COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY
The invention encompasses compounds having formula I and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK3, are therapeutically useful.
1 . A compound of formula I:
or a solvate, prodrug or pharmaceutically acceptable salt thereof, wherein:
X is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halo, nitro, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl;
Y is selected from the group consisting of hydrogen, alkyl substituted alkyl, amino, substituted amino, and halo;
R is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl and substituted cycloalkyl;
ring A is selected from the group consisting of aryl, heteroaryl, cycloalkyl, cycloalkenyl and
heterocyclic, wherein ring A is not indolyl or benzimidazolyl;
p is 0, 1, 2 or 3;
q is 1, 2 or 3 when ring A is a single ring, or q is 0, 1, 2, 3, 4, or 5 when ring A comprises multiple rings;
each R 2 independently is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, aryl, substituted aryl, aryloxy, substituted aryloxy, cycloalkyl, substituted cycloalkyl heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, heterocyclyloxy, substituted carboxyl, carboxyl ester, hydroxyl, acylamino, aminosulfonyl, alkynyl, substituted alkynyl, alkylthio, substituted alkylthio, aminocarbonyl, acyl, oxo, and halo;
each R 3 independently is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocyclic, substituted heterocyclic, halo, and aminosulfonyl; and
R 4 and R 5 independently are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, cycloalkyl, substituted cycloalkyl, and acyl; or
R 4 and R 5 together with the nitrogen atom bound thereto, form a heterocyclic or substituted heterocyclic group;
provided that:
if q=O, then X is not bromo;
if ring A is cycloalkyl, then X is not bromo;
if q=2 and each of R 2 is methoxy, halo, trihalomethyl or trihalomethoxy, then R 4 and R 5 are not one hydrogen and one methyl;
if q=2 and R 2 is fluoro and methyl, then R is not substituted alkenyl; and
if ring A is phenyl, q=1 and R 2 is chloro, then R 4 and R 5 are not one hydrogen and one methyl.
2 - 28 . (canceled)