6-alkoxy-pyrido-pyrimidines
The present invention provides compounds of the Formula I: wherein R 1 is alkyl, cycloalkyl, cycloallkylalkyl, or —CH 2 -alkenyl, X 1 is O, NH, N(alkyl), S or —C(═O), Z is N or CH; and R 2 and R 3 are as defined herein, pharmaceutical compositions comprising same, and methods for their use.
1. A method for treating a p38 mediated disorder comprising:
administering to a patient in need of such treatment, an effective amount of a compound of Formula I
or a pharmaceutically acceptable salt thereof,
wherein:
Z is CH;
X 1 is O, NR 4 (where R 4 is hydrogen or alkyl), S or C═O;
R 1 is alkyl, cycloalkyl, cycloalkylalkyl or —CH 2 -alkenyl;
R 2 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, haloalkyl, heteroalkyl, cyanoalkyl, alkylene-C(O)—R 21 (where R 21 is hydrogen, alkyl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino), amino, monoalkylamino, dialkylamino, acyl, or NR 22 —Y—R 23 (where Y is —C(O), —C(O)O—, —C(O)NR 24 , S(O) 2 or S(O) 2 NR 25 ; R 22 , R 24 and R 25 are independently hydrogen or alkyl; and R 23 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl or optionally-substituted phenyl); and
R 3 is alkyl, haloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, cycloalkylalkyl, heteroalkylsubstituted cycloalkyl, heterosubstituted cycloalkyl, heteroalkyl, cyanoalkyl, heterocyclyl, heterocyclylalkyl, or -heterocycloamino-SO 2 —R 12 (where R 12 is haloalkyl, aryl, aryalkyl, heteroaryl or heteroaralkyl).
2. The method of claim 1 , wherein said p38 mediated disorder is Alzheimer's disease.
3. The method of claim 1 , wherein X 1 is —O—.
4. The method of claim 3 , wherein R 1 is alkyl or cycloalkyl.
5. The method of claim 4 , wherein R 3 is cycloalkyl, cycloalkylalkyl, heteroalkylsubstituted cycloalkyl, heterosubstituted cycloalkyl, heteroalkyl, heterocyclyl or heterocyclylalkyl.
6. The method of claim 4 , wherein R 3 is cycloalkyl, heteroalkylsubstituted cycloalkyl, heterosubstituted cycloalkyl, heteroalkyl or heterocyclyl.
7. The method of claim 4 , wherein R 3 is optionally-substituted heterocyclyl.
8. The method of claim 4 , wherein R 3 is hydroxyalkyl or alkoxyalkyl.
9. The method of claim 4 , wherein R 2 is hydrogen, alkyl, aryl, cycloalkyl or heteroalkyl.
10. The method of claim 4 , wherein R 2 is alkyl or hydroxyalkyl.