Pyridopyrimidine derivatives and use thereof
The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.
1. A compound of formula I,
Wherein X is O or N or S;
Y is CH or N;
R 1 is selected from the group consisting of: C3-C7cycloalkyl, substituted C3-C7cycloalkyl, C3-C7heterocycloalkyl, substituted C3-C7 heterocycloalkyl, alkylcarboxy, arylamino, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, substituted arylcycloalkyl, heteroarylalkyl, and substituted heteroarylalkyl;
R 2 is selected from the group consisting of: hydrogen, halogen, acyl, amino, substituted amino, C1-C6alkyl, substituted C1-C6alkyl, C3-C7cycloalkyl, substituted C3-7Ccycloalkyl, C3-7Cheterocycloalkyl, substituted C3-C7heterocycloalkyl, alkylcarboxy, arylamino, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, arylcycloalkyl, substituted arylcycloalkyl, heteroarylalkyl, substituted heteroarylalkyl, cyano, nitro, alkoxy, C3-C7cycloalkyloxy, substituted C3-C7cycloalkyloxy, C3-C7heterocycloalkyloxy, substituted C3-7Cheterocycloalkyloxy, acyloxy, aryloxy;
R 3 =NR 4′ SO 2 R 4 or SO 2 NR 4′ R 4 ;
R 4 is selected from the group consisting of: alkyl, substituted alkyl, amino, halo, C3-C7cycloalkyl, substituted C3-C7cycloalkyl, C3-C7heterocycloalkyl, substituted C3-C7heterocycloalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl;
R 4′ is H or C1-C6 alkyl;
R 5 is selected from the group consisting of: hydrogen, halogen, C1-C6alkyl;
R 6 is selected from the group consisting of: hydrogen, halogen, acyl, alkoxy, amino, substituted amino, arylamino, C1-C6alkyl, substituted C1-C6 alkyl, C3-C7cycloalkyl, substituted C3-C7cycloalkyl, C3-C7heterocycloalkyl, substituted C3-C7heterocycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
n is 0 or 1; m is 0 or 1;
or a pharmaceutically acceptable salt, or tautomer thereof.
2. A compound according to claim 1 which is selected from the following
or a pharmaceutically acceptable salt, ester, or tautomer thereof.
3. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of any of claims 1 to 2 or a pharmaceutically acceptable salt, ester, or tautomer thereof, and a pharmaceutically acceptable carrier.