrogen or alkyl;

D is an optional oxygen;

R¹is:

ethyl;

isopropyl;

iodo;

ethynyl; or

cyclopropyl;

R², R⁴and R⁶are hydrogen;

R³is:

hydrogen;

alkyl;

alkenyl;

amino;

halo;

amido;

haloalkyl;

alkoxy;

hydroxy;

haloalkoxy;

nitro; amino;

hydroxyalkyl;

alkoxyalkyl;

hydroxyalkoxy;

alkynylalkoxy;

alkylsulfonyl;

arylsulfonyl;

cyano;

aryl;

heteroaryl;

heterocyclyl;

heterocyclylalkoxy;

aryloxy;

heteroaryloxy;

aralkyloxy;

heteroaralkyloxy;

optionally substituted phenoxy;

—C=C—R^u;

—(CH₂)_m-(Z)_n-(CO)—R^b;

—(CH₂)_m-(Z)_n-SO₂—(NR^c)_nR^b

wherein

m and n each independently is 0 or 1,

Z is O or NR^c,

R^ais hydrogen; alkyl; aryl; aralkyl; heteroaryl; heteroaralkyl; hydroxyalkyl; alkoxyalkyl; alkylsulfonylalkyl; aminoalkyl; cyanoalkyl; alkylsilyl, cycloalkyl, cycloalkylalkyl; heterocycl; and heterocyclylalkyl;

R^bis hydrogen, alkyl, hydroxy, alkoxy, amino, hydroxyalkyl or alkoxyalkyl, and

each R^cis independently hydrogen or alkyl;

or R²and R³together with the atoms to which they are attached may form a five or six-membered ring that optionally includes one or two heteroatoms selected from O, S and N;

R⁵is:

hydrogen;

alkyl;

aryl;

aralkyl;

heteroaryl;

heteroaralkyl;

hydroxyalkyl;

alkoxyalkyl;

alkylsulfonylalkyl;

aminoalkyl;

cyanoalkyl;

alkylsilyl,

cycloalkyl,

cycloalkylalkyl;

heterocycl; or

heterocyclylalkyl; and

R⁷and R⁸each independently is:

hydrogen;

alkyl;

aminoalkyl;

aminosulfonyl;

cycloalkyl;

cycloalkylalkyl;

haloalkyl;

haloalkoxy;

hydroxyalkyl;

alkoxyalkyl;

alkylsulfonyl;

alkylsulfonylalkyl;

aminocarbonyloxyalkyl;

hydroxycarbonylalkyl;

hydroxyalkyloxycarbonylalkyl;

aryl;

aralkyl;

arylsulfonyl;

heteroaryl;

heteroarylalkyl;

heteroarylsulfonyl;

heterocyclyl; or

heterocyclylalkyl.